Vancomycin

Ther Drug Monit, 2000 Jun, 22(3), 250 - 7
Effects of hepatic function on vancomycin pharmacokinetics in patients with cancer; Aldaz A et al.; Vancomycin is widely used in the prophylaxis and treatment of infections in neutropenic patients with cancer . The objective of this study was to analyze liver damage effects on vancomycin pharmacokinetics and determine the necessity for liver function evaluation when selecting vancomycin dosing schedules in these patients . A population pharmacokinetic analysis was performed using the global two-stage method . To this purpose serum vancomycin concentrations from 154 cancer patients were measured and individual vancomycin pharmacokinetic parameters were estimated by the Sawchuk and Zaske method . Mean and standard deviation of the vancomycin pharmacokinetic parameters were estimated for various subgroups of patients classified according to the degree of liver damage . Then a multiple linear regression analysis was performed to select the best predictive models for vancomycin clearance (Clvan) and steady state distribution volume (V) . Results revealed that Clvan is not influenced by liver failure . Differences in V between patients with and without hepatic failure were initially observed, but these disappeared when patients with ascites were excluded . In conclusion, vancomycin dosing schedule does not need to be modified for patients with liver failure, with the exception of patients with ascites.

J Pharm Sci, 2000 Jun, 89(6), 742 - 50
Effect of conformation on the rate of deamidation of vancomycin in aqueous solutions; Antipas AS et al.; The instability of vancomycin, a glycopeptide antibiotic, limits its shelf-life because the deamidation of its asparagine residue results in the formation of a zwitterion with limited aqueous solubility . Analysis of the pH-rate profile for vancomycin indicates that the deamidation reaction is notably sensitive to the ionic state of the molecule . This observation results in a hypothesis in which the ionic state of vancomycin may influence the conformation of the molecule and therefore affect its reactivity . Two-dimensional nuclear magnetic resonance (NMR), homonuclear Hartmann-Hahn (HOHAHA) and rotating frame Overhauser enhancement spectroscopy (ROESY) information combined with molecular dynamic simulations were used to estimate the apparent conformation of vancomycin in aqueous solution at pH 4 and pH 9 where the molecule exists primarily as a monocation and monoanion, respectively . The apparent conformation for vancomycin at pH 4 is compact, and the proximity of the backbone amide nitrogen to the side chain carbonyl carbon of asparagine is favorable for the rapid formation of the cyclic imide intermediate, thus increasing its reactivity . The apparent conformation for vancomycin at pH 9, however, is expanded in comparison with the conformation at pH 4, and the increase in distance between the reacting atoms leads to slower cyclic imide formation and thus decreased intrinsic reactivity . That cyclic imide formation was rate limiting at both pH values was confirmed by cyclic imide isolation and stability estimation . It becomes apparent from the analysis of the pH-rate and conformational profiles of vancomycin that the deamidation rate of vancomycin is largely influenced by the ionization state of the N-methyl leucine nitrogen .

Org Lett, 1999 Jul 29, 1(2), 295 - 7
Synthesis of beta-hydroxy-beta-(fluoronitrophenyl)alanines: vital components in the assembly of biologically active cyclic peptides; Hutton CA; {formula: see text} Numerous biologically active cyclic peptides, such as the antibiotic vancomycin, contain amino acid residues connected through side-chain biaryl or aryl-alkyl ether linkages . Nucleophilic aromatic substitution reactions have recently been shown to provide a general method for the formation of such ether linkages, and consequently the synthesis of functionalized fluoronitro-substituted aromatic amino acids is of great interest . Herein, a method for the stereospecific synthesis of 3-fluoro-4-nitro- and 4-fluoro-3-nitro-threo-beta-hydroxyphenylalanine is described.

Analyst, 2000 Feb, 125(2), 231 - 4
A comparison of vancomycin and sulfated beta-cyclodextrin as chiral selectors for enantiomeric separations of selenoamino acids using capillary electrophoresis with UV absorbance detection; Sutton KL et al.; The enantiomeric separation of three selenoamino acids, D,L-selenomethionine, D,L-selenoethionine and D,L-selenocystine is described . Both sulfated beta-cyclodextrin and vancomycin have been successfully used to separate all enantiomers of the compounds with UV detection . Reproducible separations, in terms of peak area and migration time were obtained using sulfated beta-cyclodextrin with reversed polarity and UV detection . With vancomycin as a chiral selector, reversed polarity was found to be more reproducible than positive polarity in terms of peak migration times.

Antimicrob Agents Chemother, 2000 Jun, 44(6), 1701 - 4
Characterization of a Mycobacterium smegmatis mutant that is simultaneously resistant to D-cycloserine and vancomycin; Peteroy M et al.; A mutant of Mycobacterium smegmatis has been isolated that is simultaneously resistant to both D-cycloserine (D-CS) and vancomycin . Genetic complementation with a PBP4 homolog restores sensitivity to both drugs . Resistance to D-CS and vancomycin in this mutant is most likely due to a novel mechanism involving peptidoglycan assembly at the cell surface.

Rinsho Byori, 2000 Jan, Suppl 111, 26 - 35
{Drug-resistant bacteria of current topics and their resistance mechanisms--VRE}; Ike Y; VRE isolates have only been detected in eight patients from four hospitals in Japan since 1996(reports of the Ministry of Health and Welfare, Japan) . In Japan, it has been shown that VRE are high frequently isolated from chickens imported from Thailand and France where avoparcin has been used in animal feed . Two types of acquired glycopeptide resistance have been reported in clinical isolates of VRE . The VanA type strain is defined as having a high-level resistance to vancomycin and teicoplanin . The vanA resistance genes are induced by both vancomycin and teicoplanin . VanB type strains are characterized as having various levels of vancomycin resistance and are susceptible to teicoplanin . The vanB resistance genes are induced by vancomycin only.

Schweiz Med Wochenschr, 2000 Apr 8, 130(14), 505 - 9
{Fever of unknown origin as a sign of calcium pyrophosphate deposition disease}; Aeberli D et al.; Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease may manifest clinically as septic fever (40 degrees C), acute pseudogout attack of knee, wrist and shoulders, or as a variety of patterns of chronic inflammatory or degenerative joint disease . The association of pseudogout with fever is less widely recognised and may lead to over-investigation, delay in appropriate treatment and disproportionate costs . We report on a 67-year-old woman with a history of recurrent episodes of fever and polyarthritis every 2 months for the last 3 years . Because of this she was hospitalised several times, finally with suspected culture-negative endocarditis, and was treated for 6 weeks with gentamicin, rifampicin and vancomycin . During this therapy the patient again developed septic fever and acute arthritis of the right wrist . Radiographs of the wrist, knee and symphysis pubis revealed prominent chondrocalcinosis and destructive arthropathy.

Clin Pharmacol Ther, 2000 Apr, 67(4), 360 - 7
Vancomycin population pharmacokinetics in neonates; de Hoog M et al.; BACKGROUND: Recently the value of vancomycin therapeutic drug monitoring, as well as the required therapeutic range, has been subject of debate, resulting in new recommendations . This study was performed to incorporate these new insights in an up-to-date dosing scheme for neonates of various gestational ages . METHODS: In this retrospective study with prospective validation, 108 newborns with suspected central line-related septicemia during the first month of life received 30 mg/kg/day vancomycin divided into two doses regardless of gestational or postconceptional age . Trough and peak vancomycin serum concentrations were determined before and after the third dose . Vancomycin data were analyzed according to a one-compartment open model with use of NONMEM population pharmacokinetic software . Model parameters were evaluated and then used to simulate vancomycin dosing for different dose and dose interval combinations . Targets were a trough concentration between 5 and 15 mg/L and a peak below 40 mg/L . In the prospective study, the optimal scheme was tested in 22 patients . RESULTS: Of the 108 patients, 34.3% of measured trough concentrations and 17.6% of peak concentrations were outside the desired therapeutic range . The model that best fitted the data included clearance and volume per kilogram and was independent of gestational age . Simulation of various dosing schemes showed that a dosing schedule of 30 mg/kg/day, irrespective of gestational age, in three doses was optimal, and this scheme was prospectively tested . Mean trough concentrations before the second dose were 8.2 +/- 2.2 mg/L versus a predicted trough of 8.9 +/- 2.5 mg/L . No peak levels higher than 40 mg/L were found . CONCLUSIONS: The use of the proposed schedule leads to adequate vancomycin trough serum concentrations, and there is no need for routine monitoring of peak serum concentrations.

Anal Biochem, 2000 May 1, 280(2), 209 - 15
Estimation of receptor-ligand interactions by the use of a two-marker system in affinity capillary electrophoresis; Mito E et al.; The study of receptor-ligand interactions by affinity capillary electrophoresis (ACE) requires an accurate form of analysis . Here, we examine the use of two noninteracting standards (markers) in the analysis of binding constant data in ACE studies . This concept is demonstrated using two model systems: carbonic anhydrase B (CAB, EC 4.2.1.1) and arylsulfonamides, and vancomycin (Van) from Streptomyces orientalis and the dipeptide N-acetyl-d-Ala-d-Ala . In this procedure a plug of receptor and noninteracting standards is injected, and analysis of the change in the relative migration time ratio of the receptor, relative to the noninteracting standards, as a function of the concentration of the ligand yields a value for the binding constant . The findings described here demonstrate that data from ACE studies can best be analyzed using two noninteracting standards, yielding values comparable to those estimated using other binding and ACE techniques .

Appl Environ Microbiol, 2000 May, 66(5), 2066 - 70
Comparison of methods for detection of Erysipelothrix spp . and their distribution in some Australasian seafoods; Fidalgo SG et al.; For many years, Erysipelothrix rhusiopathiae has been known to be the causative agent of the occupationally related infection erysipeloid . A survey of the distribution of Erysipelothrix spp . in 19 Australasian seafoods was conducted, and methodologies for the detection of Erysipelothrix spp . were evaluated . Twenty-one Erysipelothrix spp . were isolated from 52 seafood parts . Primary isolation of Erysipelothrix spp . was most efficiently achieved with brain heart infusion broth enrichment followed by subculture onto a selective brain heart infusion agar containing kanamycin, neomycin, and vancomycin after 48 h of incubation . Selective tryptic soy broth, with 48 h of incubation, was the best culture method for the detection of Erysipelothrix spp . with PCR . PCR detection was 50% more sensitive than culture . E . rhusiopathiae was isolated from a variety of different fish, cephalopods, and crustaceans, including a Western rock lobster (Panulirus cygnus) . There was no significant correlation between the origin of the seafoods tested and the distribution of E . rhusiopathiae . An organism indistinguishable from Erysipelothrix tonsillarum was isolated for the first time from an Australian oyster and a silver bream . Overall, Erysipelothrix spp . were widely distributed in Australasian seafoods, illustrating the potential for erysipeloid-like infections in fishermen.

Rapid Commun Mass Spectrom, 2000, 14(7), 578 - 84
Benefits of 2.94 micron infrared matrix-assisted laser desorption/ionization for analysis of labile molecules by Fourier transform mass spectrometry; Budnik BA et al.; A 2.94 microm Er:YAG laser was used together with a commercial Fourier transform mass spectrometer to study labile biomolecules . The combination has shown superior performance over conventional 337 nm ultraviolet matrix-assisted laser desorption/ionization (UV-MALDI) Fourier transform mass spectrometry (FTMS), especially for the analysis of peptides with post-translational modifications . With succinic acid as a matrix, the sensitivity of the single-shot analysis was increased by an order of magnitude to the low femtomole level, with significantly less fragmentation observed . Intact molecular ions of a range of O-glycosylated and sulfated peptides were detected . Urea was found to induce even less fragmentation, although at the expense of the total ion yield . Molecular ions of a noncovalent complex (vancomycin + diacetyl-L-Lys-D-Ala-D-Ala) have been observed for the first time in MALDI-FTMS . 2.94 microm infrared (IR) MALDI also produced abundant molecular ions of a range of nonbiological samples, including C60 and C70 fullerenes as well as dimetal coordination complexes.

Antimicrob Agents Chemother, 2000 May, 44(5), 1356 - 8
Cerebrospinal fluid penetration and pharmacokinetics of vancomycin administered by continuous infusion to mechanically ventilated patients in an intensive care unit; Albanese J et al.; Cerebrospinal fluid (CSF) penetration and the pharmacokinetics of vancomycin were studied after continuous infusion (50 to 60 mg/kg of body weight/day after a loading dose of 15 mg/kg) in 13 mechanically ventilated patients hospitalized in an intensive care unit . Seven patients were treated for a sensitive bacterial meningitis and the other six patients, who had a severe concomitant neurologic disease with intracranial hypertension, were treated for various infections . Vancomycin CSF penetration was significantly higher (P < 0.05) in the meningitis group (serum/CSF ratio, 48%) than in the other group (serum/CSF ratio, 18%) . Vancomycin pharmacokinetic parameters did not differ from those obtained with conventional dosing . No adverse effect was observed, in particular with regard to renal function.

J Crit Care, 2000 Mar, 15(1), 1 - 4
Vancomycin dosage requirements among pediatric intensive care unit patients with normal renal function; Glover ML et al.; PURPOSE: The purpose of this study was to determine a vancomycin dosage regimen among pediatric intensive care unit (PICU) patients with normal renal function resulting in desired peak and trough serum concentration and to determine the predictability of vancomycin peak concentrations based on reported trough concentrations . MATERIALS AND METHODS: The medical records of all PICU patients who received vancomycin over a 12-month period were identified through a hospital computer search and were obtained from the hospital's Department of Medical Records . Demographic and laboratory data as well as the patient's vancomycin dosing history were recorded . Patients who lacked appropriately timed vancomycin peak and trough concentrations or who exhibited renal dysfunction were excluded from the study population.The optimal vancomycin dose and the predictability of peak concentrations based on trough concentrations were assessed . RESULTS: A total of 135 patients were identified as having received vancomycin therapy during their PICU hospitalization between June 1997 and June 1998 . Fifty-nine patients were excluded due to renal dysfunction or inappropriate vancomycin concentrations resulting in 76 patients representing our study population . The initial mean dose of vancomycin was 47 mg/kg/day resulting in a mean peak and trough serum concentration of 19 and 6 microg/mL, respectively . A mean of 2.2 (range, 1 to 5) and 2.1 (range, 1 to 5) peak and trough serum concentrations were reported for each patient, respectively . A mean of 1.1 (range, 0 to 4) dosing changes per patient was noted resulting in a final mean dose of 60 mg/kg/day corresponding to a mean peak and trough serum concentration of 26 and 8 microg/mL, respectively . A vancomycin trough concentration >5 microg/mL was highly predictive for a corresponding peak concentration >20 microg/mL (P > .0001) . Eighty percent of the trough concentrations <5 microg/mL were associated with peak concentrations <20 microg/mL, whereas 81% of trough concentrations >5 microg/mL were associated with corresponding peak concentrations >20 microg/mL . CONCLUSIONS: PICU patients required higher doses of vancomycin than are typically prescribed to achieve conventionally accepted peak and trough vancomycin serum concentrations . In the absence of renal impairment, we recommend an initial dosage regimen of 60 mg/kg/day divided every 8 hours . Vancomycin trough concentrations are highly predictive of corresponding peak concentrations and therefore may negate the need to obtain routine peak concentrations.

Anesthesiology, 2000 Apr, 92(4), 1074 - 81
Mechanisms of nonimmunological histamine and tryptase release from human cutaneous mast cells; Veien M et al.; BACKGROUND: If mast cells are stimulated they release multiple mediators that delineate markers for immunologic and nonimmunologic reactions; histamine and tryptase are the two best known . Although histamine can be assayed in plasma, it is a nonspecific marker with a very short half-life . Tryptase has a longer half-life, but its release has not been proven to be specific for anaphylaxis . The authors investigated the mechanisms of nonimmunologic histamine release from human cutaneous mast cells to understand the mechanisms of mediator release and to determine whether tryptase was specific for allergic mediated activation . METHODS: Dispersed mast cell suspensions isolated from neonatal foreskins underwent challenge with vancomycin, calcium ionophore A23187, morphine, and atracurium, and histamine tryptase release was measured . The effects of calcium and magnesium, along with phospholipase C and phospholipase A2 inhibitors, also were investigated . RESULTS: Tryptase and histamine both were released by the known nonimmunologic stimuli (pharmacologic agents used in the current study; r2 = 0.6) . Furthermore, vancomycin- and atracurium-induced histamine release was calcium dependent . Phospholipase C and phospholipase A2 inhibitors decreased vancomycin-induced histamine release, but not calcium ionophore A23187-induced release . CONCLUSIONS: Tryptase is not a specific marker of mast cell activation (ie., anaphylaxis), and signaling mechanisms for mast cell activation involve activation of phospholipase C and phospholipase A2 pathways that are also involved in other cellular activation mechanisms.

Clin Appl Thromb Hemost, 2000 Jan, 6(1), 22 - 30
The antithrombotic factor singlet oxygen/light (1O2/h nu); Stief TW et al.; Activated phagocytes (especially polymorphonuclear granulocytes (PMNs)) by respiratory oxidative/photonic burst (activation of NADPH-oxidase and myeloper-oxidase) generate large amounts of oxidants of the hypochlorite-/chloramine-type, which are physiologic sources for singlet oxygen (1O2), a nonradical-excited (photon (h nu) emitting) oxygen species {Weiss SJ, NEJM 1989;320:365-376} . In vitro experiments show that 1O2 (1) inhibits coagulation by inactivation of thrombocytes, fibrinogen, factor V, factor VIII, and factor X and (2) activates fibrinolysis by inactivation of the main fibrinolysis inhibitors plasminogen activator inhibitor (PAI)-1 and alpha-2-antiplasmin, and by activation of single-chain urokinase by plasmin and oxidized fibrin . Additionally, this work suggests that 1O2/h nu acts antithrombotically, inducing selective thrombolysis in vivo (i.e., thrombolysis induced by 0.1 to 0.5 mmol/l chloramine within 30 to 60 minutes without changes of the plasmatic hemostasis system) . 1O2 might activate flowing to (on the endothelium) rolling PMN, increasing their chance to get in contact with fibrin/platelet aggregates deposited on the endothelial layer . Via 1O2 generation, the thrombus-activated phagocytes might call for (acute, physiologic) inflammation/fibrinolysis amplification, resulting in the "moving front" of PMN, which infiltrates and destroys the thrombus . 1O2 seems to (partially) participate in the reactivity of nitric oxide, another prooxidative agent . The inhibition of physiologic amounts of 1O2 by blood cholesterol might be involved in the pathogenesis of atherothrombosis . Consequently, it is suggested that activated PMNs modulate hemostasis, shifting it into an antithrombotic state; this cellular part of fibrinolysis seems to be of greater physiologic importance than the plasmatic one . Impaired PMN function (e.g., as occurring in patients with antineutrophil cytoplasmic antibodies or under cytostatic treatments) often results in serious thrombotic complications . Light is the only signal whose origin can be immediately recognized by a fast moving cell in the (dark) blood stream . The cell signal action of 1O2/h nu (e.g., released by chloramines such as taurine-chloramine or vancomycin, by fiberoptic, by photodynamic therapy, or by so-called redox-cycling drugs such as quinones or tetracyclines) might be a new and physiologic principle for pharmacologic intervention in atherothrombosis.

J Chromatogr A, 2000 Feb 11, 869(1-2), 395 - 409
Immobilisation and evaluation of a vancomycin chiral stationary phase for capillary electrochromatography; Wikstrom H et al.; The macrocyclic antibiotic, vancomycin, is covalently bonded to LiChrospher diol silica packed columns and evaluated in capillary electrochromatography (CEC) both in the reversed-phase and polar organic mode . Initially, capillaries were packed with 5 microm LiChrospher 100 A diol silica and evaluated in CEC with a reversed-phase biphenyl-pyrene achiral test resulting in resolution and efficiency values of ca . 2.5 and 100000 plates meter(-1), respectively . Repeatability for this test (resolution and efficiency) was also examined and found to be acceptable for both run-to-run (n=5, 0.74% and 1.5%) and column-to-column (n=5, 3.4% and 9.0%), respectively . Similar results were obtained when the 10 microm LiChrospher 1000 A diol silica was examined with the exception of efficiency, where a reduced plate height value of four times lower was obtained compared to the 100 A material . A simple three step in-situ vancomycin immobilisation procedure was subsequently carried out on these packed diol columns . Selectivity was obtained for thalidomide enantiomers on this vancomycin chiral stationary phase in reversed-phase CEC with resolution and efficiency values of ca . 2.5 and 80000 plates meter(-1), with acceptable repeatability (n=8) 0.9% and 3.0%, respectively . Selectivity was also obtained for thalidomide enantiomers on this phase in the polar organic mode with resolution and efficiency values of ca . 2.5 and 120000 plates meter(-1), with acceptable repeatability (n=7) 0.9% and 2.0%, respectively . It was possible to deduce from a chemometric design carried out for evaluating the mobile phase component effects that organic modifier ratio, MeOH/MeCN, played a significant role in controlling both resolution and efficiency . It was also possible to separate a number of basic analytes including four beta-adrenergic blocking agents in the polar organic mode albeit with lower resolution and efficiency values, ca . 1.5 and 45000 plates meter(-1), respectively.

Thromb Res, 2000 Mar 15, 97(6), 473 - 80
Singlet oxygen inactivates fibrinogen, factor V, factor VIII, factor X, and platelet aggregation of human blood; Stief TW et al.; Activated polymorphonuclear leukocytes participate in hemostasis . These phagocytes generate up to 5 mmol/l of oxidants of the HOCl- and chloramine-type . The present study shows, for the first time, that physiological concentrations of NaOCl or chloramines act as anticoagulants in human plasma . Prothrombin time, activated partial thromboplastin time, and thrombin time at chloramine concentrations greater than 1 mmol/l are prolonged proportional to the oxidant concentration . Plasmatic coagulation factors sensible to oxidation are fibrinogen, factor V, factor VIII, and factor X with a 50% effective dose of 2-3 mmol/l NaOCl or taurine-chloramine . Chloramines or chloramine-like agents (e.g., chloramine T(R) or vancomycin) also inactivate platelet aggregation (in whole blood or platelet-rich plasma) at an 50% effective dose of about 1.0 mmol . This irreversible oxidation of the hemostasis components is inhibited by addition of methionine, cysteine, ascorbic acid, or azide in 10-fold molar excess prior to oxidation . The oxy-radical inhibitors mannitol, superoxide dismutase, or catalase do not antagonize the action of NaOCl or chloramines . Therefore, the oxidant here involved has reaction characteristics of singlet oxygen (1O(2)), a nonradical, excited (i.e., light-emitting) oxidant . The hemostasis factors sensible to oxidation might dispose of oxidizable, for their function critical, methionine or cysteine residues . In conclusion, blood coagulation factors I, V, VIII, X and thrombocytes are sensible to nonradical oxidants of activated phagocytes . Via 1O(2) generation, polymorphonuclear leukocytes can generate a local pericellular zone of anticoagulation . The data suggest that the cell signal 1O(2) in physiological amounts is an antithrombotic agent.

J Antimicrob Chemother, 2000 Mar, 45(3), 329 - 35
High vancomycin dosage regimens required by intensive care unit patients cotreated with drugs to improve haemodynamics following cardiac surgical procedures; Pea F et al.; The aim of this study was to evaluate retrospectively the importance of a Bayesian pharmacokinetic approach for predicting vancomycin concentrations to individualize its dosing regimen in 18 critically ill patients admitted to intensive care units following cardiothoracic surgery . The possible influence of some coadministered drugs with important haemodynamic effects (dopamine, dobutamine, frusemide) on vancomycin pharmacokinetics was assessed . Vancomycin serum concentrations were measured by fluorescence polarization immunoassay . Vancomycin dosage regimens predicted by the Bayesian method (D(a)) were compared retrospectively with Moellering's nomogram-based dosages (D(M)) to assess possible major differences in vancomycin dosing . D(a) values were similar to D(M) in 10 patients (D(a) approximately D(M) group) (20.52 +/- 8.40 mg/kg/day versus 18.81 +/- 7.24 mg/kg; P = 0.15), whereas much higher dosages were required in the other eight patients (D(a) >> D(M) group) (26.78 +/- 3.01 mg/kg/day versus 18.95 +/- 3.41 mg/kg/day; P < 0.0001) despite no major difference in attained vancomycin steady-state trough concentration (C(min ss)) (9.22 +/- 1 . 33 mg/L versus 8.99 +/- 1.26 mg/L; = 0.75) or estimated creatinine clearance (1.23 +/- 0.49 mL/min/kg versus 1.21 +/- 0.24 mL/min/kg; P = 0.95) being found between the two groups . The ratio between D(a) and D(M) was significantly higher in the D(a) >> D(M) group than in the D(a) approximately D(M) group (1.44 +/- 0.18 versus 1.10 +/- 0 . 21; P < 0.01) . In four D(a) >> D(M) patients the withdrawal of cotreatment with haemodynamically active drugs was followed by a sudden substantial increase in the vancomycin C(min ss) (13.30 +/- 1 . 13 mg/L versus 8.79 +/- 0.87 mg/L; P < 0.01), despite no major change in bodyweight or estimated creatinine clearance being observed . We postulate that these drugs with important haemodynamic effects may enhance vancomycin clearance by inducing an improvement in cardiac output and/or renal blood flow, and/or by interacting with the renal anion transport system, and thus by causing an increased glomerular filtration rate and renal tubular secretion . Given the wide simultaneous use of vancomycin and dopamine and/or dobutamine and/or frusemide in patients admitted to intensive care units, clinicians must be aware of possible subtherapeutic serum vancomycin concentrations when these drugs are coadministered . Therefore, therapeutic drug monitoring (TDM) for the pharmacokinetic optimization of vancomycin therapy is strongly recommended in these situations.

Acta Crystallogr D Biol Crystallogr, 2000 Feb, 56 ( Pt 2), 238 - 40
P1 Shake-and-Bake: can success be guaranteed?
Xu H, Hauptman HA, Weeks CM, Miller R.
The multi-trial direct-methods procedure known as Shake-and-Bake has been applied to three small proteins (alpha-1 peptide, vancomycin and lysozyme) that crystallize in space group P1 . Phase refinement was accomplished through parameter-shift optimization using both the cosine and exponential forms of the minimal function . By extending error-free data to sufficiently high resolution, 100% convergence of trial structures to solution could be achieved in all three cases by using the exponential minimal function and a shift angle in the range 130-150 degrees . These results suggest optimum parameters for other P1 structures and emphasize the importance of collecting data to the highest possible resolution.

J Antimicrob Chemother, 2000 Feb, 45(2), 243 - 5
Pharmacokinetics and tissue penetration of vancomycin in patients undergoing prosthetic mammary surgery; Luzzati R et al.; Vancomycin concentrations in periprosthetic breast tissues were evaluated in 24 women undergoing reconstructive surgery after mastectomy for breast cancer . Patients were given a single prophylactic dose of vancomycin (1 g iv) 1-8 h before surgery, and mean capsular and pericapsular tissue concentrations were measured by HPLC . Vancomycin was not detectable in the majority of patients belonging to the 1-3 h post-dose groups, whereas in the 4-8 h post-dose groups, mean capsular and pericapsular concentrations were as follows: at 4 h, 4.0 mg/kg and 5.9 mg/kg; at 6 h, 4.1 mg/kg and 4 . 8 mg/kg; at 8 h, 5.9 mg/kg and 11.1 mg/kg, respectively . Vancomycin tissue concentrations thus were equal to or exceeded the breakpoint of 4 mg/L in most samples collected 4-8 h after dosing . In conclusion, our data suggest that appropriate timing of vancomycin prophylaxis should be considered to allow the maintenance of adequate tissue concentrations throughout the surgical procedure.

Infect Control Hosp Epidemiol, 2000 Jan, 21(1), 48 - 50
Vancomycin use in pediatric hematology-oncology patients; Hopkins HA et al.; Across-sectional study was performed of pediatric hematology-oncology patients who received vancomycin; use was compared to the Centers for Disease Control and Prevention (CDC) recommendations for vancomycin use . Thirty-seven patients received 308 doses of vancomycin . AR patients initially received vancomycin as empirical therapy; 100% of this use was not consistent with the CDC recommendations.

Infect Control Hosp Epidemiol, 2000 Jan, 21(1), 45 - 7
Practical guidelines for vancomycin usage, with prospective drug-utilization evaluation; Drori-Zeides T et al.; To strengthen guidelines for vancomycin use, practical guidelines were developed . A prospective survey was conducted of all patients receiving vancomycin during two 1-month periods, 1 year apart, during which significant improvements were noted . Practical guidelines may contribute to appropriateness of vancomycin use, serve as educational tools, and facilitate improved surveillance.

Infect Control Hosp Epidemiol, 2000 Jan, 21(1), 42 - 5
Excessive use of vancomycin: a successful intervention strategy at an academic medical center; Hamilton CD et al.; The project goal was to decrease excessive vancomycin use . Interventions included an educational chart note the first day of therapy, followed by pharmacists discussing the need for continued therapy with patients' physicians . Empirical vancomycin use improved from 20% to 90% compliance with guidelines within 6 months of the intervention.

Intensive Care Med, 1999 Nov, 25(11), 1291 - 6
Vancomycin assay performance in patients with acute renal failure; Trujillo TN et al.; OBJECTIVE: Fluorescence polarization immunoassays (FPIA) have been reported to overestimate vancomycin serum concentrations compared to high-performance liquid chromatography (HPLC) or enzyme multiplied immunoassay technique (EMIT) in patients with chronic renal disease . The assay manufacturer has modified the FPIA to remedy this overestimation . The purpose of this study was to compare the assay performance of two FPIAs to EMIT in acute renal failure patients receiving vancomycin and continuous venovenous hemofiltration . DESIGN: Open-label trial . SETTING: Intensive care unit in a university affiliated hospital . PATIENTS AND PARTICIPANTS: 15 serum and ultrafiltrate samples were obtained from 14 critically ill patients (mean +/- SD; 57 +/- 12 years; 8 males/6 females) . MEASUREMENTS AND RESULTS: Vancomycin concentrations were determined by a polyclonal FPIA (pFPIA) performed on the TDx system, a monoclonal FPIA (mFPIA) performed on the AxSYM system and EMIT . The coefficient of variation for all assays was < 5% . The mean difference +/- SDd between mFPIA vs EMIT and pFPIA vs EMIT assays in serum were: -0.08 +/- 1.55 and 1.24 +/- 2.11 mg/l, respectively . The limits of agreement between the mFPIA vs EMIT and pFPIA vs EMIT assays in serum were: -3.18 to 3.03 and -2.99 to 5.46 mg/l, respectively . CONCLUSIONS: Our data demonstrate that the manufacturer's changes to the pFPIA have reduced overestimation . The mFPIA appears to be an acceptable assay for measuring vancomycin serum concentrations in acute renal failure patients and does not significantly overestimate these concentrations.

Biomaterials, 2000 Feb, 21(3), 243 - 9
Isostatic compression, a new process for incorporating vancomycin into biphasic calcium phosphate: comparison with a classical method; Gautier H et al.; Isostatic compression has rarely been used to load calcium-phosphate biomaterials with therapeutic agents . This report, concerning four processes associating vancomycin, compares isostatic compression with wet granulation, a classical method . In the wet granulation study, vancomycin was associated with biphasic calcium-phosphate (BCP) granules either by adsorption or incorporation with a new granulation . In the isostatic compression study, BCP powder was compressed at 100, 140 and 200 MPa . The blocks obtained were crushed and 200-500 microm, sieved; thus, the vancomycin solution was absorbed on these granules . Compaction of BCP and vancomycin powders gave, after crushing and sieving, granules loaded with vancomycin . In each study, 5% vancomycin was associated with BCP . Vancomycin release profiles were assessed by an in vitro culture chamber dissolution test . Physicochemical studies of BCP and vancomycin showed their structural integrity after isostatic compression . Isostatic compression prolonged vancomycin release time from 3 to 7 days and the release time became greater as isostatic pressure increased, probably because of the porosity decrease of the granules during compression.

J Am Acad Dermatol, 2000 Feb, 42(2 Pt 2), 316 - 23
Drug-induced linear IgA bullous dermatosis after vancomycin discontinuance in a patient with renal insufficiency; Klein PA et al.; Linear IgA bullous dermatosis (LABD) is an autoimmune, subepidermal, vesiculobullous disease that has been commonly associated with the use of vancomycin hydrochloride . Lesions typically appear during vancomycin therapy, 24 hours to 15 days after the first dose . A 65-year-old white man with renal insufficiency developed pruritic, tense bullae on the right chest, right medial arm, right flank, abdomen, and right upper thigh 14 days after his last dose of vancomycin . Histopathologic examination and immunofluorescence studies were diagnostic of LABD . Vancomycin-related LABD may appear as long as 2 weeks after the drug is discontinued.

Perit Dial Int, 1999 Nov-Dec, 19(6), 534 - 9
Small and middle molecular weight solute clearance in nocturnal intermittent peritoneal dialysis; Brophy DF et al.; OBJECTIVES: To determine the dialysate-to-plasma (D/P) concentration ratios and peritoneal dialytic clearance (CI(D)) of substances with a wide range of molecular weights in subjects receiving a simulated nocturnal intermittent peritoneal dialysis (NIPD) session . DESIGN: Open-label single-dose study . SUBJECTS: Six end-stage renal disease patients undergoing peritoneal dialysis (PD) . SETTING: Clinical research center of a university-affiliated hospital . INTERVENTIONS: Subjects received intravenous gentamicin and vancomycin on the first day of the study . Subjects received no PD until their return on the following day, when subjects underwent a simulated NIPD session utilizing four 2- to 2.5-L peritoneal dialysate dwells of 2 hours . Blood and dialysate samples were collected immediately before the session and after each dialysate dwell for determination of urea, creatinine, gentamicin, vancomycin, and beta2-microglobulin (beta2M) concentrations . Each solute's D/P concentration ratio and peritoneal CI(D) were calculated . MEASUREMENTS AND MAIN RESULTS: The (mean +/- SD) 2-hour D/P concentration ratios were 0.78 +/- 0.05 (urea), 0.49 +/- 0.11 (creatinine), 0.38 +/- 0.08 (gentamicin), 0.11 +/- 0.06 (vancomycin), and 0.07 +/- 0.03 (beta2M) . Peritoneal CI(D) values (mL/min of dialysis) were 19.0 +/- 2.8 (urea), 12.1 +/- 3.5 (creatinine), 8.4 +/- 2.8 (gentamicin), 2.7 +/- 1.5 (vancomycin), and 1.7 +/- 0.8 (beta2M).The D/P concentration ratios and peritoneal CI(D) values for urea, creatinine, and gentamicin were significantly different from vancomycin and beta2M (repeated measures ANOVA, p < 0.05) . Beta2-microglobulin peritoneal CI(D) was strongly related to gentamicin peritoneal CI(D) (r = 0.96, p < 0.05) . CONCLUSION: Small molecular weight solutes have significantly greater D/P and peritoneal CI(D) than middle molecular weight solutes in NIPD . In NIPD, daily peritoneal CI(D) of beta2M is lower than that reported in continuous ambulatory PD . NIPD also results in lower drug CI(D) than that reported in continuous ambulatory PD studies.

Antimicrob Agents Chemother, 2000 Feb, 44(2), 278 - 82
A population pharmacokinetic model for vancomycin in pediatric patients and its predictive value in a naive population; Lamarre P et al.; The objectives of this study were to (i) construct a population pharmacokinetic (PK) model able to describe vancomycin (VAN) concentrations in serum in pediatric patients, (ii) determine VAN PK parameters in this population, and (iii) validate the predictive ability of this model in a naive pediatric population . Data used in this study were obtained from 78 pediatric patients (under 18 years old) . PK analyses were performed using compartmental methods . The most appropriate model was chosen based on the evaluation of pertinent graphics and calculation of the Akaike information criterion test . The population PK analysis was performed using an iterative two-stage method . A two-compartment PK model using age, sex, weight, and serum creatinine as covariates was determined to be the most appropriate one to describe serum VAN concentrations . The quality of fit was very good, and the distribution of weighted residuals was found to be homoscedastic (Wilcoxon signed rank test) . Fitted population PK parameters (mean +/- standard deviation) were as follows: central clearance (0.1 +/- 0.05 liter/h/kg), central volume of distribution (0.27 +/- 0.07 liter/kg), peripheral volume of distribution (0.16 +/- 0.07 liter/kg), and distributional clearance (0.16 +/- 0.07 liter/kg) . The predictive ability of the developed model (including the above-mentioned covariates) was evaluated in a naive population of 19 pediatric patients . The predictability was very good . Precision (+/-95% confidence interval {CI}) (peak, 4.1 {+/-1.4}, and trough, 2.2 {+/-0.7}) and bias (+/-95% CI) (peak, -0.58 {+/-2.2}, and trough, 0.63 {+/-1.1} mg/liter) were significantly (P < 0.05) superior to those obtained using a conventional method (precision {+/-95% CI}: peak, 8.03 {+/-2 . 46}, and trough, 2.7 {+/-0.74}; bias: peak, -7.1 {+/-2.9}, and trough, -1.35 {+/-1.2} mg/liter) . We propose the use of this population PK model to optimize VAN clinical therapies in our institution and others with similar patient population characteristics.he object

Ann Pharmacother, 1999 Dec, 33(12), 1329 - 35
Accuracy of measured vancomycin serum concentrations in patients with end-stage renal disease; Smith PF et al.; OBJECTIVE: To review information related to the accuracy of vancomycin serum drug concentrations in patients with end-stage renal disease, focusing on available assays and mechanisms of cross-reactivity . DATA SOURCES: Primary and review articles identified from a MEDLINE search (January 1980-June 1999) and through secondary sources . STUDY SELECTION AND DATA EXTRACTION: All articles identified were evaluated, and all relevant information was included in this review . DATA SYNTHESIS: Falsely elevated vancomycin serum concentrations may occur in patients with renal dysfunction . The underlying mechanism is due to the formation and accumulation of a pseudo-metabolite, the vancomycin crystalline degradation product (CDP) . Vancomycin is converted to CDP when exposed to heat, including normal body temperature . Because the molecular structures of CDP and vancomycin are similar, both molecules are detected by polyclonal immunoassay systems used in clinical laboratories . This cross-reactivity leads to falsely elevated serum vancomycin concentrations in excess of 50-70% . Such large assay inaccuracies may result in improper dosage adjustments and therapeutic failures . A monoclonal immunoassay system has been developed that does not significantly cross-react with CDP . CONCLUSIONS: To appropriately interpret laboratory results, it is essential for clinicians to be aware of the vancomycin-CDP cross-reactivity problem and to be familiar with the specific assay used to measure vancomycin concentrations in patients with renal dysfunction.

Anal Biochem, 2000 Jan 15, 277(2), 196 - 205
A vesicle capture sensor chip for kinetic analysis of interactions with membrane-bound receptors; Cooper MA et al.; A novel sensor chip for use in surface plasmon resonance (SPR) biosensors has been developed to capture vesicles which may contain membrane-bound receptors . Sulforhodamine-containing vesicles were shown by fluorescence microscopy to be immobilized intact on the sensor chip . Binding of cholera toxin to captured vesicles containing ganglioside GM(1) was demonstrated using SPR, and the derived kinetic and affinity constants were similar to literature values . Biotinylated vesicles captured on the sensor chip were used to bind streptavidin and then biotinylated ss-DNA . The hybridization of complementary ss-DNA to the immobilized ss-DNA was then analyzed using SPR . The values obtained were similar to those obtained for an identical interaction analyzed using a commercially available streptavidin-containing sensor chip . Binding of vancomycin-group antibiotics to captured vesicles containing a bacterial cell wall mucopeptide analogue was demonstrated . No binding of the bacterial endotoxin Cry1A(c) to captured vesicles containing its cell surface receptor could be demonstrated .

Am J Kidney Dis, 2000 Jan, 35(1), 64 - 8
Vancomycin prescribing practices in hospitalized chronic hemodialysis patients; Green K et al.; To determine the prevalence of and indications for vancomycin administration among hospitalized chronic hemodialysis patients, we performed a 3-month prospective cohort study at a tertiary care center . Modified guidelines for vancomycin use from the Hospital Infections Control Practices Advisory Committee of the Centers for Disease Control and Prevention were used . Vancomycin was administered during 56 of 144 admissions (39%) requiring chronic hemodialysis compared with 336 of 7,212 admissions (5%) not requiring hemodialysis (relative risk, 11; 95% confidence interval, 8 to 15; P < 0.001) . Among chronic hemodialysis patients, vancomycin use was judged appropriate for 131 of the 164 vancomycin doses (80%) . The most common appropriate indication was empiric therapy in a febrile patient before culture or susceptibility results . Of 32 infections identified in patients who received empiric vancomycin, 15 infections (47%) were caused by beta-lactam-resistant pathogens . Among the 33 doses (20%) judged inappropriate, continued therapy for a presumed infection despite failure to identify a beta-lactam-resistant pathogen was the most common indication . Although vancomycin administration was frequent among hospitalized chronic hemodialysis patients, its use was justified in the majority of cases . Efforts should focus on limiting vancomycin administration for treating infections caused by beta-lactam-sensitive pathogens.

Pharmacotherapy, 1999 Sep, 19(9), 1042 - 9
The effects of peracetic acid-hydrogen peroxide reprocessing on dialyzer solute and water permeability; Scott MK et al.; We characterized the effects of peracetic acid-hydrogen peroxide (PAHP) reprocessing on hemodialyzer permeability to water and solutes of various molecular weights and compared these effects within and between dialyzers . An aqueous-based solution containing urea, creatinine, vancomycin, inulin, myoglobin, and albumin was dialyzed for 60 minutes with a hemodialyzer after undergoing 0, 1 , 5, 10, and 15 reuse cycles . Solute clearance, sieving coefficient (SC), and ultrafiltration coefficient were determined . We found that PAHP reprocessing significantly decreased water and solute removal (urea, creatinine, vancomycin, inulin) by cellulose triacetate dialyzers (CT190) over 15 reuses (p<0.05) but did not affect the permeability of polysulfone dialyzers (F80A) . Inulin removal was significantly lower for F80A than for CT190 (p<0.0001 and p<0.001 for clearance and SC values, respectively) . Myoglobin and albumin removal by CT190 significantly decreased over 15 reuses (p<0.05), but no protein was detected in dialysate or ultrafiltrate at any reuse number for F80A . Reprocessing with PAHP alters dialyzer permeability; the effect is more pronounced for the CT190 dialyzer, but removal of solutes with molecular weight above 1500 Da is significantly lower with F80A dialyzers than with CT190 . These changes in dialyzer permeability should be considered when determining optimal reuse procedures.

Retina, 1999, 19(6), 553 - 7
Evaluation of toxicity of intravitreal ceftazidime, vancomycin, and ganciclovir in a silicone oil-filled eye; Hegazy HM et al.; PURPOSE: To evaluate the toxicity of intravitreal drugs in an eye filled with silicone oil for prolonged internal retinal tamponade . METHODS: Vitrectomy was performed in 21 rabbit eyes, and the vitreous was replaced with silicone oil . Different concentrations of various drugs (ceftazidime, vancomycin, and ganciclovir) were injected intravitreally . RESULTS: Silicone oil increased the toxicity of these drugs, which were injected in previously determined nontoxic doses, possibly because of a reduction of the preretinal space . Injecting one quarter of the known nontoxic dose failed to show any toxicity . CONCLUSIONS: Nontoxic concentrations of intravitreal drugs can cause toxicity in a silicone-filled eye.

Pediatr Nephrol, 1999 Nov, 13(9), 773 - 4
Treatment of vancomycin overdose using high-efficiency dialysis membranes; Bunchman TE et al.; Two children underwent acute hemodialysis using high-efficiency dialysis membranes for vancomycin intoxication (plasma levels 238 microg/ml and 182 microg/ml) . During a 3-h treatment, plasma vancomycin removal was on average 60%, with a calculated vancomycin half-life (t(1/2)) of 2 h . This is in contrast to a recent report using charcoal hemoperfusion for vancomycin intoxication (plasma level of 137 microg/ml), which resulted in a 40% relative plasma clearance and a calculated vancomycin t(1/2) of 12.5 h for a 4-h treatment . The choice of optimal modality for clearing a toxin should take into account the availability of equipment, protein or lipid binding of the toxin, and inherent risks of charcoal hemofiltration (large extracorporeal circuit, reversible hypocalcemia, heat loss, reversible coagulation defects) versus risks of high-efficiency hemodialysis (large extracorporeal circuit).

Antimicrob Agents Chemother, 2000 Jan, 44(1), 24 - 9
MICs of mutacin B-Ny266, nisin A, vancomycin, and oxacillin against bacterial pathogens; Mota-Meira M et al.; Peptide antibiotics, particularly lantibiotics, are good candidates for replacing antibiotics to which bacteria have become resistant . In order to compare two such lantibiotics with two antibiotics, the MICs of nisin A, mutacin B-Ny266, vancomycin, and oxacillin against various bacterial pathogens were determined . The results indicate that nisin A and mutacin B-Ny266 are as active as vancomycin and oxacillin against most of the strains tested . Furthermore, mutacin B-Ny266 remains active against strains that are resistant to nisin A, oxacillin, or vancomycin . The wide spectrum of activity of mutacin B-Ny266, its low MICs against bacterial pathogens, and its activity against bacteria resistant to other inhibitors support the development of this substance for therapeutic use.

South Med J, 1999 Nov, 92(11), 1098 - 9
Bivalve polymicrobial infective endocarditis; Houry D et al.; Polymicrobial infective endocarditis is uncommon, particularly vancomycin-resistant endocarditis and fugal endocarditis . The incidence of these infections is likely to . increase with advances in mediCAl technology and widespread use of central venous catheters . We report a case of bivalve endocarditis in which four organisms were identified, including vancomycin-resistant Enteroocausfaecium and Torulopsis glabrata.

Am J Infect Control, 1999 Dec, 27(6), 482 - 7
Vancomycin use in pediatric neurosurgery patients; Shah SS et al.; OBJECTIVE: The objective of this article is to describe a pediatric neurosurgery patient population receiving vancomycin and examine the indications for and appropriateness of vancomycin use . METHODS: A cross-sectional study was performed on the pediatric neurosurgery patients at Egleston Children's Hospital who received vancomycin from January 1 through December 31, 1996 . Vancomycin use was compared with the Centers for Disease Control and Prevention Hospital Infection Control Practices Advisory Committee recommendations for vancomycin use . RESULTS: Thirty patients received 115 doses of vancomycin . The median patient age was 8.0 years, and 17 (56.7%) were male . Vancomycin was used for prophylaxis in 28 (93.3%) patients and empiric therapy in 3 (10.0%) patients; one patient received vancomycin for surgical prophylaxis followed by empiric therapy for suspected meningitis . Vancomycin prophylaxis was initiated after the incision in 6 (21.4%) patients and was continued as prophylaxis for more than one dose in 26 (92.9%) patients . CONCLUSIONS: Vancomycin was used primarily as surgical prophylaxis in pediatric neurosurgery patients, and use was not consistent with the Hospital Infection Control Practices Advisory Committee recommendations . These data suggest that for certain subpopulations, such as pediatric neurosurgery patients, there is a need for more specialized recommendations . Furthermore, prudent vancomycin use is warranted to successfully decrease the risk of further emergence of vancomycin resistance . Because vancomycin use may be prevalent in this population, assessment of vancomycin use in pediatric neurosurgery patients followed by establishment of vancomycin clinical guidelines may help improve the appropriateness of vancomycin use in this population.

J Toxicol Clin Toxicol, 1999, 37(6), 731 - 51
Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning . American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists; Potentiation of vancomycin-induced histamine release by muscle relaxants and morphine in rats; Department of Hospital Pharmacy, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, JapanThe intravenous injection of vancomycin sometimes causes anaphylactoid reactions, in which histamine release may play a major role . These reactions are more frequently manifested when vancomycin is injected into anesthetized patients . We examined the vancomycin-induced histamine release and the interaction of vancomycin with muscle relaxants or opioid in rats . In an in vitro study with rat peritoneal mast cells, treatment with vancomycin at concentrations of greater than 1.25 mM produced significant histamine release . Tubocurarine, vecuronium, pancuronium, succinylcholine, and morphine up to concentrations of 0.25, 1, 5, 30, and 5 mM, respectively, produced no significant histamine release . However, the nonsignificant histamine release induced by 0.5 mM vancomycin was clearly enhanced by combining vancomycin with any of these agents . In the in vivo study, the intravenous injection of vancomycin significantly increased the plasma histamine levels in rats when vancomycin was injected at 200 mg/kg of body weight (63.2 +/- 34.0 ng/ml {mean +/- standard deviation}) but not when it was injected at 100 mg/kg (30.8 +/- 20.2 ng/ml) compared with that in the saline-treated rats (22.5 +/- 11.4 ng/ml) . Although the subcutaneous administration of morphine (10 mg/kg) never increased the plasma histamine levels, the intravenous injection of vancomycin (100 mg/kg) 30 min after this morphine treatment markedly increased the plasma histamine levels (56.0 +/- 26.9 ng/ml) . These findings provide experimental evidence that the combination of muscle relaxants or an opioid with vancomycin may increase the risk of anaphylactoid reactions by enhancing the release of histamine.

J Med Chem, 1999 Nov 4, 42(22), 4714 - 9
Vancomycin binding to low-affinity ligands: delineating a minimum set of interactions necessary for high-affinity binding; Loll PJ et al.; Bacterial resistance to vancomycin has been attributed to the loss of an intermolecular hydrogen bond between vancomycin and its peptidoglycan target when cell wall biosynthesis proceeds via depsipeptide intermediates rather than the usual polypeptide intermediates . To investigate the relative importance of this hydrogen bond to vancomycin binding, we have determined crystal structures at 1.0 A resolution for the vancomycin complexes with three ligands that mimic peptides and depsipeptides found in vancomycin-sensitive and vancomycin-resistant bacteria: N-acetylglycine, D-lactic acid, and 2-acetoxy-D-propanoic acid . These, in conjunction with structures that have been reported previously, indicate higher-affinity ligands elicit a structural change in the drug not seen with these low-affinity ligands . They also enable us to define a minimal set of drug-ligand interactions necessary to confer higher-affinity binding on a ligand . Most importantly, these structures point to factors in addition to the loss of an intermolecular hydrogen bond that must be invoked to explain the weaker affinity of vancomycin for depsipeptide ligands . These factors are important considerations for the design of vancomycin analogues to overcome vancomycin resistance.

Kidney Int Suppl, 1999 Nov, 72, S24 - 8
Pharmacokinetic principles during continuous renal replacement therapy: drugs and dosage; Bohler J et al.; Some drugs are removed significantly by continuous renal replacement therapies (CRRTs), and a substitutional dose is required to prevent underdosing of the substance . This review outlines the basic pharmacokinetic principles that determine whether a dose adjustment is required . Only the free non-protein-bound fraction of a drug can pass through the dialyzer membrane . In postdilution hemofiltration the drug clearance equals the ultrafiltration rate, while in predilution hemofiltration, the dilution of the blood prior to filtration needs to be considered when calculating clearance . In continuous hemodialysis, drugs are eliminated by diffusion . Drugs with a higher molecular weight will diffuse more slowly and show a lower clearance than smaller drugs . The clinical relevance of a given drug clearance caused by CRRT will mainly depend on the competing drug clearance by other elimination pathways . Even a high clearance for a drug may be irrelevant for overall drug removal if nonrenal clearance pathways provide a much higher clearance rate . The ideal drug to be removed by CRRT that requires a dose adjustment has: a low protein binding, a low volume of distribution, and a low nonrenal clearance . Examples include aminoglycosides, vancomycin, fosfomycin, and flucytosine . Even if there are no studies available on the pharmacokinetics of a particular drug during CRRT, knowledge of the basic concepts of drug elimination by continuous hemodialysis allows a prediction of whether or not a dose adjustment will be required during CRRT.

Intensive Care Med, 1999 Oct, 25(10), 1100 - 4
Vancomycin clearance during continuous venovenous haemofiltration in critically ill patients; Boereboom FT et al.; OBJECTIVE: To study the pharmacokinetics of vancoymcin in critically ill patients with acute renal failure treated with continuous venovenous haemofiltration (CVVHF) . DESIGN: Open-label study . SETTING: Hospital pharmacy centre and medical intensive care unit of the University Medical Centre Utrecht . MATERIALS AND METHODS: In a laboratory setting, the sieving coefficient (s) of vancomycin by polyacrilonitrile (PAN) haemofilters of different surface areas was studied . In one patient, the pharmacokinetics of vancomycin were studied following a single dose of vancomycin . Another patient was treated with a vancomycin dosing regimen based on data from the literature, but high trough concentrations made dose reduction necessary after 24 h of withholding therapy . After two doses of 250 mg, serum and ultrafiltrate samples were collected for pharmacokinetic evaluation . INTERVENTIONS++: CVVHF with the following operational characteristics: blood flow 200 ml/min, ultrafiltrate flow 25 ml/min, postdilution, PAN 06 hollow fibre haemofilter . MEASUREMENTS AND RESULTS: The average sieving coefficient in vitro was 0.73 +/- 0.06, 0.86 +/- 0.11, and 0.80 +/- 0.06 for the PAN 03, 06, and 10 haemofilters, respectively . Changes in the sieving coefficient by increasing the ultrafiltration rate were not clinically significant . The first patient was given a single dose of vancomycin, 1000 mg by intravenous infusion . The following pharmacokinetic data were obtained: apparent volume of distribution (Vd) 55.8 l, terminal half-life time (t(1/2 term)) 15.4 h, total clearance (Cl(tot)) 2.5 l/h, CVVHF clearance (CL(CVVHF, form 1)) 1.4 l/h, and body clearance (Cl(body)) 1.1 l/h . The average sieving coefficient during the study period was 0.89 +/- 0.03 . In the second patient, the pharmacokinetics of vancomycin were studied following dose reduction: Vd 41.7 l, (1/2 term) 20.3 h, Cl(tot) 1.4 l/h, Cl(CVVHF, form 1) 1.4 l/h, and Cl(body) < 0.1 l/h . The average sieving coefficient during the study period was 0.88 +/- 0 . 03 . The cumulative amount of vancomycin removed by means of CVVHF during the 12-h study period was 245 mg in patient 1 and 228 mg in patient 2 . CONCLUSIONS++: CVVHF with a PAN 06 haemofilter effectively removed vancomycin in two critically ill patients . The amount of vancomycin removed with CVVHF was about 250 mg per 12 h . A clear difference in body clearance in the two patients was observed . Our dosage recommendation for vancomycin in critically ill patients receiving CVVHF is a loading dose of 15-20 mg/kg followed after 24 h by 250 to 500 mg twice daily with close monitoring of the serum and ultrafiltrate vancomycin concentration.

Ann Pharmacother, 1999 Oct, 33(10), 1043 - 5
Life-threatening reaction to vancomycin given for noninfectious fever; Johnson JR et al.; OBJECTIVE: To report a case of vancomycin-induced anaphylaxis (or anaphylactoid reaction) in a patient with a fever of unrecognized noninfectious origin . CASE SUMMARY: An 83-year-old white man, who was a patient of the Veterans Affairs Medical Center, developed a serious anaphylactic (or anaphylactoid) reaction while receiving intravenous vancomycin as empiric therapy for a nosocomial fever of unknown origin . The fever was subsequently proved to have been due to acute polyarticular gout rather than an infection . DISCUSSION: This patient developed respiratory distress and an increased serum troponin concentration, suggestive of a myocardial enzymatic leak as a result of vancomycin therapy . Vancomycin was given before the noninfectious cause of his fever was recognized . CONCLUSIONS: Even with cautious slow infusion, intravenous vancomycin can precipitate life-threatening infusion-related reactions in some patients . Because of this, and to reduce selective pressure for vancomycin resistance, sources of fever that do not require treatment with vancomycin should be diligently investigated prior to the institution of empiric vancomycin therapy in febrile patients, particularly when the past medical history is suggestive of an alternative diagnosis.

Arch Dis Child Fetal Neonatal Ed, 1999 Nov, 81(3), F221 - 7
Pharmacokinetics and dose requirements of vancomycin in neonates; Grimsley C et al.; AIMS: To design and evaluate dosing guidelines for vancomycin based on data collected during routine use of the drug . METHODS: Following the observation that 66% of neonatal vancomycin trough concentrations were outside the target range, new dose guidelines were developed using a population pharmacokinetic approach . NONMEM (non-linear mixed effects model) was used to analyse dose histories and 347 concentration measurements collected during routine therapeutic drug monitoring in 59 neonates . RESULTS: Postconceptual ages in the patient group ranged from 26-45 weeks, weights from 0 . 57-4.23 kg, and creatinine concentrations from 18-172 micromol/l . The population estimate of vancomycin clearance (l/h/kg) was 3 . 56/creatinine concentration (micromol/l) with an interpatient coefficient of variation (CV) of 22% and volume of distribution 0.67 l/kg with a CV of 18% . Residual error was 4.5 mg/l . When the new recommendations on dosing were used prospectively in a separate group of neonates the proportion of acceptable troughs increased from 33% to 72% . CONCLUSIONS: The pharmacokinetics of vancomycin in neonates and young infants depend on weight and serum creatinine . Preliminary results from the new guidelines indicate an improvement on previous practice, but also an ongoing need to monitor concentrations.

Crit Care Med, 1999 Sep, 27(9), 1732 - 7
Antihistamine prophylaxis permits rapid vancomycin infusion; Renz CL et al.; OBJECTIVE: To determine whether pretreatment with intravenous antihistamines attenuates the symptoms of red-man syndrome associated with rapid vancomycin administration . DESIGN: Prospective, randomized, double-blinded, placebo-controlled study of patients undergoing elective arthroplasty . SETTING: Preoperative unit in a tertiary care center . PATIENTS: Forty preoperative patients (American Society of Anesthesiologists status I-III, receiving vancomycin prophylaxis for elective prosthetic joint replacement or revision . INTERVENTIONS: Elective orthopedic patients were randomly allocated to receive intravenous antihistamines (diphenhydramine, 1 mg/kg, and cimetidine, 4 mg/kg) or placebo before rapid vancomycin infusion (1 g over 10 mins) . Hemodynamic measurements, symptoms of histamine release, and plasma histamine levels were obtained in each patient during vancomycin administration . Rapid vancomycin infusion was discontinued in cases of decreases in mean blood pressure of > or =20% or intolerable itching . MEASUREMENTS AND MAIN RESULTS: Clinical symptomatology of red-man syndrome and histamine levels were assessed using Fisher's exact test or Student's t-test . Comparison of baseline and peak histamine levels for both the treated (mean +/- SD, 0.2 +/- 0.2 vs . 4.7 +/- 2.4 ng/mL; p < .0001) and placebo patients (mean +/-SD, 0.2 +/- 0.1 vs . 3.5 +/- 3.4 ng/mL; p = .0002) was statistically significant . Although there was a significant increase in plasma histamine levels during vancomycin infusion, it did not differ between the treatment groups . Only two (11%) of the treated patients developed hypotension, vs . 12 (63%) of the placebo patients (p = .002) . Rash was partially attenuated . Twelve (63%) of the treated patients developed rash, compared with 19 (100%) of the placebo patients (p = .008) . The rapid infusion was discontinued in two (11%) of the treated patients, compared with 11 (58%) of the placebo patients (p = .005) . Four treated patients had no symptoms of histamine release . CONCLUSIONS: Pretreatment with intravenous H1 and H2 antihistamines permitted rapid vancomycin administration in 89% of treated patients . Although protection was incomplete, rash did not predict a need to stop the rapid infusion of vancomycin in our patients.

Childs Nerv Syst, 1999 Sep, 15(9), 457 - 60
Pediatric neuroendoscopy in Chile . Analysis of the first 100 cases; Valenzuela S et al.; The personal series of the first 100 cases of neuroendoscopy performed at the Pediatric Neurosurgery Service of the Institute of Neurosurgery Alfonso Asenjo in Santiago-Chile is presented . The patients were the first to undergo endoscopic operations for different types of hydrocephalus and their ages ranged from newborn up to 15 years . Their clinical records, surgical protocols, radiologic results, videos and follow-up are reviewed . A mortality of 2% and a morbidity of 7% were found in this group, hemorrhage, ventriculitis and CSF leakage being the main problems . Success was achieved in more than 75% of cases in the whole series . If we only consider the group of III ventriculostomies performed in noncommunicating hydrocephalus, our success rate rises to 90% . Follow-up ranges from 30 months in the first case to 2 months in the last case considered . All patients were operated on by the author using a rigid Gaab scope with 5.8 mm OD coupled to a Codman light source and a microcamera . Surgical technique was always the same using a right precoronal burr hole . Prophylaxis with vancomycin was indicated in all cases . General, partial and specific results are presented and allow the conclusion that this is an excellent procedure when it is well indicated . It means a great saving in shunts and treatments and has become an alternative to shunts in all neurosurgical units.

Intensive Care Med, 1999 Sep, 25(9), 1017 - 20
Septic shock after liver transplantation for Caroli's disease: clinical improvement after treatment with C1-esterase inhibitor; Marx G et al.; The extent of complement and contact activation is related to outcome in sepsis . A low functional index of their main blocker C1-esterase inhibitor (C1-INH) is considered as a relative deficiency of C1-INH and might contribute to the development of fatal complications in the intensive care unit . The first results of therapeutic intervention with C1-INH concentrate in septic shock are promising . We report on our experience of C1-INH concentrate administration in a young woman with Caroli's disease as ultimate rescue therapy for septic shock with capillary leakage syndrome after combined liver and kidney transplantation . No focus of infection was detectable and thus surgical intervention was not indicated . Antibiotic therapy at that time included vancomycin, tobramycin, meropenem and fluconazol . Hemodynamic stabilization occurred within hours after administration of C1-INH concentrate . Simultaneously a reduction in vasopressor medication was possible and negative fluid balance was achieved.

Electrophoresis, 1999 Sep, 20(12), 2462 - 74
Considerations concerning interaction characterization of oligopeptide mixtures with vancomycin using affinity capillary electrophoresis-electrospray mass spectrometry; Lynen F et al.; In the past few years affinity capillary electrophoresis (ACE) has proven to be a powerful tool to study molecular interactions . In ACE the change in electrophoretic mobility between a free and a complexed ligand with a receptor dissolved in the background electrolyte is observed . It provides an accurate way to calculate binding or dissociation constants and, when coupled to mass spectrometry, it forms a promising method to analyze solution-based combinatorial libraries . We report a model study on the macrocyclic antibiotic vancomycin using a 36-component library of tetrapeptides of the type 9-fluorenylmethoxycarbonyl (Fmoc)-L-Asp-L-Asp-D-Xaa-D-Xaa . The mass spectrometry conditions were optimized by fine-tuning the background electrolyte and sheath flow composition to achieve optimal sensitivity in the negative ionization mode . Different types of capillaries were also evaluated on their potential to screen combinatorial libraries . The library components that show the strongest interaction were identified . The dissociation constants of a mixture of six compounds with a broad affinity range were simultaneously established by Scatchard analysis on ACE-MS.

Electrophoresis, 1999 Sep, 20(12), 2420 - 4
Stereoselective analysis of acid herbicides in natural waters by capillary electrophoresis; Polcaro CM et al.; A capillary electrophoretic method for the stereoselective analysis of aryloxypropionic and aryloxyphenoxypropionic acidic herbicides in ground water and river water was performed . Vancomycin and gamma-cyclodextrin were added to the background electrolyte (BGE) as chiral selectors . Water sample preconcentration was accomplished by solid-phase extraction on styrene-divinylbenzene packed cartridges (2 L of ground water and 1 L of river water) . The analytical method allowed for the resolution of mecoprop, fenoprop, fluazifop and haloxyfop racemic mixtures in natural water samples spiked with enantiomer concentration levels in the range 0.1-0.13 ppb for ground water and 0.4-0.54 ppb for river water.

J Biomed Mater Res, 1999, 48(5), 613 - 20
In vitro elution of vancomycin from biodegradable beads; Liu SJ et al.; The current antibiotics delivery system for orthopedic infection treatment uses polymethylmethacrylate (PMMA) beads as a drug release . However the nonbiodegradable nature of the PMMA necessitates a second operation to remove the beads . This article explores the alternative of using biodegradable polymers as antibiotic beads for a long-term drug release . The effect of different processing factors on the release rate of the beads was investigated . To manufacture an antibiotic bead, polylactide-polyglycolide copolymers were mixed with vancomycin . The mixture was compressed and sintered at 55 degrees C to form beads of different sizes . An elution method was employed to characterize the release rate of antibiotic over a 35-day period at 37 degrees C . Biodegradable beads released high concentrations of antibiotic (well above the breakpoint sensitivity concentration) in vitro for the period of time needed to treat bone infection; i.e., 4-6 weeks . A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics . The diameter of the sample inhibition zone ranged from 6.5-10 mm, which is equivalent to 12.5-100% of relative activity . By changing the processing parameters, we were able to control the release rate of the beads . This provides advantages of meeting the specific antibiotics requirement for patients with various surgical infections .

Ophthalmology, 1999 Sep, 106(9), 1660 - 4
Cystoid macular edema after cataract surgery with intraocular vancomycin; Axer-Siegel R et al.; OBJECTIVE: To determine whether the use of supplemental prophylactic vancomycin in the irrigating solution during extracapsular lens extraction is associated with increased incidence of cystoid macular edema . DESIGN: Prospective, randomized, double-masked clinical study . PARTICIPANTS: Consecutive series of 118 patients 60 years of age or older undergoing cataract surgery . INTERVENTION: The study group received an irrigating balanced salt solution supplemented with vancomycin (10 microg/ml), and the control group received the salt solution only . Fluorescein angiography was performed 1 and 4 months after surgery . MAIN OUTCOME MEASURES: Evidence of angiographic and clinical cystoid macular edema, and visual acuity at 1 and 4 months after surgery . RESULTS: The rate of postoperative angiographic cystoid macular edema was significantly higher in the study patients than in the control group at 1 month (55% vs . 19%, P = 0.0006) and 4 months (26% vs . 4%, P = 0.0099) . The rates of clinical macular edema were 23% and 7%, respectively, at 1 month (P = 0.011) and 20% versus 0% at 4 months (P = 0.006) . Visual acuity of 20/30 or better was noted at 4 months after surgery in 76% of the study group compared to 95.5% of the control group . CONCLUSIONS: The role of preventive intracameral vancomycin during intraocular surgery should be reassessed in view of the associated increase in the incidence of angiographic cystoid macular edema.

Enantiomer, 1999, 4(2), 79 - 90
Separation of the voriconazole stereoisomers by capillary electrophoresis and liquid chromatography; Owens PK et al.; A chiral capillary electrophoresis (CE) method has been developed for the direct separation of the four stereoisomers of a new broad spectrum antifungal agent, voriconazole . Cyclodextrin (CD) modified micellar electrokinetic chromatography employing, alpha-CD, beta-CD, gamma-CD, hydroxypropyl-beta-CD and hydroxyethyl-beta-CD was not sufficiently selective for the four neutral stereoisomers . Three anionic sulphobutyl-ether-beta-CD (SBE-beta-CD) electrolyte additives, each having a defined degree of substitution (DS) (6.5, 4.5 and 1.0) were subsequently examined . The complete CE separation of all four stereoisomers was obtained when using the medium substituted additive DS = 4.5 . In liquid chromatography (LC), two approaches were examined for the direct chiral separation of the stereoisomers of voriconazole: (a) use of the neutral and anionic CD mobile phase additives and (b) a vancomycin chiral stationary phase . The CD additives were shown to be extremely selective for two stereoisomers of voriconazole (active drug and its enantiomer) but unable to discriminate between the opposite two stereoisomers . The converse was observed, however, when the vancomycin chiral stationary phase was employed.

Bioorg Med Chem Lett, 1999 Aug 16, 9(16), 2437 - 40
Investigations into self-association of vancomycin covalent dimers using surface plasmon resonance technology; Adamczyk M et al.; Covalent dimers of vancomycin linked through the vancosamine sugar moieties of the glycopeptide antibiotic have been synthesized in one step in 67-69% yield . The propensity for self-association of these and related vancomycin covalent dimers is evaluated using surface plasmon resonance technology.

Am J Hematol, 1999 Sep, 62(1), 13 - 8
Stability and sterility of a recombinant factor VIII concentrate prepared for continuous infusion administration; Belgaumi AF et al.; Minipumps may facilitate cost-effective and convenient continuous infusion (CI) therapy for severe hemophilia A . This study evaluated the in vitro sterility, ability to support bacterial growth, and specific activity stability of a recombinant factor VIII (FVIII; Bioclate, Centeon) delivered by simulated CI at a variety of temperatures and after the addition of heparin or antibiotic . Closed system CIs of Bioclate (89.5 IU/ml) with and without heparin were sampled and cultured over a 6 day period . Bioclate (53.7 IU/ml) with and without heparin or vancomycin was inoculated with 102-105 CFU/ml of S . aureus, S . epidermidis, Escherichia coli, E . cloacae, or Y . enterocolitica and assessed by quantitative culture after 1 and 3 days . The stability of Bioclate (50, 100, and 250 IU/ml) at three temperatures (21 degrees C, 37 degrees C, and 39 degrees C) with and without heparin or vancomycin was tested over a period of 28 days . FVIII activity was measured in triplicate by a chromogenic assay (Coamatic Factor VIII, Chromogenix) and purity evaluated by Western blot . No bacterial growth was detected during CI of FVIII for up to 6 days . Following bacterial inoculation, there was rapid growth (>3 log increase) of all tested bacterial species except S . aureus which only displayed a 1 log expansion at 3 days . The addition of heparin containing 9.45 microg/U benzyl alcohol had no effect on bacterial growth . The addition of vancomycin caused a modest suppression of S . aureus growth but not of E . coli . Diluent alone did not support bacterial growth . Neither concentration, increased temperature, nor the addition of heparin or vancomycin had a significant effect on FVIII activity stability . Samples retained >75% baseline activity for between 3 and 7 days, except the infusion of Bioclate 50 IU/ml plus heparin maintained at 21 degrees C which remained stable for 28 days . Western blot analysis supported the activity assay findings . Standard and concentrated preparations of Bioclate are suitable for CI when delivered by the MiniMed 404-SP minipump . Because of the observed nutritive capability of this FVIII concentrate for sustaining bacterial growth, any contamination could result in systemic infection .

Ther Drug Monit, 1999 Aug, 21(4), 395 - 403
Non steady state and steady state PKS Bayesian forecasting and vancomycin pharmacokinetics in ICU adult patients; Polard E et al.; The pharmacokinetics of vancomycin was investigated in adult ICU patients after the first administration and at steady state . Then the predictive performance of a two-compartment Bayesian forecasting program was assessed in these patients by using population-based parameters and three non steady state vancomycin concentrations as feedback information . Finally a prospective investigation was carried out to search potential covariates . At steady state, a significant decrease (around 30%) in clearance (CL) was observed, while creatinine clearance (CLcr) was stable and a significant increase (around 30%) in volume of distribution (V(SS)) was observed . A two-fold increase in elimination half-life was found . CL was weakly correlated with CLcr at onset of therapy and at steady state . The Bayesian program tended to overpredict vancomycin peak and trough concentrations . A larger mean prediction error and a poorer precision were observed when population-based parameter estimates were used (no feedback) compared to feedback prediction, but the differences were not significant . Mechanical ventilation and concurrent opioid therapy may be pertinent covariates of vancomycin pharmacokinetics . The current work has shown that vancomycin pharmacokinetics in ICU patients displayed a significant variability and a significant change in both clearance and distribution during the course of therapy . Further investigation is necessary to clarify these findings . Moreover, the use of the Bayesian forecasting PKS program in our patients led to a prediction with low bias but rather poor precision . This outcome highlights the need to implement a population modeling approach, to determine the vancomycin pharmacokinetic parameters and covariates in our ICU patients, and to apply this information to provide more accurate concentration predictions.

J Pediatr, 1999 Aug, 135(2 Pt 1), 233 - 9
Prolonged use of pancuronium bromide and sensorineural hearing loss in childhood survivors of congenital diaphragmatic hernia; Cheung PY et al.; Sensorineural hearing loss (SNHL) is a significant neurologic morbidity in survivors of neonatal congenital diaphragmatic hernia (CDH), with a reported incidence of up to 60% . In a historical cohort study of 37 neonates with CDH, we investigated the use of pancuronium bromide (PB) and common ototoxic drugs during the neonatal period and their relationship to SNHL in childhood survivors . Survivors with SNHL (n = 23) had significantly higher cumulative dose of PB administered during the neonatal illness than survivors without SNHL (n = 14) . The cumulative dose and duration of PB use significantly correlated (r = 0.66-0.81) and independently predicted (adjusted r (2) = 0.42-0.64) the greatest intensity (in decibels) and the widest band (lowest frequency in hertz) loss of SNHL . No differences were identified between survivors with and without SNHL regarding demographic and neonatal characteristics (including oxygenation and ventilation variables and the cumulative dose and duration of therapy with aminoglycosides, vancomycin, and furosemide), although survivors with SNHL had received a modestly higher cumulative dose of ethacrynic acid than survivors without SNHL . Although we show that prolonged administration of PB during the neonatal period is associated with SNHL in childhood survivors of CDH, further multicenter studies are required to investigate the possible etiologies of SNHL in this high-risk population.

Kekkaku, 1999 Jun, 74(6), 513 - 7
{One case of chronic pyothorax with MRSA infection cured by air-plombage method}; Otsuka T et al.; It is very difficult to cure a chronic pyothorax with MRSA infection . We experienced one such case with low pulmonary function (VC 1700 ml, %VC 50.7%), 73 years old man, who had a history of esophageal cancer and was operated two years ago . As the control of bacteria and the surgical intervention are both important in the treatment of pyothorax cases, we tried to reduce MRSA by washing with Povidone-Iodine solution through the drain . Then, we selected Air-plombage method as it is expected to maintain or to increase the pulmonary function after operation . We could easily close the bronchial fistula with a muscle flap, as it was located at the centre of the cavity . During the operation we frequently used acidic electrolyzed NaCl solution against MRSA . For one month after the operation, we used Vancomycin which is effective against MRSA, however, rather severe side effects were seen, and finally and MRSA vanished . Pulmonary function has improved from the initial VC 1700 ml, %VC 50.7% to VC 2120 ml, %VC 63.6% one year later . We recommend Air-plombage method for such cases with low pulmonary function under the control of MRSA by using acidic solution.

New Microbiol, 1999 Jul, 22(3), 203 - 8
Effect of heat and acid decontamination treatments on the recovery of Legionella pneumophila from drinking water using two selective media; De Luca G et al.; Two different decontamination systems, heat and acid, and two isolation media, GVPC and MWY agar were tested for the recovery of Legionella pneumophila from drinking water . The samples were concentrated by filtration through 0.2 micron polyamide filter and the membranes were resuspended in the original water samples . The suspension was divided into three parts: the first was placed in a 50 degrees C water bath, the second was acidified in HCl-KCl solution and the third did not undergo any treatment . The isolation was made by means of media containing charcoal, yeast extract and glycine with cycloeximide (GVPC) or vancomycin, polimixin B, anysomicin and dyes (MWY) . Heating at 50 degrees C for 30 minutes was seen to be the best decontamination system above all when used with GVPC agar . Moreover, with this pretreatment higher counts were obtained both on MWY and GVPC agar . The MWY agar produced the highest isolatin percentages and the highest counts.

Pediatr Nephrol, 1999 Jun, 13(5), 423 - 5
Hemodiafiltration for vancomycin overdose in a neonate with end-stage renal failure; Goebel J et al.; We describe continuous venovenous hemodiafiltration (CVVHD) with a high-flux membrane as a novel treatment modality for vancomycin overdose associated with renal insufficiency . CVVHD was used in a 6-day-old male with a solitary hypodysplastic kidney, suspected sepsis, and anuric renal failure who subsequently received an accidental tenfold overdose of vancomycin . We furthermore present evidence for the importance of countercurrent dialysis in addition to continuous hemofiltration for optimal vancomycin removal.

Anal Biochem, 1999 Jul 15, 272(1), 94 - 9
Continuous assay for VanX, the D-alanyl-D-alanine dipeptidase required for high-level vancomycin resistance; Brandt JJ et al.; The reaction of L-alanine-p-nitroanilide with VanX was studied in an effort to develop a continuous assay for VanX activity for future kinetic and inhibition studies . VanX, containing Zn(II), Co(II), Fe(II), or Ni(II), catalyzes the hydrolysis of L-alanine-p-nitroanilide producing L-alanine and p-nitroaniline as products; the formation of the latter product (epsilon(404nm) = 10, 700 M(-1) cm(-1)) can be continuously monitored using UV-VIS spectrophotometry . Zn(II)-, Co(II)-, Fe(II)-, and Ni(II)-containing VanX exhibit saturation kinetics when L-alanine-p-nitroanilide is used as the substrate with K(m) and k(cat) values ranging from 300 to 700 microM and 0.028 to 0.080 s(-1), respectively . Inhibition studies using O-{(1S)-aminoethylhydroxyphosphinyl}-D-lactic acid as the inhibitor and L-alanine-p-nitroanilide as the substrate yielded a K(i) of 400 +/- 8 microM at pH 7.0 . These studies reveal a continuous assay of VanX activity which could be used to further study the kinetic mechanism of VanX and to allow for the development of high-throughput screening for inhibitors of VanX .

J Cataract Refract Surg, 1999 Jul, 25(7), 1004 - 8
Culture-negative ulcerative keratitis after laser in situ keratomileusis; Lam DS et al.; A 40-year old man, highly myopic in both eyes, had laser in situ keratomileusis (LASIK) in the left eye in November 1996 . Corneal melting and ulceration and fine striae-like interface infiltrates were noticed 1 day postoperatively . There was no response to intensive topical antibiotics in the form of hourly ofloxacin 3% (Tarivid), and satellite lesions developed on day 4 . Corneal scrapings for gram stain and culture were done twice . No bacterial or fungal organisms were identified . Intensive topical fortified vancomycin (50 mg/mL) was added, and the lesions resolved gradually over the ensuing 2 weeks . Eighteen months after LASIK, refraction was -1.50 - 0.75 x 105 in the left eye, and uncorrected visual acuity was 20/70, correctable to 20/25 with spectacles.

Postgrad Med J, 1999 Jan, 75(879), 41 - 3
Red-man syndrome after vancomycin: potential cross-reactivity with teicoplanin; Khurana C et al.; We report a patient with infective endocarditis who developed a severe form of Red-man syndrome after vancomycin . On substituting the antibiotic to teicoplanin, the patient went on to develop a dramatic pyrexia which settled only after the teicoplanin was discontinued . This suggested that there may be an element of cross-reactivity between teicoplanin and vancomycin in such patients and that teicoplanin may not be the most appropriate substitute in all cases of vancomycin-induced Red-man syndrome.

Pharmacotherapy, 1999 Jun, 19(6), 702 - 7
Implications of vancomycin degradation products on therapeutic drug monitoring in patients with end-stage renal disease; Somerville AL et al.; In renally impaired patients, vancomycin concentrations typically are maintained at body temperature for extended periods of time due to the drug's prolonged half-life . Both time and increased temperature potentiate production of vancomycin crystalline degradation products (CDP-1) . Commercially available vancomycin assays, such as fluorescence polarization immunoassay (FPI) and radioimmunoassay, cross-react with CDP-1 isomers . Overestimation of vancomycin concentrations by 40-53% due to cross-reactivity of CDP-1 with active factor B vancomycin occurs with FPI . As FPI is the most common method of analyzing serum vancomycin, clinicians must be aware of its potential shortcomings and be prepared to alter vancomycin dosages in renally impaired patients . The possibility of adverse affects due to elevated concentrations of CDP-1 or therapeutic failures due to subtherapeutic levels of factor B vancomycin cannot be excluded.

J Chromatogr A, 1999 Apr 30, 840(2), 261 - 8
Use of a partial-filling technique in affinity capillary electrophoresis for determining binding constants of ligands to receptors; Heintz J et al.; This work evaluates the concept of a partial-filling technique in affinity capillary electrophoresis (ACE) using two model systems: vancomycin from Streptomyces orientalis and carbonic anhydrase B (CAB, EC 4.2.1.1) . In this technique the capillary is first partially-filled with ligand followed by a sample of receptor and non-interacting standard and electrophoresed . Analysis of the change in the mobility ratio, M, of the receptor, relative to the non-interacting standard, as a function of the concentration of the ligand, yields a value for the binding constant . These values agree well with those estimated using other binding and ACE techniques . Data demonstrating the quantitative potential of this method is presented.

Pharmacotherapy, 1999 Mar, 19(3), 257 - 66
Outcome assessment of minimizing vancomycin monitoring and dosing adjustments; Karam CM et al.; An approach to minimize monitoring of vancomycin therapy was evaluated in 120 patients, and results were compared with data from 120 patients in whom vancomycin therapy was monitored and adjusted based on serum peak and trough concentrations and traditional pharmacokinetic methods . Patients dosed by the nomogram (NM) had regimens adjusted based on actual body weight, estimated creatinine clearance, and a targeted trough concentration of 5-20 microg/ml . A single trough serum concentration was drawn only after 5 or more days of therapy . Overall, the average length of therapy was similar between groups (9.9 +/- 9.4 days NM and 8.6 +/- 7.2 days pharmacokinetic) . The most common regimen for both groups was 1 g every 12 hours, although NM patients received significantly fewer grams/day (1.9 +/- 0.7 g/day) than the pharmacokinetic group (2.2 +/- 1.0 g/day, p<0.04) . Patients dosed by NM also had significantly fewer regimen changes (0.63 +/- 0.96 vs pharmacokinetic 0.92 +/- 0.97, p=0.02) as well as significantly fewer serum concentrations measured/patient (1.08 +/- 1.9 vs 1.96 +/- 2.0, p=0.001) . In addition, serum concentrations for NM patients were drawn later in therapy (5.4 +/- 2.5 vs 3.8 +/- 3.4 days, p=0.004) . Of patients dosed by NM guidelines, 77 had trough concentrations drawn; these data were used to validate the nomogram . Seventy-two patients (94%) had trough concentrations in the target range of 5-20 microg/ml . No differences were found between groups with respect to cure, improvement, failure, or days to eradication, or with respect to nephrotoxicity . Finally, total drug cost/patient was not different between groups . A considerable cost savings to our institution was noted for patients dosed by NM compared with pharmacokinetics ($232.5 +/- 50.74 vs $403.75 +/- 70.97/mo, p=0.009) based on levels saved . Caution should be applied when generalizing our results to other patient populations.

Enferm Infecc Microbiol Clin, 1999 Mar, 17(3), 126 - 9
{Evaluation of an automatic system (MB/BacT) for the isolation of Mycobacterium spp.}; Moreno R et al.; BACKGROUND: The study purpose was to evaluate the MB/BacT automated system against Lowenstein-Jensen solid media for the isolation of Mycobacterium species . METHODS: 1,511 specimens were processed from 15/10/96 to 28/4/97 . For digestion and decontamination NALC-NaOH was used . Auramine smear was performed and both culture media were inoculated after digestion-decontamination . Inoculation on MB/BacT bottles was performed according to the manufacturer's instructions, apart from a modification in MAS antibiotic supplement with the addition of vancomycin at 1 microgram/ml as final concentraction . Both media were incubated for 40 days at 37 degrees C . RESULTS: In total 101 (6.6%) mycobacteria species were isolated . 78 M . tuberculosis, 14 M . avium, 6 M . gordonae, 2 M . chelonae and 1 M . fortuitum . 98 (6.4%) Mycobacterium spp . were isolated in MB/BacT and 79 (5.2%) were isolated in Lowenstein-Jensen . 22 (1.4%) out of 101 grew only in MB/BacT and 3 (0.2%) out of 101 grew only in Lowenstein-Jensen . Sensitivity in MB/BacT was 97% compared to 78% in Lowenstein-Jensen, this difference was estatically significant (p < 0.001) . Contamination rate was 1.8% in MB/BacT and 13.3% in Lowentein-Jensen . The average time to detection of Mycobacterium spp . was 15.9 days in MB/BacT and 22.4 in Lowenstein-Jensen . CONCLUSIONS: We believe that MB/BacT is a good system for rapid and reliable detection of Mycobacterium spp.

Drug Dev Ind Pharm, 1999 Apr, 25(4), 471 - 6
Encapsulation of hydrophilic and lipophilic drugs in PLGA nanoparticles by the nanoprecipitation method; Barichello JM et al.; The purpose of this study was to assess the relative advantages and drawbacks of the nanoprecipitation-solvent displacement method for a range of drugs with respect to the particle size and drug encapsulation in polylactic-co-glycolic acid (PLGA) nanoparticles . The particle size analysis indicated a unimodal particle size distribution in all systems, with a mean diameter of 160-170 nm, except for insulin nanoparticles, which showed a smaller particle size . The results of the encapsulation efficiency analysis demonstrated that more lipophilic drugs, such as cyclosporin and indomethacin, do not suffer from the problems of drug leakage to the external medium, resulting in improved drug content in the nanoparticles . In spite of the fact that valproic acid is a liquid that is very sparingly soluble in water, very low encapsulation efficiency was obtained . Ketoprofen, a drug sparingly soluble in water, demonstrated intermediate values of encapsulation that were well correlated with its intermediate lipophilicity . More hydrophilic drugs, such as vancomycin and phenobarbital, were poorly encapsulated in PLGA nanoparticles . Insulin was preferentially surface bound on the PLGA nanoparticles . However, a strong hypoglycemic effect of the insulin was observed after administration of the suspension of PLGA nanoparticles with surface-bound insulin to the ileum loop of male Wistar rats.

Hosp Formul, 1993 Jun, 28(6), 589 - 92
Setting up an automatic pharmacist-initiated pharmacokinetic dosing service; Ament PW et al.; At Latrobe Area Hospital, a 300-bed teaching-community hospital, a unique pharmacokinetic program is in place that permits the pharmacist to initiate and adjust an aminoglycoside or vancomycin regimen and schedule serum drug concentrations and renal function lab tests without contacting a physician for verbal approval . To avoid the perception of pharmacist prescribing, a detailed policy and procedure protocol was written that defined each step conducted in the pharmacokinetic evaluation . Using this approach, the service was readily approved by the medical staff and put into practice . The program has been operational for more than 1 year and has met with high physician and nursing acceptance . Although not specifically studied, the quality of patient care was thought to be improved.

Biotechnol Bioeng, 1999 Mar 5, 62(5), 576 - 82
Vancomycin production is enhanced in chemostat culture with biomass-recycle; McIntyre JJ et al.; Production of the glycopeptide antibiotic vancomycin by Amycolatopsis orientalis ATCC 19795 was examined in phosphate-limited chemostat cultures with biomass-recycle, employing an oscillating membrane separator, at a constant dilution rate (D= 0 . 14 h-1) . Experiments made under low agitation conditions (600 rpm) showed that the biomass concentration could be increased 3.9-fold with vancomycin production kinetics very similar to that of chemostat culture without biomass-recycle . The specific production rate (qvancomycin) was maximal when the biomass-recycle ratio (R) was 0.13 (D= 0.087 h-1) . When the dissolved oxygen tension dropped below 20% (air saturation), the biomass and vancomycin concentrations decreased and an unidentified red metabolite was released into the culture medium . Using increased agitation (850 rpm), used to maintain the dissolved oxygen tension above 20% air saturation, maximum increases in biomass concentration (7.9-fold) and vancomcyin production 1.6-fold (0.6 mg/g dry weight/h) were obtained when R was 0.44 (D= 0.056 h -1) compared to chemostat culture without biomass-recycle . Moreover, at this latter recycle ratio the volumetric vancomycin production rate was 14.7 mg/L/h (a 7-fold increase compared to chemostat culture without biomass-recycle) . These observations encourage further research on biomass-recycling as a means of optimising the production of antibiotics .

J Pharm Biomed Anal, 1998 Nov, 18(3), 367 - 72
A modified HPLC method for the determination of vancomycin in plasma and tissues and comparison to FPIA (TDX); Farin D et al.; A modified high performance liquid chromatography (HPLC) method for the quantification of vancomycin levels in plasma and tissues is described . The method uses solid phase extraction (SPE) of vancomycin from the samples and reversed phase HPLC with UV detection . The method was fully validated in terms of recovery, linearity, selectivity and various stability conditions . Vancomycin was determined in plasma samples obtained from 15 patients undergoing cardiopulmonary bypass, before and repeatedly during 12 h after drug administration . The vancomycin levels in plasma were measured by HPLC and by fluorescence polarization immunoassay (FPIA) (TDX) . The following correlation was found: TDX = 0.84 HPLC + 1.04 . The mean vancomycin levels in skin, fat, atrium, pericardium and sternum, before and after bypass, are reported.

Acta Crystallogr D Biol Crystallogr, 1999 Feb, 55 ( Pt 2), 534 - 5
Crystallization and preliminary X-ray crystallographic analysis of a vancomycin-N-acetyl-D-Ala-D-Ala complex; McPhail D et al.; A vancomycin-N-acetyl-D-Ala-D-Ala complex has been crystallized by the sitting-drop vapour-diffusion method using imidazole maleic buffer at pH 7.6 . The novel crystals obtained belong to the space group P6322 with unit-cell parameters a = b = 73.43 (1), c = 277.17 (4) A, gamma = 120 degrees . The crystal density was determined as 1 . 106 g cm-3 which gives a supercell of 24 molecules (12 dimers) per asymmetric unit for an acceptable Matthews number and an estimated solvent content of 42% . Data were collected at room temperature to 2 . 8 A.

Bioconjug Chem, 1999 Mar-Apr, 10(2), 176 - 85
Structure-binding relationships for the interaction between a vancomycin monoclonal antibody Fab fragment and a library of vancomycin analogues and tracers; Adamczyk M et al.; A series of vancomycin analogues and tracers were synthesized, and their binding interactions with an anti-vancomycin Fab fragment were evaluated under mass transport limiting conditions using surface plasmon resonance detection . Differences observed in binding interactions were utilized to define the vancomycin structural elements critical for antibody recognition . Major structural regions of vancomycin shown to play an important role in anti-vancomycin Fab fragment recognition include two sugar moieties and one chlorinated phenyl ring . The N-methylleucyl residue, the carboxy terminal residue, and residues in the peptide-binding region of vancomycin have minimal impact on the anti-vancomycin Fab fragment/vancomycin binding interaction . The selection of an antibody with such binding properties plays a critical role in the development of a vancomycin immunoassay that employs stable calibrators and controls.

J Am Soc Nephrol, 1999 Mar, 10(3), 601 - 9
Quantifying the effect of changes in the hemodialysis prescription on effective solute removal with a mathematical model; Clark WR et al.; One potential benefit of chronic hemodialysis (HD) regimens of longer duration or greater frequency than typical three-times-weekly schedules is enhanced solute removal over a relatively wide molecular weight spectrum of uremic toxins . This study assesses the effect of variations in HD frequency (F: per week), duration (T: min per treatment), and blood/dialysate flow rates (QB/QD: ml/min) on steady-state concentration profiles of five surrogates: urea (U), creatinine (Cr), vancomycin (V), inulin (I), and beta2-microglobulin (beta2M) . The regimens assessed for an anephric 70-kg patient were: A (standard): F = 3, T = 240, QB = 350, QD = 600; B (daily/short-time): F = 7, T = 100, QB = 350, QD = 600; C/D/E (low-flow/long-time): F = 3/5/7, T = 480, QB = 300, QD = 100 . HD was simulated with a variable-volume double-pool model, which was solved by numerical integration (Runge-Kutta method) . Endogenous generation rates (G) for U, Cr, and beta2M were 6.25, 1.0, and 0.17 mg/min, respectively; constant infusion rates for V and I of 0.2 and 0.3 mg/min, respectively, were used to simulate middle molecule (MM) G values . Intercompartment clearances of 600, 275, 125, 90, and 40 ml/min were used for U, Cr, V, I, and beta2M, respectively, For each solute/regimen combination, the equivalent renal clearance (EKR: ml/min) was calculated as a dimensionless value normalized to the regimen A EKR, which was 13.4, 10.8, 6.6, 3.7, and 4.8 ml/min for U, Cr, V, I, and beta2M, respectively . For regimens B, C, D, and E, respectively, these normalized EKR values were U: 1.04, 0.96, 1.58, and 2.22; Cr: 1.03, 1.08, 1.80, and 2.55; V: 1.06, 1.32, 2.21, and 3.12; I: 1.05, 1.54, 2.57, and 3.62; beta2M: 1.00, 1.27, 1.73, and 2.19 . The extent of post-HD rebound (%) was highest for regimens A and B, ranging from 16% (urea) to 50% (inulin), and lowest for regimen E, ranging from 6% (urea) to 28% (beta2M) . The following conclusions can be made: (1) Relative to a standard three-times-weekly HD regimen of approximately the same total (weekly) treatment duration, a daily/short-time regimen results in modest (3 to 6%) increases in effective small solute and MM removal . (2) Relative to a standard three-times-weekly HD regimen, a three-times-weekly low-flow/long-time regimen results in comparable effective small solute removal and progressive increases in MM and beta2M removal . A daily low-flow/long-time regimen substantially increases the effective removal of all solutes.

Drugs Exp Clin Res, 1998, 24(4), 185 - 90
Serum and bone concentrations of teicoplanin and vancomycin: study in an animal model; Drago L et al.; Teicoplanin and vancomycin are antibiotics widely used in the therapy of bone and joint infections . The aim of this study was to compare bone and serum concentrations of each antibiotic in guinea pigs after administration of 50 mg/kg of teicoplanin or vancomycin by the intravenous route . Serum and bone concentrations were determined immediately before and 0.5, 1, 2, 6, 12 and 24 h after drug administration by means of high performance liquid chromatography . Teicoplanin concentrations were always higher than vancomycin levels . Area under the concentration/time curve was significantly greater for teicoplanin than for vancomycin . In bone, teicoplanin concentration increased up to 6 h, while vancomycin reached its peak after 2 h . Moreover, teicoplanin showed markedly higher levels at 6, 12 and 24 h than vancomycin . In conclusion, the ability of teicoplanin to penetrate bone in greater amount than vancomycin confirms the potential use of teicoplanin in the treatment of bone infections and in the prophylaxis of orthopedic surgery.

Anal Chem, 1999 Feb 15, 71(4), 777 - 90
A strategy for the generation of surfaces presenting ligands for studies of binding based on an active ester as a common reactive intermediate: a surface plasmon resonance study; Lahiri J et al.; This paper describes the immobilization of ten proteins and two low-molecular-weight ligands on mixed self-assembled monolayers (SAMs) of alkanethiolates on gold generated from the tri(ethylene glycol)-terminated thiol 1 (HS(CH2)11(OCH2CH2)3OH) (chi(1) = 1.0-0.0) and the longer, carboxylic acid-terminated thiol2(HS(CH2)11(OCH2-CH2)6OCH2CO2H) (chi(2) = 0.0-1.0) . The immobilization was achieved by a two-step procedure: generation of reactive N-hydroxysuccinimidyl esters from the carboxylic acid groups of 2 in the SAM and coupling of these groups with amines on the protein or ligand . Because this method involves a common reactive intermediate that is easily prepared, it provides a convenient method for attaching ligands to SAMs for studies using surface plasmon resonance spectroscopy (and, in principle, other bioanalytical methods that use derivatized SAMs on gold, silver, and other surfaces) . These SAMs were resistant to nonspecific adsorption of proteins having a wide range of molecular weights and isoelectric points . The pH of the coupling buffer, the concentration of protein, the ionic strength of the solution of protein, and the molecular weight of the protein all influenced the amount of the protein that was immobilized . For the proteins investigated in detail--carbonic anhydrase and lysozyme--the highest quantities of immobilized proteins were obtained when using a low ionic strength solution at a value of pH approximately one unit below the isoelectric point (pI) of the protein, at a concentration of approximately 0.5 mg mL-1 . Comparisons of the kinetic and thermodynamic constants describing binding of carbonic anhydrase and vancomycin to immobilized benzenesulfonamide and N-alpha-Ac-Lys-D-Ala-D-Ala groups, respectively, on mixed SAMs (by methods described in this paper) and in the carboxymethyl dextran matrix of commercially available substrates yielded (for these systems) essentially indistinguishable values of Kd, koff, and kon.

Pharmacotherapy, 1999 Feb, 19(2), 240 - 4
Vancomycin-induced neutropenia associated with fever: similarities between two immune-mediated drug reactions; Smith PF et al.; A 39-year-old woman being treated for osteomyelitis with vancomycin developed severe neutropenia and drug fever . After she discontinued therapy, both disorders quickly resolved . These adverse reactions have rarely been reported with vancomycin, and share many similarities with regard to clinical features and postulated mechanisms of induction . To our knowledge this is the first case documenting drug fever as a principal component of vancomycin-induced neutropenia, and provides further evidence in support of an immune-mediated mechanism.

Medicine (Baltimore), 1999 Jan, 78(1), 1 - 8
Clinical, demographic, and immunohistologic features of vancomycin-induced linear IgA bullous disease of the skin . Report of 2 cases and review of the literature; Nousari HC et al.; Administration of intravenous vancomycin has been associated with the development of linear IgA bullous disease (LABD) . In contrast to the idiopathic variant, vancomycin-induced LABD (VILABD) appears to be more transient and to be associated with lower morbidity . The characteristics of this entity remain undefined . Our analysis of clinical, demographic, and immunopathologic features of 2 new and 14 previously reported patients with VILABD reveals that VILABD is clinically and immunopathologically indistinguishable from its idiopathic variant . A variety of premorbid conditions and concomitant medications were observed, none of which was consistently associated with the development of VILABD . VILABD occurs independently of vancomycin trough levels, resolves promptly upon discontinuation of vancomycin, and recurs more severely and with shorter onset latency with vancomycin rechallenge . This entity should be recognized as 1 of the adverse cutaneous effects of intravenous vancomycin, and warrants prompt diagnosis through direct immunofluorescence skin examination.

Pharmacotherapy, 1999 Jan, 19(1), 108 - 13
Potential risk factors associated with thrombocytopenia in a surgical intensive care unit; Cawley MJ et al.; We conducted a retrospective chart review of 193 patients admitted during a 3-month period to determine the frequency of and potential risk factors associated with thrombocytopenia, and the association of acquired thrombocytopenia with length of stay in a surgical-trauma intensive care unit (SICU) and mortality . All records were reviewed beginning 24 hours after admission . Patients were followed for the duration of SICU stay or until death . Data collected and analyzed as potential risk factors for thrombocytopenia were age, gender, admitting diagnosis, classification (trauma, surgical, medical), APACHE II score, medical history, all scheduled drugs with start and stop dates, select laboratory values, arterial or central line placement, and complications . Thrombocytopenia occurred in 25 (13%) patients . These patients were more likely (p<0.05) than those without thrombocytopenia to have the following potential risk factors: presence of a central or arterial line (76% vs 46%, p<0.025), nonsurgical diagnosis (60% vs 37%, p<0.05), diagnosis of sepsis (p<0.001), and administration of phenytoin (p<0.01), piperacillin (p<0.005), imipenem-cilastatin (p<0.001), and vancomycin (p<0.005) . A longer SICU stay (mean 21 vs 4.5 days, p<0.05) and increased mortality (16% vs 4%, p<0.05) were significantly associated with thrombocytopenia . Cefazolin administration was significantly associated with nonthrombocytopenia (p<0.05) . Factors not associated with thrombocytopenia were age, gender, and administration of histamine2-receptor antagonists, heparin, enoxaparin, penicillins, ceftazidime, ceftriaxone, chloramphenicol, and amphotericin B . A central or arterial line was the only factor associated with the development of thrombocytopenia in a multiple linear regression analysis (p=0.0003, multiple r=0.2580) . Thrombocytopenia is not a common occurrence in the SICU, but is associated with a longer SICU stay and increased mortality.

Am J Kidney Dis, 1999 Jan, 33(1), 87 - 96
Dialyzer-dependent changes in solute and water permeability with bleach reprocessing; Scott MK et al.; The effects of bleach reprocessing on the performance of high-flux dialyzers have not been comprehensively characterized . We compared the effects of automated bleach/formaldehyde reprocessing on solute and hydraulic permeability for cellulose triacetate (CT190) and polysulfone (F80B) dialyzers using an in vitro model . Dialyzers were studied after initial blood exposure (R0) and after 1 (R1), 5 (R5), 10 (R10), and 15 (R15) reuse cycles . Ultrafiltration coefficient (K(uf)), serial clearances, and/or sieving coefficients (SCs) of urea, creatinine, vancomycin, inulin, myoglobin, and albumin were determined . Urea, creatinine, and vancomycin clearances and SCs did not significantly differ from R0 to R15 with either dialyzer . Inulin clearances and SC also did not significantly change from R0 to R15 for the CT190 . However, these same values for the F80B significantly increased (P < 0.05) . The inulin clearance and SC values for the CT190 dialyzer were significantly higher than those for the F80B at all stages except R15 . Myoglobin clearances significantly increased over 15 reuses for both dialyzers (P < 0.01) . However, CT190 myoglobin clearances were significantly higher at all stages (R0 = 37.7 +/- 9.7; R15 = 52.5 +/- 8.8 mL/min) than the F80B (R0 = negligible; R15 = 41.3 +/- 16.5 mL/min; P < 0.01) . Albumin pre- and postdialysis SCs significantly increased for both dialyzers (P < 0.01) . K(uf) for R0 and R15 were 52.3 +/- 3.3 and 52.6 +/- 7.6 mL/h/mm Hg for CT190 (P = not significant) and 48.8 +/- 4.4 and 87.3 +/- 7.0 mL/h/mm Hg for F80B (P < 0.0001) . We conclude that bleach reprocessing significantly increases larger solute and hydraulic permeability of high-flux cellulosic and polysulfone dialyzers . This effect is more pronounced for the polysulfone membrane . Until 10 reuses or greater, the removal of solutes greater than 1,500 d is significantly compromised with the polysulfone dialyzer used in this study.

J Med Chem, 1999 Jan 14, 42(1), 109 - 17
Calculation of the pKa values for the ligands and side chains of Escherichia coli D-alanine:D-alanine ligase; Carlson HA et al.; Poisson-Boltzmann electrostatics methods have been used to calculate the pKa shifts for the ligands and titratable side chains of D-alanine:D-alanine ligase of the ddlb gene of Escherichia coli (DdlB) . The focus of this study is to determine the ionization state of the second D-alanine (D-Ala2) in the active site of DdlB . The pKa of the amine is shifted over 5 pKa units more alkaline in the protein, clearly implying that D-Ala2 is bound to DdlB in its zwitterionic state and not in the free-base form as had been previously suggested . Comparisons are made to the depsipeptide ligase from the vancomycin-resistance cascade, VanA . It is suggested that VanA has different enzymatic properties due to a change in binding specificity rather than altered catalytic behavior and that the specificity of binding D-lactate over D-Ala2 may arise from the difference in ionization characteristics of the ligands.

Acta Ophthalmol Scand, 1998 Dec, 76(6), 675 - 8
Toxicity of vancomycin on corneal endothelium in rabbits; Sandboe FD et al.; PURPOSE: To evaluate the toxic effect of vancomycin on the corneal endothelium related to concentrations of vancomycin . METHODS: The toxic effect is assessed with a weighing method that gives a measure of endothelial function . Thirty-three rabbit corneas were divided into four groups . Three groups of seven corneas each were exposed to concentrations of 1.0 mg/ml, 3.0 mg/ml and 5.0 mg/ml vancomycin, respectively . The fourth group of twelve corneas served as a control group . RESULTS: The corneas exposed to 1.0 mg/ml vancomycin showed no significant weight increase, while the corneas exposed to 3.0 mg/ml and 5.0 mg/ml showed a significant weight increase as compared to the control corneas . The weight increase was significantly larger in the group of corneas exposed to 5.0 mg/ml as compared to 3.0 mg/ml . CONCLUSIONS: In the interval of tested concentrations there is a dose response relationship between vancomycin concentrations and endothelial toxicity . This experiment shows that vancomycin in the concentration of 1.0 mg/ml is non-toxic to the endothelium, while 3.0 mg/ml and 5.0 mg/ml increasingly impair endothelial function.

FEMS Immunol Med Microbiol, 1998 Dec, 22(4), 335 - 9
Mycoplasma contamination of canine gastric biopsy samples and cultures of gastric Helicobacter spp; Hanninen ML et al.; Helicobacter felis and H . bizzozeronii are canine gastric helicobacters related to H . pylori . The growth of gastric helicobacters requires a complex medium including blood and serum . We found that some of our blood agar cultures were contaminated with mycoplasmas, which were isolated from one biopsy sample and several blood agar cultures of canine gastric helicobacters by PCR or culture method . However, none of our other 18 Helicobacter strains, subcultured 10-15 times since 1990, were found to be contaminated when studied in spring 1996 . Nor was horse serum used as a growth supporter found to be contaminated with mycoplasmas . All our mycoplasma isolates grew as pure cultures and as cocultures with H . bizzozeronii on a selective medium containing vancomycin, polymyxin B and trimethoprim used in cultivation of helicobacters . Our data suggest that mycoplasmas occurring on biopsy samples can grow as contaminants on Helicobacter cultures.

Cancer, 1998 Dec 15, 83(12), 2597 - 607
Mississippi mud in the 1990s: risks and outcomes of vancomycin-associated toxicity in general oncology practice; Elting LS et al.; BACKGROUND: Discrepancies between the severity of toxicities reported in early clinical trials and recent clinical experience with vancomycin have led to confusion regarding the need for routine serum vancomycin level monitoring and discontinuation of vancomycin when toxicities occur . Therefore, the authors examined the incidence, outcomes, and predictive factors of vancomycin-associated toxicities in general oncology practice with the goal of developing clinically relevant prediction rules and guidelines . METHODS: All 742 consecutive cancer patients who received vancomycin at a comprehensive cancer center during a 3-month period were followed prospectively for the development and outcome of phlebitis, rash, ototoxicity, and nephrotoxicity . Logistic regression was used to derive a multiple variable model of the risk of nephrotoxicity . A clinical prediction rule, the Nephrotoxicity Risk Score, was developed from the risk model and validated prospectively . RESULTS: Phlebitis occurred in 3% of patients (95% confidence interval {95% CI}, 2-4%), predominantly those with recently inserted central venous catheters . Rashes occurred in 11% of patients (95% CI, 9-13%); however, all but 4 patients also were receiving beta-lactam antibiotics . Clinical evidence of ototoxicity developed in 6% of patients (95% CI, 4-9%) who were receiving vancomycin plus other ototoxic agents and only 3% of patients (95% CI, 2-5%) not receiving other ototoxic agents (P = 0.08) . Nephrotoxicity occurred in 17% of patients (95% CI, 15-20%) . Logistic regression revealed that factors associated with an increased risk of nephrotoxicity included administration of other mild to moderate (P = 0.01) or severely nephrotoxic agents (P < 0.001) or an acute physiology and chronic health evaluation (APACHE) score > 40 (P = 0.002) . Elevated serum vancomycin peak levels did not reliably predict subsequent nephrotoxicity . CONCLUSIONS: Vancomycin-associated toxicities usually are mild and self-limiting . Some patients are at a significantly higher risk of nephrotoxicity but the authors believe these individuals can be identified reliably with the Nephrotoxicity Risk Index using information available at vancomycin initiation . Further testing of the Nephrotoxicity Risk Index is ongoing.

Bioorg Med Chem Lett, 1998 Apr 7, 8(7), 721 - 4
Synthesis of the vancomycin CDE ring system; Boger DL et al.; A first generation synthesis of 22 is described constituting the first disclosure of the preparation of an appropriately protected and fully functionalized vancomycin CDE ring system complete with the C and E ring monochloro substitution pattern . The approach, which is based on two aromatic nucleophilic substitution reactions for sequential CD and DE macrocyclization, provided the opportunity to define and indirect solution to the control of the CDE atropisomer stereochemistry through selective thermal equilibration of the DE versus unaltered CD ring system . Its success provides a rationale for a preferred order to the CD and DE ring system introductions.

FEMS Microbiol Lett, 1998 Dec 15, 169(2), 349 - 54
Internal size variations in Tn1546-like elements due to the presence of IS1216V; Jensen LB; In this study, internal size variations in the VanA gene cluster Tn1546, encoding resistance to glycopeptides, is described . Studies of previously uncharacterized size variations of an internal region, encoding the vanX and vanY genes of Tn1546, revealed that these variations were due to the presence of the IS sequence, IS1216V . This IS sequence has previously been found integrated in Tn1546 . Integration of the IS1216V element created both deletions and a duplication in a non-essential region of Tn1546 . In several isolates, the entire vanY gene was deleted, proving that this gene is non-essential for vancomycin resistance.

Eur J Clin Microbiol Infect Dis, 1998 Oct, 17(10), 731 - 3
Effect of the addition of vancomycin on the performance of an automated nonradioactive system for detection of mycobacteria; Alados JC et al.; A recently developed automated, nonradioactive system for the detection of mycobacteria (MB/BacT; Organon Teknika, Belgium) has provided good results, but the contamination rate was found to be higher than that obtained with the radiometric Bactec 460 system (Becton Dickinson, USA) . In the present study, the effects of adding vancomycin (1 microg/ml) to the antibiotic mixture of the nonradioactive system were evaluated, and the performance of the system with versus without vancomycin was compared . Three hundred sputum samples were tested, using the radiometric system as the reference method . Mycobacteria were isolated from 47 (15.7%) samples . The nonradioactive system with and without vancomycin detected 42 and 43 strains, respectively; the time to detection was 1 day shorter with the medium without vancomycin (15.7 days vs . 14.3 days) . The radiometric system detected 42 strains of mycobacteria in a mean detection time of 13.6 days . Contamination rates with the nonradioactive system were 6.7% in the medium without vancomycin and 2.7% in the medium with vancomycin . The latter figure was approximately the same as the contamination rate found with the radiometric system (2.3%) . Our data suggest that the addition of vancomycin considerably reduces the number of contaminants in the MB/BacT medium without affecting the performance of the system.

Mol Gen Genet, 1998 Nov, 260(2-3), 185 - 92
A cluster of charged and aromatic residues in the C-terminal portion of maltoporin participates in sugar binding and uptake; Charbit A et al.; The maltoporin LamB of Escherichia coli K12 is a trimeric protein which facilitates the diffusion of maltose and maltodextrins through the bacterial outer membrane, and also acts as a non-specific porin for small hydrophilic molecules as well as a receptor for phages . Loop L9 (residues 375 to 405) is the most distal and largest surface-exposed loop of LamB . It comprises a central portion, which varies in size and sequence in the maltoporins of known sequence, flanked by two conserved regions containing charged and aromatic residues . In order to identify the residues within the proximal region that are specifically involved in sugar utilization, we used site-directed mutagenesis to change, individually, each of the charged (five) and aromatic (three) residues in the region 371 to 379 into alanine . None of the eight single amino acid substitutions affected the phage receptor activity of LamB . In contrast, they all affected, to variable extents, maltoporin functions . For all the mutants, very good correlations were observed between the effects on sugar binding and on in vivo uptake . In no case were maltoporin functions completely abolished . Mutants E374 A and W376 A were the most impaired (with over 60% reduction in dextrin binding and in vivo uptake of maltose and maltopentaose) . These two mutations also led to an increased bacterial sensitivity to bacitracin and vancomycin . The functional and structural implications are discussed.

Eur J Clin Pharmacol, 1998 Oct, 54(8), 621 - 5
Vancomycin dosing in morbidly obese patients; Bauer LA et al.; OBJECTIVES AND METHODS: Vancomycin hydrochloride dosing requirements in morbidly obese patients with normal renal function were computed to determine the dose of vancomycin necessary to achieve target steady-state peak and trough concentrations and compared with a normal weight population . RESULTS: Morbidly obese patients {total body weight (TBW) 165 kg, ideal body weight (IBW) 63 kg} required 31.2 mg x kg(-1) x d(-1) TBW or 81.9 mg x kg(-1) x d(-1) IBW to achieve the target concentrations . Normal weight patients (TBW 68.6 kg) required 27.8 mg x kg(-1) x d(-1) to achieve the same concentrations . Because of altered kinetic parameters in the morbidly obese patients (obese: t1/2 = 3.3 h, V = 52 L, CL = 197 ml x min(-1); normal: t1/2=7.2 h, V=46 L, CL=77 ml x min(-1), 20 of 24 patients required q8h dosing (1938 mg q8h) compared with q12h dosing (954 mg q12h) in all normal weight patients in order to avoid trough concentrations that were too low for prolonged periods . There was a good correlation between TBW and CL, but only fair correlation between TBW and V . CONCLUSION: Doses required to achieve desired vancomycin concentrations are similar in morbidly obese and normal weight patients when TBW is used as a dosing weight for the obese (approximately 30 mg x kg(-1) x d(-1)) . Shorter dosage intervals may be needed when dosing morbidly obese patients so that steady-state trough concentrations remain above 5 microg x ml(-1) in this population . Because of the large amount of variation in required doses, vancomycin serum concentrations should be obtained in morbidly obese patients to ensure that adequate doses are being administered . Dosage requirements for morbidly obese patients with renal dysfunction require further study.

FASEB J, 1998 Dec, 12(15), 1599 - 609
Aminoacyl tRNA synthetases as targets for new anti-infectives; Schimmel P et al.; Because resistance has developed to mainline antibiotics, including vancomycin, new antibiotics are now being aggressively sought . For this purpose, aminoacyl tRNA synthetases are being pursued as targets for new drugs . These enzymes are universal and are essential for cell viability . The key to their usefulness lies in being able to find drugs that inhibit a pathogen synthetase but not its human cell counterpart . The possibility for species-specific inhibition was originally demonstrated with a natural product and has now been demonstrated with prototypical drugs that are based on the structure of an intermediate of the aminoacylation reaction . Efficacy of a rationally designed inhibitor has been shown in vivo with a pathogen infection established in an animal model . Although many challenges remain, these early results suggest that synthetases will continue to be of major interest for development of new anti-infectives.

Clin Infect Dis, 1998 Nov, 27(5), 1241 - 6
Central nervous system infections due to Stomatococcus mucilaginosus in immunocompromised hosts; Goldman M et al.; We present a case of central nervous system (CNS) infection due to Stomatococcus mucilaginosus involving a patient with leukemia and summarize 12 additional published reports of CNS infection due to this organism in immunocompromised hosts . The infection was diagnosed most commonly in the setting of hematologic malignancy accompanied by chemotherapy-induced neutropenia . S . mucilaginosus was recovered from blood prior to discovery of the CNS infection in 62% of cases . Signs or symptoms of CNS infection were observed in all patients . Although a number of patients responded to regimens containing intravenous vancomycin, the addition of intrathecal vancomycin appeared to be of benefit in some cases.

J Infect, 1998 Jul, 37(1), 82 - 3
Glycopeptide-induced vasculitis--cross-reactivity between vancomycin and teicoplanin; Marshall C et al.; Teicoplanin has been suggested for use in patients suffering complications from vancomycin . We describe two patients who developed a vasculitic rash whilst on vancomycin with recrudescence of the rash with subsequent teicoplanin therapy.

Hiroshima J Med Sci, 1998 Sep, 47(3), 105 - 7
Vancomycin therapy for treatment of peritonitis in outpatients on peritoneal dialysis; Yorioka N et al.; Vancomycin therapy is frequently used for peritonitis in patients on peritoneal dialysis, but the emergence of resistance has been reported . We evaluated the efficacy of a single intraperitoneal dose of vancomycin for peritonitis in peritoneal dialysis patients . We assessed 24 episodes of peritonitis in 16 patients, and compared clinical parameters between responders and nonresponders . Vancomycin was effective for 12 patients (18 out of 24 episodes, 75.0%) . Nonresponders had a significantly higher initial C-reactive protein level and dialysis fluid leukocyte count, and the mean serum albumin over three months before onset was significantly lower than in responders . Patients with a serum albumin level 3.0 g/dl or more were significantly more likely to respond than those with a level less than 3.0 g/dl . In conclusion, it seems reasonable for peritonitis patients with a mild inflammatory response and a serum albumin 3.0 g/dl or more to receive intraperitoneal vancomycin on an outpatient basis.

Int J Clin Pharmacol Ther, 1998 Oct, 36(10), 554 - 60
Synthesis of pharmacokinetic parameters of vancomycin via bootstrap methods; Zellner D et al.; OBJECTIVE: For the adjustment of individual vancomycin dosages, we estimate the important pharmacokinetic quantities half-life, clearance, and volume of distribution . MATERIAL: To obtain reliable information 293 observations from 244 patients were extracted from 23 published studies on vancomycin . Information about vancomycin's pharmacokinetics out of different sources represents an increase in sample size and, therefore, interpretive power . METHODS: Once the whole of the data had been stratified into a small number of homogeneous clusters based on cofactors, different (robust) estimators (mean, median, Winsorized, and trimmed mean) were calculated for the expected value of the pharmacokinetic parameters of vancomycin within the clusters . Measures of the statistical accuracy such as standard error, bias, mean square error, and confidence interval were estimated via bootstrap methods from large bootstrap sample sizes to compare the quality of the estimators . RESULTS: Due to the homogenization of the data all individual estimator functions yield very similar results and the empirical mean works fairly well as an estimate . The most frequently used estimator with the smallest estimated mean square error was the Winsorized mean.

Ann Emerg Med, 1998 Nov, 32(5), 531 - 6
Appropriateness of vancomycin use in the emergency department; Wright SW et al.; STUDY OBJECTIVE: The emergence of vancomycin-resistant organisms is a major problem at many hospitals . Vancomycin use is associated with development of resistance . The objective of this study was to determine the appropriateness of vancomycin use in the emergency department . In addition, we sought to determine whether appropriateness of vancomycin use increased after the publication of the Centers for Disease Control and Prevention guidelines for prudent vancomycin use . METHODS: This retrospective study was conducted at a tertiary care university hospital, and all patients who received vancomycin while in the ED during the first 6 months of each year from 1995-1997 were eligible for study . We developed appropriateness criteria based on national and local guidelines . Vancomycin use was determined to be appropriate or inappropriate according to these guidelines . RESULTS: Vancomycin use increased each year of the 3-year study period; 40% of use was considered inappropriate . However, appropriateness increased in a linear fashion (P <.001) . A resistant organism was cultured from 17% of those with appropriate use and none of those with inappropriate use . Most patients, regardless of the appropriateness of drug use, continued to receive vancomycin after admission . CONCLUSION: Overall vancomycin use rose each year despite an increase in the proportion with appropriate use . However, inappropriate use remained common . Emergency physicians and consultants should become familiar with national and local guidelines for prudent vancomycin use.

J Chromatogr B Biomed Sci Appl, 1998 Sep 11, 715(1), 203 - 10
Use of mobility ratios to estimate binding constants of ligands to proteins in affinity capillary electrophoresis; Kawaoka J et al.; This work evaluates the use of mobility ratios (M) to estimate binding constants of proteins to ligands using affinity capillary electrophoresis (ACE) . This concept is demonstrated using two model systems: vancomycin (Van) from Streptomyces orientalis and carbonic anhydrase B (CAB, EC 4.2.1.1) . A plot of change in M (deltaM) over the concentration of ligand {L} versus deltaM yields a more useful representation of the Scatchard plot in capillary electrophoresis (CE) than traditional plots of the change in mobility delta mu over {L} versus delta mu in a wide set of circumstances, especially when comparing electropherograms obtained in the presence of substantial variations in electroosmotic flow . Altering the voltage and/or capillary length of the CE system produced only small variations in M, but much larger changes in the more standard measures of migration used by the mu form of analysis . The use of M in the Scatchard analysis offers a new approach to estimating binding constants of ligands to proteins using ACE.

J Clin Pharm Ther, 1998 Apr, 23(2), 107 - 13
Dependence of vancomycin clearance on renal function via regression and bootstrap methods; Zellner D et al.; BACKGROUND: Frequently, the estimation of vancomycin on the basis of renal function is too rough because the unknown parameters of a regression function between the vancomycin clearance (CL) and the creatinine clearance (ClCR) are based on small sample sizes . OBJECTIVE: In this study we aim to compare linear and nonlinear regression, spline interpolation and nonlinear kernel estimation for defining the relationship between measured Cl and ClCR . METHOD: We used data from published papers and appropriate numerical methods . The variability and accuracy of the estimated regression functions were determined from bootstrap methods and kernel density estimators . Tests to prove the usually assumed linearity of the regression were carried out and the influence of patient age and weight on Cl was determined . RESULTS: A linear relationship reported by several authors earlier has been determined as ClVAN = 0.763 ClCR + 2.715, (ml/min) (Cl = 0.011 ClCR + 0.055, (ml/min/ kg)) . CONCLUSION: Nonparametric regression analysis shows that a nonlinear approximately parabolic function could fit the relationship between Cl and ClCR in the present case somewhat better than a linear function.

J Pharm Biomed Anal, 1998 Apr, 16(8), 1281 - 7
Quantitation of vancomycin and its crystalline degradation product (CDP-1) in human serum by high performance liquid chromatography; Backes DW et al.; The delayed clearance of vancomycin results in accumulation of vancomycin crystalline degradation product, CDP-1, in the bodies of renally impaired patients . The 2 isomers, CDP-1-M (major) and CDP-1-m (minor), of CDP-1 are antibiotically inactive but cross-react with some immunoassays that use polyclonal antibodies resulting in falsely elevated results . A high performance liquid chromatographic (HPLC) method was developed to quantitate vancomycin and CDP-1 in the serum of renal patients . After solid phase extraction of 200 microliters serum, the separation of vancomycin, the 2 isomers of CDP-1 and the internal standard (cefazolin) was accomplished by gradient HPLC on a reversed phase C18 column with detection at 210 nm . Linearity was established from 1 to 25 and 25 to 100 micrograms ml-1 vancomycin and 1 to 25 micrograms ml-1 CDP-1 . Coefficients of variation for vancomycin and CDP-1 were 3.3-8.6% (n = 10) and 2.8-5.2% (n = 8).

Acta Crystallogr D Biol Crystallogr, 1998 Mar 1, 54 ( Pt 2), 175 - 83
Structure of balhimycin and its complex with solvent molecules; Schafer M et al.; Balhimycin is a naturally occurring glycopeptide antibiotic, related to vancomycin which acts by binding nascent bacterial cell-wall peptide ending in the sequence D-Ala-D-Ala . Crystals of balhimycin are monoclinic, space group P21, a = 20.48 (10), b = 43.93 (21), c = 27.76 (14) A, beta = 100.5 (5) degrees with four independent antibiotic molecules, three molecules of 2-methyl-2,4-pentanediol, two citrate ions, three acetate ions and 127.5 water molecules in the asymmetric unit . With an asymmetric unit larger than those of the smallest proteins and a solvent content of about 32%, the crystals have similar diffraction properties to those of small proteins . 27387 unique reflections were collected using synchrotron radiation . The structure was solved by a standard protein technique, the molecular-replacement method, using ureido-balhimycin as search model . The anisotropic refinement against all F2 data between 0.96 and 45 A converged to a conventional R value of 11.27% with R1= Sigma||Fo|-|Fc||/Sigma|Fo| for the 24623 data with I > 2sigma(I) and 12.58% for all 27387 data . The four monomers possess fairly similar conformations (r.m.s . deviation 0.7 A) . Two antibiotic molecules form a tight dimer with antiparallel hydrogen bonds between the peptide backbone as well as between the vancosamine residues and the peptide backbone . In each of the two dimers, one binding pocket is occupied by a citrate ion and the other by an acetate ion . The dimer units are linked in the crystal by hydrogen bonds to form infinite chains.

Arch Pediatr, 1998 May, 5(5), 521 - 4
{Vancomycin and cardiac arrest in the infant}; Trentesaux AS et al.; BACKGROUND: Different adverse effects induced by vancomycin bolus infusion are described, but cardiac arrest seems rare, in children as in adults . CASE REPORT: Two infants, 5 and 12 months old, were admitted after cardiac arrest, following vancomycin bolus infusion in excessive dose . They recovered after prompt resuscitation and their short term follow-up was normal . CONCLUSION: Two mechanisms are invoked: anaphylactic shock and direct cardiovascular toxicity . Both are dose- and infusion rate-dependent, and probably intersubject dependent . Usually, cardiac arrest is promptly reversed by adequate resuscitation . The rules of prescription are: adequate dilution and slow rate of infusion . If any adverse effect occurred, preventive antihistaminic drug therapy should be advised.

Bone Marrow Transplant, 1998 Sep, 22(6), 559 - 64
Bone marrow transplantation in children: consequences for renal function shortly after and 1 year post-BMT; Kist-van Holthe JE et al.; The aim of this study was to investigate the effect of a bone marrow transplantation (BMT) on renal function in children . In a 5-year period, 142 children received a BMT at the Department of Pediatrics of the University Hospital Leiden . The study was performed retrospectively using the estimated glomerular filtration rate before and 1 year after BMT, and weekly measurements of serum creatinine during the first 3 months after BMT for assessment of renal function . Patient characteristics (sex, age, diagnosis), conditioning regimen, type of BMT, major complications (sepsis, veno-occlusive disease and graft-versus-host disease (GVHD)) and the use of nephrotoxic medication were listed . In the first 3 months after BMT 17 (12%) patients died, 13 from transplant-related complications other than renal failure and four from relapse of the disease . Forty-eight children (34%) had a period with acute renal insufficiency . A high pre-BMT serum creatinine, transplantation with either a non-HLA-identical related or a matched unrelated donor were risk factors for acute renal insufficiency after BMT . Sepsis and the use of intravenous vancomycin were risk factors for acute renal insufficiency only for patients with a high pre-BMT serum creatinine . GVHD seemed to have a beneficial effect on renal function of BMT recipients . One year after BMT a total of 35 (25%) patients had died, 16 from transplant-related complications and 19 from relapse of the disease; another 17 patients could not be evaluated . Twenty-five of 90 evaluable children (28%) had chronic renal insufficiency . Chronic renal insufficiency 1 year after BMT was correlated with a high serum creatinine in the first 3 months after BMT . None of the children of this retrospective study on renal function after BMT needed dialysis.

Pharmacotherapy, 1998 Sep-Oct, 18(5), 1082 - 6
Vancomycin pharmacokinetics in neonates receiving extracorporeal membrane oxygenation; Buck ML; Vancomycin is administered as both prophylaxis and treatment in neonates receiving extracorporeal membrane oxygenation (ECMO), typically after surgery . An open-label, retrospective study was conducted to determine dosing strategies in all neonates who received vancomycin during ECMO and compare pharmacokinetic values with those of matched controls not receiving ECMO . Fifteen neonates receiving ECMO were given vancomycin infused into the circuit, with dosages based on weight and gestational age . Blood for serum concentrations was drawn around the third dose, for trough concentrations immediately before the dose, and for peak concentrations 1 hour after infusion . Samples were analyzed by fluorescence polarization immunoassay . The most frequent regimen for both groups (8 ECMO, 13 controls) was 10 mg/kg every 8 hours . It produced peak and trough concentrations of 27.5 +/- 4.3 and 13.7 +/- 2.7 microg/ml, and 23.0 +/- 5.4 and 13.2 +/- 4.5 microg/ml, respectively . Pharmacokinetic analysis using a one-compartment model revealed volume of distribution of 0.45 +/- 0.18 L/kg, half-life of 8.29 +/- 2.23 hours, and total body clearance of 0.65 +/- 0.28 ml/min/kg in ECMO recipients . Volume of distribution and clearance were not significantly different in controls (0.39 +/- 0.12 L/kg, 0.79 +/- 0.41 ml/min/kg), but half-life was shorter (6.53 +/- 2.05 hrs, p = 0.02) . Based on long volume of distribution in neonates receiving ECMO, we recommend that empiric vancomycin regimens incorporate a longer dosing interval than the 6-8 hours commonly recommended for term infants . The effects of severity of illness on drug elimination require additional study.

J Pharm Pharmacol, 1998 Aug, 50(8), 851 - 6
Prediction of serum vancomycin concentrations using one-, two- and three-compartment models with implemented population pharmacokinetic parameters and with the Bayesian method; Wu G et al.; Although previous studies have shown that vancomycin has a complicated pharmacokinetic profile requiring description using a two- or, better, three-compartment model, until recently predictions of serum vancomycin concentrations have been mainly based on one- or two-compartment models using computer software packages . In this study, we have predicted serum vancomycin concentrations in 59 patients using one-, two- and three-compartment models with implemented population pharmacokinetic parameters in the Abbott PKS program and by use of the Bayesian method . The percentage errors of predictions made using the one-compartment model were smaller when either the Bayesian method or implemented population pharmacokinetic parameters were used (medians of -8.61% and -9.49%, respectively) . Predictions using the one-compartment model with the Bayesian method were less biased (median of -1.52 microgmL(-1) . The best predictions were those made using the three-compartment model with the Bayesian method-they were most accurate (median of 3.40 microgmL(-1) and highly precise (median of 11.53 microg(2)mL(-1)) . The results suggest that predictions made using the one-compartment model with implemented population pharmacokinetic parameters are preferable if no samples are available, otherwise predictions made using the three-compartment model with the Bayesian method are preferable . The results also supported our previous argument that the greater the number of compartments involved in individualization, the better the predictions obtained using the Bayesian method.

MMWR Recomm Rep, 1998 Sep 11, 47(RR-15), 1 - 14
Preventing Emerging Infectious Diseases: A Strategy for the 21st Century . Overview of the Updated CDC plan; Tryptase levels are not increased during vancomycin-induced anaphylactoid reactions; Department of Anesthesia and Critical Care, The University of Chicago, Illinois, USABACKGROUND: Anaphylaxis, mediated by immunoglobulin E, may be clinically indistinguishable but is mechanistically different than chemically mediated anaphylactoid reactions induced by drugs such as morphine, curare, and vancomycin . A test to distinguish anaphylactic from anaphylactoid reactions would clarify therapeutic and medicolegal issues . Tryptase levels identify anaphylactic reactions but have not been evaluated in vivo during anaphylactoid reactions . A prospective, randomized, double-blinded, placebo-controlled trial of antihistamine chemoprophylaxis for rapid vancomycin infusion was performed, and plasma tryptase was measured using a new immunoassay . Histamine release was established by measurement of plasma histamine and the ability of prophylactic H1 and H2 antagonists to prevent common histamine-associated side effects . Tryptase levels were compared with histamine levels and clinical symptoms . METHODS: Before elective arthroplasty, 40 patients received vancomycin infusion (1 g over 10 min) and pretreatment with either antihistamines (1 mg/kg diphenhydramine and 4 mg/kg cimetidine) or placebo . Changes in tryptase (at peak histamine and 10 min after vancomycin infusion), histamine levels, and histamine-mediated symptoms were assessed using Fisher's exact test, the Student's t test, or the paired t test, as appropriate . Logistic regression models were used to quantify the association of clinical symptoms with antihistamine treatment and serum levels . RESULTS: Plasma tryptase levels were unchanged (99% CI, -0.5 to 1.6) independent of increased histamine levels, antihistamine pretreatment, clinical symptoms, or all of these . Histamine levels >1 ng/ml were significantly associated with hypotension, moderate-to-severe rash, and stopped infusion . Antihistamine pretreatment significantly decreased the incidence and severity of the reactions . CONCLUSION: Plasma tryptase levels were not significantly elevated in confirmed anaphylactoid reactions, so they can be used to distinguish chemical from immunologic reactions.

Kyobu Geka, 1998 Aug, 51(9), 745 - 8
{Management for the postoperative mediastinitis in infancy}; Sakamoto T et al.; Postoperative mediastinitis is a rare but life-threatening complication after cardiac surgery . We successfully managed three infants with postoperative mediastinitis . When the postoperative mediastinitis was suspected, intravenous infusion of antibiotics (Vancomycin) and local irrigation were performed . The reoperation for closure was planned when the value of c-reactive protein decreased to 1.0-2.0 . An application of a pectoral musculocutaneous flap was effective when the sternum was destroyed by infection.

J Clin Microbiol, 1998 Oct, 36(10), 3048 - 50
Evaluation of a selective transport medium for gastric biopsy specimens to be cultured for Helicobacter pylori; Siu LK et al.; Since the means of culturing Helicobacter pylori may not be available in some laboratories, prolonging the survival of this organism during transportation is a major concern in terms of improving detection rates . A selective transport medium was evaluated for the preservation of H . pylori from 254 gastric biopsy specimens collected from a rural area in China where culturing is not feasible . Gastric biopsy specimens were inoculated in sterile broth consisting of brain heart infusion (BHI) broth, horse serum, and yeast extract supplemented with vancomycin, amphotericin B, and nalidixic acid (VAN) . Of the 254 biopsy specimens, 238 were identified by histology to have H . pylori infection . Total rates of recovery of H . pylori from the H . pylori-positive gastric biopsy specimens stored in the BHI-VAN broth ranged from 76 to 46% after storage of specimens for 5 to 9 days . In conclusion, the selective medium is useful for prolonging the survival of H . pylori in gastric biopsy specimens for which immediate culture is not feasible.

Bioorg Med Chem, 1998 Jul, 6(7), 877 - 81
A rational strategy for enhancing the affinity of vancomycin towards depsipeptide ligands; Axelsen PH et al.; Glycopeptide antibiotics with enhanced affinity for model depsipeptide ligands may also exhibit enhanced efficacy against bacteria exhibiting the vanA resistance phenotype . To design modified agents with enhanced affinity for these ligands, and better understand why traditional agents have low affinity for depsipeptide ligands, free energy perturbation studies were performed on vancomycin derivatives by means of molecular dynamics simulation . The results suggest that modifications of the asparagine side chain on residue 3 of the antibiotic which enhance its hydrophobicity will enhance the affinity of glycopeptide antibiotics for depsipeptide ligands, and act synergistically with other modifications that enhance the efficacy of these agents against vanA-positive bacteria.

Anesth Analg, 1998 Sep, 87(3), 681 - 5
Oral antihistamines reduce the side effects from rapid vancomycin infusion; Renz CL et al.; Rapid infusion of vancomycin causes histamine-mediated side effects, hypotension, and rash, known as "red man syndrome." In this prospective, randomized, double-blind, placebo-controlled study, we examined the ability of oral antihistamines to attenuate three clinical end points: rash, hypotension, and vancomycin discontinuation, and we compared these findings with those of a similar study using IV antihistamines . Patients (ASA physical status I-III) who required vancomycin prophylaxis for elective arthroplasty received either oral antihistamines (diphenhydramine < or = 1 mg/kg and cimetidine < or = 4 mg/kg, n = 20) or placebo (n = 10) 1 h before rapid vancomycin infusion (1 g over 10 min) . The vancomycin infusion was discontinued if the mean arterial blood pressure decreased by > or = 20% or if itching was intolerable for the patient . Clinically significant hypotension developed in no treated patients, compared with five (50%) patients in the placebo group (P = 0.001) . Rapid infusion was stopped for one treated patient (5%) and for five (50%) patients in the placebo group (P = 0.004) . Incidence (P = 0.011) and severity of rash (P = 0.015) were also reduced in treated patients . Peak histamine levels were increased but were similar for patients in both groups (mean +/- SD, 1.9+/-2.5 vs 1.6+/-2.4 ng/mL; P = 0.75) . Oral antihistamines were as effective as IV antihistamines . In conclusion, oral H1 and H2 antihistamine pretreatment is a practical, safe, and inexpensive option to attenuate histamine-mediated side effects associated with rapid vancomycin infusion . IMPLICATIONS: Clinicians often must administer vancomycin faster than the 1-h recommended time, which can cause "red man syndrome" (rash, itching, hypotension) . Our randomized, double-blind, placebo-controlled study showed that oral H1 and H2 antihistamine pretreatment significantly reduced the histamine-related side effects of rapid vancomycin infusion.

Burns, 1998 Aug, 24(5), 475 - 7
Burn wound excision and massive blood transfusion did not affect perioperative vancomycin levels; Cameron DR et al.; INTRODUCTION: The effect of burns surgery that requires intraoperative transfusion of five or more units of blood on serum vancomycin levels was assessed . METHODS: Serum vancomycin levels were measured 10 min and 6 h after vancomycin administration with surgery being performed in the interval . The following day the same dose of vancomycin was given and serum vancomycin levels measured at the same times without intervening surgery . RESULTS: Thirteen operations involving nine patients who required a mean blood transfusion of 9.2 units were studied . There was very little difference between 10-min levels, 6-h levels and the change over interval (absolute and percentage) on the day of surgery and the following day . The recorded serum levels were often at the lower end of the desired range, especially in patients who underwent the larger operations . This was the case on both day of surgery and the control day . CONCLUSIONS: Large volume blood loss and replacement during burns surgery did not significantly affect perioperative vancomycin levels . 1998 Elsevier Science Ltd for ISBI.

Int J Antimicrob Agents, 1998 May, 10(2), 143 - 52
Comparative safety of teicoplanin and vancomycin; Wilson AP; Teicoplanin have different safety profiles which can affect choice . Nephrotoxicity is significantly less likely to occur during treatment with teicoplanin than vancomycin when an aminoglycoside is being given concurrently . 'Red man' syndrome is a troublesome effect of vancomycin infusion which is extremely uncommon with teicoplanin use . Rash and fever can be dose-related phenomena but patients reacting to one glycopeptide may not react to both . Although thrombocytopenia is more frequent with teicoplanin, it is reversible and seldom seen at standard doses.

Clin Nephrol, 1998 Jul, 50(1), 51 - 5
Pharmacokinetics of vancomycin when administered during high flux hemodialysis; Foote EF et al.; This study was undertaken to evaluate the pharmacokinetics of relatively high-dose vancomycin when administered during high-flux hemodialysis using a polysulfone membrane (F-80, Fresenius) . Five noninfected, anuric patients received a single dose of 25 mg/kg of vancomycin infused during hemodialysis at a rate of one gram per hour and timed such that the end of the infusion coincided with the end of dialysis . Blood samples were drawn during the infusion, up to six hours after the end of dialysis and then prior to the next three dialysis treatments . Spent dialysate was collected during the infusion . Samples were analyzed using the EMIT assay . The percent of vancomycin lost during the first dialysis session ranged from 39.1 to 55.1% (mean, 45.7+/-6.4) . The concentration of vancomycin at 6 hours after hemodialysis ranged from 18.2 to 45.1 mg/L (mean, 29.6+/-10.0 mg/l) . Dialysis clearance ranged from 96.1 to 158.1 ml/min (mean, 130.7 +/-30.0 ml/min) . One week after dosing, serum concentrations ranged from 8.14 mg/l to 10.1 mg/l (mean, 9.0+/-1.0 mg/l) . This study suggests than an initial dose of 25 mg/kg of vancomycin, given during high-flux dialysis, may provide adequate serum concentrations in anuric hemodialysis patients for up to seven days . This dosing scheme reduces inconvenience to the patient and staff, and potentially can reduce nursing costs associated with post-dialysis administration; its cost is minimal . At this point, subsequent dosing is best determined by therapeutic drug monitoring.

Biol Blood Marrow Transplant, 1998, 4(1), 20 - 6
Intravenous immunoglobulin and the risk of hepatic veno-occlusive disease after bone marrow transplantation; Sullivan KM et al.; Recent reports using historical controls or registry cohorts suggest, respectively, either an increase in the mortality or a decrease in the incidence of hepatic veno-occlusive disease (VOD) with the administration of intravenous immunoglobulin (i.v.Ig) after bone marrow transplantation . These divergent results prompted us to conduct a retrospective analysis of two randomized clinical trials conducted at our center to determine the effect of i.v.Ig infusions on the development and severity of VOD . Patients were randomized to receive (n=318) or not to receive (n=315) i.v.Ig prophylaxis after human leukocyte antigen-identical sibling (n=414), mismatched or unrelated (n=178), or autologous or syngeneic (n=41) marrow transplantation . To determine the relationship of i.v.Ig to the development and severity of VOD, a single observer reviewed data displays created for each patient for grading VOD without knowledge of patient i.v.Ig use . In this analysis, VOD was defined as hyperbilirubinemia > or =2.0 mg/dL before day 20 and abrupt weight gain > or =2% before day 14 posttransplant in the absence of other causes of liver disease . Hepatic VOD developed in 235 (37%) of the 633 randomized patients . No evidence for VOD was found in 230 (36%) patients . The remaining 168 (27%) patients were classified as having liver disease of uncertain etiology . Hepatic VOD was judged to be severe in 63 (10%) and mild or moderate in 172 (27%) patients . The number of patients developing any VOD or severe VOD was similar between those randomized to i.v.Ig prophylaxis and untreated controls (115 vs . 120 and 32 vs . 31, respectively) . Logistic regression models identified several covariates as significant (p < 0.01) factors associated with the development of severe VOD . Increased risk occurred with elevated pretransplant serum aspartate aminotransferase (odds ratio {OR} = 2.64) and earlier year of transplant (OR = 3.73); decreased risk occurred with autologous or twin donors (OR = 0.09) and acute myeloid leukemia (OR = 0.39) . The development of any VOD was associated with an elevated pretransplant alkaline phosphatase (OR = 4.1), pretransplant use of vancomycin (OR = 1.6) or amphotericin (OR = 3.0), posttransplant use of cyclosporine (OR = 2.5), older patient age (OR = 1.03), and obesity (OR = 0.78) . We concluded from the controlled trials of 633 patients that the administration of i.v.Ig did not influence the development or severity of VOD after bone marrow transplantation.

Jt Comm J Qual Improv, 1998 Jul, 24(7), 379 - 85
A vancomycin monitoring program at a community hospital; Goeckner BJ et al.; BACKGROUND: Because of concern about patients' increased risk of developing resistance to vancomycin, a vancomycin monitoring program involving education, not restriction, on the prudent use of vancomycin was developed at the Barnes-Jewish Christian (BJC) North Region hospitals in St Louis . The program was spearheaded by the pharmacy department and monitored by interdisciplinary committees within the hospital . METHODS: An educational note based on a Centers for Disease Control and Prevention (CDC) guideline for prudent use of vancomycin was prepared and placed in patient charts by a designated pharmacist . This intervention was tracked along with the medical staff's response to the note . In a one-year period, the rate of appropriate use of vancomycin increased from 59% to 80% (p < 0.01), whereas the number of care interventions involving vancomycin usage decreased by approximately 75% . DISCUSSION: A community hospital can promote appropriate use of antibiotics, in this case vancomycin . The fact that the rate at which vancomycin was appropriately prescribed increased and the number of pharmacist interventions (notes) decreased suggests that the vancomycin note reminders and related educational material were successful . Although these numbers do not represent 100% compliance, treatment with vancomycin may have been clinically appropriate for some of the cases even if the situation was not listed as an appropriate use in the CDC guideline . CONCLUSION: The vancomycin monitoring program, which represents a simple means of intervening and maintaining continuous monitoring and quality improvement in a clinical area, continues at the BJC North Region hospitals.

Am J Health Syst Pharm, 1998 Jul 1, 55(13), 1386 - 8
Stability of vancomycin in an extemporaneously compounded ophthalmic solution; Fuhrman LC Jr et al.; The stability of vancomycin 31 mg/mL (as the hydrochloride) in an artificial tears solution at -10, 4, 25, and 40 degrees C was studied . Vancomycin power was reconstituted with sterile water for injection to a concentration of 50 mg/mL . Artificial tears solution containing 0.3% hydroxypropyl methylcellulose, 0.1% dextran 70, 0.01% benzalkonium chloride, and 0.05% edetate disodium was used to produce a final concentration of 31 mg/mL . Triplicate solutions for each storage temperature and sampling time were prepared . The solutions were stored at -10, 4, 25, and 40 degrees C . Samples were taken initially and at 3, 7, 10, 21, 30, 45, and 60 days for visual inspection and analysis by high-performance liquid chromatography . All solutions remained clear and colorless at -10, 4, and 25 degrees C throughout the study period . By day 3, crystalline particles formed in the solutions stored at 40 degrees C . No substantial change in pH was observed at any time . At -10 degrees C, the solutions retained more than 90% of their initial vancomycin concentrations throughout the study period . The solutions retained a mean of at least 90% of the initial drug concentration for 21 days at 4 degrees C and for 7 days at 25 degrees C . For the solutions stored at 25 or 40 degrees C, less than 85% of the initial vancomycin concentration remained after 10 and 3 days, respectively . Vancomycin 31 mg/mL (as the hydrochloride) in an artificial tears solution was stable for 45 days at -10 degrees C, 10 days at 4 degrees C, and 7 days at 25 degrees C in the tears solution's original container.

Ther Drug Monit, 1998 Jun, 20(3), 261 - 5
Therapeutic drug monitoring of vancomycin in a morbidly obese patient; Penzak SR et al.; The authors describe the therapeutic drug monitoring of vancomycin in a man who is morbidly obese . Because serum vancomycin concentration (SVC) monitoring continues to be deemphasized, nomogram use will likely increase . However, vancomycin dosing nomograms have not been studied in patients who are morbidly obese . Furthermore, in nomograms that incorporate body weight, it is unclear whether ideal or total body weight (IBW and TBW, respectively) should be used to dose the morbidly obese . Therefore, the authors retrospectively evaluated four nomograms (Moellering, Matzke, Lake-Peterson, and Rodvold) and an individualized method in the simulated vancomycin dosing of their patient . Total body weight was more accurate than IBW in selecting a vancomycin dose when using the individualized method and in all nomograms except the Matzke nomogram . The Rodvold nomogram and the individualized method yielded the most appropriate doses . All nomograms suggested dosing intervals that were unacceptably short; the individualized method suggested an appropriately longer interval . Thus, if nomograms or the individualized method are used to empirically dose vancomycin, TBW--not IBW--should be used . Because these nomograms yielded inappropriately short dosing intervals in the patient, it is likely that patients who are morbidly obese represent a unique population in which at least one set of SVCs are necessary to select an appropriate dosing regimen.

Am J Kidney Dis, 1998 Jun, 31(6), 1019 - 27
Determinants of vancomycin clearance by continuous venovenous hemofiltration and continuous venovenous hemodialysis; Joy MS et al.; The clearance of vancomycin is significantly reduced in patients with acute, as well as, chronic renal failure . Although multiple-dosage regimen adjustment techniques have been proposed for these patients, there is little quantitative data to guide the individualization of vancomycin therapy in acute renal failure patients who are receiving continuous renal replacement therapy (CRRT) . To determine appropriate vancomycin dosing strategies for patients receiving continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD), we performed controlled clearance studies in five stable hemodialysis patients with three hemofilters: an acrylonitrile copolymer 0.6 m2 (AN69), polymethylmethacrylate 2.1 m2 (PMMA), and polysulfone 0.65 m2 (PS) . Patients received 500 mg of vancomycin intravenously at least 12 hours before the start of the clearance study . The concentration of vancomycin in multiple plasma and dialysate/ultrafiltrate samples was determined by EMIT (Syva, Palo Alto, CA) . The diffusional clearance and sieving coefficient (SC) of vancomycin were compared by a mixed-model repeated-measures analysis of variance (ANOVA) with filter and blood (Q(B)), dialysate inflow (Q(DI)), or ultrafiltration rate (Q(UF)) as the main effects and patient as a random effect . Vancomycin was moderately protein bound in these patients; free fraction ranged from 49% to 83% . The SCs of the three filters were similar and significantly correlated with the free fraction of vancomycin (P = 0.01; r2 = 0.465) . Significant linear relationships were observed between the diffusional clearance of vancomycin and Q(DI) for all three filters: AN69 (slope = 0.482; r2 = 0.880); PMMA (slope = 0.853; r2 = 0.966); and PS (slope = 0.658; r2 = 0.887) . The slope of this relationship for the PMMA filter was significantly greater than that of the AN69 and PS filters . The clearance of vancomycin, urea, and creatinine, however, was essentially constant at all Q(B)s for all three filters . Thus, the clearance of vancomycin was not membrane dependent during CVVH . However, during CVVHD, membrane dependence of vancomycin clearance was noted at a Q(DI) greater than 16.7 mL/min; vancomycin clearance with PMMA at a Q(DI) of 25 mL/min was 66% and 43% greater than that with the AN69 and PS filters, respectively . CVVH (62% to 262%) and CVVHD (90% to 540%) can significantly augment the clearance of vancomycin in acute renal failure patients . Dosing strategies for individualization of vancomycin therapy in patients receiving CVVH and CVVHD are proposed.

J Med Chem, 1998 Jun 4, 41(12), 2090 - 9
Vancomycin: conformational consequences of the sugar substituent; Grdadolnik SG et al.; High-resolution, three-dimensional structures of vancomycin and aglyco-vancomycin in DMSO were determined by nuclear magnetic resonance, metric matrix distance geometry, and molecular dynamics calculations . Conformational flexibility fast on the NMR time scale was examined by ensemble-based calculations which apply the experimentally derived restraints as an ensemble average . Two families of conformations of vancomycin, differing in the positioning of the vancosamine substituent, were observed . In contrast, the aglyco-vancomycin adopts only one conformation in solution . The conformations of vancomycin and the aglyco-vancomycin differ in the alignment of the amide protons which participate in the hydrogen-bonding network with the cell-wall precursor and orientation of the aromatic rings relative to the backbone . Therefore, the high-resolution structural characterization provides insight into a possible role of glycosylation on the activity of this important family of antibiotics.

Chemotherapy, 1998 May-Jun, 44(3), 181 - 9
Interaction between levofloxacin and vancomycin in rats--study of serum and organ levels; Mori H et al.; The changes of pharmacokinetic parameters when levofloxacin (LVFX) and vancomycin (VCM) were administered concomitantly were studied in rats . There was an increase in the AUC and Tmax of LVFX with concomitant administration, but no effect on Cmax . There was also an increase in the AUC and T1/2 of VCM with concomitant administration, while Vd was reduced . Concomitant administration had no effect on the correlation between the serum and hepatic tissue concentrations of LVFX, but it markedly decreased the correlation between the serum and renal tissue concentrations of VCM . BUN was increased at 8 h after the administration of VCM . There have been reports that renal dysfunction can be caused by VCM, and our findings suggested that concomitant administration of LVFX and VCM must be performed with caution.

Infect Control Hosp Epidemiol, 1998 Apr, 19(4), 248 - 53
Vancomycin control measures at a tertiary-care hospital: impact of interventions on volume and patterns of use; Singer MV et al.; OBJECTIVE: Evaluate vancomycin prescribing patterns in a tertiary-care hospital before and after interventions to decrease vancomycin utilization . DESIGN: Before/after analysis of interventions to limit vancomycin use . SETTING: 420-bed academic tertiary-care center . INTERVENTIONS: Educational efforts began August 10, 1994, and involved lectures to medical house staff followed by mailings to all physicians and posting of guidelines for vancomycin use on hospital information systems . Active interventions began November 15, 1994, and included automatic stop orders for vancomycin at 72 hours, alerts attached to the medical record, and, for 2 weeks only, computer alerts to physicians following each vancomycin order . Parenteral vancomycin use was estimated from the hospital pharmacy database of all medication orders . Records of a random sample of 344 patients receiving vancomycin between May 1, 1994, and April 30, 1995, were reviewed for an indication meeting published guidelines . RESULTS: Vancomycin prescribing decreased by 22% following interventions, from 8.5 to 6.8 courses per 100 discharges (P<.05) . The estimated proportion of vancomycin ordered for an indication meeting published guidelines was 36.6% overall, with no significant change following interventions . However, during the 2 weeks that computer alerts were in place, 60% of vancomycin use was for an approved indication . CONCLUSIONS: Parenteral vancomycin prescribing decreased significantly following interventions, but the majority of orders still were not for an indication meeting published guidelines . Further improvement in the appropriateness of vancomycin prescribing potentially could be accomplished by more aggressive interventions, such as computer alerts, or by targeting specific aspects of prescribing patterns.

Science, 1998 May 1, 280(5364), 711 - 4
An analysis of the origins of a cooperative binding energy of dimerization; Williams DH et al.; The cooperativity between binding of cell wall precursor analogs (ligands) to and antibiotic dimerization of the clinically important vancomycin group antibiotics was investigated by nuclear magnetic resonance . When dimerization was weak in the absence of a ligand, the increase in the dimerization constant in the presence of a ligand derived largely from changes associated with tightening of the dimer interface . When dimerization was strong in the absence of a ligand, the increase in the dimerization constant in the presence of a ligand derived largely from changes associated with tightening of the ligand-antibiotic interface . These results illustrate how, when a protein has a loose structure, the binding energy of another molecule to the protein can derive in part from changes occurring within the protein.

Science, 1998 May 1, 280(5364), 708 - 11
A trivalent system from vancomycin.D-ala-D-Ala with higher affinity than avidin.biotin; Rao J et al.; Tris(vancomycin carboxamide) binds a trivalent ligand derived from D-Ala-D-Ala with very high affinity: dissociation constant (Kd) approximately 4 x 10(-17) +/- 1 x 10(-17) M . High-affinity trivalent binding and monovalent binding are fundamentally different . In trivalent (and more generally, polyvalent) binding, dissociation occurs in stages, and its rate can be accelerated by monovalent ligand at sufficiently high concentrations . In monovalent binding, dissociation is determined solely by the rate constant for dissociation and cannot be accelerated by added monomer . Calorimetric measurements for the trivalent system indicate an approximately additive gain in enthalpy relative to the corresponding monomers . This system is one of the most stable organic receptor-ligand pairs involving small molecules that is known . It illustrates the practicality of designing very high-affinity systems based on polyvalency.

Otolaryngol Head Neck Surg, 1998 Apr, 118(4), 551 - 8
Vancomycin administration in continuous ambulatory peritoneal dialysis: the risk of ototoxicity; Gendeh BS et al.; A prospective study was undertaken in 16 patients with chronic renal failure on continuous ambulatory peritoneal dialysis, with 22 episodes of peritonitis treated with vancomycin, a known ototoxic agent . Twelve patients had one episode each, and four had recurrent peritonitis . Each treatment course consisted of two infusions of vancomycin (30 mg/kg body weight) in 2 L of peritoneal dialysate administered at 6-day intervals . Serum vancomycin analyzed by enzyme immunoassay showed a mean trough level of 11.00 microg/ml on day 6 and mean serum levels of 33.8 and 38.6 microg/ml about 12 hours after administration on days 1 and 7, respectively . Similar levels, well within the therapeutic range, were encountered with repeated vancomycin therapy for recurrent episodes of peritonitis, suggesting that no changes occurred in the pharmacokinetic profile of the drug . Pure-tone audiometry, electronystagmography, and clinical assessment performed during each course of treatment showed no evidence of ototoxicity even on repeated courses of vancomycin therapy . The results suggest that vancomycin therapy when given in appropriate concentrations as a single therapeutic agent is both effective and safe . We believe, however, that vancomycin administered in combination with an aminoglycoside may produce ototoxic effects that may be greatly aggravated, possibly because of synergism.

Ther Drug Monit, 1998 Apr, 20(2), 231 - 5
New modified fluorescence polarization immunoassay does not falsely elevate vancomycin concentrations in patients with end-stage renal disease; Smith PF et al.; Recent literature has urged caution in the interpretation of vancomycin serum concentrations in patients with end-stage renal disease (ESRD), because falsely elevated levels in excess of 70% have been reported with the most commonly used fluorescence polarization immunoassay (FPIA) . The purpose of this study was to evaluate the performance of a recently modified FPIA assay for use in patients with ESRD, in comparison to high-performance liquid chromatography (HPLC) and an enzyme-mediated immunoassay technique (EMIT) . Serum vancomycin samples were prospectively collected from adults with ESRD undergoing chronic hemodialysis . Each sample was stored at -70 degrees C until analyzed in duplicate by FPIA, EMIT, and HPLC . In an in vitro experiment, blank serum samples with 15 microg/ml vancomycin were spiked with increasing amounts of CDP and analyzed in duplicate with the modified FPIA assay . When compared to HPLC, no statistically significant difference was found in patients with ESRD with the use of the modified FPIA assay (mean concentrations, HPLC 14.92 microg/ml, FPIA 15.96 microg/ml), with FPIA exhibiting a positive bias of 0.64 microg/ml and a precision of +/-3.49 microg/ml (n = 18, p = 0.44) . The mean EMIT concentration was 18.34 microg/ml, with a positive bias of 3.43 microg/ml and a precision of +/-5.17 microg/ml (p < 0.01) . The addition of increasing amounts of CDP to vancomycin in vitro resulted in concentrations similar to those expected in the absence of significant cross-reactivity with the modified FPIA assay . The modified FPIA assay is a satisfactory tool for monitoring vancomycin serum concentrations in patients with ESRD undergoing hemodialysis . Results obtained with EMIT were not as precise as with FPIA.

Ther Drug Monit, 1998 Apr, 20(2), 191 - 201
Development of a quantitative vancomycin immunoassay for the Abbott AxSYM analyzer; Adamczyk M et al.; A novel fluorescence polarization immunoassay for vancomycin on Abbott AxSYM analyzer is described . The immunoassay allows for the accurate quantification of vancomycin in the presence of the crystalline degradation product (CDP) . It displays dilution linearity from 1.0 microg/ml to 100.0 microg/ml, coefficients of variation ranging from 2.94% to 4.26%, recovery from 98% to 105%, and a sensitivity of <2.0 microg/ml . The assay demonstrates no cross-reactivity to crystalline degradation product, and to commonly-prescribed and over-the-counter drugs, as well as a minimum interference from endogenous substances.

Electrophoresis, 1998 Mar, 19(3), 367 - 82
Affinity capillary electrophoresis: a physical-organic tool for studying interactions in biomolecular recognition; Colton IJ et al.; Affinity capillary electrophoresis (ACE) is a technique that is used to measure the binding affinity of receptors to neutral and charged ligands . ACE experiments are based on differences in the values of electrophoretic mobility of free and bound receptor . Scatchard analysis of the fraction of bound receptor, at equilibrium, as a function of the concentration of free ligand yields the dissociation constant of the receptor-ligand complex . ACE experiments are most conveniently performed on fused silica capillaries using a negatively charged receptor (molecular mass < 50 kDa) and increasing concentrations of a low molecular weight, charged ligand in the running buffer . ACE experiments that involve high molecular weight receptors may require the use of running buffers containing zwitterionic additives to prevent the receptors from adsorbing appreciably to the wall of the capillary . This review emphasizes ACE experiments performed with two model systems: bovine carbonic anhydrase II (BCA II) with arylsulfonamide ligands and vancomycin (Van), a glycopeptide antibiotic, with D-Ala-D-Ala (DADA)-based peptidyl ligands . Dissociation constants determined from ACE experiments performed with charged receptors and ligands can often be rationalized using electrostatic arguments . The combination of differently charged derivatives of proteins - protein charge ladders - and ACE is a physical-organic tool that is used to investigate electrostatic effects . Variations of ACE experiments have been used to estimate the charge of Van and of proteins in solution, and to determine the effect of the association of Van to Ac2KDADA on the value of pKa of its N-terminal amino group.

J Med Chem, 1998 Mar 26, 41(7), 1201 - 4
Simultaneous measurement of nineteen binding constants of peptides to vancomycin using affinity capillary electrophoresis-mass spectrometry; Dunayevskiy YM et al.; On-line affinity capillary electrophoresis-electrospray ionization-mass spectrometry (ACE-MS) was used for the simultaneous measurement of multiple binding constants of an all-D-tetrapeptide library to the model receptor, vancomycin . Determination of Kd values for the 19 peptides of the form Fmoc-DXYA is demonstrated . The data are compared with the results obtained for individual compounds using ACE-UV, and good correlation between the two detection methods is shown . Simultaneous determination of multiple Kd values by ACE-MS is achieved in one set of experiments, whereas only one Kd value can be obtained by ACE-UV during the same time . ACE-MS measures multiple binding constants in solution in a fast and reliable manner using femtomole amounts of samples.

Sao Paulo Med J, 1997 May-Jun, 115(3), 1452 - 5
Adverse effects of vancomycin in children: a review of 22 cases; Reis AG et al.; Vancomycin has been frequently recommended for the treatment of multi-resistant infections . Twenty-two children undergoing vancomycin treatment were observed . Nine adverse effects were registered in 6 children: eosinophilia in 5 cases, skin rash in 2 cases, and an increase in plasma creatinine in 2 cases . All adverse effects remitted with withdrawal of the drug.

Pediatr Med Chir, 1997 Jul-Aug, 19(4), 259 - 62
{Glycopeptides and the newborn infant's kidney}; Fanos V et al.; The aim of this paper was to evaluate glycopeptide nephrotoxicity in the newborn . The exact mechanism of nephrotoxicity has not been defined . Basal mechanism of vancomycin nephrotoxicity seems related to the energy-dependent tubular transport of the drug from blood to tubular cell across the basolateral membrane . Moreover a tubular reabsorption is probably involved, but it is not relevant for nephrotoxicity . Considering the widespread use of this antibiotic, the question of nephrotoxic side effects in humans is of great importance . However, the results of studies published to date are controversial . Results differ considerably depending on the period considered and on the sensitivity of the methods used to indicate renal damage . In paediatric patients (including neonates) the nephrotoxicity of vancomycin appears to be less than that in adults, thus confirming a number of experimental observations . It is commonly suggested that pharmacokinetic monitoring of doses in children should minimize nephrotoxicity . The most important risk factors for the development of the nephrotoxic action of vancomycin are: pre-dose values > 10 mg/l, prolonged therapy (> 21 days), and concomitant treatment with aminoglycosides . In most cases nephrotoxicity associated with vancomycin is reversible, even after high doses . In conclusion it could be speculated that vancomycin nephrotoxicity relates to the combined effect of a large area under the concentration-time curve and duration of therapy . Teicoplanin is a new glycopeptide that is effective in the treatment of both children and neonates and offers the advantages of once daily administration, choice of administration route (intramuscular or rapid intravenous bolus) and lack of requirement for routine therapeutic drug monitoring . Finally it seems less nephrotoxic than vancomycin . In the neonatal age bracket, none of the 173 patients treated presented abnormalities of traditional kidney function parameters.

Pediatr Nephrol, 1998 Jan, 12(1), 63 - 4
Charcoal hemoperfusion in a child with vancomycin overdose and chronic renal failure; Panzarino VM et al.; A 14-month-old girl with chronic renal insufficiency received a massive overdose of vancomycin, resulting in worsened renal failure and ototoxicity . We report the use of combined charcoal hemoperfusion and dialysis to accelerate vancomycin removal in this patient.

Ann Pharmacother, 1998 Feb, 32(2), 176 - 81
Predictive performance of a vancomycin-aminoglycoside population model; Beringer PM et al.; OBJECTIVE: To evaluate the Wragge-Cooper method of predicting vancomycin serum concentrations utilizing knowledge of aminoglycoside pharmacokinetic parameters in general medicine and intensive care unit populations, and to develop a revised model if necessary . DESIGN: This study consists of two phases evaluating 50 adults receiving concurrent vancomycin and aminoglycoside therapy . Patients were identified by a retrospective review of medical records . Bayesian analysis of measured serum aminoglycoside and vancomycin concentrations was performed to determine the individualized pharmacokinetic parameters . Phase I of the study tested the predictive performance of a published model incorporating aminoglycoside elimination (Wragge-Cooper) in 25 patients (group 1), and a revised model was developed . Phase II determined the predictive performance of the revised model (revised) and its performance relative to the Wragge-Cooper model and a traditional model incorporating estimated creatinine clearance (traditional) in an additional 25 patients (group 2) . SETTING: Two tertiary care university teaching hospitals . MAIN OUTCOME MEASURES: The predictive performance of the models was determined by comparing predicted with measured vancomycin serum concentrations . Bias and precision were evaluated by calculating the mean prediction error (ME) and mean absolute error (MAE), respectively . Linear regression was performed to determine relationships between parameters . RESULTS: The Wragge-Cooper model consistently underpredicts vancomycin serum concentrations in general medicine and intensive care unit populations (ME = -5.18, MAE = 6.63) . Relative predictive performance analysis indicates no significant difference in bias or precision between the traditional and Wragge-Cooper models (delta ME 1.17, delta MAE -0.80) . Regression analysis of individualized aminoglycoside and vancomycin elimination derived from patients in group 1 reveals the following relationship: vancomycin k10 (1/h) = 0.081 + 1.037ke,amg, r = 0.73 . The revised model is significantly less biased and more precise compared with the traditional model (delta ME -4.48; delta MAE 1.22), and is significantly less biased (delta ME 4.29) but no more precise than the Wragge-Cooper model (delta MAE -0.58), using patients from group 2 . CONCLUSIONS: The revised model is an accurate method of predicting vancomycin serum concentrations in both general medicine and intensive care unit populations . Use of this model enables individualization of vancomycin dosage in patients receiving concurrent aminoglycoside therapy and minimizes vancomycin serum concentration monitoring.

Clin Perform Qual Health Care, 1998 Apr-Jun, 6(2), 60 - 2
Phlebotomy teams reduce blood-culture contamination rate and save money; Surdulescu S et al.; OBJECTIVE: To determine the extent of resource utilization due to contaminated blood cultures . DESIGN: Case-control retrospective analysis . Twenty-three patients who had contaminated blood cultures were matched by age, underlying diseases, and discharge diagnoses with 23 patients who had negative blood cultures . SETTING: St Luke's Medical Center, a community teaching hospital in Cleveland, Ohio . The phlebotomy team was eliminated in November 1993 to reduce the costs . RESULTS: Blood cultures drawn by the phlebotomy team had a lower contamination rate compared with those drawn by nonphlebotomists (2.6% vs 5.6%) . Patients with contaminated blood cultures were compared to those with negative blood cultures . The following parameters were found to be statistically significant: total hospital length of stay (LOS; 13.9 vs 5.5 days; P = .002), postculture LOS (8.9 vs 4.6; P = .01), postculture number of days on antibiotics (5.9 vs 2.9; P = .03), vancomycin use (9 vs 2 patients; P = .03), postculture cost of antibiotics ($762 vs $121; P = .004), and postculture hospital cost per patient ($10,515 vs $4,213; P = .001) . CONCLUSIONS: This study demonstrated a substantial increase in resource utilization in our hospital due to contaminated blood cultures . The reinstitution of a phlebotomy team could be a cost-effective solution with savings between $950,000 and $1.5 million per year for our hospital.

J Am Acad Dermatol, 1998 Feb, 38(2 Pt 2), 352 - 6
Phenytoin-induced linear IgA bullous disease; Acostamadiedo JM et al.; Drug-induced linear IgA bullous disease most commonly occurs after exposure to vancomycin, but other medications may also trigger the eruption . We describe a 78-year-old man with linear IgA bullous disease related to treatment with phenytoin.

Cesk Slov Oftalmol, 1997 Dec, 53(6), 368 - 70
{Vitreoretinal complications of cataract surgery . II . Subluxation of the lens, endophthalmitis}; Hakenova J et al.; The second evaluated group of vitreoretinal complications after cataract surgery were patients with lens luxation into the vitreous body . During the investigation period the authors treated two cases of luxation of the patient's own lens into the vitreous body and three cases of luxation of intraocular lenses, a total of five eyes, i.e . 0.06% of all operated cataracts . The third group was formed by five patients with postoperative endophthalmitis which was treated by pars plana vitrectomy and intraocular ATB administration in a permanent infusion (Vancomycin 20 mg/500 ml) . The frequency of postoperative endophthalmitis treated by PPV was 0.06% . The final mean visus was 0.21.

Clin Pharmacol Ther, 1998 Jan, 63(1), 26 - 38
Urea kinetics and dialysis treatment time predict vancomycin elimination during high-flux hemodialysis; Schaedeli F et al.; BACKGROUND: Hemodialysis sessions with high-flux filters ask for a reconsideration of the kinetics of xenobiotics . The aim of this study was to analyze whether individual high-flux hemodialysis treatment parameters are of predictive value for dosing guidelines, with use of vancomycin as a model compound . METHODS: Twenty-six patients receiving high-flux hemodialysis were studied prospectively . After an intravenous infusion of 1000 mg or 500 mg vancomycin, respectively, six to eight blood samples were collected within a period of 5 to 9 days, including one hemodialysis session . Serum vancomycin concentrations were measured by HPLC . Nonlinear mixed-effects modeling (NONMEM) was used to fit a two-compartment population pharmacokinetic model to the data of 20 patients; the data of the remaining six patients (group II) were used for a prospective evaluation of the model . RESULTS: A linear relationship was found between vancomycin filter clearance (CLDV) and urea filter clearance (CLDBUN), derived from Kt/V (the product of urea clearance {K} and dialysis treatment time {t}, standardized for the urea volume of distribution {V}) . Mean (coefficient of variation) steady-state volume of distribution was 1.05 L/kg (22%), CLDV was 0.336.CLDBUN (13%), and residual interdialytic clearance was 2.25 ml/min (90%) in patients with creatinine clearance values (CLCR) below 2 ml/min and 2.25 ml/min + 0.59.CLCR (32%) in patients with CLCR values above 2 ml/min . The model predicted predialysis vancomycin concentrations before the first and the second postinfusion dialysis session in the six patients of group II, with a deviation of 1.8 +/- 1.0 mg/L and 0.8 +/- 0.5 mg/L, respectively . CONCLUSION: The described population pharmacokinetic model allows individualization of vancomycin dosing intervals in patients receiving hemodialysis, based on patient characteristics and urea kinetic modeling.

J Microencapsul, 1998 Jan-Feb, 15(1), 31 - 44
Incorporation and release of vancomycin from poly(D,L-lactide-co-glycolide) microspheres; Atkins TW et al.; Spherical monolithic microspheres, with a honeycomb-like internal architecture, composed of PLCG 50:50 and PLCG 75:25 and containing a range of vancomycin loadings, have been fabricated using a W/O emulsification with solvent evaporation technique . Microspheres were generated in high yield (80 wgt%) and vancomycin incorporation, confirmed using the displacement of DSC thermograms, had no significant effect on microsphere size distribution (5-50 microns) . The vancomycin encapsulation efficiency was high (> 64%) and release profiles were characterized by a substantial initial burst release and a subsequent low-level sustained release extending up to 30 days depending upon the fabrication polymer, % vancomycin loading and incubation medium used . In both Hank's buffer and newborn calf serum the mean total cumulative release of vancomycin from microspheres increased significantly with theoretical percentage loading.

Helicobacter, 1997 Mar, 2(1), 36 - 9
Comparative evaluation of selective and nonselective media for primary isolation of Helicobacter pylori from gastric biopsies; Fresnadillo Martinez MJ et al.; BACKGROUND: In this study, we compared and evaluated the efficacy of five culture media for the primary isolation of Helicobacter pylori from gastric biopsies . MATERIALS AND METHODS: A total of 1,174 biopsies (antrum and corpus) taken from 587 patients were plated in parallel on two selective media--Skirrow's medium and brain-heart infusion (BHI) agar supplemented with 10% sheep blood, polymyxin B, vancomycin, trimethoprim, and amphotericin B (HPA medium), and on three nonselective media--chocolate agar with Isovitalex, Columbia blood agar, and BHI-10% sheep blood agar . RESULTS: An isolation rate of 57.9% (680 of 1,174) was obtained with a combination of all media . HPA medium gave the highest isolation rate, 99.4% (676 of 680) . Chocolate agar, Columbia blood agar, brain-heart blood agar, and Skirrow's medium showed very poor performance (23.5%, 28.5%, 65.9%, and 71% of all isolates, respectively) . The number of cultures in HPA medium discarded due to contamination was only 2 (0.32%) . There was no difference in the positive rate of culture in HPA medium between the antrum and the corpus of the stomach . CONCLUSIONS: The HPA medium is superior to Skirrow's medium and nonselective media in promoting growth of H . pylori and, on the basis of these results, we recommended the use of HPA medium for primary isolation of H . pylori from gastric biopsies.

Nephrol Dial Transplant, 1997 Dec, 12(12), 2647 - 53
Vancomycin mass transfer characteristics of high-flux cellulosic dialysers; Scott MK et al.; BACKGROUND: In comparison to conventional haemodialysis membranes, highly permeable membranes allow a broader spectrum of solute removal, including enhanced elimination of vancomycin (1448 Daltons) . However, the mass transfer characteristics of vancomycin removal by highly permeable membranes have not been adequately assessed . An understanding of vancomycin's predominant dialytic mass transfer mechanism under a given set of operating conditions, including dialyser type and flow rates, may permit more accurate dosing of the drug . METHODS: We performed a mass transfer analysis of vancomycin removal by a high-flux dialyser, cellulose triacetate (CT) . In a cross-over fashion with a 3-week washout between treatments, eight subjects received vancomycin 1000 mg (1) during the last hour of CT haemodialysis; or (2) after dialysis . Serial urea and vancomycin serum concentrations were used to assess dialytic removal . RESULTS: Dialysis removed 26.2% (mean; range 16-44%) of the administered vancomycin dose . While vancomycin removal and (Kt/V)urea were directly correlated (r = 0.88; P < 0.005), no correlation was observed between vancomycin removal and weight-normalized ultrafiltration rate . CONCLUSIONS: These findings suggest that for the CT dialyser and dialysis operating conditions employed in this study, vancomycin clearance was primarily mediated by diffusion . As such, these data challenge the general concept that convection is primarily responsible for the removal of solutes in the same molecular weight class as vancomycin during high-flux dialysis.

Eur J Med Res, 1995 Dec 18, 1(3), 137 - 43
Significance of prophylactic urodilatin (INN: ularitide) infusion for the prevention of acute renal failure in patients after heart transplantation; Brenner P et al.; Acute renal failure is a serious problem following heart transplantation . In first uncontrolled clinical trials, Urodilatin revealed beneficial effects in the prophylaxis and therapy of acute renal failure following heart and liver transplantation . Here, we present the first randomized, placebo-controlled, double-blind study on 24 patients following heart transplantation to investigate whether prophylactic i.v . Urodilatin infusion can prevent acute renal failure requiring renal replacement therapy . Postoperative drug management was characterized by intravenous application of high furosemide, cyclosporine, and vancomycin doses . Urodilatin infusion was started postoperatively with a dose of 40 ng / kg bw / min for 6 days . 6 of the 12 patients in the Urodilatin group and 6 of the 12 patients in the placebo group had a stable diuresis (3 - 4 l / day) during the study period of 6 days . In contrast, the remaining 6 patients of each group developed oliguria / anuria and required subsequent hemofiltration / hemodialysis . Cumulative duration of hemofiltration (88 +/- 7.39 hours in the placebo treated patients versus 44 +/- 5.35 hours in the Urodilatin treated patients, p < 0 . 05) as well as frequency of hemodialysis (3.0 +/- 0.49 times in the placebo group vs 1.2 +/- 0.29 times in the Urodilatin group, p < 0 . 05) were significantly reduced using Urodilatin . Mean arterial blood pressure was stable during the Urodilatin infusion period and was not different to that observed in placebo patients . We conclude that Urodilatin does not reduce the incidence of acute renal failure and the subsequent requirement for hemofiltration / hemodialysis in our patient population, but seems to reduce the duration of hemofiltration and frequency of hemodialysis compared to the placebo group.

Bone Marrow Transplant, 1997 Dec, 20(11), 1001 - 3
Inhaled vancomycin-induced allergic reaction in decontamination of respiratory tracts for allogeneic bone marrow transplantation; Kahata K et al.; A 34-year-old male suffered from an allergic reaction after inhalation of decontaminating drugs for BMT . Clinical challenge tests were undertaken to determine the causal drug . It was found that vancomycin hydrochloride (VCM) repeatedly induced dyspnea, fever, hypoxia, eosinophilia, and elevation of CRP . Therefore, clindamycin (CLDM) was used instead of VCM for decontamination of patient respiratory tract . Although complete decontamination of the respiratory tract was not achieved during the leukocytopenic period, BMT was successful, and there were no life-threatening infectious complications . Although inhaled VCM-induced allergic reaction may be a very rare complication in the BMT setting, careful clinical attention should be paid to such patients.

Ther Drug Monit, 1997 Dec, 19(6), 614 - 9
Vancomycin monitoring: one or two serum levels?
Andres I, Lopez R, Pou L, Pinol F, Pascual C.
Based on the principle that vancomycin therapy requires sustained therapeutic concentrations while avoiding high peaks, some authors reported that optimal vancomycin levels could be ensured by measuring trough levels alone (Cmin) . The aim of this work was to assess the performance of a one-compartment Bayesian forecasting method for estimating vancomycin 2 hours after infusion (C2h) and mean vancomycin concentration in steady state (Cavgss) on the basis of a single trough sample (Cmin), in different conditions (steady state, patient renal function, and age), and according to clinical significance . Vancomycin serum concentrations (n = 108) were analyzed by fluorescence polarization immunoassay, from 79 adult patients . The predictive performance of the Bayesian method was determined by calculating the mean prediction error (ME), the mean absolute error (MAE) and the root squared prediction error (RMSE) . A linear regression analysis was carried out between estimated and observed concentrations . The predicted C2h were not significantly different from the observed, and the least biased (ME = -1.08) and most precise (MAE = 3.81) predictions were from patients with normal renal function and steady state conditions . In this population, the concordance in dosage recommendations with the data pair results was 75% of patients . The best correlation between observed and predicted concentrations was found for Cavgss (r = 0.94; p < 0.00005) . Predictions of the Cavgss were more precise (ME = -0.54) and accurate (MAE = 1.74) than the C2h predictions . Vancomycin can be monitored by determining one level in steady state for most patients with normal renal function.

Int J Clin Pharmacol Res, 1997, 17(1), 1 - 10
Predictions of serum vancomycin concentrations by means of six different equations for calculation of creatinine clearance; Wu G et al.; Serum vancomycin concentrations were predicted in 59 patients by means of the PKS programme using six different equations to calculate creatinine clearance . These equations are (i) Chiou & Hsu equation, (ii) Cockroft-Gault lean body-weight equation, (iii) Cockroft-Gault total body-weight equation, (iv) Jelliffe equation, (v) Jelliffe & Jelliffe equation, and (vi) Siersback-Neilsen equation . The predictions were made by using (i) the implemented population pharmacokinetic parameters (IPPP), and (ii) the Bayesian method (BM) . The results show that (i) if IPPP can lead to under-predictions, and Chiou & Hsu equation is most suited for predictions, and (ii) if IPPP can lead to over-predictions, the Cockroft-Gault total body-weight equation is the most suited for predictions.

Infect Control Hosp Epidemiol, 1997 Nov, 18(11), 780 - 2
Evaluation of vancomycin use in a pediatric teaching hospital based on CDC criteria; Logsdon BA et al.; This study was performed to determine whether vancomycin use at our pediatric hospital was consistent with modified Centers for Disease Control and Prevention guidelines . Vancomycin use was inappropriate in 54% of patients . Inappropriate use briefly decreased by 14% after educational efforts . Further education regarding vancomycin use was deemed necessary and is continuing.

Mol Gen Genet, 1997 Oct, 256(3), 306 - 19
In vivo and in vitro studies on interactions between the components of the hemolysin (HlyA) secretion machinery of Escherichia coli; Schlor S et al.; The glycopeptide antibiotic vancomycin blocks cell wall synthesis in Escherichia coli only when it can reach its target site in the periplasm . In vivo, sensitivity to vancomycin is enhanced in the presence of the hemolysin (hly) determinant of E . coli or its translocator portion hlyBD . Two different mutations in hlyD alter the cell's susceptibility to vancomycin: mutations in the tolC-homologous region of hlyD increase vancomycin resistance, whereas mutations at the 3'-terminus of hlyD lead to hypersensitivity to vancomycin and to the accumulation of large periplasmic and cytoplasmic pools of this antibiotic in E . coli . These effects are only observed in the presence of functional HlyB and TolC, the two other components of the hemolysin secretion machinery . A defect in TolC causes hyperresistance to vancomycin, even when present together with a mutant HlyD protein which in the presence of TolC renders E . coli hypersensitive to vancomycin . Lipid bilayer experiments in vitro revealed specific interactions between TolC and vancomycin or HlyD protein . Second-site suppressor mutations in hlyD and hlyB were obtained, which abolish the hypersensitive phenotype caused by the 3'-terminal mutations in hlyD . Our results are compatible with the idea that (a) TolC, together with the TolC-homologous part of HlyD, forms a pore in the outer membrane through which hemolysin is released and vancomycin taken up; and (b) the C-terminal sequence of HlyD interacts with periplasmic loop(s) of HlyB to form a closed channel spanning the periplasm.

Ann Pharmacother, 1997 Nov, 31(11), 1321 - 4
Agranulocytosis induced by vancomycin or ticarcillin/clavulanate; Mandl DL et al.; OBJECTIVE: To reacquaint clinicians with a reportedly rare adverse event of agranulocytosis occurring after long-term administration of vancomycin and ticarcillin/clavulanate, with a subsequent review of other reported cases in the literature . CASE SUMMARY: A 45-year-old white woman with spina bifida developed agranulocytosis (2.7 x 10(3)/mm3 white blood cells with only 3% polymorphonuclear leukocytes and no reported eosinophils or basophils) after long-term administration of vancomycin and ticarcillin/clavulanate for decubitus ulcers and chronic osteomyelitis . Consequently, the cell counts rebounded rapidly on discontinuation of both medications and returned to normal within 1 week . DISCUSSION: The incidence of vancomycin-associated neutropenia is presumably rare, but the increased use of vancomycin may disclose a more frequent occurrence . It is suggested that the mechanism for the reaction is immunologically mediated, yet this remains unclear . Although it is difficult to determine the causative agent in this case, vancomycin was most suspect clinically . Ticarcillin/clavulanate is less likely because our patient has since been readmitted and treated with oxacillin, imipenem/cilastatin, and amoxicillin/clavulanate without affecting the white blood cell count . In that regard, it could be reasoned that an immunologic reaction to ticarcillin would have resulted in a similar outcome with other penicillins . CONCLUSIONS: This case serves as a reminder to clinicians that patients receiving long-term treatment with vancomycin should have their white blood cell count monitored at least weekly.

Clin Perform Qual Health Care, 1998 Jan-Mar, 6(1), 12 - 6
A clinical decision process model for evaluating vancomycin use with modified HICPAC guidelines . Hospital Infection Control Practice Advisory Committee; Salemi C et al.; OBJECTIVE: The objective of this study was to evaluate a clinical decision process model for the appropriateness of vancomycin use, using modified Hospital Infection Control Practice Advisory Committee (HICPAC) guidelines . DESIGN: All nondialysis vancomycin use was reviewed using the retrospective chart review method . The HICPAC guidelines were modified to distinguish between documented and suspected infections and appropriateness of vancomycin use initially and after 3 days of therapy . Data were collected on both vancomycin-use orders and vancomycin-use days . SETTING: 446-bed health maintenance organization teaching hospital . RESULTS: 758 uses of vancomycin from 1993 through 1995 were evaluated using the modified HICPAC guidelines . Initial use was appropriate in 71% of the cases, with 26% used for documented infections and 74% for suspected infections . Of the 536 orders of initial appropriate use, 176 courses of treatment with vancomycin were discontinued appropriately within 3 days . Ongoing use evaluation after 3 days revealed appropriate use in 45%, inappropriate ongoing use in 25%, and empirical ongoing use in 30% of the cases . There were adequate clinical or laboratory data available in 70% of cases after 3 days to discontinue vancomycin or to reclassify from suspected to documented infections or indications . Vancomycin-use evaluation solely after 3 days would not have disclosed 537 initial inappropriate vancomycin-use days, which were 44% of the total inappropriate use days . CONCLUSIONS: Comprehensive evaluation of vancomycin use with HICPAC guidelines should include a modification to encompass initial and 3-day reevaluation, because most initial use is for suspected, and not documented, infections . HICPAC guidelines do not address the issues of differentiating suspected from documented infection indications or ongoing empirical use . The clinical decision process model is a framework for documentation and data collection for use evaluation and addresses issues not covered in HICPAC vancomycin guidelines . This model could be used by other medical centers for evaluation of vancomycin or other antibiotics.

Epidemiol Infect, 1997 Oct, 119(2), 245 - 50
A 1-year study of Escherichia coli O157 in cattle, sheep, pigs and poultry; Chapman PA et al.; Samples of rectal faeces were collected immediately after slaughter from 400 cattle each month for a 1-year period and from 1000 each of sheep, pigs and poultry over the same period . Samples were examined for Escherichia coli O157 by enrichment culture in buffered peptone water with vancomycin, cefixime and cefsulodin followed by immunomagnetic separation and culture of magnetic particles onto cefixime tellurite sorbitol MacConkey agar . E . coli O157 was isolated from 752 (15.7%) of 4800 cattle, 22 (2.2%) of 1000 sheep and from 4 (0.4%) of 1000 pigs, but not from any of 1000 chickens . Of the cattle sampled . 1840 (38.4%) were prime beef animals, 1661 (34.6%) were dairy animals being culled and the status could not be determined for the other 1299 (27%) animals . E . coli O157 was found in 246 (13.4%) of the 1840 beef cattle and 268 (16.1%) of the 1661 dairy cattle . The monthly prevalence of E . coli O157 in cattle was 4.8-36.8% and was at its highest in spring and late summer . Seventeen of the 22 isolates from sheep were also made over the summer period . All E . coli O157 isolates from sheep and 749 (99.6%) of the 752 E . coli O157 isolates from cattle were verocytotoxigenic as determined by Vero cell assay and DNA hybridization, eaeA gene positive, contained a 92 kb plasmid and were thus typical of strains causing infections in man . In contrast isolates from pigs were non-toxigenic, eaeA gene negative and did not contain a 92 kb plasmid and would, therefore, be unlikely to be a source of infection for man.

Adv Perit Dial, 1997, 13, 218 - 20
Cefazolin and netilmycin versus vancomycin and ceftazidime in the treatment of CAPD peritonitis; Gucek A et al.; In spite of several recommendations, choosing the initial antibiotic to treat continuous ambulatory peritoneal dialysis (CAPD) peritonitis remains difficult . In our prospective randomized study we attempted to evaluate the efficacy and safety of less toxic combinations of cephalosporins with vancomycin or netilmycin . From November 1993 to September 1996 we treated 52 episodes of peritonitis in 34 patients . Peritonitis was diagnosed according to the valid criteria . Patients were treated for 14 - 28 days with a combination of either cefazolin plus netilmycin or vancomycin plus ceftazidime . The most frequent bacteria causing peritonitis in the two groups were comparable . The efficacy of the cefazolin/netilmycin combination was 91.6% (22/24) without yeasts and 84.0% (21/25) in the vancomycin/ceftazidime combination . There were no statistically significant differences between the two otherwise efficient combinations of antibiotics . No side effects were observed . We believe that the frequent use of vancomycin could be avoided thus reducing the risks of resistance and ototoxicity.

Ann Pharmacother, 1997 Oct, 31(10), 1132 - 6
Removal of vancomycin during plasmapheresis; McClellan SD et al.; OBJECTIVE: To examine the removal of vancomycin during plasmapheresis, determine whether drug administration should be withheld prior to or a supplemental dose given after the procedure, and determine whether a redistribution phenomenon in vancomycin serum concentrations occurs after plasmapheresis . DESIGN: Prospective, cohort study . SETTING: An 800-bed, tertiary-care, teaching hospital . PATIENTS: Twelve patients receiving vancomycin as prescribed who were also undergoing therapeutic plasmapheresis . METHODS: Blood samples for determination of vancomycin concentrations were obtained from each patient immediately before, during, immediately after, and 2 hours after plasmapheresis . Vancomycin concentration in plasma removed by plasmapheresis and volume of plasma removed were measured . Patient-specific pharmacokinetic parameters were determined for each patient using serum concentration data and a one-compartment model . Percent of drug removed by plasmapheresis and percent increase in vancomycin total clearance secondary to plasmapheresis were calculated . RESULTS: A mean of 6.3% of the total body store of vancomycin was removed by plasmapheresis . Vancomycin clearance during plasmapheresis averaged 1.6 L/h, which was an average increase of 285% in the total clearance of vancomycin from the body . Nine of 10 patients had a higher observed vancomycin concentration 2 hours after plasmapheresis than that predicted by degrading the concentration observed immediately after the procedure, suggesting that redistribution in serum concentrations occurs after the procedure . CONCLUSIONS: A single one-volume plasmapheresis does not remove a clinically important amount of vancomycin; therefore, supplemental dosing after the procedure is not necessary . A redistribution phenomenon in vancomycin concentrations appears to exist after plasmapheresis . Further study is needed to determine how long the redistribution phase lasts and when vancomycin concentrations should be measured after plasmapheresis.

Antimicrob Agents Chemother, 1997 Sep, 41(9), 1985 - 90
Nephrotoxicity of vancomycin and drug interaction study with cilastatin in rabbits; Toyoguchi T et al.; The nephrotoxic effects of vancomycin hydrochloride (VCM) and the potential drug-drug interaction with cilastatin sodium (CS) were examined in rabbits . The aim of the study was to measure the possible dose-related suppressive effects or elimination by cilastatin of the adverse reactions generated by vancomycin in the kidneys of rabbits . To clarify the interactions of these two drugs, we examined the nephrotoxicity and pharmacokinetics of VCM in the rabbit when administered alone and when coadministered with CS . VCM administered alone (300 mg/kg of body weight as an intravenous bolus; n = 5) caused typical symptoms of nephrotoxicity, such as increases in serum creatinine and blood urea nitrogen (BUN) levels, as well as morphological changes in the kidneys . A lack of such signs of nephrotoxicity was observed in the groups administered VCM plus CS (i.e., CS at 150 mg/kg plus VCM at 300 mg/kg or CS at 300 mg/kg plus VCM at 300 mg/kg, intravenous bolus; n = 5/group) . At a reduced combination ratio of VCM plus CS (4:1 ratio, VCM at 300 mg/kg plus CS at 75 mg/kg, intravenous bolus; n = 5) some symptoms of nephrotoxicity induced by VCM were present, but the degree of this effect was much reduced and was significantly different from preadministration values by only modest increases of the BUN and N-acetyl-beta-D-glucosaminidase levels (P < 0.05) . Overall clearance of VCM was accelerated by coadministration of CS and was found to be dose dependent upon CS . No changes in renal function values from the preadministration values were observed for animals receiving CS alone (300 mg/kg, intravenous bolus; n = 3) . These results suggest that CS has the ability to reduce or eliminate in a dose-dependent manner the nephrotoxic effects caused by VCM administration in rabbits.

Clin Chem, 1997 Sep, 43(9), 1732 - 7
Effect of hemoglobin- and Perflubron-based oxygen carriers on common clinical laboratory tests; Ma Z et al.; Polymerized hemoglobin solutions (Hb-based oxygen carriers; HBOCs) and a second-generation perfluorocarbon (PFC) emulsion (Perflubron) are in clinical trials as temporary oxygen carriers ("blood substitutes") . Plasma and serum samples from patients receiving HBOCs look markedly red, whereas those from patients receiving PFC appear to be lipemic . Because hemolysis and lipemia are well-known interferents in many assays, we examined the effects of these substances on clinical chemistry, immunoassay, therapeutic drug, and coagulation tests . HBOC concentrations up to 50 g/L caused essentially no interference for Na, K, Cl, urea, total CO2, P, uric acid, Mg, creatinine, and glucose values determined by the Hitachi 747 or Vitros 750 analyzers (or both) or for immunoassays of lidocaine, N-acetylprocainamide, procainamide, digoxin, phenytoin, quinidine, or theophylline performed on the Abbott AxSym or TDx . Gentamycin and vancomycin assays on the AxSym exhibited a significant positive and negative interference, respectively . Immunoassays for TSH on the Abbott IMx and for troponin I on the Dade Stratus were unaffected by HBOC at this concentration . Tests for total protein, albumin, LDH, AST, ALT, GGT, amylase, lipase, and cholesterol were significantly affected to various extents at different HBOC concentrations on the Hitachi 747 and Vitros 750 . The CK-MB assay on the Stratus exhibited a negative interference at 5 g/L HBOC . HBOC interference in coagulation tests was method-dependent-fibrometer-based methods on the BBL Fibro System were free from interference, but optical-based methods on the MLA 1000C exhibited interferences at 20 g/L HBOC . A 1:20 dilution of the PFC-based oxygen carrier (600 g/L) caused no interference on any of these chemistry or immunoassay tests except for amylase and ammonia on the Vitros 750 and plasma iron on the Hitachi 747.

Pharm World Sci, 1997 Aug, 19(4), 191 - 6
Dosage recommendation of vancomycin during haemodialysis with highly permeable membranes; Zoer J et al.; The standard dosage of vancomycin in haemodialysis patients is usually 1 gram, once a week . The aim of our study was to investigate vancomycin clearance by two highly permeable membranes and to determine whether dosage adjustment is necessary in regular haemodialysis settings when using these type of dialyzers . 12 patients on regular haemodialysis and treated with vancomycin either prophylactically or therapeutically were prospectively randomised to either dialysis with a polyacrylonitril parallel membrane (AN-69) or a cellulose-acetate hollow fiber membrane . After administering vancomycin to the patient vancomycin plasma levels were measured at different intervals . The vancomycin clearance by the dialyzer was calculated from blood samples taken 1 hour after commencing dialysis . The data were used for pharmacokinetic computer simulation in order to develop a vancomycin dosage regimen for patients on regular haemodialysis with highly permeable membranes . The mean vancomycin dialysis clearance was 46 +/- 5 ml/min and did not differ between the two artificial kidneys . Dialysis clearance of vancomycin was independent of blood flow rate . Together with the dialyzer data a pharmacokinetic profile of each patient was calculated from the plasma samples . The average non-renal clearance was 3.3 ml/min/1.73 m2 while renal vancomycin clearance, as a fraction of creatinine clearance, was found to be 0.83 +/- 0.20 . The computer calculations predicted that, irrespective of residual renal function, in most patients on regular haemodialysis and treated with these type of artificial kidneys, therapeutic and non-toxic vancomycin levels could be obtained by giving 1000 mg of vancomycin intravenously as a loading dosage and 500 mg during every subsequent dialysis.

Ann Pharmacother, 1997 Sep, 31(9), 980 - 3
Evaluation of a sparse sampling strategy for determining vancomycin pharmacokinetics in preterm neonates: application of optimal sampling theory; Burstein AH et al.; OBJECTIVE: To use optimal sampling theory to determine the fewest vancomycin concentrations required and the appropriate sampling times to calculate vancomycin pharmacokinetic parameters in neonates . DESIGN: Unblinded evaluation in neonates with presumed sepsis . SETTING: Level 3 community-based neonatal intensive care unit . PATIENTS: Eleven neonates with presumed sepsis . INTERVENTIONS: Twelve courses of intravenous vancomycin 20 mg/kg were administered . Blood samples were collected 3 and 9 hours after initiation of a 1-hour infusion of the first dose . MEASUREMENTS AND MAIN RESULTS: A two-compartment model was fit to vancomycin concentrations using iterative two-stage analysis . Pharmacokinetic parameter estimates were used for determination of optimal sampling times for two-, three-, and four-sample strategies with subsequent generation of two-, three-, and four-sample concentration data for 100 cases . Relative performance of strategies was compared through calculation and comparison of D efficiency for the determined strategies . Bias (median percent error) and precision (median percent absolute error) of pharmacokinetic parameter estimates for each strategy in the 100 simulated cases were determined . CONCLUSIONS: For estimation of total clearance and volume in the central and peripheral compartments, all strategies performed similarly with no difference in efficiency or bias and precision of estimates . Our results suggest that for clinical evaluations two appropriately timed samples (0.5 h after a 1-h infusion, trough concentration) are adequate for estimation of vancomycin clearance in neonates.

J Biomed Mater Res, 1997 Sep 15, 36(4), 564 - 7
Subcutaneous tissue distribution of vancomycin from a fibrin glue/Dacron graft carrier; Fujimoto K et al.; We investigated the tissue distribution of vancomycin (VCM) incorporated in fibrin glue (FG) in a rat model . One VCM-loaded FG Dacron graft (VCM-FG, VCM 0.6 mg/ graft) was implanted in the subcutaneous tissue of the anterior abdominal wall of each rat . VCM was injected intravenously at an equal dose (0.6 mg/rat) after implantation of one control graft (without VCM-FG) . After the implantation and the iv injection of an equal dose of VCM (0.6 mg/rat), the tissue distribution of VCM for up to 24 h was determined through analysis of the implanted VCM-FG grafts, which released VCM over a 24 h period . The area under the VCM concentration-time curve (AUC) of the tissue was 89.58 micrograms.h/g after the implantation of the VCM-FG graft, and 7.40 micrograms.h/g after the iv injection of VCM, respectively . The targeting index of the tissue, defined as the ratio of AUC after the implantation of the VCM-FG graft to that after VCM iv injection, was 12.11 . None of the six VCM-FG Dacron grafts after implantation became infected following inoculation with S . aureus ATCC 25923 (0.1 mL 10(8) CFU/mL) . These results suggest that this VCM-FG Dacron graft delivery may be useful in preventing local infection by enhancing the delivery of VCM to the local areas of the implanted site in rats.

Am J Kidney Dis, 1997 Sep, 30(3), 343 - 8
Preoperative vancomycin prophylaxis decreases incidence of postoperative hemodialysis vascular access infections; Zibari GB et al.; The role of vancomycin in the treatment of infected arteriovenous chronic dialysis access is well established . However, the role of preoperative vancomycin administration in preventing infection in newly placed, revised, or surgically thrombectomized grafts has not been determined . We performed a prospective randomized study to examine whether vancomycin prophylaxis can decrease the incidence of postoperative graft infections . Over a 5-year period, 206 patients undergoing 408 permanent vascular access procedures were randomized into two groups . Group 1 (206 procedures) received a single intravenous dose of 750 mg of vancomycin approximately 6 to 12 hours before vascular access placement procedures, while group 2 (202 procedures) did not . Patients were evaluated for access infection within the following 30 days and before use of the access for chronic dialysis . Access infection developed in two patients (1%) in group 1 and in 12 patients (6%) in group 2 (P = 0.006) . All 14 infections occurred in upper extremity polytetrafluoroethylene grafts . We conclude that the use of preoperative single-dose intravenous vancomycin prophylaxis for hemodialysis vascular graft procedures reduces the risk of postoperative access infection.

Scand J Clin Lab Invest, 1997 Aug, 57(5), 401 - 7
Inhibition of serum phospholipase-A2 in acute pancreatitis by pharmacological agents in vitro; Makela A et al.; Phospholipase-A2 has been suggested as having a role in the pathophysiology of acute pancreatitis . The inhibition of phospholipase-A2 was studied in vitro using 17 pharmacological agents in the search for a specific therapy for acute pancreatitis . The inhibitory effect was tested using an isotopic assay system with 2-palmitoyl-(1-14C)-labelled dipalmitoyl phosphatidylcholine as a substrate and 10 microliters of serum from patients with acute necrotizing pancreatitis as an enzyme source . Among all agents tested, anti-inflammatory drugs inhibited enzyme activity most significantly: indomethacin (9.0 x 10(-3) mol l-1) decreased the phospholipase-A2 activity to one- tenth . The weak inhibitory effect could also be demonstrated using a lower concentration of 2 x 10(-5) mol l-1, which can be achieved after intravenous administration of 50 mg of this drug . The other drugs inhibited the enzyme activity at concentrations higher than those achieved after intravenous injections in clinical use . Diclofenac (3.1 x 10(-2) mol l-1) reduced the phospholipase-A2 activity by 93%, ketoprofen (2.0 x 10(-2) mol l-1) or chlorpromazine (1.4 x 10(-2) mol l-1) by 90%, tobramycin (1.7 x 10(-2) mol l-1) by 84%, doxycycline (9.0 x 10(-3) mol l-1) by 61%, dexamethasone (1.7 x 10(-3) mol l-1) by 62%, methylprednisolone (3.8 x 10(-2) mol l-1) by 50%, and pindolol (1.0 x 10(-4) mol l-1) by 59% . A weak inhibition of phospholipase-A2 activity was demonstrated by betamethasone, bupivacaine, digoxin, hydrocortisone, lidocaine, metoprolol, propranolol, and vancomycin . Indomethacin proved the most potent of the tested agents in inhibiting phospholipase-A2 activity in serum from patients with acute pancreatitis and should be further studied in vivo.

Chem Biol, 1997 Jul, 4(7), 507 - 12
A limitation of two-state analysis for transitions between disordered and weakly ordered states; Williams DH et al.; BACKGROUND: The stability of the secondary structure of particular peptide regions is often used to investigate the involvement of the region in protein folding . When analysing the relatively small populations of associated states that are formed by weak interactions (i.e . those interactions that are comparable to thermal energies), it is common practice to characterise the associated state by a parameter that is measured when this state is highly occupied . The accuracy of this method, however, has not yet been determined . RESULTS: Using as a model the vancomycin group of antibiotics, either forming dimers or binding to cell wall precursors, we have investigated the dependence of the limiting (i.e . fully associated) chemical shifts of two protons on the equilibrium constants for the formation of the fully associated states . The chemical shift shows a large variation with the equilibrium constant for the formation of the fully associated state . CONCLUSIONS: The results demonstrate, in two systems, that a parameter representing a fully associated state (chemical shift) varies greatly with the equilibrium constant for the formation of that associated state . The results have implications for two-state analyses of populations of protein fragments in which a parameter representing the fully associated state is taken to be independent of the equilibrium constant for its formation . Using two-state analysis to determine the population of associated states of protein fragments could result in an underestimation of the population of these associated states.

Clin Pharmacokinet, 1997 Jul, 33(1), 32 - 51
Pharmacokinetics and administration regimens of vancomycin in neonates, infants and children; Rodvold KA et al.; The increased use of vancomycin in neonatal and paediatric patients has prompted numerous pharmacokinetic studies and the development of many empirical administration methods . The majority of dosage guidelines use the relationship between pharmacokinetic parameters and patient variables such as chronological age, bodyweight, and/or measures of renal function . Currently, those dosage guidelines which are based upon postconceptional age and bodyweight seem to provide the best options for empirical administration in neonates and infants . In addition, serum creatinine may prove to be a useful guide to the empirical administration of vancomycin in neonates older than 7 to 14 days . Several investigators have reported the individualisation of dosage regimens based on pharmacokinetic-based administration methods . The most common techniques employed have been Sawchuk-Zaske method and Bayesian forecasting . However, only a limited number of studies have evaluated either empirical administration or individualised administration techniques in patient populations outside those of the original reports; this makes choosing between the methods difficult . Pharmacokinetic data and administration recommendations have gradually become available in special paediatric patient populations . The majority of studies have focused on patients requiring cardiopulmonary bypass surgery or with burns, cancer or central nervous system infections . However, a limited amount of information is available regarding vancomycin disposition in children older than 1 year of age with and without end-stage renal failure . The monitoring of serum vancomycin concentrations may be useful in selected neonatal and paediatric patient populations, especially where large interpatient variability occurs and administration guidelines are not clearly established . Similar to the literature on adults, the lack of conclusive evidence concerning the relationship between serum vancomycin concentrations and therapeutic responses leaves this topic open to debate.

Bone Marrow Transplant, 1997 Jun, 19(12), 1229 - 32
Liposomal amphotericin (AmBisome) is safe in bone marrow transplantation for primary immunodeficiency; Pasic S et al.; The use of conventional amphotericin B is limited by toxicity, side-effects, drug interactions and the need for large infusion volumes, especially for infants . Use of liposomal amphotericin B (AmBisome) in 15 paediatric BMT patients with primary immunodeficiency (PID) was therefore studied . Adverse clinical reactions to AmBisome and biochemical profiles were monitored daily for 2 weeks before, during and after each treatment episode . Fungal cultures were obtained weekly and when patients were pyrexial . There were 18 treatment episodes . Mean daily dose was 5 mg/kg (2-6 mg/kg) . Mean duration of treatment was 25 days (5-90 days) . Clinical reactions to AmBisome were observed in one infant who had a pyrexia of 38 degrees C . One of the 15 infants had a significant increase in creatinine level while on concomitant nephrotoxic therapy . Four developed mild hypokalaemia on AmBisome which resolved with increased potassium supplementation . AmBisome was well tolerated and without significant renal or hepatic toxicity in severely ill immunodeficient infants receiving multiple nephrotoxic and hepatotoxic drugs such as cyclosporin, vancomycin and foscarnet.

Ther Drug Monit, 1997 Jun, 19(3), 265 - 70
Special considerations for monitoring vancomycin concentrations in pediatric patients; Miles MV et al.; The objectives of this study were to estimate the prevalence of low or excessive vancomycin dosing after initiation of treatment in pediatric patients and to determine the factors that are most predictive of optimized vancomycin dosage in this group . Among 74 patients who underwent vancomycin concentration monitoring, low trough (< 4.0 micrograms/ml) and/or peak (< 15.0 micrograms/ml) concentrations were noted in 28 (38%) patients after the initiation of therapy but in only four of the 28 (14%) patients (p = 0.29) after optimization of the initial dosage . There were not toxic peak concentrations (> 60 micrograms/ml) reported during the study . In patients older than 1 month old, 11 low peaks were associated with troughs less than 7.5 micrograms/ml, whereas no low peaks were associated with troughs more than 7.5 micrograms/ml . The significant predictive variables of optimized vancomycin dosage in the reduced regression model (p < 0.00001; adjusted r2 =0.85; n = 36) were (log) initial dose (p < 0.0001), initial trough (p < 0.0001), and age (p = 0.009) . Initial peak concentrations were not associated with the optimized dosage (p = 0.50) . The results of this study indicate that approximately 40% of all pediatric patients will be at risk of significant underdosing if standard vancomycin dosing guidelines are followed and that patients older than 1 month old with initial trough concentrations less than 7.5 micrograms/ml are at a greater risk of low peak concentrations than individuals with trough concentrations more than 7.5 micrograms/ml . Monitoring vancomycin concentrations appears to be essential to prevent the underdosing of many pediatric patients; however, only initial trough vancomycin concentrations may be needed to optimize dosages.

Bone Marrow Transplant, 1997 May, 19(10), 1029 - 32
Suppression of progenitor cell growth by vancomycin following autologous stem cell transplantation; Meehan KR et al.; The occurrence of hematologic side-effects resulting from the use of vancomycin is rare . Prior to this report, vancomycin-induced neutropenia was believed to be due to a hypersensitivity reaction since antibodies directed against circulating neutrophils have been discovered in the serum of some patients . We demonstrate suppression of hematopoietic bone marrow progenitor cells in a patient experiencing vancomycin-induced neutropenia after an autologous hematopoietic stem cell transplantation for multiple myeloma . A bone marrow (BM) specimen obtained at the time of neutropenia demonstrated direct suppression of progenitor cell growth in vitro when vancomycin was added at increasing concentrations (1, 10 and 50 microg/ml) . No such trend was noted in a BM sample from the same patient obtained 11 months prior to transplantation and a normal control BM . The decrease in the total number of colony-forming units (CFU) was statistically significant at all the dose levels of vancomycin when compared to the number of CFU in the baseline BM sample (P < 0.05) . The myeloid maturation arrest observed in the bone marrow sample obtained during the period of neutropenia and the dose dependent growth inhibition by vancomycin observed in vitro suggest a novel nonimmune mechanism of hematologic effects due to suppression of bone marrow progenitor cell growth.

Arch Phys Med Rehabil, 1997 May, 78(5), 459 - 62
A simple method for administering vancomycin in the spinal cord injured population; Griver AR et al.; OBJECTIVE: To examine the applicability in patients with spinal cord injury (SCI) of a modified version of the commonly used Lake and Peterson dosing regimen for vancomycin . DESIGN: Nonrandomized, prospective clinical trial with a historical control . SETTING: Spinal cord injury unit at a Veterans Affairs Medical Center . PATIENTS: Hospitalized patients with a history of SCI at least 6 months earlier and an estimated creatinine clearance of > or = 15 mL/min who required vancomycin therapy . The experimental group consisted of 15 evaluable patients, 8 with tetraplegia and 7 with paraplegia . INTERVENTION: Vancomycin regimens were initiated using a modified version of the guidelines of Lake and Peterson . MAIN OUTCOME MEASURE: After 4 to 8 doses, peak vancomycin concentrations in serum were obtained 15 minutes after a 1-hour infusion, and trough concentrations were drawn within 30 minutes of the next scheduled dose . RESULTS: Only 3 of 15 (20%) patients in the experimental group required a single adjustment in the dosing interval to achieve the targeted serum vancomycin concentrations . The proportion of patients who required dosing modification was significantly lower in the experimental group than in a group of 16 SCI control patients who received vancomycin according to the dosing recommendations in the drug insert (20% vs 75%, respectively; p = .002) . CONCLUSION: These results support the need for tailored vancomycin dosing in the SCI population and the efficacy of this simple method of administering vancomycin in achieving desirable concentrations of vancomycin in the serum of SCI patients.

Chirurg, 1997 Apr, 68(4), 416 - 24
{Cost savings by disinfection for prevention of surgical wound dehiscence after gastrectomy}; Schardey HM et al.; The aim of this study was to examine the effect of decontamination as compared to placebo medication on post-gastrectomy treatment costs . The results of a prospective double-blind placebo-controlled multicenter trial indicate that perioperative i.v . prophylaxis with cefotaxim and topical decontamination with polymyxin B, tobramycin, vancomycin and amphotericin B from the day before surgery until the 7th postoperative day is most effective in the prevention of esophagojejunal anastomotic leakage following total gastrectomy . For the cost analysis, only patients who had been decontaminated according to the study protocol (n = 90) were compared to the non-decontaminated patients (n = 103) . The esophagojejunal leakage rate was 10.6% in placebo patients (n = 103) and could be reduced significantly to 1.1% in decontaminated patients (n = 90, P = 0.0061; two-tailed Fisher's exact test) . There was only one asymptomatic leakage detected on Gastrografin swallow . The pulmonary infection (P = 0.0173) and overall complication rates (p = 0.0238) were significantly reduced in the decontamination group as well . During the observation period, 9 (8.7%) patients in the placebo group and 3 (3.3%) in the decontaminated group died (P = n.s.) . Patients were followed up for the initial 42 postoperative days and treatment costs were calculated for this time period only . The parameters compiled in the study pertaining to use of medical resources formed the basis for the determination of the postoperative treatment costs . These were the costs for decontaminating drugs, intravenous antibiotics, reoperations and non-surgical reinterventions as well as daily treatment costs of the general ward, the intensive care unit (ICU) and rehabilitation . The average costs per patient in the placebo group amounted to DM 20,000 while the costs for decontaminated patients were only DM 16,200, which was due to a significantly lower number of patients requiring treatment in the ICU (P = 0.0082), significantly fewer patients requiring i.v . antibiotics (P = 0.0232) and fewer patients with reoperations (P = 0.0909) . The prophylaxis employing decontaminating drugs in the amount of DM 400 lowered post-gastrectomy treatment costs by DM 3800 or 19% . The prophylaxis can be recommended, because it lowers morbidity, mortality and the costs of total gastrectomy.

Dtsch Tierarztl Wochenschr, 1997 Apr, 104(4), 140 - 6
Pharmacokinetics and tissue residues of netilmicin and vancomycin in chickens; el-Sayed MG et al.; Following a single intravenous injection of 10 mg netilmicin or 30 mg vancomycin/kg b.w . to normal chickens, the tested drugs obeyed a two or three compartments open model, with half-lives of distribution of 0.30 and 0.20 hours, respectively . The elimination half-lives following intravenous injection were 0.41 and 4.85 hours, respectively . Following a single intramuscular injection of 10 mg netilmicin or 30 mg vancomycin/kg b.w . to normal chickens, the serum drug concentrations peaked 2 hours post-injection with half-lives of absorption equal to 0.63 and 0.56 hours, respectively . The mean systemic bioavailability of netilmicin and vancomycin following a single intramuscular administration in normal chickens was 27.29 and 43.61%, respectively . These values indicated a limited and moderate absorption for netilmicin and vancomycin from intramuscular site, respectively . During repeated intramuscular administrations of both antibiotics for five consecutive days in normal chickens, the serum drug concentrations peaked two hours post each dose . The drugs concentrations during multiple dosage regimens were significantly increased in 2nd, 3rd, 4th and 5th days in comparison to the 1st day . Netilmicin and vancomycin persisted in liver and kidney for 96 and 120 hours, respectively, after the last intramuscular administration . The withdrawal time of netilmicin and vancomycin could be considered as five and six days, respectively . The in-vitro protein binding percents of netilmicin and vancomycin were 7.45 and 5.81%, respectively.

J Antimicrob Chemother, 1997 Mar, 39(3), 371 - 81
Risk factors for adverse cutaneous reactions associated with intravenous vancomycin; Korman TM et al.; We retrospectively studied adverse cutaneous reactions associated with intravenous vancomycin therapy over a 14-month period when two different brands of vancomycin were used . Of 224 adults, 12 (5.4%) had infusion-related reactions; ten of 174 patients who received more than one day of vancomycin (5.7%) had delayed cutaneous reactions . Age less than 40 years was a risk factor for both infusion-related and delayed reactions by both univariate and multivariate analysis . Duration of therapy greater than 7 days was a risk factor for delayed reactions . There was a significant increase in adverse cutaneous reactions associated with the use of a particular batch of vancomycin, although analytical testing of this batch failed to identify any difference from other batches associated with routine rates of adverse reactions . Awareness of vancomycin-associated infusion-related and delayed cutaneous reactions is necessary, and the risk factors associated with these reactions may have important clinical implications.

Pharmacotherapy, 1997 Mar-Apr, 17(2), 256 - 62
Effects of dialysis membrane on intradialytic vancomycin administration; Scott MK et al.; STUDY OBJECTIVE: To quantify the influence of hemodialyzers on vancomycin removal when the drug was infused during hemodialysis . DESIGN: Prospective, controlled, crossover study with three arms . SETTING: A university-affiliated medical center . PATIENTS: Eight subjects receiving outpatient hemodialysis . INTERVENTIONS: The three treatment arms were vancomycin 1000 mg infused after dialysis was completed (control), and the same dosages infused during the last hour of hemodialysis with a cellulose triacetate (CT) and a cellulose acetate (CA) hemodialyzer . MEASUREMENTS AND MAIN RESULTS: The areas under the curve from time zero to 44 hours (AUC0-44 hrs) for the three study arms were significantly different (p < 0.05), with the mean vancomycin AUC0-44 hrs being significantly lower when administered during CT and CA dialysis (73.7% and 87.2% of control; p < 0.05 vs control) . The mean vancomycin peak concentration achieved during CT dialysis was significantly lower than for the CA and control arms (20.5, 23.9, 27.0 mg/L, respectively) . Forty-four-hour postinfusion concentrations were similarly lower . CONCLUSION: Clinicians should recognize that the composition of the hemodialyzer significantly influences vancomycin serum concentrations when the drug is administered during hemodialysis.

J Pharm Pharmacol, 1997 Feb, 49(2), 154 - 7
Renal excretion of vancomycin in rats with acute renal failure; Nakamura T et al.; We have investigated the renal excretion of vancomycin in rats with acute renal failure (ARF) induced by uranyl nitrate or cisplatin . The renal clearance of the antibiotic after uranyl nitrate or cisplatin injection was separately evaluated by calculating the glomerular filtration rate (GFR) and secretory clearance . The reduced renal clearance of vancomycin in these ARF rats was a result of a decrease in both GFR and secretory clearance . The extents of the decreases in GFR and in secretory clearance were not, however, proportional, the extent of the decrease in secretory clearance being more pronounced . These results suggest that the renal tubular secretion of vancomycin was reduced more predominantly than glomerular filtration in these ARF models.

Arch Ophthalmol, 1997 Feb, 115(2), 165 - 70
Postoperative contamination after using vancomycin and gentamicin during phacoemulsification; Ferro JF et al.; OBJECTIVE: To investigate if the addition of vancomycin and gentamicin to the irrigating solutions during phacoemulsification with lens implantation reduces the incidence of positive postoperative intraocular cultures . DESIGN: Two-part double-masked, placebo-controlled, randomized clinical trial . PATIENTS: In the preliminary study, intracameral antibiotic concentrations were measured immediately after surgery (in 10 eyes) and 2 hours after surgery (in 10 eyes) in patients treated with antibiotics . In the primary study, 120 eyes underwent uncomplicated surgery . The treatment group and the placebo group were composed of 60 eyes each . INTERVENTION: The treatment group received vancomycin, 20 micrograms/mL, and gentamicin, 8 micrograms/mL, in the irrigating fluid . The placebo group received only irrigating fluid . All patients in the primary study underwent anterior chamber aspiration following surgery, and culturing was performed 2 hours later . MAIN OUTCOME MEASURE: Identification and quantification of positive cultures in thioglycolate broth and chocolate agar . RESULTS: In the preliminary study, the half-life of both intraocular antibiotics was less than 2 hours . In the primary study, intraocular aspirates yielded positive cultures in 3 specimens (5.0%) in the antibiotic-treated group and in 7 specimens (12.0%) in the placebo group . CONCLUSIONS: Although we found a higher rate of positive postoperative cultures in the placebo group (odds ratio = 2.51), 2 hours of contact between the antibiotic solution and bacteria did not produce results that reached statistical significance (P =.18) to support adding vancomycin and gentamicin to the irrigating solutions during phacoemulsification . Further studies are needed to evaluate the clinical implications of using antibiotics in irrigating solutions.

Ther Drug Monit, 1997 Feb, 19(1), 117 - 9
Interference with vancomycin fluorescence polarisation immunoassay in a nonuraemic patient; Bowhay S et al.; Commercially available immunoassays for vancomycin have been reported to overestimate serum vancomycin concentrations by varying degrees in patients with renal impairment, particularly those on peritoneal dialysis, by interference with crystalline degradation product-1 (CDP-1) . To date this interference has not been reported in any other patient population . This report describes vancomycin fluorescence polarisation immunoassay (FPIA) interference in a patient with only mildly impaired renal function . At this time it is not possible to confirm that the interference was caused by CDP-1.

New Microbiol, 1997 Jan, 20(1), 47 - 54
Comparative growth of pure cultures of human intestinal spirochaetes on six selective media; Calderaro A et al.; The growth of pure cultures of 24 human intestinal spirochaetes (HIS) was analysed comparatively in six selective media with antibiotics and in a control medium without antibiotics . The selective media SR and SP were the only two media among the six tested which allowed the growth of all the strains studied . These media contained spectinomycin (400 micrograms/ml) and rifampin (30 micrograms/ml) (SR), and spectinomycin (400 micrograms/ml) and polymyxin B (5 micrograms/ml) (SP), respectively . Moreover, most of the strains tested showed in these two media a number of CFU/ml equal to, or, for a few strains, not more than ten-fold lower than that observed in the control medium . The other four selective media tested were: SRVC (spectinomycin 200 micrograms/ml; rifampin 12.5 micrograms/ml; vancomycin 6.25 micrograms/ml; colistin 6.25 micrograms/ml), CSp (colistin 6.25 micrograms/ml; spiramycin 25 micrograms/ml), SRSp (spectinomycin 200 micrograms/ml; rifampin 12.5 micrograms/ml; spiramycin 25 micrograms/ml) and SRVCSp (spectinomycin 200 micrograms/ml; rifampin 12.5 micrograms/ml; vancomycin 6.25 micrograms/ml; colistin 6.25 micrograms/ml; spiramycin 25 micrograms/ml) . The growth of most of the spirochaetes was strongly reduced in the media SRVC, CSp, SRSp and SRVCSp . Furthermore, several of the 24 HIS examined did not grow in the medium SRVC (3 spirochaetes, 11%), CSp (15 spirochaetes, 62%), SRSp (17 spirochaetes, 70%), SRVCSp (19 spirochaetes, 79%) . The results reported in this paper indicate that the media SR and SP, of the six selective media tested, may profitably be used in the isolation of HIS as they did not significantly affect the growth of the HIS tested.

Biomaterials, 1997 Jan, 18(2), 141 - 5
Dynamic compaction: a new process to compact therapeutic agent-loaded calcium phosphates; Trecant M et al.; The sintering stage in the classical process of preparing bone substitution materials prevents therapeutic agents from being loaded into calcium phosphate powder . However, dynamic compaction, a new process, requires no external heat, allowing the therapeutic agent to be incorporated into ceramics . This report presents the results of an in vitro study of therapeutic agents associated with calcium phosphate powder and involving this new process . A mixture of vancomycin lyophilized powder (0.15 g) and biphasic calcium phosphate (BCP) powder (1.85 g) was compacted . In addition, 2 ml of human growth hormone (1 mg ml-1) were associated with BCP powder by physical adsorption on bead surfaces before compaction . Detection by monoclonal antibodies and sodium dodecyl sulphate polyacrylamide gel electrophoresis demonstrated the structural integrity of the two therapeutic agents after consolidation . This new compaction process should be useful in developing ceramics that contain a therapeutic agent.

Structure, 1996 Dec 15, 4(12), 1509 - 15
Crystal structure of vancomycin; Schafer M et al.; BACKGROUND: Vancomycin and other related glycopeptide antibiotics are clinically very important because they often represent the last line of defence against bacteria that have developed resistance to antibiotics . Vancomycin is believed to act by binding nascent cell wall mucopeptides terminating in the sequence D-Ala-D-Ala, weakening the resulting cell wall . Extensive NMR and other studies have shown that the formation of asymmetric antibiotic dimers is important in peptide binding . Despite intensive efforts the crystal structure of vancomycin has been extremely difficult to obtain, partly because high-resolution data were unavailable, and partly because the structure was too large to be solved by conventional "direct methods' . RESULTS: Using low-temperature synchrotron X-ray data combined with new ab initio techniques for solving the crystallographic phase problem, we have succeeded in determining the crystal structure of vancomycin at atomic resolution . The structure provides much detailed information that should prove invaluable in modelling and mechanistic studies . CONCLUSIONS: Our structure confirms that vancomycin exists as an asymmetric dimer . The dimer conformation allows the docking of two D-Ala-D-Ala peptides in opposite directions; these presumably would be attached to different glycopeptide strands . In the crystal, one of the binding pockets is occupied by an acetate ion that mimics the C terminus of the nascent cell wall peptide; the other is closed by the asparagine sidechain, which occupies the place of a ligand . The occupied binding pocket exhibits high flexibility but the closed binding pocket is relatively rigid . We propose that the asparagine sidechain may hold the binding pocket in a suitable conformation for peptide docking, swinging out of the way when the peptide enters the binding pocket.

Proc Natl Acad Sci U S A, 1996 Dec 10, 93(25), 14361 - 6
Altered recognition mutants of the response regulator PhoB: a new genetic strategy for studying protein-protein interactions; Haldimann A et al.; Two-component regulatory systems require highly specific interactions between histidine kinase (transmitter) and response regulator (receiver) proteins . We have developed a novel genetic strategy that is based on tightly regulated synthesis of a given protein to identify domains and residues of an interacting protein that are critical for interactions between them . Using a reporter strain synthesizing the nonpartner kinase VanS under tight arabinose control and carrying a promoter-lacZ fusion activated by phospho-PhoB, we isolated altered recognition (AR) mutants of PhoB showing enhanced activation (phosphorylation) by VanS as arabinose-dependent Lac+ mutants . Changes in the PhoBAR mutants cluster in a "patch" near the proposed helix 4 of PhoB based on the CheY crystal structure (a homolog of the PhoB receiver domain) providing further evidence that helix 4 lies in the kinase-regulator interface . Based on the CheY structure, one mutant has an additional change in a region that may propagate a conformational change to helix 4 . The overall genetic strategy described here may also be useful for studying interactions of other components of the vancomycin resistance and P1 signal transduction pathways, other two-component regulatory systems, and other interacting proteins . Conditionally replicative oriRR6K gamma attP "genome targeting" suicide plasmids carrying mutagenized phoB coding regions were integrated into the chromosome of a reporter strain to create mutant libraries; plasmids encoding mutant PhoB proteins were subsequently retrieved by P1-Int-Xis cloning . Finally, the use of similar genome targeting plasmids and P1-Int-Xis cloning should be generally useful for constructing genomic libraries from a wide array of organisms.

Electrophoresis, 1996 Dec, 17(12), 1938 - 44
Enantioseparation of amino acids and dipeptides using vancomycin as chiral selector in capillary electrophoresis; Wan H et al.; Vancomycin was applied as chiral selector for the enantiomeric separation of derivatized amino acids and dipeptides . The influence of vancomycin concentration, pH and presence of 2-propanol in the buffer were examined in order to find optimal separation conditions . Optimization was by factorial design . Further, chiral separation of derivatives prepared with three different reagents was compared . These reagents were 9-fluorenylmethyl chloroformate (FMOC), 2-(9-anthryl)ethyl chloroformate (AEOC) and dansyl chloride (dansyl) . Optimum resolution was at high vancomycin concentrations, while optimum efficiency was at low vancomycin concentrations . As a consequence of the very high enantioselectivity of vancomycin, the vancomycin concentration below the amount necessary for maximal resolution can be used . Separation efficiency was relatively low, and this could be attributed to adsorption of the selector at the capillary wall . Three factors led to decreased adsorption: application of a pH above the zero mobility pH value, low vancomycin concentrations and the presence of 2-propanol . For amino acids, the resolutions of the different derivatives were: dansyl > AEOC > FMOC, while for dipeptides, the highest selectivity was with AEOC.

Kansenshogaku Zasshi, 1996 Dec, 70(12), 1279 - 83
{A SLE case with toxic shock syndrome after delivery}; Kadoya A et al.; We experienced a SLE patient with TSS after delivery . A 32-year-old SLE patient was transferred to our division due to fever, diarrhea, erosive rash, pericardial effusion, myalgia, low blood pressure, thrombocytopenia and hypoproteinemia which appeared two days after transvaginal delivery . At the time of admission, we considered these symptoms as the exacerbation of SLE, and treatment with high doses of steroid was started . It was when TSST-1-producing-MRSA was cultured from the vagina and uterus that TSS was suspected . 2 g/day of vancomycin was administered and her symptoms improved . As observed in this case, it is important to consider TSS as one of the complications seen with SLE patients after delivery.

J Arthroplasty, 1996 Dec, 11(8), 939 - 44
Elution characteristics of vancomycin and tobramycin combined in acrylic bone-cement; Penner MJ et al.; Combining two antibiotics in antibiotic-loaded bone-cement is common in clinical practice . As the effect this has on elution characteristics is unknown, an in vitro quantitative elution study was carried out . Three groups of five antibiotic-loaded cement disks were prepared and placed in individual saline baths for 5 weeks . The elution of tobramycin from the disks in the study group (containing 2.4 g tobramycin and 1.0 g vancomycin per 40-g packet of Palacos-R cement powder {Smith & Nephew Orthopaedics, Memphis, TN}) was increased by 68% over that of the tobramycin control disks (2.4 g tobramycin only) (P = .024) . The release of vancomycin from the study group disks was increased by 103% over the vancomycin control disks (1.0 g vancomycin only) (P = .007) . Combining two antibiotics in bone-cement improves elution of both antibiotics in vitro and may translate into enhanced elution in vivo.

Clin Orthop, 1996 Dec, (333), 245 - 51
Effect of cefazolin and vancomycin on osteoblasts in vitro; Edin ML et al.; The effect of cefazolin and vancomycin on osteoblast-like cells was studied . Cells from the MG-63 human osteosarcoma cell line were grown in antibiotic free media and exposed to concentrations of cefazolin and vancomycin at order of magnitude intervals between 0 and 10,000 microg/ml . For cefazolin, a second interval was performed between 100 and 1000 microg/ml to define toxic levels more accurately . Cell number and 3H-thymidine incorporation at 0, 24, and 72 hours were determined . The results of this study show that local levels of vancomycin of 1000 microg/ml and less have little or no effect on osteoblast replication, and concentrations of 10,000 microg/ml cause cell death . Concentrations of cefazolin of 100 microg/ml and less have little or no effect on osteoblast replication, 200 microg/ml significantly decrease cell replication, and 10,000 microg/ml cause cell death . The authors conclude that vancomycin is less toxic than is cefazolin to osteoblasts at higher concentrations and may be a better antibiotic for local administration in the treatment of similarly sensitive bacterial infections.

Am J Health Syst Pharm, 1996 Dec 1, 53(23), 2840 - 7
National survey of hospital-based pharmacokinetic services; Murphy JE et al.; The status of pharmacokinetic services in the nation's hospitals was studied . A questionnaire was mailed in February 1995 to all 252 respondents to ASHP's 1994 national survey of hospital-based pharmaceutical services who indicated the provision of pharmacokinetic services in their institution . Ninety-eight completed questionnaires were returned (40.2% response rate) . The pharmacokinetic services provided required an average of 19.1 person-hours per week, tended to be provided by staff pharmacists, were managed by the pharmacy department, tended to be most focused on aminoglycosides and vancomycin, required an average of 60 notes in patient charts per month, and relied on both computers and calculators for deriving values . There was little contact with patients during the consultation process . Drug concentration measurements tended to be scheduled by service providers, but confidence in the accuracy of the timing of dose administration and blood sampling was limited . Respondents believed that the services tended to be supported by other hospital personnel and that they were successful . There was very little expectation that the workload for providing pharmacokinetic services would increase in the near future . A national survey of hospital-based pharmacokinetic services showed that it took 19 hours per week on average to provide the services, that the focus was on aminoglycosides and vancomycin, and that the services were perceived to be supported by other departments.

Ther Drug Monit, 1996 Dec, 18(6), 647 - 53
Vancomycin serum concentrations in patients with renal dysfunction: a comparison of fluorescence polarization immunoassay and the enzyme-multiplied immunoassay technique; Peckman HJ et al.; A study was conducted to determine whether assay-specific quantitative differences exist in the determination of vancomycin serum concentrations obtained from patients with renal dysfunction . Vancomycin serum concentrations were obtained during the first week of therapy for each of three time intervals: 48-96 h, 96-144 h, and 144-192 h after administration of the first dose of vancomycin . Vancomycin serum concentrations were measured using the enzyme-multiplied immunoassay technique (EMIT) and fluorescence polarization immunoassay (FPIA) . Twenty patients with an estimated creatinine clearance < 40 ml/min who were receiving intravenous vancomycin were evaluated . Hemodialysis was required in 16 of 20 patients . Fifty samples were included in the data analysis . The mean (+/-SD) serum concentrations obtained with EMIT and FPIA were 10.9 mg/L (+/-5.3) and 12.6 mg/L (+/-5.7), respectively (p = 0.13), and were not statistically different . A linear relationship was observed between EMIT and FPIA (EMIT = 0.89 x FPIA - 0.24; r2 = 0.93) . No statistically significant differences were observed in the calculated pharmacokinetic parameters between methods . FPIA and EMIT are comparable methods in determining vancomycin serum concentrations within the first week of vancomycin therapy in patients with moderate to severe renal dysfunction.

Yakugaku Zasshi, 1996 Nov, 116(11), 876 - 83
{Bayesian forecasting of plasma vancomycin concentration using time-dependent pharmacokinetics}; Nakamura T et al.; A new prediction method of vancomycin (VCM) pharmacokinetics has been developed using the modified Bayesian forecasting method involved in time-dependent pharmacokinetics in clearance . We investigated to evaluate the usefulness of this new prediction method compared with that of the ordinary Bayesian forecasting method . Serum samples, obtained from 4 patients at least 3 different days during the period for the VCM treatment were assayed by fluorescence polarization immunoassay . VCM pharmacokinetic parameters and predicted serum VCM concentrations were calculated using this new method and the ordinary one according to the one-compartment model . The precision of the predicted serum VCM concentrations by these two methods at the third experimental day were evaluated with the mean prediction error (ME), mean absolute prediction error (MAE) and root mean squared error (RMSE) . The most precise and least-bias prediction of serum VCM concentrations were observed using this new prediction method (ME: -0.36 +/- 1.40, MAE: 1.13 +/- 0.82 and RSME: 1.37) . The time-dependent decrease of VCM clearance was observed in all patients . Therefore, the fitting of the actual serum VCM concentrations obtained using the ordinary method produced less precise results than that using this new method . These results suggest the usefulness of this new prediction method considering time-dependent changes in VCM clearance.

Pharmacotherapy, 1996 Nov-Dec, 16(6), 1024 - 9
Vancomycin-binding characteristics in patients with serious infections; Li L et al.; STUDY OBJECTIVE: To examine the extent, variability, and factors affecting vancomycin protein binding . DESIGN: Prospective, open-label, cohort study . SETTING: A general hospital . PATIENTS: Forty-four adults {mean (+/- SD) age 50.9 +/- 17.1 yrs, range 16.8-92.0 yrs} with serious infections . INTERVENTIONS: Unbound (Vu) and total (Vtot) vancomycin concentrations were determined by fluorescence polarization immunoassay . A statistical analysis model used the maximum likelihood method to evaluate the association between several important variables and log Vu while controlling for log Vtot effects . MEASUREMENTS AND MAIN RESULTS: The mean fraction percentage of unbound vancomycin was 79.5 +/- 6.0% (range 53.0-96.3%) . While controlling for Vtot the total variability of Vu was 8.3%, suggesting that vancomycin binding is relatively constant in sick adults . We were able to demonstrate a significant statistical interaction effect between gender and globulin protein concentration on Vu (p = 0.022) . Globulin protein concentration in men was negatively associated with Vu (p = 0.0009), but there was no association in women (p = 0.645) . Age, race, peak-trough association, serum creatinine, serum albumin, serum prealbumin, and hemodialysis were not significantly associated with log Vu in the statistical model . CONCLUSION: Compared with earlier studies in healthy adults, vancomycin binding appears to be decreased during acute illness, and intrapatient and interpatient variability are relatively small . Unbound vancomycin concentration appears to be gender dependent.

Bone Marrow Transplant, 1996 Oct, 18(4), 761 - 5
Nephroprotective effect of cilastatin in allogeneic bone marrow transplantation . Results from a retrospective analysis; Gruss E et al.; Cilastatin, an inhibitor of the tubular brush border enzyme dehydropeptidase-I, is added in a fixed combination to imipenem . Cilastatin has been demonstrated in different animal models and in one clinical trial, to reduce the nephrotoxicity associated with cyclosporin A . To evaluate a possible nephroprotective effect of cilastatin following allogeneic BMT we conducted a retrospective analysis of 104 patients transplanted in our BMT Unit from January 1991 to January 1995 . Imipenem/cilastatin (I/C) was used in a non-randomized manner in 64 patients during this period . Acute renal failure (ARF) was diagnosed in 32 patients (30%) . ARF was not associated with gender, sepsis, conditioning regimen, underlying disease, bilirubin, or age . VOD occurred in 12/32 (37.5%) of patients with ARF whereas it occurred in only 7/72 (9.7%) of patients without ARF (P < 0.0007) . ARF was not correlated with use of aminoglycosides, vancomycin, ciprofloxacine, ceftazidime or amphotericin-B . However, 13 patients of 64 exposed to I/C (20.3%) developed ARF vs 19 of 40 patients (47.5%) who were not exposed to I/C (P < 0.003; OR 0.28) . Stratified analysis and multiple logistic regression confirmed the I/C nephroprotective action . The mean cyclosporin A levels in the I/C group were significantly decreased (208.6 +/- 64.9) vs the non-I/C group (265 +/- 118) . We conclude that these results suggest I/C may counteract acute cyclosporin A nephrotoxicity following BMT and further prospective clinical trials are needed to confirm if routine administration of cilastatine confers benefit in the BMT setting.

Pharmacotherapy, 1996 Sep-Oct, 16(5), 924 - 31
Pharmacokinetics of aztreonam and imipenem in critically ill patients with pneumonia; McKindley DS et al.; STUDY OBJECTIVE: To evaluate the pharmacokinetic profiles of aztreonam and imipenem in critically ill trauma patients with pneumonia . METHODS: Trauma patients in intensive care units who were intubated within 3 days of hospital admission were eligible for the study . Patients with the clinical diagnosis of pneumonia were consecutively randomized to receive either aztreonam plus vancomycin or imipenem-cilastatin . Serial blood samples were taken and sputum was collected to determine aztreonam and imipenem concentrations after 2-3 days and 7-8 days of therapy . Pharmacokinetics of both agents were estimated and compared with estimates from healthy volunteers . RESULTS: Twenty patients were enrolled in the study, 10 patients received imipenem-cilastatin, and 10 received aztreonam plus vancomycin . Steady-state volume of distribution (Vss) for aztreonam at 2-3 days and 7-8 days was significantly greater in patients than in historical controls, whereas the Vss for imipenem was greater at 2-3 days . The beta-half-life for aztreonam at both sampling periods was significantly greater in patients than in controls . No significant changes in pharmacokinetics occurred over time for either antibiotic . Sputum concentrations of aztreonam and imipenem were highly variable when sampled 2 hours after the infusion . CONCLUSION: Larger volumes of distribution were observed for both aztreonam and imipenem in trauma patients than in volunteers, suggesting that standard initial dosages of the antibiotics may result in lower concentrations in these critically ill patients . Both antibiotics penetrated into the sputum of most patients; however, the degree of penetration was highly variable in relation to serum concentrations.

Kidney Int, 1996 Sep, 50(3), 929 - 36
Use of vancomycin in high-flux hemodialysis: experience with 130 courses of therapy; Barth RH et al.; Vancomycin is often administered to hemodialysis patients at long dosage intervals because its removal by hemodialysis is considered to be negligible . We and others, however, have demonstrated significant removal of vancomycin by high-flux hemodialysis . This report describes our experience with 89 courses of vancomycin using a revised regimen with a loading dose followed by 500 mg doses after each dialysis treatment, and compares results with 41 courses using single weekly dosing . All patients were dialyzed with high-flux membranes using volumetric ultrafiltration and bicarbonate dialysate . Serum vancomycin levels were obtained two hours after completion of infusion (peak) and immediately prior to dialysis (trough) and were measured by Abbot TDx fluorescence polarization immunoassay . Duration of multiple-dose therapy was 11 +/- 8 days, with mean total dose 3.6 +/- 1.8 g . Initial doses of 20 mg/kg rapidly and reliably established therapeutic pre-dialysis serum levels (10 to 25 micrograms/ml) . In patients treated with multiple dosing 431 pre-dialysis levels were obtained . The mean level was 15.9 +/- 5.7 micrograms/ml; 55 levels (13%) were less than 10 micrograms/ml and 22 (5%) were above 25 micrograms/ml . In patients treated once weekly, 77% of levels were below 10 micrograms/ml by five days after administration, and 84% at one week . No patient developed demonstrable ototoxicity . Twenty-five patients were treated for > or = two weeks, five for > or = four weeks, and two for > five weeks, with no evidence of toxic accumulation . Mean peak level was 20.1 +/- 4.6 micrograms/ml, with a mean difference from preceding pre-dialysis level of 7.2 +/- 2.2 micrograms/ml . We conclude that in high-flux hemodialysis, a 20 mg/kg loading dose of vancomycin followed by 500 mg doses after each dialysis treatment achieves predictable, adequate and safe therapeutic levels, does not lead to unacceptably high peaks, and does not accumulate during long treatment courses . By contrast, once-weekly vancomycin dosing resulted in subtherapeutic serum levels after five to seven days, and should be abandoned in the high-flux setting.

Clin Pharmacol Ther, 1996 Sep, 60(3), 332 - 40
Cost-effectiveness analysis of serum vancomycin concentration monitoring in patients with hematologic malignancies; Fernandez de Gatta MD et al.; OBJECTIVE: This study evaluates the cost-effectiveness of vancomycin serum concentration monitoring in patients with hematologic malignancies . METHODS: The study was designed as a prospective randomized study . Seventy immunocompromised febrile patients with hematologic malignancies were randomly assigned to either a vancomycin therapeutic drug monitoring group (TDM group; n = 37) or to a control group (n = 33) . Intervention in the TDM group involved patient follow-up by a clinical pharmacist to obtain and pharmacokinetically interpret serum vancomycin concentrations for dosage individualization . RESULTS: Evaluation of all patients included global clinical response and nephrotoxicity, as well as the economic costs and effectiveness derived from the vancomycin monitoring program . There were no significant differences between the TDM and control groups in the outcome measures, except for the incidence of nephrotoxicity: the rates of minor nephrotoxicity were 33.3% and 13.5% in the control and TDM groups, respectively . The corresponding figures for moderate nephrotoxicity were 9.1% and 0% . Logistic regression analysis confirmed that TDM independently reduced the incidence of nephrotoxicity in this patient population . On the basis of this reduced nephrotoxicity, a incremental cost of $435 per case of nephrotoxicity prevented was found for vancomycin serum concentration monitoring . CONCLUSIONS: A decreased incidence of nephrotoxicity provides evidence of a real clinical benefit to patient management in patients with hematologic malignancies . The TDM for vancomycin therapy in this high-risk population has been shown to be a cost-effective procedure.

Biochemistry, 1996 Aug 13, 35(32), 10464 - 71
Gain of D-alanyl-D-lactate or D-lactyl-D-alanine synthetase activities in three active-site mutants of the Escherichia coli D-alanyl-D-alanine ligase B; Park IS et al.; Escherichia coli D-Ala-D-Ala ligase (Ddl) and the vancomycin resistance-conferring protein VanA are homologues, but VanA has gained the ability to activate D-lactate (D-Lac) and make the depsipeptide D-Ala-D-Lac as well as D-Ala-D-Ala . This depsipeptide ligase activity of VanA is its crucial catalytic function necessary for phenotypic vancomycin resistance . We report here that three E . coli DdlB active-site mutants that we made previously based on X-ray structure/function predictions have gained interesting new ligase activities . Y216, S150, and E15 form a hydrogen-bonding triad that orients an omega-loop to close over the active site and also to orient substrate D-Ala1 . Mutants Y216F and S150A have gained depsipeptide (D-Ala-D-Lac, D-Ala-D-hydroxybutyrate) ligase activity with dipeptide/depsipeptide partition ratios that mimic the pH behavior of VanA . E15Q has negligible depsipeptide synthetase activity but now uniquely activates D-Lac as the electrophilic rather than the nucleophilic partner for condensation with D-Ala to make a regioisomeric D-Lac-D-Ala, an amide rather than an ester product . These results provide insights into the active-site architecture of the ligases and the subsites for recognition of D-Ala VS D-Lac and predict the Y216F substitution will impart D-Ala-D-Lac synthetase activity to Ddls from Grampositive bacteria with intrinsic resistance to vancomycin.

An Esp Pediatr, 1996 Aug, 45(2), 167 - 71
{Pharmacokinetics of vancomycin in neonates of postconceptional age less than or equal to 32 weeks}; Ginovart Galiana G et al.; The objective of the present study was to analyze the pharmacokinetic behavior of vancomycin in neonates of postconceptional age < or = 32 weeks (n = 44) . The elimination of the antibiotic was influenced by the concomitant treatment with indomethacin and mechanical ventilation . Close monitoring of renal function of the neonate and vancomycin dosage individualization are mandatory when the above factors are present . Vancomycin dosage guidelines have been determined according to serum creatinine of these premature patients.

Pharmacol Toxicol, 1996 Aug, 79(2), 55 - 9
Influence of biochemical parameters of liver function on vancomycin pharmacokinetics; Marti R et al.; The influence of biochemical parameters of hepatic function on vancomycin pharmacokinetics was retrospectively evaluated in 76 adult patients (age 18 to 81 years), from biochemistry data gathered during routine therapeutic drug monitoring . All subjects had normal serum creatinine levels . Vancomycin concentrations were determined by fluorescence polarization immunoassay in 101 paired serum samples . All data for vancomycin concentration versus time were fitted to a one-compartment model using the bayesian approach . Bilirubin, transaminases (n = 101), gamma-glutamyl transferase (n = 97), alkaline phosphatase (n = 95), albumin (n = 92) and lactate dehydrogenase (n = 42) were determined . No strong correlation was seen between any of the pharmacokinetic and biochemistry parameters studied . In patients with hyperbilirubinaemia, the mean Vss and t1/2 were increased (Vss: 0.75 +/- 0.31 versus 0.92 +/- 0.42 1.kg-1, p = 0.020; t1/2 5.93 +/- 3.30 versus 7.48 +/- 4.44 hr, p = 0.049) . When liver function was evaluated according to hepatic profile (normal, mildly altered and severely altered), no significant differences were observed in vancomycin pharmacokinetics among the groups . In conclusion, vancomycin pharmacokinetics are only weakly influenced by the biochemistry parameters of liver function.

Masui, 1996 Aug, 45(8), 994 - 7
{A case of toxic shock syndrome induced by MRSA after sinus surgery}; Nakayama M et al.; We present a case of toxic shock syndrome (TSS) induced by MRSA after sinus surgery . The patient was a 64-year-old woman who had undergone sinus surgery because of chronic sinusitis . Nine days after the surgery, she began to have sore throat, fever, and diffuse erythroderma followed by severe hypotension and renal dysfunction . Culture of sputum, nasal discharge and stool showed MRSA . Blood culture was negative . She was treated with intravenous fluids, catecholamines and antibiotics (vancomycin and fosfomycin) . Continuous hemodiafiltration was started because of oliguria . Her condition improved gradually and she was discharged about a month after the onset of her illness . We should recognize that TSS can occur as a fatal complication after nasal surgery.

Anesth Analg, 1996 Aug, 83(2), 223 - 7
Heparin neutralization with methylene blue, hexadimethrine, or vancomycin after cardiopulmonary bypass; Kikura M et al.; There are no clinically available alternatives for reversing heparin in protamine-allergic patients . This study examined the ability of methylene blue, hexadimethrine, and vancomycin to reverse circulating heparin so that these compounds can be carefully examined in future placebo-controlled studies in humans . Heparin activity in blood obtained from extracorporeal circuits was reversed by adding protamine (13.5, 27.0, 81.1, 135.1, and 270.3 micrograms/mL), methylene blue (13.5, 27.0, 135.1, 202.7, 270.3, 337.8, 405.4, 473.0, 540.5, and 810.8 micrograms/mL), hexadimethrine (6.8, 13.5, 20.3, 27.0, 81.1, and 135.1 micrograms/mL), or vancomycin (13.5, 27.0, 135.1, 270.3, 540.5, and 810.8 micrograms/mL), and activated clotting times (ACTs) were measured with kaolin (n = 18) . Heparinase-ACT was obtained to determine complete reversal . Heparin concentrations were 3.3 +/- 0.3 U/mL with ACT values of 485 +/- 97 s . The ACT at a protamine concentration of 81.1 micrograms/mL and at hexadimethrine concentrations of 81.1 and 135.1 micrograms/mL was not statistically different from heparinase-ACT; however, methylene blue or vancomycin did not reverse the anticoagulation at any concentrations . Hexadimethrine can reverse heparin-induced anticoagulation after cardiopulmonary bypass as well as protamine, although methylene blue or vancomycin did not neutralize heparin in vitro.

Anal Chem, 1996 Aug 1, 68(15), 2501 - 14
Comparison and modeling study of vancomycin, ristocetin A, and teicoplanin for CE enantioseparations; Gasper MP et al.; The structurally related glycopeptide antibiotics vancomycin, ristocetin A, and teicoplanin can all be used as chiral selectors in capillary electrophoresis (CE) . Both experimental and modeling studies were done to elucidate their similarities and differences . There are identifiable morphological differences in the aglycon macrocyclic portions of these three compounds . In addition, there are other structural distinctions that can affect their CE enantioselectivity, migration times, and efficiency . Teicoplanin is the most distinct of the three and is the only one that is surface active . Its aggregational properties appear to affect its enantioselectivity among other things . The similar but not identical structures of the three glycopeptides produce similar but not identical enantioselectivities . This leads to the empirically useful "principle of complementary separations", in which a partial resolution with one chiral selector can be brought to baseline with one of the others . Overall, ristocetin A appears to have the greatest applicability for CE enantioseparations.

Eur J Clin Chem Clin Biochem, 1996 Jul, 34(7), 585 - 9
Statistical analysis of heterogeneous pharmacokinetic data from the literature; Zellner D et al.; To obtain the reliable pharmacokinetic quantities necessary for the adjustment of individual drug dosages, the pharmacokinetic data in the literature must be analysed by various appropriate statistical methods . Generally, pharmacokinetic quantities have been calculated from small sample sizes and published in different ways (the coefficient of variation of an estimated pharmacokinetic quantity is often higher than 40 percent) . In the present study data were therefore structured and clustered according to the important influence variables . The important influence variables were obtained by known multivariate statistical methods . To obtain optimal estimators (uniformly minimum variance unbiased estimators) for the quantities inside the clusters, goodness of fit tests must be performed . Skewed distributions and samples with heterogeneous variances must be subjected to transformation procedures to obtain normally distributed values with homogeneous variances . The population-derived estimate of the a priori knowledge of pharmacokinetic quantities can be obtained by a statistical algorithm proposed in this paper . Information on the quantities half-life, total body clearance and volume of distribution of vancomycin were extracted from over 200 publications . These data were analysed with the proposed statistical algorithm, yielding population-based estimates for half-life, clearance and volume of vancomycin, taking into consideration the detected influence variables--renal function and the age of the patient . Important dependencies between different variables are discussed.

Electrophoresis, 1996 Jul, 17(7), 1214 - 21
Vancomycin as a chiral selector in capillary electrophoresis: an appraisal of advantages and limitations; Vespalec R et al.; The properties of the macrocyclic antibiotic vancomycin, used as a chiral selector, were studied with aminoquinolycarbamate derivatives of amino acids, containing sulfur and selenium, as well as with other organic ions . Vancomycin combines the ability to resolve fully ionized anionic enantiomers, typical of proteins, with excellent separation efficiency, exceeding that of cyclodextrins . It allows better than baseline chiral separations of several anionic analytes within 3-5 min . The resolving power of vancomycin results from its great skill in discriminating enantiomers rather than from high affinities to the separated enantiomers . The association constants of vancomycin are of the same order of magnitude, 10(2) L/mol, as that found for beta-cyclodextrin (beta-CD) . The difference in association constants of separated cystine enantiomers with vancomycin, 2 x 10(2) L/mol, is one order of magnitude higher than that of enantiomers separated with beta-CD . Analytically convenient mobility differences up to 1-2 x 10(9) m2V-1s-1, with only one of the enantiomers appreciably decelerated, are obtained at submillimolar vancomycin concentrations . Typical separation efficiencies are close to 250,000 theoretical plates per meter of capillary . Deceleration of various organic ions by millimolar vancomycin implies that chiral separations with vancomycin need not be restricted to carboxylic acids . The vancomycin-analyte interactions are strongly affected by the chemical composition and concentration of the buffer . An additional experimental variable, highly effective in manipulating the separation selectivity of analytes, is the buffer pH.

Pharmacotherapy, 1996 Jul-Aug, 16(4), 698 - 700
Clinical pharmacokinetic pearls: bolus versus infusion equations; Murphy JE et al.; Using a nonprogrammed calculator to solve lengthy pharmacokinetic equations is time consuming and carries the potential for entry error . Shorter equations reduce both the time and the risk . The aminoglycosides and vancomycin are usually administered as short infusions . The pharmaco-kinetic equation describing multiple-dose administration of short infusions is much longer than the corresponding equation for bolus dosing . This study examined the percentage errors that would occur using the bolus equation instead of the infusion equation at various drug half-lives . When the half-life is 5 or more times the duration of infusion, the error in predicting concentration is 6.8% or less . Although clinicians should make their own decisions on how much error is acceptable and whether introducing guaranteed error is appropriate to save time and reduce risk of potential error, it appears that the simpler bolus equation may be used safely when the half-life is at least 5 times the duration of the infusion.

Antimicrob Agents Chemother, 1996 May, 40(5), 1098 - 103
Lack of effect of vancomycin and gentamicin on auditory function in guinea pigs; Nishihara K et al.; The dispositions of vancomycin (VCM) and gentamicin (GM) in plasma and perilymph after single and multiple administrations and the effects of multiple administrations of VCM or GM alone and the combination of both drugs on auditory function were studied in male guinea pigs . The pharmacokinetic parameters of VCM and GM obtained from plasma drug concentration-time data after single and multiple (22 days) intramuscular administrations of VCM (200 mg/kg of body weight) alone and GM (50 mg/kg) alone were not significantly different from those after combined administration of VCM (200 mg/kg) and GM (50 mg/kg) . There was no change in the penetration ratio of VCM and GM into perilymph between administration of VCM or GM alone and the combination of both drugs . Furthermore, the hearing threshold of guinea pigs was not affected by VCM or GM alone or the combination of both drugs within the range of therapeutic VCM and GM levels in plasma in humans.

J Am Acad Dermatol, 1996 May, 34(5 Pt 2), 890 - 1
Vancomycin-induced linear IgA bullous dermatosis (LABD); Whitworth JM et al.; We report the eleventh case of vancomycin-induced linear IgA disease . Our case is unusual because symptoms developed within minutes of administration of the drug . We discuss the pathogenesis and review the literature.

Ther Drug Monit, 1996 Apr, 18(2), 149 - 53
Changes in vancomycin pharmacokinetics during treatment; Pou L et al.; Using data gathered in routine monitoring, the pharmacokinetics of vancomycin during the first 10 days of treatment were compared with the pharmacokinetics after 10 days of treatment in 46 adult patients with normal renal function, ages 17-85 years old (mean +/- SD: 50.8 +/- 17.5) . The mean time from initiation of treatment to the first sample determination was 5.5 days, and the mean time to the second determination was 13.4 days . Statistical differences between the two periods were observed for all pharmacokinetic parameters, except for the steady-state distribution volume . After 10 days of treatment, the mean +/- SD of the vancomycin clearance and elimination rate constant decreased from 1.31 +/- 0.82 to 1.13 +/- 0.72 ml/kg/min (p = 0.0044) and from 0.13 +/- 0.08 to 0.10 +/- 0.06 h-1 (p = 0.091), respectively . The half-life (t1/2) increased from 8.01 +/- 6.82 to 10.02 +/- 8.00 h (p = 0.012) . The median percentage of the increment of t1/2 was 9.4% . The increase in t1/2 was > 50% in 12 patients and > 100% in nine cases . No association was found between the increment of t1/2 and the cumulative vancomycin dose . Frequent monitoring of serum vancomycin seems indicated, given the risk of decreased elimination during prolonged treatment.

Ther Drug Monit, 1996 Apr, 18(2), 145 - 8
Influence of pharmacokinetic model on vancomycin peak concentration targets; Fernandez de Gatta MM et al.; The aim of this study was to adapt the vancomycin therapeutic range to the kinetic models usually employed in clinical settings (one- and two-compartment models) . Estimates of vancomycin pharmacokinetic parameters were obtained for both models in 22 hematologically malignant patients on vancomycin treatment using two serum concentrations and a bayesian algorithm . From these individually estimated pharmacokinetic parameters, an estimation of the maximum (Cssmax), 2 h postinfusion (Css2), and minimum (Cssmin) steady-state vancomycin serum concentrations for the one- and two-compartment models was made for a fixed 30 mg/kg/day dose . The linear regression equations between the predicted Css2 and Cssmin for the one- and two-compartment models do not differ significantly from the identity line, whereas the corresponding equation for Cssmax points to a 61% underestimation of Cssmax when the one-compartment model is used . From this latter regression equation, it is possible to define 20 mg/L (range of 18-21 mg/L) as a target Cssmax vancomycin serum concentration when a one-compartment model is used to monitor vancomycin therapy . Another practical approach would be to define the target concentration by a desired range at 2 h, which corresponds to a Cssmax value of 30-40 mg/L.

Nephrol Dial Transplant, 1996 Apr, 11(4), 734 - 6
Congress report: What is new in CAPD? (Highlights of the 7th Congress of the International Society of Peritoneal Dialysis, June 1995)
Gokal R.
Key words . adequacy; advanced glycation end-products; aquaporin; cholesterol; glucose polymer; host defence; insulin-like growth factor; Kt/V; Lp(a); malnutrition; mupirocin; nursing; nutrition; peritoneal dialysis; peritonitis; quality of life; solute transport; Staph . aureus; vancomycin

Cancer, 1996 Apr 1, 77(7), 1386 - 94
A comparison of aztreonam plus vancomycin and imipenem plus vancomycin as initial therapy for febrile neutropenic cancer patients; Raad II et al.; BACKGROUND . The improved efficacy of imipenem over other beta-lactam antibiotics in the treatment of febrile neutropenic patients has been attributed to its broad spectrum of activity . METHODS . A prospective, randomized, clinical trial was performed comparing vancomycin 1 g every 12 hours plus imipenem/cilassatin 500 mg every 6 hours and the same dose of vancomycin plus aztreonam 2 g every 6 hours for empiric treatment of febrile episodes in neutropenic patients with cancer . RESULTS . The imipenem regimen cured 76% of the 148 evaluable episodes compared with a 67% cure rate for the 152 episodes treated with the aztreonam regimen (p = 0.1) . Most of the polymicrobial infections (77% or 10/13) treated with the imipenem responded, whereas only 38% (5/13) of these infections responded to the aztreonam regimen . Although the cost of the imipenem regimen was less than the cost of the aztreonam regimen, it was associated significantly more with skin rashes (12/194 vs 3/189, p = 0.02) . In a multivariate analysis, a poor outcome was independently associated in both instances with the persistence of neutropenia and the presence of pneumonia (p < 0.001) . CONCLUSIONS . Overall, in a multifactorial analysis that included efficacy, toxicity, and cost, the imipenem and aztreonam regimens were comparable.

J Chromatogr A, 1996 Mar 15, 727(2), 231 - 8
High-performance liquid chromatographic determination of vancomycin in rabbit serum, vitreous and aqueous humour after intravitreal injection of the drug; Del Nozal MJ et al.; A high-performance liquid chromatographic method for the determination of vancomycin in rabbit serum, vitreous and aqueous humour has been developed . No clean-up step was necessary for vitreous and aqueous humour samples . For serum samples liquid-liquid and solid-phase extraction were tested and the best results were achieved using C18 cartridges . The extracts were analyzed on a C18 reversed-phase column, using a mixture of 0.05 M phosphate buffer (pH 4) with 10% of acetonitrile as mobile phase . The detection was carried out at 198 nm, which allows higher sensitivity . The average quantitation limit obtained was 0.03 micrograms/ml . The method has been applied to the study of the residual quantities of vancomycin in serum and rabbit eyes after intravitreal administration of the drug in endophthalmitis treatment.

J Antimicrob Chemother, 1996 Mar, 37(3), 623 - 33
Impact of glycopeptide therapy after hospital discharge on inpatient costs: a comparison of teicoplanin and vancomycin; Davey PG et al.; Data were collected prospectively from 59 patients receiving vancomycin and 20 patients receiving teicoplanin . The mean daily drug cost was 52.40 pounds for teicoplanin and 31.13 pounds for vancomycin; the 95% Confidence Intervals (CI) for the difference in mean drug costs varied between 14.40 pounds and 28.10 pounds in favour of vancomycin . Use of a loading dose of teicoplanin significantly increased mean daily drug costs if the duration of treatment was less than 10 days . Costs of preparation, administration and monitoring were consistently higher for vancomycin than for teicoplanin and inclusion of these costs reduced the difference in mean daily costs to 13.01 pounds (95% CI 6.10 to 19.90 pounds) . In Dundee 11 of 20 patients who received teicoplanin had received some of their treatment after discharge from the hospital and a survey of UK hospitals confirmed that teicoplanin treatment after discharge is being used in a wide range of conditions . The median proportion of teicoplanin treatment in Dundee given after discharge was 28.4% for each patient who received the drug: the median proportion of non-inpatient therapy was 50% per patient of those who received any teicoplanin treatment after discharge . Assuming that teicoplanin costs 20 pounds per day more than vancomycin, use of teicoplanin implies an investment of 70.42 pounds to gain one hospital day through earlier discharge of patients receiving teicoplanin.

Allergy Asthma Proc, 1996 Mar-Apr, 17(2), 75 - 8
Vancomycin-induced Stevens-Johnson syndrome; Alexander II et al.; Stevens-Johnson syndrome is a rare immunologic reaction that may involve skin or various mucosal surfaces . The etiology may range from multiple pharmacologic agents to viral infections . Associated findings can range from minimal skin and mucosal involvement to extensive dermal exfoliation, nephritis, lymphadenopathy, hepatitis, and multiple serologic abnormalities . We report a 36 year-old caucasian male who developed a pruritic, raised maculopapular eruption on Day 17 of intravenous vancomycin for treatment of probable bacterial endocarditis . The vancomycin was discontinued . The patient had received a prosthetic aortic valve subsequent to acute rheumatic valve disease 20 years earlier, but had been well until development of endocarditis . The rash became more extensive to involve the torso, abdomen, legs, and arms . His fever persisted, and he developed neutropenia and eosinophilia . Axillary and inguinal lymphadenopathy, pharyngeal irritation, lip swelling, conjunctival injection, and elevated liver function studies also developed following cessation of the vancomycin . Eight days after eruption and fever began, corticosteroid therapy was instituted, with subsequent improvement of symptoms in less than 24 hours . Allergic reactions to vancomycin have included Stevens-Johnson syndrome rarely, and only one other case of adenopathy has been recorded . Most reactions have been in patients with severe renal insufficiency . We believe this patient is the first case of vancomycin-induced Stevens-Johnson syndrome in a previously healthy patient to be complicated by lymphadenopathy, hepatitis, and multiple serologic abnormalities.

Chem Biol, 1996 Mar, 3(3), 207 - 15
Cooperativity and anti-cooperativity between ligand binding and the dimerization of ristocetin A: asymmetry of a homodimer complex and implications for signal transduction; Cho YR et al.; BACKGROUND: Recent work has indicated that dimerization is important in the mode of action of the vancomycin group of glycopeptide antibiotics . NMR studies have shown that one member of this group, ristocetin A, forms an asymmetric dimer with two physically different binding sites for cell wall peptides . Ligand binding by ristocetin A and dimerization are slightly anti-cooperative . In contrast, for the other glycopeptide antibiotics of the vancomycin group that have been examined so far, binding of cell wall peptides and dimerization are cooperative . RESULTS: Here we show that the two halves of the asymmetric homodimer formed by ristocetin A have different affinities for ligand binding . One of these sites is preferentially filled before the other, and binding to this site is cooperative with dimerization . Ligand binding to the other, less favored half of the dimer, is anti-cooperative with dimerization . CONCLUSIONS: In dimer complexes, anti-cooperativity of dimerization upon ligand binding can be a result of asymmetry, in which two binding sites have different affinities for ligands . Such a system, in which one binding site is filled preferentially, may be a mechanism by which the cooperativity between ligand binding and dimerization is fine tuned and may thus have relevance to the control of signal transduction in biological systems.

Clin Lab Manage Rev, 1996 Mar-Apr, 10(2), 160 - 6
Improving outcomes in therapeutic drug monitoring--a case history; Jones H et al.; A case history describes quality improvement initiatives undertaken by the Laboratory, the Pharmacy, and the Department of Nursing at Children's Medical Center in Dallas, Texas, a 266-bed pediatric teaching hospital affiliated with the University of Texas Southwestern Medical School . The initial purpose of the study was to correct problems identified by a retrospective review of randomly selected patient charts . The problems included laboratory schedules for drug assays, the timing and documenting of blood collections, the reporting of toxic results to physicians, and the interpreting of serum drug concentrations . The major changes in the program included increased frequency of testing in the laboratory, educating nurses as to sample collection guidelines, introducing a clinical pharmacy consultation service, daily reporting of all drug levels to the pharmacy from the laboratory computer, and reporting toxic levels to the clinical pharmacist who then notified the physician and offered a consult . The study then began to focus on attempting to monitor the service related to outcome indicators . Outcome data included a comparison of test volumes (15.7% decrease), tests per adjusted patient day (15.4% decrease), and tests per patient day of therapy for aminoglycosides (gentamicin decreased 6.8%) before and after the changes were implemented . Data also included aminoglycoside tests reported as therapeutic and as toxic . Plans for further improvement have been identified and include differentiating peak and trough serum drug concentrations for aminoglycosides, possibly developing protocols for vancomycin and cyclosporine monitoring, continuing to educate laboratory technologists and nurses, and continuing to monitor usage and outcome indicators.

Ther Drug Monit, 1996 Feb, 18(1), 80 - 5
Instability of standard calibrators may be involved in overestimating vancomycin concentrations determined by fluorescence polarization immunoassay; Morishige H et al.; Fluorescence polarization immunoassay (FPIA) is widely used to determine serum vancomycin concentrations, and it has been shown to over-estimate vancomycin concentrations in sera from renally impaired patients . This phenomenon has generally been thought to result from interference by vancomycin crystalline degradation products (CDP-1) . In this study, we confirmed that serum vancomycin concentrations in various patients determined by FPIA were higher than those determined by high-performance liquid chromatography (HPLC) or enzyme multiplied immunoassay (EMIT) . However, the quantitative differences in the serum vancomycin concentrations determined by FPIA versus HPLC were higher than the CDP-1 concentrations, even when the cross-reactivity of FPIA to CDP-1 is assumed to be 100% . When the vancomycin calibrators for FPIA were stored at 4 degrees C for 30 days, their concentrations determined by FPIA and HPLC decreased by 14 and 20%, respectively, and CDP-1 corresponding to 20% of primary vancomycin was formed . When stored at 25 degrees C, the degradation of vancomycin was more marked . We concluded that not only the cross-reactivity of FPIA to CDP-1 but also the instability of calibrators may cause the overestimation of serum vancomycin concentrations determined by FPIA.

Burns, 1996 Feb, 22(1), 57 - 61
Unusual development of granulomas on the healing surface of burn wounds associated with MRSA infections; Gang RK et al.; Ten patients with a mean age of 14.5 years and partial skin thickness burns involving 3-5 per cent body surface areas developed rapidly proliferating tumour-like growths on the surface of their healing wounds within 10-21 days of sustaining the injuries . The number of tumours on every patient was either single or multiple and each increased in size daily . The growths were unique in their fulminating-type fleshy mass, with a consistency varying from soft to firm, absence of purulent material or head, and extension up to the fibrous layer covering the musculatuve . Histopathology was suggestive of granulomatous rather than a suppurative nature of the lesions . Isolation of MRSA from the burn wounds of four cases on the first day of dressing and then from the surface of the tumours of all of them and the excised tissues, as well as from the environment of the dressing room, indicated its involvement in the causation of the growths through contaminations of wounds with a hospital endemic strain while handling or dressing . The organisms were resistant to most antibiotics except vancomycin and teicoplanin . The growths in four cases subsided within 72 h with daily dressing, using an injectable solution of either vancomycin or teicoplanin, while the rest required radical excision and immediate cover with split skin grafts and systemic administration of either of the antibiotics . The wounds healed over a period of 8-10 days.

J Clin Oncol, 1996 Feb, 14(2), 579 - 85
Renal toxicity after allogeneic bone marrow transplantation: the combined effects of total-body irradiation and graft-versus-host disease; Miralbell R et al.; PURPOSE: To evaluate retrospectively the cumulative risk probability and factors correlated with renal dysfunction after allogeneic bone marrow transplantation (BMT) . PATIENTS AND METHODS: From October 1984 to July 1994, 84 patients with malignant hematopoietic diseases received allogeneic BMT after conditioning with high-dose chemotherapy and total-body irradiation (TBI) . Seventy-nine patients with normal renal function before conditioning are included in this study . Conditioning included high-dose cyclophosphamide without (n = 46) or with (n = 33) other agents (daunorubicin, busulfan, cytarabine, and thiotepa) followed by TBI . The TBI dose prescribed to the center of the abdomen was 10 Gy for 24 patients, 12 Gy for 32, and 13.5 Gy for 23 . In vitro T-cell depletion was undertaken in 48 cases . The post-BMT nephrotoxicity of aminoglycosides, vancomycin, amphotericin, and cyclosporine was assessed . Time to renal dysfunction was defined as the time to a persistent increase of serum creatinine (SCr) level greater than 110 mumol/L . The potential influence of sex, age, diagnosis, chimerism, and graft-versus-host disease (GvHD) on renal dysfunction was also assessed . RESULTS: The 18-month probability of renal dysfunction-free survival (RDFS) for the whole group was 77% . Only TBI dose and presence of GvHD were significantly correlated with renal dysfunction by multivariate analysis . The 18-month probabilities of RDFS were 95%, 74%, and 55% for the patients conditioned with 10, 12, and 13.5 Gy, respectively . The 18-month RDFS probabilities were 88% and 61% for patients without and with GvHD, respectively . Combining both variables, we have defined two risk categories: low-risk (ie, 10 Gy TBI with/without GvHD and 12 Gy TBI without GvHD) and high-risk (ie, 12 Gy TBI with GvHD and 13.5 Gy TBI with/without GvHD) . The predicted 18-month RDFS rates were 93% and 52% for the low- and high-risk groups, respectively . CONCLUSION: Renal dysfunction after allogeneic BMT is strongly related to the delivered TBI dose (and dose per fraction) and to the presence of GvHD . Renal shielding should be recommended if a TBI dose greater than 12 Gy (fractionated twice daily over 3 days) is to be prescribed . Furthermore, in those cases with a high risk of developing GvHD (eg, unrelated allogeneic BMT, absence of T-cell depletion), these data suggest that kidney doses greater than 10 Gy should be avoided.

Cornea, 1996 Jan, 15(1), 41 - 5
The effect of vancomycin on the corneal endothelium; Lindquist TD et al.; Possible toxic effects of vancomycin on the corneal endothelium were assessed in rabbit eyes and subsequently in corneal transplant recipients . Fifteen New Zealand White rabbits were divided into five groups of three rabbits each . A paracentesis was performed on right eyes only . One hundred microliters of aqueous humor was removed followed by anterior chamber injection of 100 mu l of balanced salt solution (BSS) or varying concentrations of vancomycin (150, 750, 1,875, 7,500 mu g/ml) . Left eyes served as untreated controls . Endothelial cell morphology and density were assessed by contact specular microscopy 48 h postinjection . There was no statistically significant difference in endothelial cell density between left (control) or right (treated) eyes receiving either BSS or varying concentrations of vancomycin . Transmission electron microscopy of rabbit corneal endothelium exposed to varying concentrations of vancomycin (150, 750, 1,875, 7,500 mu g/ml) showed no toxic effects . Six patients undergoing penetrating keratoplasty (PKP) received donor corneas stored in Optisol containing gentamicin to which vancomycin was added to make a final concentration of 150 mu g/ml . Eight patients undergoing PKP received corneas stored in Optisol alone . Specular microscopy was performed preoperatively and 3, 6, and 12 months postoperatively . No statistically significant difference in mean endothelial cell change was observed (Wilcoxon signed-rank test) at any time point postoperatively . Endothelial cell morphology and function are not adversely affected by therapeutic doses of vancomycin.

Wien Klin Wochenschr, 1996, 108(11), 321 - 5
Influence of stress ulcer prophylaxis on translocation of bacteria from the intestinal tract in rats; Georgopoulos A et al.; Clinical studies in critically ill patients suggest an increased rate of septicemia during stress ulcer prophylaxis with H2-blockers when compared with sucralfate, a topically active compound . In the present study we examined the effect of stress ulcer prophylaxis with sucralfate as compared with ranitidine versus untreated animals in a rat model on intestinal flora and on the translocation of bacteria from the intestinal tract . The translocation of bacteria was also determined after induction of hemorrhagic shock and, in addition, we examined bacterial translocation in animals infected with a multiple resistant Escherichia coli and following antibiotic therapy with vancomycin and gentamicin during stress ulcer prophylaxis with and without hemorrhagic shock . Male Wistar rats, which received standard meals either without stress ulcer prophylaxis or with ranitidine/sucralfate were investigated . After induction of hemorrhagic shock we analysed qualitatively and quantitatively the bacterial flora in the gastrointestinal tract, blood, mesenteric lymph nodes and visceral organs (liver, spleen) . In the absence of shock no changes of the intestinal flora and no translocation of bacteria from the gut were observed in control animals nor during stress ulcer prophylaxis . However, after induction of hemorrhagic shock there was a pronounced bacterial translocation in control animals and during ranitidine, whereas the translocation rate was reduced in animals treated with sucralfate (p < 0.05) . During massive E . coli challenge both without and with shock a significantly higher rate of translocation was found in all three experimental groups there were no significant differences between the three groups . We conclude that a) bacterial translocation is low or absent in healthy animals, b) hemorrhagic shock induces a massive increase in bacterial translocation, c) stress ulcer prophylaxis with sucralfate reduces translocation of bacteria during the shock state and c) during massive bacterial overgrowth and/or concomitant shock none of the treatments can reduce the massively elevated rate of bacterial translocation.

J Clin Microbiol, 1996 Jan, 34(1), 185 - 7
Natamycin as a selective antifungal agent in media for growth of Legionella spp; Edelstein PH et al.; The growth of 18 different Legionella sp . strains and 76 different yeast isolates was tested on buffered charcoal yeast extract medium supplemented with alpha-ketoglutarate (BCYE alpha medium) and with natamycin, an antifungal agent . Bacterial growth was no different on BCYE alpha medium made with or without natamycin, whereas complete inhibition of yeasts occurred in BCYE alpha medium containing 200 to 500 micrograms of natamycin per ml . Selective BCYE alpha media made with natamycin rather than anisomycin had no (formulation with vancomycin, polymyxin B, and agar) or little (formulation with cefamandole, polymyxin B, and agar) inhibitory effect on the growth of 14 different Legionella sp . bacteria . Natamycin is an inexpensive alternative to anisomycin in the formulation of selective BCYE alpha media.

Blood Purif, 1996, 14(1), 20 - 5
Effects of slowly performed daytime hemodialysis (slow HD) on the pharmacokinetics of vancomycin in hemodynamically unstable patients with renal failure; Kihara M et al.; Effects of slowly performed daytime hemodialysis (slow HD) using a high-flux hemodialyzer on the pharmacokinetics of vancomycin were determined in 5 critically ill patients with renal failure . Following intravenous administration of 0.5 g of vancomycin, concentrations in the serum and dialysate were monitored . Pharmacokinetic parameters were calculated after fitting individual concentration-time curves to a two-compartment model . The volume of distribution at steady state was 0.58 +/- 0.12 liters/kg . Total body clearance was 37.46 +/- 3.20 ml/min with an elimination phase half-life of 8.72 +/- 0.99 h . Slow HD clearance was 20.19 +/- 2.30 ml/min . During a 10-hour session of slow HD, the serum vancomycin concentration decreased from 44.2 +/- 3.8 to 10.0 +/- 5.0 mg/l and 30.10 +/- 5.34% of the dose was eliminated . Dialyzer clearance of this drug and urea was 18.71 +/- 1.40 and 28.77 +/- 1.77 ml/min, respectively . Slow HD may effectively eliminate vancomycin by a diffusive mechanism and this elimination should be taken into consideration for designing the dosage schedule during the treatment.

J Toxicol Clin Toxicol, 1996, 34(1), 83 - 6
Multiple-dose activated charcoal in an accidental vancomycin overdose; Kucukguclu S et al.; BACKGROUND: Multiple-dose activated charcoal may enhance the enterocapillary clearance of vancomycin . CASE REPORT: A 17-day-old female neonate born with congenital meningomyelocele and Arnold-Chiari malformation was iatrogenically overdosed with a 500 mg intravenous bolus of vancomycin during a shunt operation . The Red Man's Syndrome developed within minutes, characterized by sudden hypotension, skin rash and cyanosis . Serum vancomycin level at one hour after the injection was 165.7 micrograms/mL, as measured by an enzyme immunoassay method (EMIT) . Multiple dose activated charcoal, 1 g/kg, was first given five hours after injection, and continued every four hours for 12 doses . The half-life of vancomycin during charcoal administration was calculated to be 9.4 h or less than the reported 13.4-33.7 h half-life in normal neonates . The neonate's renal function tests and brainstem auditory responses remained normal . CONCLUSIONS: Gastrointestinal dialysis with multiple-dose activated charcoal without cathartics appeared to shorten the elimination half-life of vancomycin.

J Bacteriol, 1996 Jan, 178(1), 94 - 102
Amplification of a novel gene, sanA, abolishes a vancomycin-sensitive defect in Escherichia coli; Rida S et al.; We have isolated an Escherichia coli gene which, when overexpressed, is able to complement the permeability defects of a vancomycin-susceptible mutant . This gene, designated sanA, is located at min 47 of the E . coli chromosome and codes for a 20-kDa protein with a highly hydrophobic amino-terminal segment . A strain carrying a null mutation of the sanA gene, transferred to the E . coli chromosome by homologous recombination, is perfectly viable, but after two generations at high temperature (43 degrees C), the barrier function of its envelope towards vancomycin is defective.

Am J Kidney Dis, 1996 Jan, 27(1), 67 - 74
Falsely elevated serum vancomycin concentrations in hemodialysis patients; Follin SL et al.; Fluorescence polarization immunoassay (FPIA) is the most widely used clinical vancomycin assay in the United States . Questions exist regarding the accuracy of this polyclonal assay in patients with end-stage renal disease (ESRD) . While several studies have reported discrepancies in vancomycin serum concentrations determined by FPIA compared with other vancomycin assays, no study has investigated the accuracy of vancomycin serum concentrations determined by FPIA in patients with ESRD undergoing maintenance hemodialysis . Therefore, we compared the assay performance of FPIA and enzyme multiplied immunoassay technique (EMIT) in six subjects with ESRD receiving high-efficiency hemodialysis . Subjects underwent 6 consecutive weeks of hemodialysis treatment with a cellulose acetate dialyzer (CA210) and received 1 g vancomycin intravenously once weekly during the last hour of dialysis . Vancomycin serum concentrations were determined by both EMIT and FPIA methodologies . From the serum concentration results of both assays, vancomycin dosing recommendations were calculated to achieve a desired steady-state peak concentration of 35 mg/L and trough concentration of 10 mg/L . Overall, vancomycin serum concentrations reported by FPIA were significantly higher than those reported by EMIT . The mean difference between assays in the peak serum concentrations at weeks 1, 4, and 6 was 7.5, 11.5, and 11.2 mg/L, respectively . The mean difference in trough serum concentrations at weeks 1, 4, and 6 was 4.2, 6.2, and 5.2 mg/L, respectively . The FPIA overestimation of the EMIT values (calculated as FPIA-EMIT) varied widely among study subjects with a range of 0.0 mg/L to 27.0 mg/L for peak serum concentrations and 0.0 mg/L to 12.8 mg/L for trough serum concentrations . The mean doses calculated based on FPIA results were significantly lower than the EMIT-derived doses . No significant difference was observed in the calculated dosing intervals . These results demonstrate that FPIA significantly overestimates vancomycin serum concentrations compared with EMIT in patients with ESRD undergoing high-efficiency hemodialysis . The overestimation by FPIA may result in significantly different vancomycin dosing recommendations, leading to underdosing and the potential for therapeutic failures . Due to the unpredictability of the overestimation by FPIA, we were unable to formulate vancomycin dosing guidelines for institutions that use FPIA . Therefore, we recommend that the EMIT vancomycin assay be used in patients with ESRD to ensure appropriate dosing.

Am J Kidney Dis, 1996 Jan, 27(1), 147 - 50
Rusty peritoneal dialysis fluid after intravenous administration of iron dextran; Carter TB et al.; Rusty-colored peritoneal dialysate fluid was observed after intravenous administration of iron dextran to a patient with peritonitis being treated with vancomycin and rifampicin . The discoloration gradually cleared over a 24-hour period . Analysis of the fluid demonstrated that the discoloration could not be explained by the presence of erythrocytes or free hemoglobin . Iron (52 micrograms/dL) was detected in the fluid and decreased to undetectable levels as the discoloration cleared . Addition of iron dextran to an unused bag of peritoneal dialysis fluid to achieve an iron concentration of 52 micrograms/dL resulted in no discoloration . Addition of rifampicin at a clinically relevant serum concentration (10 micrograms/dL) to a different unused bag caused a light orange discoloration . Addition of iron dextran and rifampicin simultaneously in the concentrations mentioned to an unused bag caused a rusty discoloration almost as dark as that observed in our patient . We postulate, therefore, that a combination of iron and rifampicin caused the marked discoloration of our patient's peritoneal effluent.

J Clin Pharm Ther, 1995 Dec, 20(6), 319 - 25
Stability of vancomycin in plastic syringes measured by high-performance liquid chromatography; Wood MJ et al.; The shelf-life of vancomycin in infusion fluids was studied using high-performance liquid chromatographic (HPLC) methods . Vancomycin was stable (loss in potency less than 10%) for 47 days and 29 days, respectively, when dissolved in water-for-injections BP at 25 degrees C and stored in plastic syringes (Becton Dickinson Plastipak (three-piece) and B . Braun Medical Injekt (two-piece)) . In sodium chloride solution (0.9%; pH 5.4) it was stable for 62 and 34 days, while in dextrose solution (5%; pH 4.2) it was stable for 55 and 33 days, respectively, at the same temperature . At 4 degrees C vancomycin was stable in all three infusion fluids and both types of syringe for at least 84 days.

Anaesth Intensive Care, 1995 Dec, 23(6), 678 - 82
Changes in vancomycin pharmacokinetics in critically ill infants; Gous AG et al.; We aimed to assess the pharmacokinetics of vancomycin in critically ill infants, and to evaluate the standard recommended dose of 10 mg/kg 6 hourly . All infants admitted to the Baragwanath Hospital ICU who had arterial lines in situ, and for whom vancomycin 10 mg/kg 6 hourly was prescribed for an infective insult and who had parental consent, were included in the study . Vancomycin was infused over 60 minutes . Serum samples were taken immediately before the dose and at 30, 60, 120 and 300 minutes after the end of the vancomycin infusion, on days 2 and 8 of therapy . Extrapolated peak concentration (Cmax), trough concentration (Cmin), apparent volume of distribution (Vd), elimination half-life (t1/2el) and clearance (CL) were determined for each patient . Day 2 values were compared with those of day 8 . Day 2 serum concentrations were assayed on 20 patients and day 8 concentrations in 15 . The mean vancomycin Vd on day 2 (0.81 l/kg) was significantly (P = 0.007) larger than that on day 8 (0.44 l/kg) . The change in Vd resulted in a significant change in mean Cmax (29.1 vs 35.5 micrograms/ml) (P = 0.02) and mean t1/2el (5.3 vs 3.4h) (P = 0.01) over the treatment period . Critically ill infants displayed a large initial volume of distribution which probably resulted from aggressive fluid resuscitation . This also results in a large variation in other pharmacokinetic parameters, namely Cmax and t1/2el . Although the routine monitoring of vancomycin serum concentrations remain controversial, we feel that in view of these large pharmacokinetic variations, the critically ill infant is a specific group where monitoring of vancomycin serum levels is indicated.

Ceska Slov Farm, 1995 Dec, 44(6), 322 - 6
{Determination of serum vancomycin using capillary isotachophoresis}; Sadecka J et al.; The paper aims to study the possibilities of determining vancomycin in the serum by the method of capillary isotachophoresis . The leading electrolyte contained Na+ as the leading ion, morpholinoethanesulphonic acid as the counter-ion (pH 6,2), and methylhydroxyethyl cellulose as the additive . The terminating electrolyte was morpholinoethanesulphonic acid . The conductivity detector was employed for detection . Ethanol was selected for precipitation of proteins . The yield of vancomycin from the serum was 89-91% . The calibration curve is linear in an interval of 0.02-0.5 microgram (the absolutely dosed amount) . The limit of vancomycin determination in the serum is 4 micrograms/ml . The method was employed to determine vancomycin in the serum of patients . The obtained results correlated well with those obtained by fluorescent polarizing immunoanalysis (TDx) in a concentration interval of 4-30 micrograms/ml.

J Clin Microbiol, 1995 Dec, 33(12), 3102 - 5
Identification of Actinobacillus actinomycetemcomitans in subgingival plaque by PCR; Flemmig TF et al.; The purpose of this study was to assess the sensitivity and specificity of the PCR in detecting Actinobacillus actinomycetemcomitans . The PCR's detection capability was compared with those of three other methods: culture-enhanced PCR (CE-PCR), colony hybridization (CH), and conventional culture with presumptive biochemical identification . A 285-bp stretch of the leukotoxin gene lktA of A . actinomycetemcomitans was amplified by PCR with primers TT-15 and TT-16 . For CH, the PCR product was labeled with digoxigenin and used as a hybridization probe . Nucleotide sequence analysis of the PCR product of A . actinomycetemcomitans 1D4 and 1664 and three clinical isolates revealed complete homology among the tested strains, with only one base substitution (at position 1344) in comparison with the published sequence . With artificially infected subgingival plaque, the detection limit of PCR for A . actinomycetemcomitans was 10(3) CFU/ml of plaque suspension . Culturing subgingival plaque on tryptic soy-serum-bacitracin-vancomycin agar prior to PCR (CE-PCR) improved the limit of detection to 10(2) CFU/ml . Analysis of subgingival plaque samples from 35 patients with periodontal disease and 10 periodontally healthy subjects revealed that CE-PCR and CH had the highest overall rate of A . actinomycetemcomitans detection (both 58%), followed by PCR and culture (both 42%) . With CH as the "gold standard", the sensitivities of CE-PCR, PCR, and culture were 88, 65, and 58%, respectively; the specificities were 84, 89, and 79%, respectively . The CE-PCR provided acceptable positive and negative predictive values (> or = 70%) when the prevalence of A . actinomycetemcomitans varied between 30 and 70% . PCR alone provided comparable predictive values over a narrower range of prevalence rates (30 to 50%), while culture did not afford acceptable predictive values at any prevalence rate . PCR and CE-PCR were found to be superior to culture with presumptive biochemical identification and should be the preferred methods for the detection of A . actinomycetemcomitans in subgingival plaque.

Am J Health Syst Pharm, 1995 Nov 15, 52(22), 2560 - 4
Compatibility and stability of aztreonam and vancomycin hydrochloride; Trissel LA et al.; The physical compatibility and chemical stability of aztreonam and vancomycin hydrochloride when combined at clinically used high and low concentrations were studied . Admixtures consisting of aztreonam 4 mg/mL and vancomycin 1 mg/mL (as the hydrochloride salt) in 5% dextrose injection, aztreonam 4 mg/mL and vancomycin 1 mg/mL in 0.9% sodium chloride injection, aztreonam 40 mg/mL and vancomycin 10 mg/mL in 5% dextrose injection, and aztreonam 40 mg/mL and vancomycin 10 mg/mL in 0.9% sodium chloride injection were prepared in triplicate in polyvinyl chloride containers . Three containers of each type of admixture were stored at 4, 23, and 32 degrees C . Samples were removed immediately and at various time points over 31 days . Compatibility was assessed by visual examination, with a turbidimeter, and with a particle sizer-counter . Stability was determined by stability-indicating high-performance liquid chromatography (HPLC) . All the admixtures initially appeared clear to the unaided eye after the disappearance of a transient white swirl in the high-concentration admixtures (aztreonam 40 mg/mL and vancomycin 10 mg/mL) . However, the high-concentration admixtures immediately developed unacceptable levels of a microcrystalline precipitate when viewed with a high-intensity fiber-optic light source . Easily visible gross turbidity and precipitation formed after various periods but often within 24 hours . HPLC showed aztreonam 4 mg/mL and vancomycin 1 mg/mL in 5% dextrose injection to be a stable combination for 7 days at 32 degrees C, 14 days at 23 degrees C, and 31 days at 4 degrees C . In 0.9% sodium chloride injection, the drugs in the low-concentration admixtures were stable for 7 days at 32 degrees C and for 31 days at 4 and 23 degrees C . Stability of the combination in the high-concentration admixtures was maintained for 3 days at 23 and 32 degrees C and for 14 days at 4 degrees C . Aztreonam and vancomycin hydrochloride were considerably less compatible and stable in the high-concentration admixtures than in the low-concentration ones.

Ann Pharmacother, 1995 Nov, 29(11), 1110 - 4
Polyethylene glycol nephrotoxicity secondary to prolonged high-dose intravenous lorazepam; Laine GA et al.; OBJECTIVE: To report a patient with a probable acute tubular necrosis (ATN) induced by chronic exposure to polyethylene glycol (PEG)-400 via long-term, massive dosage of intravenous lorazepam . CASE SUMMARY: A 57-year-old man with a history of alcohol abuse was admitted to the intensive care unit for acute respiratory failure . Lorazepam therapy was initiated in anticipation of alcohol withdrawal . Dosages up to 18 mg/h were required to provide adequate sedation and optimize ventilation . On day 43, the patient developed oliguric ATN of unknown etiology . The cumulative intravenous lorazepam dose was 4089 mg, equivalent to approximately 220 mL of PEG-400 . Blood urea nitrogen concentrations followed a pattern that paralleled lorazepam dosage increases and decreases . Protein and granular casts were evident in urinalyses performed on days 12 and 29 . The patient eventually experienced complete recovery . DISCUSSION: ATN associated with intravenous PEG was last reported in 1959 in 6 of 32 patients receiving a cumulative PEG-300 dose of 120-200 mL over 3-5 days via an intravenous nitrofurantoin preparation . Two of the 6 patients died . Chronic administration of intravenous PEG to rabbits over a 5-week period has caused cloudy swelling of the renal tubular epithelium, increased blood urea concentrations, and death in some animals . CONCLUSIONS: ATN probably resulted from chronic PEG exposure via massive doses of lorazepam injection, possibly enhanced by concurrent administration of vancomycin.

J Chromatogr B Biomed Appl, 1995 Oct 20, 672(2), 295 - 9
Comparison of high-performance liquid chromatography with fluorescence polarization immunoassay for the analysis of vancomycin in patients with chronic renal failure; Najjar TA et al.; Eighty-two plasma samples from patients with chronic renal failure undergoing vancomycin treatment and hemodialysis (HD) were analyzed with fluorescence polarization immunoassay (FPIA) and high-performance liquid chromatography (HPLC) . Vancomycin was infused once and the samples were collected during three subsequent HD sessions at 2 h, 3 days and 5 days post-infusion . The HPLC method, modified from an earlier assay, was simple . There was a wide variation in the estimated concentration between the two assay methods . The results obtained by HPLC were 69% lower than those obtained by FPIA . This difference in vancomycin concentration was independent of the sampling time after vancomycin infusion . HPLC analysis commenced approximately 1.5 year after that of FPIA . To study the effect of in vitro degradation, the vancomycin concentration in ten of the samples was redetermined with FPIA during HPLC analysis . The concentrations of those samples decreased to 78-98% (average 92%) of the original concentration . Because FPIA appears to lack specificity, there is a need of other methods such as HPLC for vancomycin measurements, particularly in samples from patients with end-stage renal failure.

Dtsch Med Wochenschr, 1995 Oct 20, 120(42), 1430 - 4
{Collagenous sprue}; Hafkemeyer P et al.; HISTORY AND FINDINGS: A 45-year-old man with type I diabetes mellitus was admitted to hospital because of colicky abdominal pain and 5-6 watery stools daily . Upper gastrointestinal endoscopy showed nearly total atrophy of the villi in the duodenum and jejunum suggesting coeliac disease . However, gluten-free diet for 2 weeks brought no improvement . Another examination of the biopsy 6 weeks after the first endoscopy revealed extensive collagen deposition in the lamina propria of the small intestine, giving the diagnosis of collagenous sprue . TREATMENT AND COURSE: Parenteral nutrition, lactulose, cisapride, cholestyramine, doxycycline, paromomycin, vancomycin and octreotide failed to affect the loss of fluid from the gut which 12 weeks after admission had increased to 221 daily . However, it was stopped after prednisolone was administered (100mg daily) . 7 months after starting the steroid treatment the collagen layer had disappeared and the villous atrophy had partially regressed . Over the next 6 months the prednisolone dosage was decreased to 10 mg daily . Shortly thereafter a perimembranous glomerulonephritis occurred, with proteinuria (up to 60 g/d) and oedema . It regressed to 6 g/d when the steroid dose was increased and cyclosporin, 0.5 g/d, had been added . On maintenance dosage of cyclosporin the histological and clinical remission of the collagenous sprue has now lasted for over 2 years . CONCLUSIONS: This case suggests that steroid administration is an effective treatment of collagenous sprue . The presence of diabetes and other immune-related diseases in this case also suggests that an immunological mechanism may play a causative role in collagenous sprue.

J Spinal Cord Med, 1995 Oct, 18(4), 233 - 5
Vancomycin pharmacokinetics in spinal cord injured patients: a comparison with age-matched, able-bodied controls; Lavezo LA et al.; To compare the pharmacokinetics of vancomycin in chronic spinal cord injured patients and hospitalized, age-matched, able-bodied controls, we evaluated 14 spinal cord injured patients and 14 controls . Pharmacokinetic parameters of total body clearance (CL), distribution volume (V), elimination rate constant (k) and elimination half-life (t1/2) were calculated from two steady-state vancomycin serum concentrations by the method of Sawchuk and Zaske . Demographic data such as age, ideal body weight (IBW), total body weight (TBW) and serum creatinine at start of therapy (SCr), pharmacokinetic parameters and predicted dosages to achieve specific peak (30 mcg/ml) and through concentrations (5-10 mcg/ml) were calculated for both groups . Statistical comparisons were made using a two sample, Student's t-test . Demographic data between groups differed only in mean serum creatinine (p = 0.04) . There were no statistically significant differences in mean pharmacokinetic parameters of CL and V or mean predicted dosages . Mean elimination rate constant was significantly smaller and mean elimination half-life was significantly longer in spinal cord injured patients (p = 0.02 and p = 0.04, respectively) . The longer dosing interval predicted in spinal cord injured patients trended toward statistical significance (p = 0.10) . We conclude that with chronic spinal cord injury, 1) the elimination half-life of vancomycin is increased and these patients may require longer dosing intervals and 2) distribution volume and predicted vancomycin doses are unaltered compared with controls.

J Am Soc Nephrol, 1995 Oct, 6(4), 1284 - 90
Influence of cellulose triacetate hemodialyzers on vancomycin pharmacokinetics; Welage LS et al.; This study was designed to evaluate the pharmacokinetics of vancomycin during hemodialysis with cellulose triacetate (CT) high-flux dialyzers and to assess the influence of membrane surface area on intradialytic clearance . In a randomized crossover fashion, the pharmacokinetics of vancomycin were evaluated during dialysis with the CT 110 and CT 190 membranes . Six hemodialysis patients received 1 g of vancomycin immediately after the completion of a dialysis session, and subsequently, blood samples were obtained over a 5-day study period . On Day 3 subjects were dialyzed with CT 110 or CT 190 membranes . The mean intradialytic clearance of vancomycin was 56.7 +/- 7.5 and 100.70 +/- 10.7 mL/min with the CT 110 and CT 190 membranes, respectively (P < 0.05) . Significant rebound in vancomycin serum concentrations occurred after dialysis; this rebound appeared to be complete 3 h postdialysis . On the basis of postrebound concentrations, the apparent percent removal of vancomycin was 23.6 +/- 1.2 and 25.2 +/- 8.6% for CT 110 and CT 190 membranes, respectively (not significant) . Vancomycin is significantly cleared during dialysis with cellulose triacetate membranes, and its clearance is dependent on membrane surface area . Although a small supplemental dose of vancomycin could be administered after dialysis to replace drug lost during dialysis, it may be more efficient to give a larger dose of vancomycin after several dialysis periods . The determination of vancomycin removal can be used to estimate vancomycin serum concentrations as well as dosage requirements . This in conjunction with serum concentration monitoring can be used to optimize vancomycin dosing.

Therapie, 1995 Sep-Oct, 50(5), 447 - 50
{Neutropenia during treatment with fusidic acid: analysis of 5 cases}; Vial T et al.; Two cases of moderate neutropenia and 3 cases of severe neutropenia in the course of fusidic acid treatment for sepsis related to a hip prothesis or septic osteitis are reported . Neutropenia was always observed following routine blood cell count, after a mean of 21 days' treatment (16 to 27 days) . Moderate fever was observed only once, in a patient with profound neutropenia . A complete recovery of blood cell count was noted in all cases, 5 to 9 days upon discontinuation of fusidic acid . A sternal bone-marrow aspiration was performed in 4 cases, showing normocellularity or hypercellularity in two cases, and moderate hypoplasia of granulocytic cells . The respective roles of other treatments are discussed . Overall, these five cases suggest that reversible granulocytopenia can be caused by protracted treatment with fusidic acid . Although nine different associated drugs could also have been involved in four patients, the causal relationship was less suggestive for three of them due to chronological events . In other cases, the drugs never or very rarely caused neutropenia . Finally, the possibility of vancomycin-induced neutropenia cannot be excluded in one case.

Pharmacotherapy, 1995 Sep-Oct, 15(5), 673 - 6
Evaluation of plasmapheresis on the removal of tobramycin; Kale-Pradhan PB et al.; A 26-year-old man with thrombotic thrombocytopenic purpura resulting in respiratory and renal failure was treated with plasmapheresis (PP) . Coexisting pulmonary infiltrates were empirically treated as pneumonia with various antibiotics, including vancomycin and tobramycin . The half-life of tobramycin was 6.93 hours . During PP the half-life of tobramycin decreased to 4.47 hours as determined by three random levels . The fraction eliminated due to PP was 35.5% and the fraction cleared by PP was 10.9% . We conclude that PP contributed significantly to the total clearance of tobramycin . The need for supplemental doses must be evaluated in each patient based on post-PP serum concentrations.

Ann Pharmacother, 1995 Sep, 29(9), 835 - 42
Thrombocytopenia in intensive care patients: a comprehensive analysis of risk factors in 314 patients; Bonfiglio MF et al.; OBJECTIVE: To define the incidence and severity of thrombocytopenia in a mixed medical-surgical population of critically ill patients and to examine factors that may be related to the development of thrombocytopenia . DESIGN: Retrospective chart review of 314 critically ill patients requiring at least 3 days of critical care . SETTING: A 17-bed combined medical-surgical intensive care unit (ICU) in a 560-bed tertiary care community hospital . PATIENTS: Medical and surgical patients admitted to the ICU . INTERVENTIONS: All medical records over the duration of the ICU stay were reviewed . All scheduled medications, including dosage and start/stop dates, were recorded . All platelet counts, placement of pulmonary artery catheters, liver function test results, and admission serum creatinine concentrations were collected . MEASUREMENT AND MAIN RESULTS: Thrombocytopenia (platelet count less than 200 x 10(9)/L) was observed frequently, but rarely reached a severe stage (7 patients) . No single diagnostic category was significantly associated with thrombocytopenia alone, although the combination of sepsis syndrome/septic shock and respiratory failure was strongly correlated (p < 0.0001) with thrombocytopenia . Liver function abnormalities were correlated strongly with thrombocytopenia, and the majority of patients (5 of 7) with severe thrombocytopenia (less than 20 x 10(9)/L) were found to have concurrent severe alterations in liver function test results . Pulmonary artery catheter placement and heparin exposure were associated strongly with thrombocytopenia (p < 0.0001) . Drug therapies that were correlated with thrombocytopenia included heparin and vancomycin (p < 0.05) . Hemodynamic instability was correlated strongly with the presence and severity of thrombocytopenia . In a stepwise linear regression model, the admission platelet count accounted for the largest proportion of the variance (43%), followed by hemodynamic instability (8%) and the requirement for inotropic agents (2%) . CONCLUSIONS: Thrombocytopenia in the critically ill occurs frequently, rarely reaches severely depressed concentrations, and primarily represents a manifestation of disease processes initiated prior to admission . Hemodynamic instability and/or heparin exposure appear to be the strongest identifiable correlates with thrombocytopenia . Although these may cause infrequent isolated cases, other specific drug causes of thrombocytopenia are not responsible for the majority of cases of thrombocytopenia in the critically ill.

Am J Kidney Dis, 1995 Sep, 26(3), 469 - 74
Vancomycin removal by high-flux polysulfone hemodialysis membranes in critically ill patients with end-stage renal disease; Touchette MA et al.; To define the pharmacokinetics of vancomycin in patients undergoing maintenance hemodialysis in an acute care setting and to characterize the rebound phenomenon occurring after hemodialysis, vancomycin t1/2 during the interdialytic and intradialytic phases and intradialytic clearance were measured in eight critically ill patients undergoing high-flux hemodialysis using F-80 or F-60 polysulfone dialyzers . Intradialytic clearance was determined using the recovery method . In patients dialyzed with F-80 dialyzers, interdialytic and intradialytic t1/2 for vancomycin were 162 +/- 69.8 hours and 4.7 +/- 1.3 hours, respectively . Intradialytic clearance was 108.5 +/- 16.3 mL/min, and 238 +/- 55 mg of vancomycin was recovered in the dialysate . In patients dialyzed with F-60 dialyzers, interdialytic and intradialytic t1/2 were 211.0 +/- 166.8 and 4.6 +/- 0.4 hours, respectively . Intradialytic clearance was 100.6 +/- 18.3 mL/min and the amount of vancomycin recovered was 252 +/- 79 mg . Vancomycin concentrations rebounded by 16% to 37% between 3 and 6 hours in patients dialyzed with the F-80 dialyzer and 15% to 38% between 2 and 3 hours in patient dialyzed with F-60 dialyzers . Hemodialysis with high-flux polysulfone dialyzers removes significant amounts of vancomycin in patients dialyzed in an acute care setting . A suggested scheme for vancomycin dosage adjustments in these patients is presented.

Pediatr Infect Dis J, 1995 Aug, 14(8), 667 - 73
Influence of malignancy on the pharmacokinetics of vancomycin in infants and children; Chang D; This prospective, controlled study evaluates the influence of malignancy on the pharmacokinetics and dosage requirements of vancomycin in 33 infants and children with cancer (age 5.72 +/- 4.11 years, mean +/- SD) compared with 31 patients without cancer (age 4.18 +/- 5.10 years) using a two-compartment Bayesian pharmacokinetic program . Patients in the malignancy group required a vancomycin dosage regimen of 71.5 +/- 13.9 mg/kg/day to attain a mean peak serum vancomycin concentration (SVC) of 22.38 +/- 4.54 mg/liter and a mean trough SVC of 6.84 +/- 2.78 mg/liter . Patients without cancer in the control group required a mean vancomycin dosage regimen of 50.2 +/- 13.0 mg/kg/day to attain a mean peak SVC of 21.70 +/- 6.70 mg/liter and a mean trough SVC of 8.05 +/- 3.01 mg/liter . Comparative analysis of pharmacokinetic data revealed an increase in vancomycin clearance (0.149 +/- 0.028 liter/hour/kg) in the malignancy group as compared with that (0.114 +/- 0.031 liter/hour/kg) in the control group . There were no significant differences with respect to the mean values of volume of distribution between two groups (0.638 +/- 0.079 liter/kg vs . 0.618 +/- 0.102 liter/kg) . Analysis of the predictive performance of the Bayesian program indicated that final sets of peak and trough SVCs were predicted with minimal bias and accurate precision in both study groups . This study showed that the presence of malignancy in infants and children increased vancomycin clearance resulting in larger dosage requirements.

J Antimicrob Chemother, 1995 Aug, 36(2), 411 - 5
Assay of vancomycin by fluorescence polarisation immunoassay and EMIT in patients with renal failure; Saunders NJ et al.; Serum with vancomycin concentrations between 5 and 15 mg/L from patients on dialysis were assayed by fluorescence polarization immunoassay (FPIA) and enzyme multiplied immunoassay technique (EMIT) . The concentrations as determined by FPIA were higher than those using EMIT (mean difference 2.1 mg/L, S.D . 1.5; range -0.8-6.3) with substantial interpatient variability in the difference between the two assays . This suggests that concentrations of active vancomycin are lower than indicated by FPIA and thresholds for redosing may need to be adjusted.

J Pharmacol Exp Ther, 1995 Aug, 274(2), 695 - 9
Enhancement of tobramycin binding to rat renal brush border membrane by vancomycin; Yano Y et al.; Effects of vancomycin (VCM) on tobramycin (TOB) binding to rat renal brush border membrane were examined by using isolated brush border membrane vesicles . The binding of TOB to the membrane vesicle was enhanced by the preincubation of the vesicle with VCM . The Scatchard analysis showed that this enhancement was due mainly to the increase in the number of binding sites . D-Glucose uptake was not affected by VCM, which suggests that the vesicles were not damaged by VCM . The binding of spermine, a typical polycationic compound, to the membrane vesicles also was increased by VCM treatment, and this also was because of the increase in the number of binding sites . These results suggested that the enhanced binding of these cationic compounds by VCM was due to the change in the negative charge on the membrane surface . Considering that the binding of aminoglycosides to brush border membranes is the initial step for the renal accumulation followed by the aminoglycosides-induced nephrotoxicity, this enhancement of TOB binding to the membrane by VCM may be one of the reasons for the enhanced TOB nephrotoxicity by VCM, which has often been reported in experimental animals and patients.

J Pediatr Hematol Oncol, 1995 Aug, 17(3), 234 - 47
Infections in children with acute myelogenous leukemia . Concepts of management and prevention; Feusner JH et al.; The child with acute myelogenous leukemia (AML) is at high risk for infection, especially during the induction phase of therapy . Appreciation of special risk factors and the changing spectrum of infecting pathogens is critical to development of the most appropriate initial evaluation and therapy for these children . Based on the available data in pediatrics, and extrapolation from studies in adult populations, we make recommendations for the initial empiric management of the febrile child with AML, the proper use of vancomycin, and management of special infectious complications related to central venous catheter use . Fungal infections are rapidly becoming the single most serious supportive care problem for children with AML . Optimal initial empiric therapy, treatment of proven systemic infections, and current status of attempts at prophylaxis are reviewed . Finally, the issue of colony stimulating factor use in AML is broached . Hopefully, studies underway will demonstrate the benefits and risks of these agents in AML . The time is long past due for large, well designed studies of supportive care in AML . Therapeutic trials addressing this very important aspect of the total care of the child with AML need to accompany the advancing new anti-oncologic therapies of the disease.

Rinsho Ketsueki, 1995 Aug, 36(8), 768 - 73
{Vancomycin-induced thrombocytopenia for MRSA pneumonia}; Kishimoto T; Thrombocytopenia occurred after 17 days of administration of vancomycin (VCM) in 2 cases of MRSA pneumonia . The drug lymphocyte stimulation test using VCM and anti-platelet antibody were negative for these 2 cases . However, platelet bound IgG significantly increased and the total number of immature megakaryocytes in the bone marrow increased . Corticosteroid administration after VCM was very effective for thrombocytopenia . In case 1, thrombocytopenia occurred three times after using of VCM, suggesting to have been induced by VCM . The mechanism of thrombocytopenia was immunological destruction . It has been reported that VCM-induced neutropenia might be induced via an immunological mechanism . We reported here 2 cases of thrombocytopenia induced by VCM, which is frequently used for MRSA pneumonia.

J Clin Microbiol, 1995 Aug, 33(8), 2118 - 23
Comparison of culture methods for monitoring Legionella species in hospital potable water systems and recommendations for standardization of such methods; Ta AC et al.; A lack of standardization of environmental monitoring techniques for Legionella spp . complicates the interpretation of results and comparisons of results from different institutions . A comparative assessment of techniques recommended by the Centers for Disease Control and Prevention, the Hygiene Institute (Graz, Austria), and our laboratory was performed . Variables investigated were sampling method (swabbing and collection of water samples {250 ml} before and after swabbing), method of concentration (none, filtration, and centrifugation), acid buffer treatment (no acid treatment, treatment for 3 min, and treatment for 15 min), and choice of medium (five formulations of buffered charcoal yeast extract agar with glycine, vancomycin, polymyxin B, anisomycin, or cycloheximide) . Thirty-three sites in seven hospital buildings were studied . Recovery by swab correlated with recovery from water after swabbing (P < 0.05) . However, the quantity of Legionella spp . recovered from swab specimens (mean, 3.0 x 10(4) CFU per swab) was greater than that recovered from water (mean, 4.7 x 10(3) CFU/250 ml) . Filtration resulted in recovery rates (mean, 5.2 x 10(3) CFU/250 ml) higher than those by centrifugation (mean, 2.3 x 10(3) CFU/250 ml) . Three minutes of acid buffer treatment to reduce overgrowth by commensal flora did not improve selectivity or sensitivity for Legionella spp . if glycine-containing selective media were used . Fifteen minutes of acid buffer treatment reduced recovery compared with that after a 3-min treatment . All glycine-containing media tested effectively inhibited background flora, but one selective medium containing dyes, glycine, vancomycin, and polymyxin B (DGVP) resulted in the greatest quantitative recovery of Legionella pneumophila . Use of buffered charcoal yeast extract agar and the acid buffer treatment gave the greatest recovery of non-pneumophila species . A standardized protocol with an emphasis on the culturing of swab samples is presented.

Ther Drug Monit, 1995 Aug, 17(4), 366 - 70
An improved micromethod for vancomycin determination by high-performance liquid chromatography; Li L et al.; A micromethod using reversed-phase high-performance liquid chromatography for the analysis of vancomycin in human serum or plasma was developed . Ristocetin was used as the internal standard . Chromatographic conditions included an amino propyl column, a mobile phase with 62% acetonitrile and 38% sodium phosphate buffer (pH 7.0), a total run time of 10 min, and ultraviolet absorbance detection at 225 nm . Multilevel calibration was found to be linear between 1.0 and 100 micrograms/ml with correlation coefficients of the calibration line slope consistently > 0.999 . Recovery of vancomycin from serum was nearly complete, and no interference from commonly used drugs was observed . This procedure is simple, sensitive, rapid, precise, selective, and requires only 50 microliters of serum or plasma for completion.

Ther Drug Monit, 1995 Aug, 17(4), 319 - 26
Vancomycin pharmacokinetics and dosing in premature neonates; McDougal A et al.; We prospectively studied the pharmacokinetic parameters of vancomycin in premature neonates given vancomycin according to a dosage protocol developed in our neonatal unit . Study infants were administered vancomycin according to four postconceptional age (PCA) groups: (0) 18 mg/kg every 36 h for PCA < 27 weeks; (I) 16 mg/kg every 24 h for PCA 27-30 weeks; (II) 18 mg/kg every 18 h for PCA 31-36 weeks; and (III) 15 mg/kg every 12 h for PCA > or = 37 weeks . Pharmacokinetic parameters were calculated from peak and trough serum vancomycin concentrations at steady state . Results in 44 infants (PCA, 27-44 weeks) showed that our dosage regimen achieved target peak serum vancomycin concentrations in 64% of neonates in Groups I-III, although it tended to undershoot the target trough concentrations . Volume of distribution (Vd), normalized for body weight, remained constant throughout the PCA range, with a mean value of 0.56 L/kg, whereas absolute clearance (r = 0.81) and normalized clearance (r = 0.48) increased with PCA (p < 0.005) . The increase in clearance with PCA is associated with a greater elimination rate constant and shorter half-life . Vancomycin therapy can be initiated in a standard fashion according to our protocol or by individualizing the dosage regimen based on a Vd of 0.56 L/kg and clearance estimated from the infant's body weight and PCA groups.

Kyobu Geka, 1995 Jul, 48(7), 592 - 4
{A successful case report of conservative treatment of MRSA empyema after right pneumonectomy}; Kondo D et al.; We have successfully treated MRSA empyema after right pneumonectomy by the closed drainage and irrigation alone . The patient was a 70-year-old male who had received right pneumonectomy for p-III a squamous cell carcinoma originating in the right upper lobe bronchus . The operation wound was infected on the 6th postoperative day and became pleural fistula and finally MRSA empyema was developed on the 10th postoperative day . The chest drainage and irrigation of the infected pneumonectomy space with physiological saline containing antiseptic povidone iodine (Isodine) were performed 3 times a day for 14 days, however, the empyema was not cured completely . In addition, nausea and vomiting considered as the side effect of Isodine severely appeared . Therefore the antiseptic agent was exchanged to vancomycin hydrochloride from povidone iodine . Empyema space became sterile 4 days after the exchange and the drainage tube was removed 7 days after sterilization . Further empyema has not been developed for 8 months . We discussed the method and antiseptic agents in irrigation of empyema space.

Vnitr Lek, 1995 Jun, 41(6), 427 - 31
{Present possibilities of prevention of infectious complications associated with central venous catheter systems}; Hajek R et al.; Central venous access devices are a major source of nosocomial infection . The skin and catheter hub are the two major sources for the introduction of the colonizing organisms . Authors reviewed up-to-date prophylactic possibilities in this paper . Prophylactic measures include a skilled team, topical disinfectants, topical antibiotics, new types of devices such as coating catheter with antiseptic agent and catheter with silver impregnated cuffs, maximal barrier precautions during insertion, systemic vancomycin therapy of high risk patients . Exchanging central venous catheters over a guidewire might be useful diagnostically but have not been used to be of any therapeutic or prophylactic goal . Prophylactic antibiotic lock of device and use of fibrinolytic agent to clean the device may be useful but can not be a standard recommendation.

Ther Drug Monit, 1995 Jun, 17(3), 239 - 46
Bayesian forecasting of serum vancomycin concentrations in neonates and infants; Rodvold KA et al.; A dynamic pharmacokinetic model for i.v . vancomycin administration was developed and tested in 47 neonates and infants . Twenty-nine patients (Group 1), having two or more concentrations, were used to estimate population parameters by nonlinear least-squares analysis . Multiple stepwise linear regression techniques showed that estimated creatinine clearance, Clcr, and postnatal age were significant demographic factors related to vancomycin clearance (CL) . No strong associations were found for the apparent volume of distribution . A one-compartment model was constructed using the associations of CLcr and postnatal age with vancomycin CL . Eighteen patients (Group 2), receiving 35 courses of vancomycin therapy, with both initial and subsequent sets of peak and trough concentrations, were used to test the predictive performance of the model with and without the use of Bayesian forecasting . Using only population-based parameters, the respective mean error (ME) (bias) and mean absolute error (MAE) (precision) for predicting subsequent peak concentrations were -1.20 and 3.89 mg/L and for trough concentrations, 0.83 and 2.23 mg/L, respectively . For the Bayesian method, these values were, respectively, 0.45 and 4.13 mg/L for peak concentrations and 1.55 and 2.40 mg/L for trough concentrations . When predicted concentrations occurred within 30 days of feedback concentrations, the Bayesian method tended to be slightly less biased and more precise than the population-based parameters . The opposite was true > 30 days of the initial set of feedback concentrations . The use of population-specific pharmacokinetic parameters and Bayesian forecasting should allow accurate dosage regimen design as well as minimize the need for monitoring serum vancomycin concentrations in neonates and young infants.

Clin Infect Dis, 1995 Jun, 20(6), 1526 - 30
Epidemiology of nosocomial fungal infections, with emphasis on Candida species; Jarvis WR; Currently, about 180 hospitals participate in the National Nosocomial Infections Surveillance (NNIS) system . From January 1980 through April 1990, 27,200 fungal isolates causing nosocomial infections were reported from these hospitals; Candida species accounted for 19,621 (72.1%) of these isolates . Immunocompromised patients are at particularly high risk for candidemia . In patients with acute lymphocytic leukemia, treatment with vancomycin and/or imipenem appears to be an independent risk factor for candidemia; colonization of stool by Candida species may be another important predisposing factor in these patients . Rapid detection of invasive candidemia in these high-risk patients is particularly important to the improvement of rates of survival . Methods for rapid detection, such as the measurement of mannan (the major cell-wall polysaccharide of Candida), may be useful for diagnosing invasive candidiasis and for monitoring the response of this infection to antifungal therapy . Further studies of risk factors and the development of new methods for rapid diagnosis and monitoring should help decrease the morbidity and mortality associated with nosocomial fungal infections.

J Chromatogr B Biomed Appl, 1995 May 19, 667(2), 277 - 81
Rapid high-performance liquid chromatographic determination of vancomycin in human plasma; Luksa J et al.; A rapid simple and robust reversed-phase HPLC method was developed for rapid screening in bioavailability studies or comparative bioequivalence studies . The method is specific for vancomycin as no interference from acetylsalicylic acid, paracetamol and caffeine was observed . The mean intra-day precision was from 11.7% (low concentration) to 0.3% (high concentration) and the within-day precision from 15.0 to 0.3%, determined on spiked samples . The accuracy of the method was 106.4-99.8% (intra-day) and 103.5-100.2% (inter-day).

Intensive Care World, 1995 Jun, 12(2), 48 - 53
Vascular access in neonates and infants--indications, routes, techniques and devices, complications; Moller JC et al.; Venous cannulation has been in regular use in neonates since the 1940s . This was at first through the umbilical vein, but the frequency of complications lead to other central and peripheral routes being used for infusion of fluid, nutrients and drugs . Today, peripheral venous access is preferred except for high volume fluid resuscitation, reliable infusion of irritant drugs and long-term parenteral nutrition . Intraosseous infusion provides a reliable alternative to peripheral veins for rapid infusion of fluid . Long, thin silastic catheters can be inserted through a peripheral venous cannulae for parenteral nutrition or other central venous infusions as an alternative to direct central venous cannulation using the Seldinger or other techniques . Broviac or Hickman catheters, inserted through a subcutaneous tunnel are only considered when central venous cannulation is likely to be needed for more than six weeks . The most common serious complication of vascular access is infection . Infection associated with central venous catheters is reduced by prophylactic vancomycin or teicoplanin . Other complications of central venous infusion are associated with cannulae malpositioning, bleeding and thrombosis . Distal hypoperfusion may follow arterial cannulation . Modern emergency and intensive care paediatrics is impossible without adequate venous and arterial vascular access . However no other skill for neonatal intensive care causes more anxiety in primary care providers or is more difficult to teach.

Allergy Proc, 1995 May-Jun, 16(3), 115 - 8
Recurrent dermopathy after remission of Stevens-Johnson syndrome secondary to mild dermal trauma; Patterson R et al.; We report on three patients who had an apparent recurrence of the dermatitis of Stevens-Johnson Syndrome (SJS) after remission had been induced with corticosteroids . The recurrences were related to mild trauma to the skin, including the Red Man Syndrome, after vancomycin in two patients . Both responded to corticosteroids, and vancomycin could be continued with modification in the rate of infusion . The third patient had dry, pruritic skin and the exacerbation of SJS appeared related to the trauma associated with intense scratching . A post SJS inflammatory dermatitis may occur after remission of SJS secondary to cutaneous trauma . This recurrent SJS dermopathy is rapidly responsive to moderate dose corticosteroid therapy.

Clin Pharmacokinet, 1995 Apr, 28(4), 327 - 42
Pharmacokinetic optimisation of vancomycin therapy; Leader WG et al.; Renewed interest in vancomycin over the past decade has led to an abundance of data concerning the pharmacokinetics of vancomycin, and its dosage selection and concentration-response relationships . No definitive data exist that correlate vancomycin serum concentrations with clinical outcomes . However, inconsistencies in sampling times for peak serum concentrations and differences in infusion times make interpreting vancomycin serum concentrations difficult . Furthermore, the evidence implicating vancomycin as a cause of oto- or nephrotoxicity is circumstantial, and these adverse effects may occur only in high-risk populations . Owing to the variability in its dose-serum concentration relationship and multicompartmental pharmacokinetics, several methodologies have been developed for instituting and adjusting vancomycin dosages . Nomograms rely on a fixed volume of distribution and the relationship between vancomycin clearance and creatinine clearance . Since both of these factors may be altered in certain populations, dosage methodologies (both traditional and Bayesian) that use population- or patient-specific pharmacokinetic data perform better than standard nomograms for initiating vancomycin therapy . Controversy still exists as to whether a 1- or a 2-compartment model is more appropriate for making dosage adjustments; however, steady-state rather than non-steady-state vancomycin serum concentrations should be used for dosage adjustments . Certain pathophysiological states such as age, bodyweight and renal function contribute to altered pharmacokinetics and may alter the design of the dosage regimen . Since no definitive relationship exists between vancomycin serum concentrations and either clinical outcome or adverse effects, considerable controversy surrounds the utility of monitoring serum vancomycin concentrations . Therefore, routine vancomycin serum concentration monitoring may be warranted only in specific populations, such as patients receiving concurrent aminoglycoside therapy or those receiving higher than usual dosages of vancomycin, patients undergoing haemodialysis and patients with rapidly changing renal function.

Ann Pharmacother, 1995 Apr, 29(4), 374 - 7
Cyclosporine and vancomycin disposition during continuous venovenous hemodiafiltration; Munar MY et al.; OBJECTIVE: To report cyclosporine and vancomycin disposition during continuous venovenous hemodiafiltration (CVVHD) in a 41-year-old heart transplant patient while in the intensive care unit at a primary and tertiary care teaching hospital . CASE SUMMARY: The patient received a 60-mg infusion of cyclosporine over 24 hours and vancomycin 1 g over 1 hour . Blood samples subsequently were collected and analyzed using whole blood monoclonal radioimmunoassay and fluorescence polarization immunoassay, respectively . Blood samples were measured every hour from the arterial and venous lines of the apparatus, as were ultrafiltrate drug concentrations . Drug clearance rates into the ultrafiltrate subsequently were calculated . DISCUSSION: Measurements of ultrafiltrate detected no cyclosporine . A slight variation existed between arterial and venous drug concentrations, which was not statistically significant (p > 0.05, paired Student's t-test) . Analysis of vancomycin samples revealed a steady decline of drug concentration, with 4.75% of the dose eliminated in the ultrafiltrate . Vancomycin arterial and venous concentrations decreased from 24.4 and 23.3 mg/L to 15.7 and 12.3 mg/L, respectively . CONCLUSIONS: Vancomycin is eliminated by CVVHD and it may be necessary for these patients to receive the drug more frequently . In contrast, cyclosporine is not removed effectively by CVVHD; therefore, replacement doses are not warranted.

Aliment Pharmacol Ther, 1995 Feb, 9(1), 63 - 8
The effect of oral vancomycin on chronic idiopathic constipation; Celik AF et al.; BACKGROUND: A case study reporting the efficacy of oral vancomycin in a patient with chronic idiopathic constipation prompted this prospective trial of oral vancomycin in eight female patients (aged 21-61 years) with severe constipation resistant to the action of dietary fibre . METHODS: The trial was divided into two consecutive 14-day periods . During the first period, each patient was given ispaghula, 3.5 g twice a day, and during the subsequent period they took 250 mg vancomycin t.d.s . per os, as well as the fibre supplement . During both periods they collected stools and recorded daily bowel symptoms (stool frequency, straining, stool consistency, subjective stool volume) in a diary . At the end of each period whole gut transit time and the breath hydrogen response to a standard meal, giving oro-caecal transit time, were measured along with gastrointestinal symptoms which were assessed on visual analogue scales . RESULTS: Vancomycin caused a significant improvement in stool frequency, consistency, ease of defecation and the amount of stool patients felt they produced (all P < 0.05), but objective measures of daily stool weight and whole gut or oro-caecal transit time were not significantly different . Basal breath hydrogen levels were higher after vancomycin treatment in seven out of eight patients . One patient experienced a complete remission of symptoms when she took vancomycin and remains in remission after 14 months . This patient showed no elevation in basal breath hydrogen level . CONCLUSION: Although this study does not support the use of vancomycin for most patients with constipation, the results suggest that modification of the intraluminal flora may be of value in the treatment of the occasional case of idiopathic constipation.

Clin Nucl Med, 1995 Feb, 20(2), 99 - 106
Colonic localization of labeled leukocytes in critically ill patients . Scintigraphic detection of pseudomembranous colitis; Nathan MA et al.; This study assesses the causes of colonic localization of labeled white blood cells (WBCs) in critically ill patients who had undergone leukocyte scintigraphy for suspected infection . Forty-two patients showed abdominal or pelvic WBC localization; 20 of these had a pattern of colonic localization, and some also showed a pattern of small bowel activity . Eight of the 20 patients had documented gastrointestinal bleeding . White blood cell scintigraphy in these eight patients showed a pattern of multifocal and/or regional bowel activity that changed in intensity and location from early (3-5-hour) to delayed (18-28-hour) images . In contrast, 5 of the 6 patients with documented pseudomembranous colitis (PMC) showed intense WBC localization involving most of the colon . In 3 of these 5 patients, early and delayed images were acquired and showed a relatively constant pattern of WBC localization . The sixth PMC patient had been treated with vancomycin before leukocyte scintigraphy and showed minimal distal small bowel activity on early images and only mild regional colonic activity on delayed images . As in the patients with gastrointestinal bleeding, the remaining six patients showed either focal or regional activity of variable intensity that changed over time . In critically ill patients, gastrointestinal bleeding and PMC accounted for 14 of the 20 patients in which labeled leukocyte scintigraphy exhibited colonic activity . A pattern of diffuse, intense colonic radiotracer activity which persists from early to delayed imaging strongly suggests the presence of PMC in this patient population.(ABSTRACT TRUNCATED AT 250 WORDS)

Medinfo, 1995, 8 Pt 2, 1106 - 10
Pharmaco-informatics: more precise drug therapy from 'multiple model' (MM) adaptive control regimens: evaluation with simulated vancomycin therapy; Jelliffe RW et al.; A multiple model (MM) stochastic control of dosage regimens permits essentially optimal use of the information contained in either a population pharmacokinetic model or in a MM Bayesian updated parameter set to achieve and maintain selected therapeutic goals with optimal precision . The regimens are visibly more precise than those achieved using mean parameter values . Feedback has now also been incorporated into the MM software . An evaluation of MM adaptive control precision versus control achieved using population mean parameter values is presented using a real population model (Vancomycin) . Further feedback control was evaluated, incorporating simulated clinical errors in the preparation and administration of doses.

J Med, 1995, 26(3-4), 175 - 81
Analysis of responses to vancomycin in carotid blood flow in the male rat; Jahr JS et al.; Vancomycin is known to cause vasodilation, and hypotension secondary to histamine release . We studied the actions of two forms of vancomycin, a clinically available preparation, clinical vancomycin, and a research grade preparation, laboratory vancomycin, in the presence of an H1 receptor blockade and during H2 receptor blockade with Doppler flow probe analysis of carotid artery flow rate . Clinical vancomycin, laboratory vancomycin, and histamine, increased the mean carotid artery blood flow from baseline in a dose-dependent manner . Diphenhydramine, H1 receptor antagonist, attenuated the increase in mean carotid artery blood flow for the highest dose of clinical vancomycin and for each dose of histamine . Famotidine, H2 receptor antagonist, significantly attenuated the increase in mean carotid artery blood flow for the highest dose of clinical vancomycin, the two higher doses of laboratory vancomycin, and with each dose of histamine . Both diphenhydramine and famotidine attenuated the increase of mean carotid artery blood flow with clinical vancomycin, laboratory vancomycin, and histamine . These data suggest that the change in carotid flow produced by vancomycin, is dependent, in part, on either H1 or H2 receptor activation.

Adv Perit Dial, 1995, 11, 48 - 51
Rat model of peritoneal fibrosis: preliminary observations; Wieczorowska K et al.; The aim of this study was to establish a rat model of peritoneal fibrosis . After insertion of peritoneal catheters into 18 rats, the rats were divided into three groups . All animals were dialyzed twice a day with 4.25% Dianeal containing heparin . Group 1 rats (control) received antibiotics (vancomycin and gentamicin) in each exchange: group 2 rats were inoculated with Escherichia coli (5 x 10(6) in 5 mL of saline) at the beginning of the study; group 3 rats were treated with antibiotics after Escherichia coli inoculation; they also received a second inoculation of Escherichia coli after the second week of the study . By the end of the second week, group 2 rats were sacrificed because of catheter problems . Group 1 and 3 rats were sacrificed after 4 weeks of dialysis . A weekly peritoneal equilibration test (PET) was performed in each rat . The comparison of the PET results from the beginning and end of the study showed an increased permeability to glucose (p < 0.05) and total protein (p < 0.05) in group 3, which was not noted in group 1 . In histology samples there was only delicate fibrosis with cellular infiltration in the peritoneum in group 1 rats . These changes were much more prominent in group 3 rats . This study suggests that E . coli peritonitis causes peritoneal fibrosis in rats, but to have a sclerosing encapsulating peritonitis (SEP) model this experiment must be carried out for a longer time.

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