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