Vancomycin

Adv Perit Dial, 1995, 11, 179 - 81
A prospective randomized comparison of single versus multidose gentamicin in the treatment of CAPD peritonitis; Lye WC et al.; There is an increasing trend towards the use of aminoglycosides in a once-daily dose administration for the treatment of severe infections in nonrenal failure patients . The use of once-daily dose aminoglycoside therapy may be associated with a reduction in toxicity . We performed a prospective randomized study comparing once-daily versus multiple-dose gentamicin in the treatment of continuous ambulatory peritoneal dialysis (CAPD) peritonitis . Seventy-three patients with 100 new episodes of peritonitis were enrolled in the study . At presentation of peritonitis, the patients were alternately assigned to receive either intraperitoneal gentamicin at a dose of 40 mg/2 L dialysate administered as a once-daily dose or gentamicin at a dose of 10mg/2 L dialysate administered 4 times per day . All patients also received intraperitoneal vancomycin at a dose of 1 g per week . There were no significant differences in the treatment success (88% vs 82%, p = NS) and relapse (18% vs 20%, p = NS) rates between the once-daily dose and multiple-dose groups . The mean trough serum gentamicin level was higher in the once-daily dose group compared to the multiple-dose group (0.75 +/- 0.72 vs 1.50 +/- 1.40 mg/L) . In conclusion, gentamicin administered in a once-daily dose is as effective as multiple-dose administration in the treatment of CAPD peritonitis . The lower gentamicin level with once-daily dose administration may be associated with a reduction in aminoglycoside toxicity.

ASAIO J, 1995 Jan-Mar, 41(1), 100 - 4
A comparison of solute clearance during continuous hemofiltration, hemodiafiltration, and hemodialysis using a polysulfone hemofilter; Reeves JH et al.; The clearance of urea, creatinine, amino acids, vancomycin, and phenytoin was measured in vivo in a small animal model during continuous venovenous (CVV) hemofiltration, CVV hemodiafiltration, and CVV hemodialysis using a 0.25 m2 polysulfone hemofilter . Six domestic piglets (weighing 6-11.8 kg) each received 1 hr of all three techniques in random order . Blood flow was 50 ml/min . During CVV hemofiltration, filtrate production was 500 ml/hr and dialysate flow was zero . During CVV hemodiafiltration, filtrate production was 250 ml/hr and dialysate flow was 250 ml/hr . During CVV hemodialysis, net filtrate production was zero and dialysate flow was 500 ml/hr . The ratio of concentration of solute in filter effluent to concentration in whole plasma was derived for each solute during each of the three techniques . Mean (SD) effluent:plasma ratio for urea during CVV hemofiltration was 0.957 (0.038), CVV hemodiafiltration 0.876 (0.109), and CVV hemodialysis 0.754 (0.123); creatinine 0.942 (0.05), 0.934 (0.056), and 0.814 (0.057); amino acids 0.996 (0.344), 0.904 (0.196), and 0.778 (0.18) . For small unbound solutes, there is a decrease in clearance of 6% from CVV hemofiltration to CVV hemodiafiltration and a further decrease of 14% from hemodiafiltration to hemodialysis . The effluent:plasma ratio for vancomycin during CVV hemofiltration was 0.739 (0.082), CVV hemodiafiltration 0.643(0.063), and CVV hemodialysis 0.509 (0.081), corresponding to a decrease of 30% from CVV hemofiltration to CVV hemodialysis . The effluent:plasma ratio for phenytoin was 0.302 (0.028) during CVV hemofiltration and was not significantly different during CVV hemodiafiltration or CVV hemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopharm Drug Dispos, 1995 Jan, 16(1), 23 - 35
An in vitro study of the influence of a drug's molecular weight on its overall (Clt), diffusive (Cld) and convective (Clc) clearance through dialysers; Mac-Kay MV et al.; The dialyser clearance of a drug is the sum of two components: one diffusive, arising from the concentration gradient across the membrane, and the other convective, arising from the ultrafiltration of plasma water, produced by the increases in hydraulic pressure that the membrane undergoes . To demonstrate the importance of these clearances during haemodialysis, this study analyses the influence of a drug's molecular weight on them . To this end, an experimental study of dialysis in vitro was carried out to determine the clearances, in aqueous solution, of five drugs of increasing molecular weights (theophylline, quinidine, tobramycin, digoxin, and vancomycin), using two series of dialysers with the same type of membrane (Cuprophan), differing in effective surface area and ultrafiltration coefficient . From the data obtained in this study, the importance of quantifying convective clearance during haemodialysis becomes apparent since if it is not taken into account errors of up to 20% and more may be made . This is particularly so if the drug is of high molecular weight and if a high filtration rate is being used.

Ther Drug Monit, 1994 Dec, 16(6), 612 - 5
Effect of heating sera under conditions necessary for deactivation of human immunodeficiency virus on commonly monitored therapeutic drugs; Dasgupta A et al.; Minimizing the risk of infection of laboratory staff from contaminated blood samples is a major safety goal in a clinical laboratory . One dangerous pathogen, the human immunodeficiency virus (HIV) can be deactivated by heating sera at 56 degrees C for 30 min . We studied the effect of such heat treatment on serum concentrations of 11 commonly monitored therapeutic drugs . We used blood specimens collected in serum separator tubes (SSTs), which were routinely submitted for therapeutic drug monitoring in our laboratory for this study . Concentrations of digoxin in sera were measured using a fluorescence polarization immunoassay (FPIA), while concentrations of tobramycin, gentamicin, vancomycin, theophylline, valproic acid, procainamide, N-acetylprocainamide (NAPA), phenytoin, phenobarbital, and carbamazepine were measured by enzyme-multiplied immunoassay technique assays using a Monarch 2000 analyzer . We observed no significant change in the concentration of any drug except phenytoin and carbamazepine following heating at 60 degrees C . The decrease in concentration of phenytoin and carbamazepine after heating was related to absorption of the drug to the gel rather than the instability of the drug under heating conditions . We conclude that blood contaminated with HIV may be deactivated by heating prior to analysis for most of the routinely monitored therapeutic drugs.

Ann Pharmacother, 1994 Dec, 28(12), 1335 - 9
Impact of vancomycin therapeutic drug monitoring on patient care; Welty TE et al.; OBJECTIVE: To document differences in the outcome of vancomycin therapy in patients managed through a therapeutic drug monitoring (TDM) service and patients managed empirically, without the participation of a TDM service . DESIGN: Prospective, cohort study . SETTING: An 1100-bed, tertiary-care, teaching hospital . PATIENTS: Those who received vancomycin for more than four days, were at least 18 years old, had an estimated creatinine clearance of more than 0.33 mL/s (20 mL/min), were not neutropenic at the start of vancomycin therapy, and were not treated in a critical care unit were enrolled in the study . A total of 116 patients (61 TDM; 55 non-TDM) were monitored prospectively from June 1990 through March 1991 . INTERVENTIONS: Patients in the TDM group had vancomycin drug therapy monitored daily by a pharmacist and vancomycin dosages adjusted following a pharmacokinetic analysis of vancomycin serum concentrations . For patients in the non-TDM group, the pharmacist only completed a data collection form . The patients and physicians were unaware of the monitoring . MAIN OUTCOME MEASURES: Duration of therapy, total vancomycin dosage, infection site, concomitant antibiotics, body temperature, and white blood cell counts were compared between the two groups . Length of stay data were also compared . Nephrotoxicity was evaluated by comparing serum creatinine concentration and estimated creatinine clearance . RESULTS: TDM of vancomycin appeared to reduce the incidence of vancomycin-related renal insufficiency (TDM 7 percent; non-TDM 24 percent) . Patients managed through the TDM service received an average of 5 g less of vancomycin than did the patients in the non-TDM group . The duration of vancomycin therapy was an average of 2 days less for patients in the TDM group . Mean length of stay was 38.0 days for the TDM group and 44.5 days for the non-TDM group . Other measures of efficacy, infection site, and concomitant antibiotics were the same for both groups . CONCLUSIONS: TDM of vancomycin was associated with fewer cases of vancomycin-related renal insufficiency . Vancomycin efficacy was not compromised by TDM . Provision of TDM for vancomycin therapy aided in patient management.

Mol Gen Genet, 1994 Nov 15, 245(4), 431 - 40
Identification and preliminary characterization of temperature-sensitive mutations affecting HlyB, the translocator required for the secretion of haemolysin (HlyA) from Escherichia coli; Blight MA et al.; We have carried out a genetic analysis of Escherichia coli HlyB using in vitro(hydroxylamine) mutagenesis and regionally directed mutagenesis . From random mutagenesis, three mutants, temperature sensitive (Ts) for secretion, were isolated and the DNA sequenced: Gly10Arg close to the N-terminus, Gly408Asp in a highly conserved small periplasmic loop region PIV, and Pro624Leu in another highly conserved region, within the ATP-binding region . Despite the Ts character of the Gly10 substitution, a derivative of HlyB, in which the first 25 amino acids were replaced by 21 amino acids of the lambda Cro protein, was still active in secretion of HlyA . This indicates that this region of HlyB is dispensable for function . Interestingly, the Gly408Asp substitution was toxic at high temperature and this is the first reported example of a conditional lethal mutation in HlyB . We have isolated 4 additional mutations in PIV by directed mutagenesis, giving a total of 5 out of 12 residues substituted in this region, with 4 mutations rendering HlyB defective in secretion . The Pro624 mutation, close to the Walker B-site for ATP binding in the cytoplasmic domain is identical to a mutation in HisP that leads to uncoupling of ATP hydrolysis from the transport of histidine . The expression of a fully functional haemolysin translocation system comprising HlyC,A,B and D increases the sensitivity of E . coli to vancomycin 2.5-fold, compared with cells expressing HlyB and HlyD alone . Thus, active translocation of HlyA renders the cells hyperpermeable to the drug . Mutations in hlyB affecting secretion could be assigned to two classes: those that restore the level of vancomycin resistance to that of E . coli not secreting HlyA and those that still confer hypersensitivity to the drug in the presence of HlyA . We propose that mutations that promote vancomycin resistance will include mutations affecting initial recognition of the secretion signal and therefore activation of a functional transport channel . Mutations that do not alter HlyA-dependent vancomycin sensitivity may, in contrast, affect later steps in the transport process.

Presse Med, 1994 Nov 5, 23(34), 1554 - 8
{Continuous administration of vancomycin in patients with severe burns}; Conil JM et al.; OBJECTIVES: In the severely burned patient, a marked, rapid fall in serum concentrations is often observed after intermittent infusion of vancomycin at the usual dose of 30 mg/kg . This specific "jagged" pharmokinetic course with inadequate residual concentrations raises the problem of the efficacy of this time-dependent antibiotic . Studies in patients in general resuscitation units have shown the interest of vancomycin administration in continuous infusion . METHODS: We analyzed variations in serum concentrations of vancomycin during continuous infusion in 18 patients with burns involving a mean of 40% total body surface and reported the doses necessary to maintain serum vancomycin at therapeutic levels; the possible correlations between serum vancomycin concentrations, burn parameters, age and renal function; and clinical and biological tolerance . RESULTS: Higher initial doses were required in burn patients (40 mg/kg in patients aged under 60) than in other patients . Impairment of renal function is a contra-indication of continuous infusion . CONCLUSION: This mode of administration has the advantage of ensuring greater efficacy by preventing fluctuations in serum concentrations.

Ann Allergy, 1994 Nov, 73(5), 402 - 4
Vancomycin anaphylaxis and successful desensitization; Anne' S et al.; This report describes vancomycin anaphylaxis and successful desensitization . A 35-year-old woman who tolerated vancomycin initially, developed generalized urticaria and respiratory distress when the drug was readministered . Symptoms recurred following infusion of vancomycin at a lowered rate and dose despite premedication with antihistamines and corticosteroids . Intradermal skin tests with vancomycin were positive at a concentration of 0.1 micrograms/mL . Control subjects reacted at a concentration of 10 micrograms/mL or greater . A rapid 1-day desensitization protocol was unsuccessful . The patient then was "desensitized" by sequential increments in intravenous vancomycin doses over 13 days . After the full therapeutic dose was tolerated, there was a loss of skin test reactivity to vancomycin . We conclude that desensitization to vancomycin is possible and may be the only means to treat an allergic patient adequately when there are no viable therapeutic alternatives.

Fundam Appl Toxicol, 1994 Nov, 23(4), 590 - 7
Developmental toxicology studies of vancomycin hydrochloride administered intravenously to rats and rabbits; Byrd RA et al.; Pregnant CD rats were given vancomycin intravenously in doses of 0, 40, 120, or 200 mg/kg on Gestation Days (GD) 6-15; pregnant New Zealand white rabbits were given 0, 40, 80, or 120 mg/kg intravenously on GD 6-18 . Cesarean sections were performed on rats and rabbits on GD 20 and 28, respectively . In rats, maternal toxicity was indicated in the 120- and 200-mg/kg treatment groups by cortical tubular nephrosis . Maternal body weight gain and food consumption and fetal viability, weight, and morphology were not adversely affected by vancomycin . Maternal and developmental no observed adverse effect levels (NOAELs) in the rat were 40 and 200 mg/kg, respectively . In rabbits, maternal toxicity was indicated by cortical tubular nephrosis in the 80- and 120-mg/kg treatment groups; a single death and depression of body weight gain and food consumption occurred in the 120-mg/kg treatment group . Developmental toxicity was indicated by depression of fetal weight in the 120-mg/kg treatment group; fetal viability and morphology were not adversely affected by vancomycin . Maternal and developmental NOAELs in the rabbit were 40 and 80 mg/kg, respectively . Based on these data, vancomycin did not exhibit selective toxicity toward the developing rat or rabbit conceptus.

Pediatr Infect Dis J, 1994 Nov, 13(11), 969 - 74
A prospective study of vancomycin pharmacokinetics and dosage requirements in pediatric cancer patients; Chang D et al.; Pharmacokinetics of vancomycin and dosage requirements were evaluated prospectively in 28 pediatric cancer patients 9 months to 13 years of age . The predictive performance of a two-compartment Bayesian forecasting program was also evaluated . A mean (+/- SD) daily dosage of 75 +/- 22 mg/kg/day was necessary to attain a mean peak serum vancomycin concentration (SVC) of 23.1 +/- 5.8 mg/liter and a mean trough SVC of 6.2 +/- 2.3 mg/liter . Mean vancomycin clearance, volume of distribution and serum half-life were 0.153 +/- 0.033 liter/hour/kg, 0.63 +/- 0.08 liter/kg and 2.95 +/- 0.48 hours . Final peak SVCs, which reflected the last dosage regimens received, were predicted with minimal bias (mean prediction error, -1.2 mg/liter) and accurate precision (root mean-squared prediction error, 2.0 mg/liter) whereas trough SVCs were predicted with even smaller bias (mean prediction error, -0.1 mg/liter) and greater precision (root mean-squared prediction error, 0.8 mg/liter) . This study showed that pediatric cancer patients with normal renal function required vancomycin dosage regimens substantially greater than the standard 40 mg/kg/day to attain the desired SVCs.

Ther Drug Monit, 1994 Oct, 16(5), 513 - 8
Vancomycin pharmacokinetics in a patient population: effect of age, gender, and body weight; Ducharme MP et al.; The effects of age, gender, and body weight on the pharmacokinetics of vancomycin were examined using data collected as part of routine therapeutic drug monitoring in patients . One thousand eighty-five sets of steady-state peak and trough serum concentrations obtained from 704 different patients were used to calculate elimination rate constant (k), volume of distribution (V), and clearance (Cl) using a one-compartment model . The median half-life of vancomycin was 6.5 h . Clearance was significantly correlated with creatinine clearance as estimated using the Cockcroft-Gault equation {Cl = 0.771 (Clcr) + 18.9; r = 0.63} . V averaged 0.69 L/kg ideal body weight (IBW) with increased values in females, patients over age 60, and obese patients . V ranged from 0.58 L/kg IBW in normal weight males under age 40 to 1.17 L/kg IBW in obese females over age 60 . V was not different in underweight patients and those of normal weight (43.8 vs . 44.4 L) . Regression analysis indicated that V was more predictable in women than in men and that vancomycin distributed into excess body weight (EBW) to a greater extent in women . However, the correlation coefficients from multiple regression analysis of V with IBW, EBW, and age did not exceed 0.60, and the high root mean square error values of 11-15 L suggest considerable variability in V is not accounted for by these factors alone . Despite these limitations, dosing of vancomycin may be improved by adjusting initial estimates of V for patient age, gender, and obesity.

Biotechnol Prog, 1994 Sep-Oct, 10(5), 503 - 12
Partitioning of vancomycin using poly(ethylene glycol)-coupled ligands in aqueous two-phase systems; Singh M et al.; Affinity partitioning describes a process in which a biospecific ligand is used to manipulate the partitioning behavior of a biomolecule by coupling a ligand to one of the phase-forming polymers . It combines the high selectivity of affinity chromatography with the scalability of aqueous two-phase extractions . Fundamental studies have been made on the factors affecting affinity partitioning of the antibiotic vancomycin using a series of polymer-ligands composed of the D-Ala-D-Ala peptide coupled to poly(ethylene glycol) in methoxypoly(ethylene glycol)/dextran aqueous two-phase systems . The effects of varying the ligand molecular weight, the ligand binding interaction, the number of binding sites, the tie-line length, and the aggregation of vancomycin have been measured . A modification of the Flanagan and Barondes model for affinity partitioning has been suggested to explain the results . The modified model accounts for the changes in the surface properties of the biomaterial on complex formation.

Epidemiol Infect, 1994 Aug, 113(1), 31 - 9
Immunomagnetic separation as a sensitive method for isolating Escherichia coli O157 from food samples; Wright DJ et al.; Minced beef samples inoculated with Escherichia coli O157 were cultured in buffered peptone water supplemented with vancomycin, cefsulodin and cefixime (BPW-VCC) and subcultured to cefixime tellurite sorbitol MacConkey (CT-SMAC) agar both directly and after immunomagnetic separation (IMS) of the organism with magnetic beads coated with an antibody against E . coli O157 (Dynabeads anti-E . coli O157, Dynal, Oslo) . E . coli O157 was recovered from initial inocula of 200 organisms/g by direct subculture and 2 organisms/g by IMS . Twelve strains of E . coli O157 of different combinations of phage type, H antigen and toxin genotype were all recovered from initial inocula of two organisms/g by IMS . Non-specific binding of other organisms to the magnetic beads could be reduced by washing of the beads in PBS with Tween-20 0.002-0.005% E . coli O157 was not bound by magnetic coated with an unrelated antibody . During investigation of a dairy herd that was possibly linked to a small outbreak of infection with E . coli O157, the organism was isolated from 2 of 279 forestream milk samples from individual cattle; both isolates were made only by the IMS technique . IMS is rapid, technically simple, and a specific method for isolation of E . coli O157 and will be useful in epidemiological studies.

Clin Pharmacol Ther, 1994 Aug, 56(2), 169 - 75
Population pharmacokinetics of vancomycin in neonates; Seay RE et al.; OBJECTIVE: To determine population pharmacokinetic parameters of vancomycin in neonates . METHODS: This was a retrospective design, with prospective validation . Two hundred ten sequential neonates were evaluated at the neonatal intensive care units of Minneapolis Children's Medical Center and Children's Hospital of St . Paul . Five hundred twenty serum concentrations from 192 patients were included . A mean +/- SD gestational age of 29.5 +/- 5.1 weeks, postnatal age of 16.5 +/- 19.6 days, and dosing weight of 1492 +/- 1053 gm described the population . Thirty additional patients were studied for validation . Dosing, serum concentrations, and 28 covariates were collected . Data were evaluated with NONMEM . Forward selection and backward elimination regression identified significant covariates . One- and two-compartment population pharmacokinetic parameters and predictive performance of the models were measured . RESULTS: Two-compartment final regression equations were as follows: Clearance (CL) = 0.0590 L/kg/hr (multiplied by 0.460 if exposed to dopamine and 0.643 if gestational age was < or = 32 weeks), central volume (VC) = 0.440 L/kg, intercompartmental clearance (Q) = 0.0313 L/hr/kg, and steady-state volume of distribution (Vss) = 0.764 L/kg . Interindividual variability was 40.6% for CL, 54.1% for Vss, and 16.8% for VC . Residual variability was 3.3 micrograms/ml . One-compartment final regression equations were: CL = 0.0626 L/kg/hr (multiplied by 0.455 if exposed to dopamine and 0.656 if gestational age was < or = 32 weeks), and Vd = 0.496 L/kg . Differences in relative performance were insignificant by use of one- or two-compartment parameters . CONCLUSIONS: Gestational age < or = 32 weeks and concurrent use of dopamine were significant factors in prediction of vancomycin clearance . alpha Half-lives of 2.8 to 3.7 hours and beta half-lives of 13.4 to 33.7 hours suggest that some individuals in this neonatal population have considerably longer half-lives than those previously reported.

Foot Ankle Int, 1994 Jul, 15(7), 354 - 9
Tibiocalcaneal arthrodesis for nonbraceable neuropathic ankle deformity; Alvarez RG et al.; Seven patients with nonbraceable, neuropathic ankle joints have been successfully treated by tibiocalcaneal arthrodesis utilizing an adolescent condylar blade plate, large cannulated AO screws, and a special cancellous allograft mixture . All patients had fragmentation and partial resorption of the talus . This procedure was considered as an alternative to below-knee amputation . Goals were limb salvage and limited community ambulation . Criteria for proceeding with the fusion were a commitment by the patient to 6 to 8 months of nonweightbearing ambulation, a biopsy and culture of the talus revealing no evidence of infection, and a nonbraceable deformity of the foot and ankle that would otherwise require amputation . A toe-level Doppler index or a transcutaneous oxygen index of greater than 0.45 was required . All patients were treated initially in a total contact cast or bivalved total contact ankle-foot orthosis (AFO) until wounds and swelling were controlled and there was no erythema . Presence of an ulcer did not preclude surgery . The arthrodesis used a combination of 7.0-mm AO cannulated screws and an adolescent condylar blade plate . A special preparation of fresh-frozen, irradiated, cancellous allograft mixed with tobramycin and vancomycin powder was used . All ankles fused solidly in an average of 5.2 months . No infectious complications were encountered . Two patients developed a stress fracture of the tibia at the proximal aspect of the blade plate before use of a bivalved AFO . These healed with nonoperative treatment in 6 weeks . All patients were satisfied with their result at their latest follow-up (average 26.9 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Am J Hosp Pharm, 1994 Jul 1, 51(13), 1672 - 5
Pharmacokinetics services in Department of Veterans Affairs medical centers; Howard CE et al.; The provision of pharmacokinetics services in Veterans Affairs (VA) medical centers was studied . In October 1992 a questionnaire was mailed to the chief of pharmacy at each of the nation's 160 VA medical centers . The survey was designed to determine the percentage of centers providing pharmacokinetics services, the general characteristics of pharmacokinetics services provided, and whether the presence of these services was associated with specific characteristics of the medical centers . Of the 160 questionnaires mailed, 148 (93%) were returned and analyzed . Pharmacokinetics services were provided by 104 (70%) of the respondents . Of the 104 services, 58 (56%) had existed for less than five years . Of the 44 VA medical centers without a pharmacokinetics service, almost two thirds planned to start one in the future . Aminoglycosides, vancomycin, and theophylline were the drugs most frequently monitored . Fifty-four percent of the pharmacokinetics services evaluated 1-24 patients per month, and another 24% evaluated 25-49 patients monthly . VA medical centers with a pharmacy residency program were more likely to have a pharmacokinetics service than centers without such a program; an association with geographic region was also identified . Nearly three fourths of responding VA medical centers indicated that they provided pharmacokinetics services.

Jpn J Antibiot, 1994 Jun, 47(6), 731 - 5
{Clinical efficacy of arbekacin on MRSA infections}; Ichiyama S et al.; Clinical efficacy of arbekacin (ABK) was examined on patients with MRSA infection during hospitalization in Nagoya University Hospital . A total of 15 analysed cases of 5 sepsis, 3 pneumonias, 6 wound infections and one abdominal abscess . ABK was administered intravenously by drip infusion of 200 mg per day divided into 2 doses with or without other antibiotics . Overall clinical efficacy rate was 76.9%, and eradication rate for the MRSA was 54.5% . Adverse effects were noted in 3 cases (one each case of urticaria, disorder of liver function, and renal disorder) . The renal disorder was found in the case where ABK was used in combination with vancomycin.

Jpn J Antibiot, 1994 Jun, 47(6), 664 - 75
{A study on nephrotoxicity of arbekacin and vancomycin in rats}; Niizato T et al.; Nephrotoxicities of arbekacin (ABK) and/or vancomycin (VCM) were examined by administrating rats intravenously with single doses or 10 times repeated daily doses . ABK was found less toxic to kidney than VCM, and the toxicity was strengthened by combined treatment with VCM and ABK . Fosfomycin decreased the nephrotoxicity when added to the single or combined treatment with ABK and VCM.

Artif Organs, 1994 Jun, 18(6), 425 - 8
A comparison of molecular clearance rates during continuous hemofiltration and hemodialysis with a novel volumetric continuous renal replacement system; Jeffrey RF et al.; We developed a continuous, volumetrically controlled veno-venous renal replacement system that can be operated in filtration or dialysis modes . We compared the clearances of substances with a range of molecular weights (MW) in each mode . Ten patients with acute renal failure underwent serial postdilutional hemofiltration and hemodialysis, for 30 min each, in sequence and in randomized order . All were receiving vancomycin for concurrent sepsis . The system incorporated a Filtral 10 AN69 artificial kidney; blood flow rate was 200 ml/min, and dialysate/filtrate flow rate was 25 ml/min . Sieving (SC) and diffusion (DC) co-efficients, for hemofiltration and hemodialysis, respectively, were identical for urea (MW 60; 1.01 +/- 0.05 vs 1.01 +/- 0.07) and creatinine (MW 113; 1.00 +/- 0.09 vs 1.01 +/- 0.06), and clearance equated with dialysate/filtrate flow . There was a modest difference in uric acid clearance (MW 168; SC 1.01 +/- 0.04 vs DC 0.97 +/- 0.04; p < 0.05) . Vancomycin (MW 1,800) removal was 19% greater during filtration compared with dialysis (SC 0.87 +/- 0.10 vs DC 0.74 +/- 0.06; p < 0.01) . For small solutes, the two modalities were equivalent . Vancomycin clearance was appreciably greater with hemofiltration, which is consistent with a greater potential for convection-based therapy in the removal of uremic and other middle molecules.

Ann Pharmacother, 1994 Jun, 28(6), 723 - 6
Vancomycin-induced neutropenia during treatment of endocarditis in a pediatric patient; Shinohara YT et al.; OBJECTIVE: To report a case of reversible vancomycin-associated neutropenia occurring during long-term therapy with vancomycin using weight and age-adjusted dosing . CASE SUMMARY: A 2-year-old boy was started on vancomycin therapy for presumed endocarditis resulting from his ventriculoseptal defect . After 18 days of treatment, neutropenia with an absolute neutrophil count (ANC) of 990 x 10(6) cells/L was noted . The neutropenia progressed over the next 3 days and reached a nadir concentration of 459 x 10(6) cells/L . Vancomycin therapy was discontinued after 17 days (antibiotic day 20) . A rise in the ANC occurred within 2 days of discontinuation . An improved ANC of 1672 x 10(6) cells/L occurred within 5 days . Vancomycin serum concentrations remained within an acceptable range: a peak of 30 micrograms/mL and a trough of 9 micrograms/mL . DISCUSSION: Case reports in the literature of vancomycin-associated neutropenia in adults were briefly reviewed and compared . The onset and resolution and mechanism of vancomycin-induced neutropenia were studied . The potential relationship between vancomycin, weight-, and age-adjusted dosing and the occurrence of neutropenia in our pediatric patient was postulated . CONCLUSIONS: Vancomycin is identified as a possible cause of drug-induced neutropenia . More data are needed that clearly indicate vancomycin as the offending agent in children . The vancomycin-induced neutropenia is believed to be immunologically based and independent of drug concentrations.

Ann Pharmacother, 1994 May, 28(5), 572 - 6
Stability of ceftazidime and vancomycin alone and in combination in heparinized and nonheparinized peritoneal dialysis solution; Vaughan LM et al.; OBJECTIVE: To examine the stability of ceftazidime, vancomycin, and heparin, alone and in combination, in dialysis solution over six days at three temperatures . DESIGN: Nine 250-mL Dianeal PD-2 dextrose 1.5% bags were prepared with ceftazidime, vancomycin, and heparin alone and in combination at set concentrations of 100 micrograms/mL, 50 micrograms/mL, and 1 unit/mL, respectively . Three bags of each mixture were stored at 4, 25, and 37 degrees C . Duplicate samples for analysis were removed from each bag at the following time points: premix, 0, 12, 24, 48, 72, 96, 120, and 144 hours . MAIN OUTCOME MEASURES: Each sample was examined visually for signs of cloudiness and precipitation . Each sample was analyzed by stability-indicating HPLC assay for ceftazidime and vancomycin, with stability defined as less than 10 percent degradation of drug over time . RESULTS: No color change or precipitation was observed in any bag . Vancomycin with or without heparin was stable for 5-6 days at 4, 25, and 37 degrees C . Ceftazidime with and without heparin was stable for 6 days at 4 degrees C, 4 days at 25 degrees C, and less than 12 hours at 37 degrees C . Vancomycin plus ceftazidime with and without heparin was stable for 6 days at 4 degrees C and 25 degrees C, and 4-5 days at 37 degrees C . Ceftazidime plus vancomycin with or without heparin was stable for 6 days at 4 degrees C, 2-3 days at 25 degrees C, and 12 hours at 37 degrees C . CONCLUSIONS: Bulk preparations of ceftazidime and vancomycin, alone and in combination and with or without heparin in Dianeal PD dextrose 1.5% solution, are sufficiently stable for use up to 6 days under refrigeration or 48 hours at room temperature.

J Antimicrob Chemother, 1994 Apr, 33(4), 811 - 21
A comparative assessment of vancomycin-associated nephrotoxicity in the young versus the elderly hospitalized patient; Vance-Bryan K et al.; The incidence of vancomycin-associated nephrotoxicity was determined in a younger (age < 60 y) versus elderly (age > or = 60 y) hospitalized adult population to identify associated drug- and nondrug-related risk factors . Nephrotoxicity was defined as an acute increase in serum creatinine of > or = 44.2 mumol/L if baseline serum creatinine was < or = 221 mumol/L or an increase in serum creatinine of > or = 88.4 mumol/L if baseline serum creatinine > 221 mumol/L . A total of 289 patients, 141 younger (mean age, +/- S.D . 37.9 +/- 12.4 y) and 148 elderly (73.6 +/- 8.5 years), was retrospectively reviewed . Nephrotoxicity occurred in 7.8% younger vs 18.9% elderly patients (P = 0.003) . Using multivariate logistic regression models for the pooled patient population, concurrent loop diuretic use was significantly associated with vancomycin-associated nephrotoxicity (relative risk (R.R.) = 5.06); for the younger population, only concurrent amphotericin B use was significantly associated with vancomycin-associated nephrotoxicity (R.R . = 6.65); and for the elderly population, only concurrent loop diuretic use was significantly associated with vancomycin-associated nephrotoxicity (R.R . = 9.70) . These data suggest that elderly patients are at significantly greater risk of vancomycin-associated nephrotoxicity than are younger patients . However, because age was not a significant risk factor for nephrotoxicity in comparing the pooled vancomycin-associated nephrotoxicity group compared to the non-nephrotoxicity group, the differences observed between age groups probably reflect differences in risk factor prevalence.

Clin Infect Dis, 1994 Apr, 18(4), 533 - 43
Serum vancomycin concentrations: reappraisal of their clinical value; Cantu TG et al.; Although monitoring serum vancomycin concentrations in clinical practice is commonplace, the data supporting this practice are meager . The rationale for monitoring these concentrations is to improve the effectiveness and/or reduce the toxicity of the drug . However, there are no data to suggest that monitoring serum vancomycin concentrations improves the effectiveness of therapy . In addition, despite many case reports of vancomycin-associated nephrotoxicity and ototoxicity, it is unclear whether this agent truly causes such conditions . Moreover, there is no evidence that adherence to specific ranges of vancomycin concentrations will preclude these events . Finally, vancomycin pharmacokinetics are sufficiently predictable that adequate serum drug concentrations can be obtained with dosing methods that take into account the patient's age, weight, and renal function . Safe and effective vancomycin dosage regimens can be constructed with these empirical dosing methods, whereas monitoring vancomycin levels increases the cost of therapy without improving the safety or efficacy of treatment.

Am J Hosp Pharm, 1994 Mar 15, 51(6), 798 - 800
Vancomycin pharmacokinetics in middle-aged and elderly men; Leonard AE et al.; A study was conducted to establish new values for vancomycin volume of distribution (V) and clearance (CL) that would result in more accurate predictions of serum vancomycin concentrations (SVCs) . All patients who had received vancomycin at a Veterans Affairs medical center were divided into two groups: those for whom SVCs had been measured between August 13, 1990, and February 12, 1991 (group 1), and those for whom SVCs had been measured between February 13, 1991, and October 4, 1991 (group 2) . Data for group 1 were used to derive new values for V and CL by means of Bayesian analysis . SVCs for each patient in group 2 were calculated by using the new pharmacokinetic values, and the predictive performance of these values was compared with that of accepted population values (V = 0.70 L/kg, CL = 0.65 times creatinine clearance {CLcr}) . Forty-four men with 95 SVCs were entered into group 1, and 69 men with 171 SVCs were entered into group 2 . The mean +/- S.D . ages for groups 1 and 2 were 61.6 +/- 12.9 and 64.3 +/- 11.3 years, respectively . There were no significant differences between the groups . V could not be evaluated because of inadequate sample size . Compared with the method employing the conventional CL value, the method that assumed a CL of 0.90CLcr was more precise and less biased in estimating group 2 SVCs . In middle-aged and elderly men, use of a CL value of 0.90CLcr produced estimates of serum vancomycin concentration that were more precise and less biased than did use of a CL value of 0.65CLcr.

Pharmacotherapy, 1994 Mar-Apr, 14(2), 196 - 201
Individualizing vancomycin dosing regimens: an evaluation of two pharmacokinetic dosing programs in critically ill patients; Fernandez de Gatta MM et al.; We evaluated the predictive performance of two commercial computer programs (Abbott and Simkin) for pharmacokinetic dosing of vancomycin in 50 critically ill patients, 40 with hematologic malignancies and 10 in intensive care . Predictive performance was assessed for both pharmacokinetics and forecasting vancomycin serum levels by using a set of peak and trough drug levels per patient . The effect of renal function and serum sampling (steady state, nonsteady state) on predictive performance of both programs was also analyzed . No statistically significant differences were found between the programs for predicting either pharmacokinetics or serum levels, regardless of a patient's renal function or serum sampling . The Abbott and Simkin programs were similar for individualizing vancomycin dosage regimens.

Am J Hosp Pharm, 1994 Feb 1, 51(3), 321 - 7
Bayesian and threshold probabilities in therapeutic drug monitoring: when can serum drug concentrations alter clinical decisions?
Schumacher GE, Barr JT.
The use of Bayesian and threshold probabilities is examined with respect to the range of probabilities of toxicity for which obtaining a patient's serum drug concentration leads to information that is potentially useful in altering a clinical decision . For the situation of potential drug-induced toxicity, three threshold probabilities are needed to characterize the decision process: the decision threshold for deciding between continuing and discontinuing the drug regimen, the testing threshold that separates the decision to continue the regimen without testing the serum drug concentration from the decision to test before deciding, and the companion testing threshold that separates the decision to discontinue the regimen without testing from the decision to test before deciding . For digoxin, theophylline, aminoglycosides, vancomycin, and phenytoin, three prototypical decision threshold probabilities, 0.33, 0.2, and 0.1, are used, along with published true-positive and false-positive rates, to calculate serum concentration testing thresholds for each drug . Practitioners can be more effective in their use of serum drug concentration data when a Bayesian approach to probability assessment is used in conjunction with testing thresholds.

Ther Drug Monit, 1994 Feb, 16(1), 37 - 41
Bayesian forecasting of serum vancomycin concentrations with non-steady-state sampling strategies; Rodvold KA et al.; The application of three non-steady-state sampling strategies and the fitting of either three or five pharmacokinetic parameter estimates by a two-compartment Bayesian forecasting program was evaluated retrospectively in 27 adult patients with stable renal function . Sampling strategies included a single midpoint concentration, a set of peak and trough concentrations, and three serial vancomycin concentrations . The most precise and least-bias predictions of steady-state peak vancomycin concentrations were observed by using population-based parameter estimates {mean prediction error (ME) = -0.40 and mean absolute error = 5.77} . The addition of non-steady-state feedback concentration(s) did not provide additional information for predictions of future steady-state peak concentrations . The least-bias prediction of steady-state trough vancomycin concentrations was seen when a single midpoint non-steady-state concentration was used (ME = 0.92 and -0.17 for five and three fitted parameter estimates, respectively) . The MEs of serial and peak and trough feedback strategies were similar in magnitude to those obtained using population parameters, but in opposite directions (underprediction vs . overprediction, respectively) . The fitting of only three parameters produced results similar to those using five parameters . The results from this study confirm our previous evaluation that non-steady-state concentrations provide very minimal information to Bayesian forecasting of future steady-state concentrations.

Int J Artif Organs, 1994 Jan, 17(1), 19 - 26
Vancomycin dosing in haemodialysis patients and Bayesian estimate of individual pharmacokinetic parameters; Keller F et al.; A dose reduction of vancomycin to 1000 mg once a week usually is recommended for haemodialysis patients . Our modified dosing schedule consists of a loading dose of 1000 mg and a maintenance dose of 500 mg administered 3 times a week after haemodialysis . Different vancomycin regimens were retrospectively evaluated by therapeutic drug monitoring and bayesian parameter estimates in 39 dialysis patients . The mean (+/- SD) trough level in 7 patients receiving only the conventional dosage regimen was significantly lower than in 17 patients strictly treated by the modified schedule (7 +/- 4 versus 17 +/- 8 mg/L; p = 0.001) . The corresponding peaks were low in both groups and no different (23 +/- 10 versus 27 +/- 12 mg/L) . The one week average vancomycin clearance was significantly lower in the conventional dosage group compared to the modified dosage group (6 +/- 3 versus 10 +/- 3 ml/min; p = 0.001) . High-flux dialysers were not used in the conventional dosage group but for 30 percent of the procedures in the modified dosage group, where the vancomycin one week average elimination half-life was 66 hours (+/- 18) and the volume of distribution 50 litres (+/- 5) . As compared to the bayesian programme, NONMEM calculated comparable pharmacokinetic parameters but could be applied only in 5 cases with a sufficient number of concentration measurements . Ototoxicity occurred in 1 patient, whereas vancomycin treatment was judged as ineffective against infection in 5 of the 39 patients . Their troughs were below 15 mg/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathology, 1994 Jan, 26(1), 56 - 8
Catheter-related septicemia caused by a vancomycin-resistant Coryneform CDC group A-5; Campbell PB et al.; A case of catheter-related septicemia, due to Coryneform CDC group A-5, in an 11 yr old boy with acute myelomonocytic leukemia is discussed . The child failed to respond to initial antibiotic therapy, even following the addition of vancomycin . Laboratory studies later showed the organism to be vancomycin resistant but cefotaxime susceptible.

Kidney Int, 1994 Jan, 45(1), 232 - 7
Vancomycin redistribution: dosing recommendations following high-flux hemodialysis; Pollard TA et al.; Although increased vancomycin clearance has been reported with highly permeable hemodialysis membranes (such as polysulfone), failure to consider post-dialysis redistribution could lead to unnecessary dosage supplementation . In protocol 1, twelve hemodialysis patients admitted for vascular access thrombectomy received 15 mg/kg of vancomycin as surgical prophylaxis . Post-operatively, patients underwent high-flux hemodialysis (HFHD) for two hours using a Fresenius F-80 polysulfone dialyzer (QB = 417 +/- 49, QD = 800 ml/min) . Vancomycin's intradialytic clearance increased 13-fold compared to the patient's endogenous clearance (120 +/- 59 vs . 9 +/- 8 ml/min, respectively) yet dialysate recovery indicated that only 17% of body stores were removed (179 +/- 70 mg) . Although serum vancomycin levels decreased 33% during HFHD, vancomycin levels increased in all patients following dialysis and the post-rebound values reached 87% of the pre-dialysis concentration . In protocol 2, eight outpatients receiving maintenance HFHD with a F-80 dialyzer (Kt/V = 1.29 +/- 0.08) were given 20 mg/kg of vancomycin immediately following dialysis on Monday; pre- and post-levels were measured during the next three dialysis treatments . The predialysis serum vancomycin levels were > 7.5 micrograms/ml (9.7 +/- 1.0 micrograms/ml; range 8.0 to 11.0) in all patients the following Monday . Thus, vancomycin clearance is increased during HFHD, but redistribution post-HD minimizes changes in serum levels . We recommend a 20 mg/kg i.v . loading dose and subsequent doses of 15 mg/kg every seven days; to account for individual variability, weekly vancomycin levels should be drawn before dialysis.

Int Urol Nephrol, 1994, 26(2), 223 - 8
Comparison of the effects of three haemodialysis membranes on vancomycin disposition; Alwakeel J et al.; Polysulfone (PSF) and polyacrylonitrile (PAN) were recently introduced haemodialysis (HD) membranes . The effect of each on vancomycin disposition was compared with cuprophan (SCE) in 12 chronic HD patients who received 14 infusions . Vancomycin (1 g) was infused over 1 hour, followed by three 4-hour HD sessions over 5 days, beginning 1 hour after the end of infusion . The intradialytic clearances of vancomycin were 73, 54 and 15 ml/min for PSF, PAN and SCE, respectively . At the end of the third HD session, vancomycin concentration dropped to subtherapeutic level (< 7.5 micrograms/ml) only in patients dialysed with PSF and PAN . The corresponding elimination half-lives (t1/2 beta) were 61, 60 and 86 hours for the three membranes, respectively . According to these findings, vancomycin should be given every three HD sessions for PSF and PAN . The dosage interval should be extended up to every 5 HD sessions for patients on SCE . The peak (mean +/- S.D.) obtained one hour after the end of infusion was 34.2 +/- 11.4 micrograms/ml, which is within the therapeutic range.

Proc Annu Symp Comput Appl Med Care . 1994;:972.
Pharmaco-informatics: more precise drug therapy from "multiple model" (MM) stochastic adaptive control regimens: evaluation with simulated vancomycin therapy; Jelliffe RW et al.; MM stochastic control of dosage regimens permits essentially full use of information, either in a population pharmacokinetic model or a Bayesian updated MM parameter set, to achieve and maintain selected therapeutic goals with optimal precision . The regimens are visibly more precise than those developed using mean parameter values . Bayesian MM feedback has now also been implemented.

J Basic Microbiol, 1994, 34(6), 387 - 99
Effect of inhibitors of cell envelope synthesis on beta-sitosterol side chain degradation by Mycobacterium sp . NRRL MB 3683; Sedlaczek L et al.; The role of the lipid bilayer and the peptidoglycan of the mycobacterial cell wall in the permeation of beta-sitosterol into the cell and its transformation to androst-1-ene-3,17-dione (AD) and androsta-1,4-diene-3,17-dione (ADD) was studied . Specific inhibitors were used at concentrations affecting the biosynthesis of the assumed target structures, but causing only partial cell growth inhibition or exerting no effect on growth . m-Fluorophenylalanine and DL-norleucine which are known to disorganize the biosynthesis of amphipatic components of the outer layer of the lipid bilayer, used at concentrations 250 micrograms/ml and 400 micrograms/ml, respectively, increased the formation rate of AD+ADD from 0.3 (control) to 0.7 and 0.8 mg products/g dry weight/h . The disorganization of the underlying mycolyl-arabinogalactan structure by the action of the ethambutol at the concentration 40 micrograms/ml, at which the cell growth was apparently not affected, caused the decrease of the product formation from 135 mg/l to 70 mg/l . In the presence of isoniazid (350 micrograms/ml) only trace amounts of AD accumulated during 48 hours of transformation indicating much lower activity than that of the intact cells . The most effective among the tested inhibitors of peptidoglycan synthesis were glycine (15 mg/ml) and vancomycin (150 micrograms/ml) which enhanced the transformation activity of the treated cells nearly three times . Increased transformation rate was also obtained by the action of colistin at concentrations ranging from 10 micrograms/ml to 15 micrograms/ml.

Ophthalmic Res, 1994, 26(4), 202 - 6
Previous ocular compression increases intraocular penetration of systemic drugs; Murube J et al.; Intraocular drug penetration is dependent upon the physical and chemical characteristics of the drug, the manner of drug administration and the drug's ability to pass through the blood/aqueous barrier . Most systemically administered drugs do not achieve intraocular therapeutic levels . The authors present a new method to increase the intraocular concentration of intravenously administered drugs based on the premise that ocular hypotony by ocular compression produces a temporary break in the blood/aqueous barrier during the period of hypersecretion that follows to regain normal intraocular pressure levels . Vancomycin introduced parenterally was used as the drug model . The right eye of 22 rabbits served as experimental eye, while the left eye served as control . The concentrations of vancomycin in the aqueous humor half an hour after intravenous injection of 40 mg/kg vancomycin in 50 ml of lactated Ringer's solution were as follows: 30.17 +/- 20.68 micrograms/ml in the right (hypotonized) eyes and 4.92 +/- 3.33 micrograms/ml in the left (control) eyes . The difference in drug levels between the two sets of eyes had a high statistical significance at p = 0.001.

Eur J Pediatr Surg, 1993 Dec, 3 Suppl 1, 17 - 8
Control of hydrocephalus by endoscopic choroid plexus coagulation--long-term results and complications; Pople IK et al.; Endoscopic choroid plexus coagulation has been used for the control of hydrocephalus regularly at this unit for the past 20 years . 156 of these operations have been performed on 116 patients and the aim of this study was to assess the rate of long-term control of hydrocephalus and the complications of the procedure . Data have so far been found for 98 patients with a median age at operation of 5 months (range 1 week-30 years) . After a mean follow-up period of 10.5 years there were 32 (33%) patients continuing without a ventricular shunt . One patient developed papilloedema and required ventricular shunting 16 years after choroid plexus coagulation . There were no deaths resulting from operation . 5 patients developed post-operative meningitis and 3 patients had post-operative infections of implants (2 shunts and 1 reservoir) . No cases of post-operative meningitis have occurred since vancomycin and gentamicin have been added to the solution used to perfuse the ventricles after operation (28 cases) . Other complications included post-operative fits (2), respiratory arrest in a premature baby (10, low-pressure state (1), blocked or leaking external ventricular drain (4), drain displacement (4), subdural effusion (1) and per-operative minor ventricular bleeding forcing abandonment of the procedure (2).

Neonatal Netw, 1993 Dec, 12(8), 27 - 30
Safety of vancomycin with or without gentamicin in neonates; Linder N et al.; Short- and long-term side effects of vancomycin, or the combination of vancomycin and gentamicin, were retrospectively evaluated for 65 treatment courses in 47 premature infants who were exposed to high vancomycin serum concentrations . Thirty-five treatment courses involved treatment with the combination; 30 courses involved treatment with vancomycin alone . No immediate side effects were noted . Nephrotoxicity, defined as an increase in serum creatinine 0.5 mg/dl or more above baseline, was found in only 1 patient receiving vancomycin as the only antibiotic; that patient had pre-existing renal dysfunction . Three treatment courses involving the vancomycin-gentamicin combination resulted in nephrotoxicity; renal function returned to normal by 14 days after treatment . Thrombocytopenia was noted in 5 patients, but none exhibited clinical bleeding . Low platelet counts persisted throughout treatment, but by two weeks after treatment, this was resolved . In conclusion, the use of vancomycin or the combination of vancomycin and gentamicin in seriously ill premature infants is usually safe . The adverse effects noted were reversible, and monitoring creatinine and platelet counts during treatment is recommended.

Ann Pharmacother, 1993 Nov, 27(11), 1383 - 8
Drug disposition in neonates with patent ductus arteriosus; Gal P et al.; OBJECTIVE: To review the literature on the physiologic changes created by neonatal patent ductus arteriosus (PDA) and the potential impact on drug disposition in these infants . DATA SOURCES: An Index Medicus and bibliographic search of the English-language literature pertaining to neonatal PDA and drug usage in newborns . DATA SYNTHESIS: PDA in premature infants is associated with a variety of physiologic changes that could alter drug disposition . Perfusion of drug-elimination organs (i.e., liver and kidney) may be diminished, resulting in decreased drug elimination . Further, the general fluid overload state associated with PDA may result in larger volumes of distribution (Vd), and dilutional effects for many drugs . Drug absorption, Vd, tissue penetration, and clearance may be affected by the physiologic changes incurred by a PDA . Although the pharmacokinetics of several categories of therapeutic agents may be affected by a PDA, disposition changes with the aminoglycosides and indomethacin have been the best documented . The most reliable pharmacokinetic change appears to be related to drug Vd . The interpretation of many of these studies is confounded by a potential drug interaction with the concurrent administration of indomethacin for PDA closure . CONCLUSIONS: Close therapeutic drug monitoring is indicated in newborns with PDAs as abrupt changes in drug disposition can occur with PDA closure . PDA-induced changes in specific pharmacokinetic parameters of agents such as the aminoglycosides, indomethacin, and perhaps vancomycin may prove to be a valuable diagnostic adjunct for the identification of babies with undiagnosed PDA . More research into this pharmacophysiologic aspect of pharmacokinetics is warranted.

Ann Pharmacother, 1993 Nov, 27(11), 1346 - 8
Correlation of aminoglycoside and vancomycin pharmacokinetic parameters; Wragge TM et al.; OBJECTIVE: To investigate a correlation between the elimination rate constants (Ke) of aminoglycosides (AG) and vancomycin; to investigate the correlation between actual Ke and creatinine clearance (Clcr) for AG versus vancomycin; to investigate the calculated versus actual Ke for AG and vancomycin; and to investigate a correlation between volumes of distribution (Vd) between AG and vancomycin . DESIGN: Retrospective data collection . METHODS: Patients in our institution who received AGs or vancomycin concomitantly or within six weeks of each other were identified retrospectively . Patient subpopulations were identified and analyzed collectively as well as individually . Steady-state serum concentrations of AG and vancomycin (more than four half-lives) were obtained and kinetic parameters (Ke, Vd) were calculated using first-order pharmacokinetic equations . Linear regression was used to determine correlation coefficients . RESULTS: In the total population and all subpopulations, the correlation between Ke of AG and vancomycin was superior to the correlation between Ke and Clcr . The correlations (r2) between Ke for AG and vancomycin in the total, general medicine, oncology, and intensive care units (ICU) populations were 0.572, 0.878, 0.349, and 0.561, respectively . The correlations (r2) between Ke and Clcr for AG in the total, general medicine, oncology, and ICU populations were 0.235, 0.430, 0.005, and 0.238, respectively . The correlations (r2) between Ke and Clcr for vancomycin in the total, general medicine, oncology, and ICU populations were 0.300, 0.407, 0.055, and 0.309, respectively . CONCLUSIONS: The correlation between Ke of AG and vancomycin may be beneficial for predicting Ke of vancomycin when AG concentrations have already been obtained or vice versa, and may give more accurate estimations of dosing intervals and require less time adjusting, ordering, and interpreting concentrations and dosages.

J Pediatr Gastroenterol Nutr, 1993 Oct, 17(3), 291 - 7
Development of lipolytic activity in gastric aspirates from premature infants; Lee PC et al.; Neonates, having little or no pancreatic lipase, would have a compromised ability to digest lipids if not for lingual and gastric lipases . To document the postnatal developmental profile of preduodenal lipase activity, 350 premature infants who were at various gestational ages and who had an orogastric tube had their gastric aspirates collected . Two hundred one infants had their gastric aspirates collected within 12 h after delivery . Serial collections were performed in 25 infants at various postnatal ages . Gastric aspirates collected from premature infants had a pH activity profile similar to that of lingual and gastric lipase but different from that of pancreatic lipase, indicating that their origin was from the tongue and/or stomach . Lipolytic activity and pH of these aspirates were quite variable, but no correlation was found between pH and enzyme activity . At birth, lipase activity was lower in the younger infants (< or = 26 weeks, n = 13) . It increased to a peak at 30-32 weeks of gestational age and then declined to a lower level at term (> or = 40 weeks, n = 40) . Postnatally, a composite plot of the serially collected aspirates also showed a predominant peak at 28-33 weeks of age . Comparison among siblings in twins (n = 12 pairs) and triplets (n = 3) showed great variations in their lipolytic activities, suggesting that the hereditary factor is not a major determinant . Various combinations of antibiotic medications (ampicillin, cefotaxime, gentamicin, and vancomycin) and drugs (dexamethasone, heparin, furosemide, phenobarbital, albumin, and vitamin K) apparently had no effect on the level and development of gastric lipolytic activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimicrob Agents Chemother, 1993 Oct, 37(10), 2139 - 43
Vancomycin skin tests and prediction of "red man syndrome" in healthy volunteers; Polk RE et al.; The purpose of the present study was to assess the cutaneous response to intradermally administered vancomycin in healthy adults and to determine whether the magnitude of the cutaneous response correlated to the severity of "red man syndrome" (RMS) following intravenous administration of vancomycin to the same subjects . Eleven healthy males were skin tested with intradermally administered histamine and saline controls and intradermally administered vancomycin at different concentrations . Vancomycin caused a dose-dependent area of flare in all subjects . The sigmoidal maximal flare model was used to fit each dose-response curve, and cutaneous responsiveness to vancomycin was quantified by various methods, including the flare area at each dose, maximum flare area (maximal flare), dose required to produce 50% of maximum flare, dose required to produce a flare area of 400 mm2, and the slope of the dose-response curve . One week after skin testing, subjects received an infusion of vancomycin, 15 mg/kg of body weight over 60 min . For the assessment of the severity of RMS, we used previously described methods . Although all subjects experienced erythema from the intravenously administered vancomycin and 10 subjects had pruritus, there was no significant correlation between vancomycin skin test results and the severity of RMS . We conclude that vancomycin skin tests do not predict the severity of RMS . In addition, vancomycin skin tests may be of no benefit for assessing immunoglobulin E-mediated allergy to vancomycin, since all subjects had a positive reaction at concentrations of > or = 10 micrograms/ml.

J Clin Microbiol, 1993 Oct, 31(10), 2764 - 8
Growth of 28 Legionella species on selective culture media: a comparative study; Lee TC et al.; We compared the growth of 28 Legionella spp . on four manufacturers' buffered charcoal-yeast extract (BCYE) agar media and selective BCYE media that contained polymyxin B, anisomycin, and vancomycin or cefamandole . With BCYE as a "gold standard," growth for Legionella pneumophila was significantly better than for the nonpneumophila species on all media tested . L . pneumophila and 24 other Legionella spp . grew on vancomycin-containing media, while L . santicrucis, L . rubrilucens, and L . erythra grew poorly . In contrast, 11 of 28 species (notably L . micdadei and L . bozemanii) did not grow on cefamandole-containing media and 8 of 28 species only grew marginally . We demonstrated that selective BCYE media that contain vancomycin or cefamandole may not support the growth of all Legionella spp . One commercial manufacturer's media were consistently suboptimal . Laboratories should not rely on a manufacturer's quality control testing in lieu of their own.

Ann Pharmacother, 1993 Oct, 27(10), 1187 - 9
Inadvertent intravenous administration of an elemental enteral nutrition formula; Malone M et al.; OBJECTIVE: To report a case of intravenous infusion of an elemental enteral nutrition formula . CASE SUMMARY: A 65-year-old woman with a high-output jejunostomy required fluid and electrolyte replacement via a central line and enteral nutrition support via a gastrostomy tube . She inadvertently received 160 mL of half-strength elemental enteral nutrition formula (Vivonex TEN) via her central venous catheter . After four hours of the infusion, the patient felt ill and was found to by hypotensive and pyrexic . Over the next 24 hours she developed severe back pain and diffuse muscle tenderness . Her creatine kinase concentration was mildly elevated and there were no electrocardiographic changes . There was no rise in serum amylase concentration . Her renal function deteriorated markedly over the following three hours but responded to hydration and diuretic therapy . Liver enzymes, slightly elevated prior to this event, remained unchanged . Blood cultures were negative, but prophylactic therapy with vancomycin and ceftazidime was instituted . The patient recovered and was discharged eight days later . DISCUSSION: Previous reports of inadvertent intravenous administration of enteral feedings have described such complications as osmolarity, microembolism, hypersensitivity, and septicemia . This patient's nonfatal outcome may have been related to the infusion of the enteral formula via the central rather than the peripheral route, the infusion of an elemental rather than a whole protein formula, and the use of sterile water to reconstitute the formula . CONCLUSIONS: Particular care should be taken when a patient has more than one catheter implanted on the chest or abdomen (e.g., central venous or peritoneal dialysis catheter) . It is important that inservice training is provided and written protocols are available for the safe infusion of enteral formulas.

Int J Syst Bacteriol, 1993 Oct, 43(4), 715 - 20
Amycolatopsis alba sp . nov., isolated from soil; Mertz FP et al.; A new Amycolatopsis species isolated from soil produces a new glycopeptide antibiotic related to vancomycin . Traditional taxonomic methods and contemporary fatty acid analysis techniques were used to establish the position of this species . The hyphae fragment extensively when the organism is cultured in liquid media . The organism is characterized by white aerial hyphae that bear long chains of cylindrical conidia . The reverse side is yellowish brown; a faint light brown soluble pigment is occasionally produced . The organism has a type IV cell wall (meso-diaminopimelic acid), a type A whole-cell sugar pattern, and a type PII phospholipid pattern . Mycolic acids are not present in whole-cell hydrolysates . The major menaquinone is MK-9(H4); there is also a minor amount of MK-8(H4) . The name proposed for this new species is Amycolatopsis alba . The type strain is strain A83850 (= NRRL 18532).

Otolaryngol Clin North Am, 1993 Oct, 26(5), 821 - 8
Ototoxicity of vancomycin and analogues; Brummett RE; This article details clinical reports and animal studies of ototoxicity associated with vancomycin and its analogues . From these studies, the ototoxicity of these agents is still not clear . In the author's opinion, vancomycin must affect the auditory system in a manner that results in augmentation of the usual ototoxicity of aminoglycoside antibiotics . This postulated effect may manifest as a temporary hearing loss in humans . More studies are needed, however, before a definitive conclusion can be made.

J Clin Pharmacol, 1993 Oct, 33(10), 918 - 22
Comparison of vancomycin pharmacokinetics in hospitalized elderly and young patients using a Bayesian forecaster; Guay DR et al.; Limited data have been published that compare the pharmacokinetic parameters of vancomycin in elderly versus young patients . This study was designed to assess vancomycin pharmacokinetics in 148 elderly (> or = 60 years of age) and 140 young (18-59 years of age) hospitalized infected patients . Serum vancomycin concentrations were determined using fluorescence polarization immunoassay . Serum concentration-versus-time data were fitted to a two-compartment Bayesian forecasting program . Elderly versus young vancomycin pharmacokinetic parameters derived were as follows (patients with serum creatinine < or = 1.5 mg/dL); mean +/- standard deviation terminal disposition half-life (t1/2) of 17.8 +/- 11.8 versus 7.5 +/- 6.7 hours, respectively, P < .05; volume of distribution (Vz) of 74.2 +/- 32.3 versus 67.0 +/- 30.7 L, respectively, P = .16; and total body clearance (CL) of 0.71 +/- 0.41 versus 1.22 +/- 0.50 mL/min/kg, respectively, P < .05 . Comparing subjects with normal serum creatinine values (< or = 1.5 mg/dL), the elderly required smaller daily doses as compared with the young group to maintain target peak and trough vancomycin serum concentrations (18.2 +/- 5.8 verus 25.2 +/- 7.8 mg/kg/day, P < .05) . Stepwise multiple regression models for the pharmacokinetic parameters were developed to assess the predictive power of age, controlling for the effects of gender, total body weight, serum creatinine, and creatinine clearance . Age was consistently an independent and significant predictor of t1/2, Vz, and CL . These data demonstrate that elderly patients exhibit significant differences in vancomycin pharmacokinetic parameters compared with young patients and constitute a patient population in need of individualized vancomycin dosing due to substantial heterogeneity in physiologic and pharmacokinetic parameters.

J Infect Dis, 1993 Sep, 168(3), 773 - 6
Prospective evaluation of red man syndrome in patients receiving vancomycin; O'Sullivan TL et al.; The incidence of red man syndrome (RMS) and its relationship to histamine were investigated in patients receiving vancomycin or an aminoglycoside (control) . During the 60-min infusions, patients were observed for signs or symptoms consistent with RMS, including pruritus, erythema, angioedema, and cardiovascular depression . Four blood samples were obtained at 30-min intervals for determination of histamine concentrations . One (3.4%) of 29 vancomycin- and none of 8 aminoglycoside-treated patients had documented RMS . The mean maximum changes in blood pressure and heart rate were not significant and were similar between groups . Increases in histamine concentrations to > 1 ng/mL occurred only in 25% (2/8) of the aminoglycoside patients . Vancomycin induced minimal changes in histamine concentrations despite the occurrence of RMS . From these observations, it appears that RMS is not closely associated with histamine release, and elevated histamine concentrations do not predict RMS . Further investigation is needed to elucidate other mediators of RMS.

Clin Pharmacokinet, 1993 Sep, 25(3), 243 - 57
Drug dosage in end-stage renal disease (ESRD) patients undergoing haemodialysis . A predictive study based on a microcomputer program; Mac-Kay MV et al.; Drug dosage in end-stage renal disease (ESRD) patients undergoing haemodialysis is a very complex problem because of numerous variables relating to the patient, the type of drug administered and the type of dialysis and dialyser . We carried out a multifactorial study of these parameters using a microcomputer program written in BASIC . Three sets of data were fed into the computer: those relating to the biophysical characteristics of the patient, the type of dialysis and dialyser to be used, and others relating to the chemical and pharmacokinetic characteristics of the drug . From these, a predictive intravenous dosage regimen (bolus and infusion) was compiled for each ESRD patient . To check the program we used 2 drugs (tobramycin and vancomycin) and several types of dialyser . The findings were that, with tobramycin, an ESRD patient should be given different postdialytic doses, depending on the type of dialyser used . The maintenance doses calculated by the program were similar to those usually administered to patients receiving clinical treatment with this drug . In the case of vancomycin, the program calculated the clearance value in vivo through the 'Hemoflow F60' dialyser with a polysulphone membrane . The computer program calculated the maintenance dosage of vancomycin that should be given after each dialysis cycle so that its concentration did not fall below its minimum therapeutic concentration.

Agents Actions, 1993 Sep, 40(1-2), 28 - 36
Mechanisms of vancomycin-induced histamine release from rat peritoneal mast cells; Horinouchi Y et al.; The mechanisms of vancomycin (VCM)-induced histamine release were studied with rat peritoneal mast cells . VCM (> 1 x 10(-3) M) released histamine from the isolated mast cells in a dose-dependent and noncytotoxic manner . In the absence of extracellular Ca2+, the histamine release was reduced markedly . When the intracellular Ca2+ was depleted, it was further decreased . The Fura-2-loaded single mast cells showed a biphasic increase in the intracellular Ca2+ concentration ({Ca2+}i) by VCM: the first transient and the second sustained components . In the absence of extracellular Ca2+, the transient component was unchanged, while the sustained component was eliminated completely . The IP3 content in the mast cells increased within 10 s after the application of VCM . These results suggest that VCM release histamine from rat peritoneal mast cells via an IP3 production and increase in {Ca2+}i.

Ther Drug Monit, 1993 Aug, 15(4), 263 - 6
Preliminary studies of the effects of extracorporeal membrane oxygenator on the disposition of common pediatric drugs; Dagan O et al.; There is an increased use of extracorporeal membrane oxygenation (ECMO) in the last 15 years for critically ill neonates . While receiving ECMO therapy, the critically ill infant needs various medications . We performed an in vitro study to evaluate the potential effect of the membrane oxygenator on drug extraction . Two closed ECMO circuits were set up at rates of 320 ml/min . One circuit was new and the other was used clinically for 5 days . Morphine at 8 ng/ml, gentamicin 10 micrograms/ml, vancomycin 40 micrograms/ml, phenobarbital 20 micrograms/ml, and phenytoin 20 micrograms/ml were injected into the circuit at 1-h intervals . Blood samples were drawn from the circuit at 10, 30, 60, and 240 minutes after injection . In the new circuit, drugs were eliminated as follows: vancomycin 36%, gentamicin 10%, phenobarbital 17%, phenytoin 43%, morphine 36% . In the used system, levels fell to a much smaller extent: vancomycin 11%, phenobarbital 6%, gentamicin 0%, phenytoin 0%, and morphine 16% . In a child receiving 20 micrograms/kg/h infusion of morphine, steady-state concentrations of 68.2 ng/ml fell to 11.6 ng/ml after changing the membrane . Our data indicate that the ECMO is associated with lowering of the concentrations of commonly used medications and that this process may depend partially on how new the membrane is . Before these changes may lead to new dosing guidelines for small children receiving ECMO, more experiments with new and used systems are warranted, as well as with different types of ECMO.

Curr Opin Ophthalmol, 1993 Aug, 4(4), 75 - 83
Storage, surgery, outcome, and complications of corneal and conjunctival grafts; Williams KA et al.; Corneal transplantation is still limited by a shortage of donor material, but the type of storage medium used once a cornea has been acquired is probably irrelevant to graft outcome . Vancomycin HCl shows promise as a supplement to gentamicin sulfate in storage media . New methods of HLA typing using donor ocular tissue have largely helped to overcome the problems associated with typing of cadaveric blood, but the value of HLA typing in improving corneal graft survival is now in doubt . Alternative regimens of immunosuppression are being tested in animal models, but there is still no consensus on the best ways to use existing agents such as corticosteroids . Rejection remains the most common cause of unsuccessful corneal grafting in large cohorts, but glaucoma and astigmatism also limit postoperative graft function . Limbal stem cell grafts are promising for the management of many ocular surface diseases and conjunctival limbal autografts for pterygia may be the most successful surgical method for preventing recurrence.

Ann Pharmacother, 1993 Jul-Aug, 27(7-8), 912 - 21
Vancomycin administration into the cerebrospinal fluid: a review; Luer MS et al.; OBJECTIVE: To discuss administering vancomycin directly into the cerebrospinal fluid (CSF) to treat serious central nervous system (CNS) infections . DATA SOURCES: References were obtained through an online search of MEDLINE, limited to material published in English . In addition, information was extracted from clinical trials, review articles, abstracts, and textbooks . STUDY SELECTION: Systematic evaluation of this topic in humans has not been done in a prospective manner . Related research articles describing the pathophysiology of CNS infections, intrathecal drug administration, and case reports of CSF vancomycin administration were reviewed . DATA EXTRACTION: Case reports regarding CSF vancomycin dosing were evaluated and included: drug dosing, infecting organism, infectious disease state, infectious outcome, CSF dynamics/flow abnormalities, methods of drug administration, drug monitoring, and toxicities . DATA SYNTHESIS: The results of this review are based on qualitative evaluations of anecdotal case reports and a basic understanding of intrathecal and intraventricular drug dosing principles . CSF administration of vancomycin is an effective means of bypassing the blood-brain barrier to achieve greater drug concentrations within the CSF . Current limitations to the CSF administration of vancomycin include a lack of data describing its safety, efficacy, and pharmacokinetics . CONCLUSIONS: CNS infections may require the CSF administration of vancomycin for successful eradication . Recommendations for dosing in the literature vary . Because of the potential toxicities associated with elevated CSF concentrations of vancomycin, dosing should be conservative.

Antimicrob Agents Chemother, 1993 May, 37(5), 1132 - 6
Serum protein-binding characteristics of vancomycin; Sun H et al.; A synthesis of studies of serum protein binding of vancomycin and its reported abnormal binding in serum with very high concentrations of immunoglobulin A (IgA) suggests that this antibiotic may be bound to more than one serum protein . Using an ultrafiltration method for separating free from bound drug and high-performance liquid chromatography to measure drug concentration, we studied the binding characteristics of vancomycin for alpha-1 acid glycoprotein, IgG, IgM, IgA, and albumin . The results showed that vancomycin does not bind to alpha-1 acid glycoprotein, IgG, or IgM . Major binding to albumin and IgA occurs, and total drug binding to serum proteins can be fully explained by binding to these two proteins . We calculated an N (number of binding sites per molecule) of 1.3 +/- 0.4 and a K (association constant) of 3.3 x 10(5) +/- 6.3 x 10(4) M-1 (NK = 4.3 x 10(5) M-1) for binding to IgA, whereas the corresponding NK value for albumin was only 527.5 M-1, indicating that vancomycin preferentially binds to IgA . Very high concentrations of IgA in serum (i.e., grams per deciliter), such as in patients with IgA myeloma, may result in the paradox of high (total) concentrations of vancomycin in serum that may be clinically ineffective.

Clin Pharmacokinet, 1993 May, 24(5), 362 - 79
Drug dosage in patients during continuous renal replacement therapy . Pharmacokinetic and therapeutic considerations; Reetze-Bonorden P et al.; The advantages of continuous haemofiltration and haemodialysis over intermittent haemodialysis for the treatment of acute renal failure are well recognised . In intensive care patients, 4 different continuous procedures, arteriovenous and venovenous haemofiltration (CAVH and CVVH) or haemodialysis (CAVHD and CVVHD), are employed . These effective detoxification treatments require knowledge of their influence on drug disposition . Data on kinetics of drugs during continuous treatment are scarce and limited almost exclusively to the oldest and least effective procedure (CAVH) . Selected dialysis membranes may adsorb drugs, as in the case of aminoglycosides . In addition, elimination of substances with large molecular weights may vary depending on the pore size of the membrane, as in the case of vancomycin . Thus, even if drug dosages can be based on pharmacokinetic studies, selection of a dialysis membrane not studied may cause unpredictable drug concentrations . With these limitations in mind and considering the available literature on pharmacokinetics in patients with renal failure, general guidelines for drug dosage during continuous renal replacement therapy can be given . In haemofiltration, drug protein binding is the major factor determining sieving, i.e . the appearance of the drug in the ultrafiltrate . In haemodialysis, diffusion is added to ultrafiltration, and therefore the saturation of the combined dialysate and ultrafiltrate will decrease further with increasing dialysate flow rate . In continuous haemofiltration or haemodialysis the extracorporeal clearance can be calculated by multiplying the saturation value (estimated or, better, measured) with the ultrafiltrate and dialysate flow rate . Dividing the extracorporeal clearance by the total clearance (including the nonrenal clearance) gives the fraction of the dose removed due to extracorporeal elimination . Whether dosage recommendations available for anuric patients have to be modified or not can be decided on the basis of this value . In case of high nonrenal clearance, the degree of saturation is without clinical significance . Based on these considerations guidelines have been constructed for the effect of extracorporeal elimination on more than 120 different drugs commonly used in intensive care patients.

Cornea, 1993 May, 12(3), 222 - 7
Stability and activity of vancomycin in corneal storage media; Lindquist TD et al.; Gentamicin is the only antibiotic currently added to commercially available corneal storage media . To reduce the potential for bacterial dissemination from donor corneal tissue to the recipient eye, we evaluated the addition of vancomycin to corneal storage media . When added to Dexsol at a concentration of 200 micrograms/ml, vancomycin levels were maintained, showing a 7% decrease in vancomycin concentration per month, measured < or = 90 days after its addition . Human corneas were stored in gentamicin-free Dexsol (Chiron Ophthalmics, Inc., Irvine, CA, U.S.A.) containing 150 micrograms/ml vancomycin . Corneal tissue levels of vancomycin determined by agar diffusion bioassay were 201, 226, 292 micrograms/ml at 1, 3, and 7 days of storage respectively, suggesting that corneal tissue concentrates vancomycin with time . No differences in endothelial cell count or cell death were seen in corneas stored in Dexsol (containing gentamicin) or Dexsol plus vancomycin when followed for < or = 14 days . Vancomycin added to corneal storage media should reduce the potential for endophthalmitis due to gentamicin-resistant organisms.

Pediatr Infect Dis J, 1993 Apr, 12(4), 300 - 4
Pharmacokinetics of intravenous vancomycin in pediatric cardiopulmonary bypass surgery; Hatzopoulos FK et al.; The purposes of this investigation were to characterize the disposition of vancomycin in children undergoing cardiopulmonary bypass (CPB) surgery and to determine whether a 15-mg/kg intravenous dose provides adequate serum concentrations during and after CPB . Six children (age range, 0.8 to 4.8 years) received intravenous vancomycin 15 mg/kg 1 to 2 hours before CPB surgery . Serial blood samples (mean, 10/patient) were collected before, during and after CPB surgery . The mean (+/- SD) vancomycin concentrations at the end of the infusion and 5 hours after the infusion were 27.3 +/- 5.7 and 5.9 +/- 3.0 mg/liter, respectively . The initiation of CPB resulted in an abrupt decrease (44.5%) in serum vancomycin concentrations; however, concentrations remained constant (range, 6.2 to 14.1 mg/liter) throughout the rest of the CPB procedure . The mean (+/- SD) values for the apparent volume of distribution, total body clearance and elimination half-life were 0.59 +/- 0.15 liter/kg, 2.94 +/- 0.93 ml/min/kg and 2.4 +/- 0.8 hours, respectively . These values were similar to those reported in the literature for children not undergoing CPB surgery . A single vancomycin dose of 15 mg/kg before pediatric CPB surgery provides serum concentrations greater than 5 mg/liter throughout the duration of the CPB procedure . To sustain these concentrations subsequent dosing of vancomycin is necessary within 6 hours after the initial vancomycin dose.

Arch Ophthalmol, 1993 Apr, 111(4), 492 - 4
Ocular penetration of ceftriaxone, ceftazidime, and vancomycin after subconjunctival injection in humans; Barza M et al.; Vancomycin (25 mg), ceftriaxone (125 mg), and ceftazidime (100 mg) were given by subconjunctival injection before vitrectomy to patients with uninfected eyes . Most of the patients had diabetic vitreous hemorrhage with or without traction retinal detachments, and some had rhegmatogenous retinal detachments with proliferative vitreoretinopathy . Samples of vitreous were obtained by pars plana vitrectomy at intervals from 46 minutes to 4 hours 13 minutes after the subconjunctival injection . The median vitreous concentrations of all three drugs were below the limit of detection . Vitreous concentrations of these drugs after a single subconjunctival injection are exceedingly low.

Anesth Analg, 1993 Apr, 76(4), 809 - 11
Vancomycin does not enhance hypotension under anesthesia; von Kaenel WE et al.; The rapid administration of vancomycin is associated with flushing and hypotension, a consequence of histamine release . The manufacturer discourages administering vancomycin to anesthetized patients, stating that vancomycin aggravates the hypotensive effects of anesthetics . To test this, we randomly assigned 36 adults (ASA classes I through III) to one of two groups: preinduction (Preind, n = 19) and postinduction (Postind, n = 17) . Both groups received two different infusions: vancomycin (1 g/250 mL normal saline) and saline (250 mL normal saline) over 30-60 min . The Preind group received vancomycin before anesthesia was induced and saline was administered immediately after anesthesia was induced; for the Postind group, this order was reversed . This was done in a double-blind fashion . The anesthetic induction was standardized by the intravenous administration of thiopental and vecuronium and anesthetic maintenance by inhalation of nitrous oxide and enflurane . End-tidal enflurane, heart rate (HR), and blood pressure (BP) were measured every 3 min . Independent (unpaired) t-test was used in data analysis . The groups did not differ significantly . We conclude that vancomycin infusion may be given under anesthesia without significant adverse hemodynamic consequences if administered over a 30-60 min period of time.

Int Ophthalmol, 1993 Apr, 17(2), 85 - 8
Use of vancomycin in vitrectomy infusion solution and evaluation of retinal toxicity; Borhani H et al.; The retinal toxicity of vancomycin in infusion solution used in vitrectomy and lensectomy was investigated in rabbit eyes by means of electroretinography and histologic study (light microscopy) . Concentrations of 8 micrograms/ml, 16 micrograms/ml, and 32 micrograms/ml of vancomycin in balanced salt solution caused no abnormal ERG or histologic changes . However, ERG amplitude depression and abnormal histologic changes occurred when the concentration of 100 micrograms/ml of vancomycin was used.

Antimicrob Agents Chemother, 1993 Mar, 37(3), 436 - 40
Effect of obesity on vancomycin pharmacokinetic parameters as determined by using a Bayesian forecasting technique; Vance-Bryan K et al.; Few data exist concerning the effect of obesity on the pharmacokinetic parameters of vancomycin . The purpose of this investigation was to assess the effect of obesity on vancomycin pharmacokinetic parameters in 95 nonobese and 135 obese adult patients (age range, 18 to 92 years) receiving vancomycin . All subjects had normal renal function as defined by a creatinine concentration in serum of < or = 1.5 mg/dl (mean estimated creatinine clearance +/- 1 standard deviation, 76 +/- 34; range, 23 to 215 ml/min) . Vancomycin concentrations in serum were determined by the fluorescence polarization immunoassay . All data for vancomycin concentration in serum versus time for each course of therapy were fitted by using a two-compartment Bayesian forecasting program . Subjects were stratified into nine groups on the basis of the percent difference between actual body weight (ABW) and lean body weight (LBW) (> -10%, -10 to 0%, > 0 to 10%, > 10 to 20%, > 20 to 30%, > 30 to 40%, > 40 to 50%, > 50 to 60%, > 60%) . Analysis of variance with post hoc Scheffe's testing revealed that statistically significant differences occurred in terminal disposition half-life (t1/2 beta) between the extremes of modestly obese (group 4) and morbidly obese (group 9, P < 0.05) patients . Similar analysis with distribution volume (V) identified significant differences in patients at or near their LBW (groups 2 to 4) and patients who were morbidly obese (groups 8 and 9, P < 0.05) . Multiple regression models for the pharmacokinetic parameters V, t1/2beta, and vancomycin total body clearance were developed to assess the joint predictive power of LBW, ABW, and percent over LBW, controlling for the effects of age, initial creatinine concentration in serum, initial creatinine clearance, and gender . In the final model for V, both ABW and percent over LBW were independent and significant predictors . For total body clearance, only ABW was significant and predictive . Percent over LBW was a significant and independent predictor of t1/2beta . LBW is not predictive of these pharmacokinetic parameters and should not be used for initial dosing . On the basis of these data, ABW appears to be superior to LBW for calculating initial dose requirements for vancomycin.

Ann Intern Med, 1993 Feb 15, 118(4), 255 - 67
Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients; McDonald GB et al.; OBJECTIVE: To determine the incidence and clinical course of veno-occlusive disease of the liver (VOD) after bone marrow transplantation and to analyze risk factors for severe VOD . DESIGN: Cohort study of 355 consecutive patients . SETTING: A bone marrow transplantation center . MEASUREMENTS: Each patient was prospectively evaluated for VOD, and many risk factors for severe VOD were analyzed using logistic regression models . The relation of VOD to renal and cardiopulmonary failure was analyzed using time-dependent proportional hazards models . RESULTS: Veno-occlusive disease developed in 190 of 355 patients (54%; 95% CI, 48% to 59%): Fifty-four patients had severe VOD and 136 had mild or moderate VOD . Independent variables derived from a multivariate model for predicting severe VOD included elevated transaminase values before transplantation (relative risk, 4.6; P < 0.0001); vancomycin therapy during cytoreductive therapy (relative risk, 2.9; P = 0.003); cytoreductive therapy with a high-dose regimen (relative risk, 2.8; P = 0.01); acyclovir therapy before transplantation (relative risk, 4.8; P = 0.02); mismatched or unrelated donor marrow (relative risk, 2.4; P = 0.02); and previous radiation therapy to the abdomen (relative risk, 2.2; P = 0.04) . Vancomycin therapy was a marker for persistent fever . Multiorgan failure was more frequent among patients with VOD and usually followed the onset of liver disease . CONCLUSIONS: Veno-occlusive disease, which developed in 54% of bone marrow transplant recipients, is frequently associated with renal and cardiopulmonary failure . Pretransplant transaminase elevations, use of high-dose cytoreductive therapy, and persistent fever during cytoreductive therapy are independent predictors of severe VOD.

Clin Pharm, 1993 Feb, 12(2), 126 - 30
Computer dosing program for the initiation of vancomycin therapy; Ito MK et al.; The predictive performance of a computer dosing program used for initiating vancomycin therapy was studied . Initial serum vancomycin concentrations in 31 adult patients receiving vancomycin were estimated by using a computer program (T.D.M.S.) incorporating a two-compartment open model . Sixty-two serum vancomycin concentrations at steady state (Css) were obtained before and after one-hour infusions and compared with estimated Css values . Bias and precision were evaluated by calculating median error (ME) and median absolute error (MAE), respectively . Population-based estimates of volume of distribution (V) and clearance (CL) were compared with those obtained by fitting each patient's data set by using Bayesian analysis (BA) and non-linear least-squares regression (NLLS) . Median (mean +/- S.D.) bias and precision for peak Css were 7.7 (10.2 +/- 10.8) and 7.7 (10.6 +/- 10.5) mg/L, and for trough Css were 7.4 (7.7 +/- 7.6) and 7.4 (8.8 +/- 6.2) mg/L . The medians were significantly different from zero . Estimated median (mean +/- S.D.) V, CL, and half-life were 0.72 L/kg, 0.60 (0.67 +/- 0.21) mL/min/kg, and 11.59 (12.87 +/- 3.91) hours . Median (mean +/- S.D.) CL values determined by BA and NLLS were 0.86 (0.89 +/- 0.32) and 0.85 (0.92 +/- 0.34) mL/min/kg, respectively . Both CL values were significantly greater than the population-based estimate . However, median V values determined by BA and NLLS did not differ from the population-based estimate . A revised clearance model derived from Bayesian analysis of data for the first 21 patients was tested in the 10 other patients and appeared to improve the predictive performance of the a priori model.(ABSTRACT TRUNCATED AT 250 WORDS)

Ann Pharmacother, 1993 Feb, 27(2), 224 - 7
Vancomycin and tobramycin clearance in an infant during continuous hemofiltration; Armstrong DK et al.; OBJECTIVE: To report a case of vancomycin and tobramycin clearance by continuous veno-venous hemofiltration in an infant . Hemofiltration clearance (ClHF) was calculated by two methods and compared for ease and reliability . METHODOLOGY: Case report of a hospitalized four-month-old infant . With method A, ClHF calculation for vancomycin and tobramycin was determined by accurate collection of ultrafiltrate in five 24-hour periods and a midpoint serum sample . With method B, ClHF calculation was determined by obtaining prefilter sample, postfilter sample, and blood flow through filter (Fick principle) over three study periods, correlating to three of five study periods in method A . RESULTS: The infant received continuous veno-venous hemofiltration . With method A, vancomycin ClHF ranged from 0.27 to 0.80 mL/min; tobramycin ClHF ranged from 0.32 to 0.91 mL/min . With method B, ClHF for vancomycin ranged from 0 to 2.08 mL/min . Tobramycin ClHF ranged from 0 to 1.6 mL/min when calculated with method B . CONCLUSIONS: Continuous veno-venous hemofiltration increased the clearance of vancomycin and tobramycin requiring dosage modifications . It appears that method A, which uses the ultrafiltration concentration compared with the serum concentration is more accurate than method B, as it averages fluctuations in ultrafiltrate flow rates . Method B compares a single pre- to postfilter drug concentration and relies on an accurate measurement of ultrafiltration flow rate . Determining ClHF based upon one point in time may overestimate ClHF when the ultrafiltration flow rate varies, as it does in the critically ill . Daily serum concentrations for vancomycin and tobramycin are recommended during continuous veno-venous hemofiltration.

Ann Pharmacother, 1993 Feb, 27(2), 174 - 7
Hypersensitivity reactions associated with parenteral nutrition: case report and review of the literature; Nagata MJ; OBJECTIVE: To report a case of hypersensitivity reaction to total parenteral nutrition (TPN) and to review the available literature on this rare adverse effect . CASE SUMMARY: The reaction occurred in a 52-year-old woman with pancreatic carcinoma who received intravenous metronidazole, tobramycin, vancomycin, ranitidine, morphine, TPN, and lipid emulsion postoperatively . Within 30 minutes of starting the TPN and lipid emulsion, the patient complained of dyspnea and pruritus . She began hyperventilating and was hypoxic . The reaction resolved after discontinuation of the TPN and lipid emulsion . The reaction recurred when lipid-free TPN was initiated on two subsequent occasions, and resolved spontaneously following the discontinuation of the lipid-free TPN . The antibiotics, ranitidine, and morphine therapy were continued with no further adverse effects and the patient was discharged on postoperative day 17 . DISCUSSION: Case reports in the literature on TPN-related hypersensitivity reactions were reviewed . It was speculated that the multivitamin preparation (MVI) may have been the causative agent in our patient; however, this was not confirmed by MVI-free TPN administration or by epicutaneous allergy testing . CONCLUSIONS: Hypersensitivity reactions to TPN can be managed by withholding the TPN and treating with antihistamines if needed until the reaction resolves . Identification, possibly by epicutaneous allergy testing, and removal of the offending agent(s) from the TPN is necessary if TPN therapy must be restarted.

Perit Dial Int, 1993, 13 Suppl 2, S355 - 6
Single daily dose of aminoglycosides in the treatment of continuous ambulatory peritoneal dialysis peritonitis; Vas SI; Toxicity of aminoglycosides is a major concern in the treatment of continuous ambulatory peritoneal dialysis (CAPD) peritonitis . The relatively high blood levels and prolonged and repeated usage may all be contributory . The recognition of the so-called postantibiotic effect, together with the increased phagocytosis of antibiotic-treated cells, may introduce a new mode of therapy with once-daily dosage . Intermittent therapy with vancomycin is already generally accepted . The extension of this modality to antibiotic therapy is discussed.

Perit Dial Int, 1993, 13 Suppl 2, S348 - 50
Intraperitoneal vancomycin/oral pefloxacin versus intraperitoneal vancomycin/gentamicin in the treatment of continuous ambulatory peritoneal dialysis peritonitis; Lye WC et al.; Sixty patients were enrolled in a prospective, randomized study to evaluate the efficacy of two different regimens for the empirical treatment of continuous ambulatory peritoneal dialysis (CAPD) peritonitis . At presentation, Group I received intraperitoneal vancomycin (1 g) and oral pefloxacin (400 mg b.i.d.), and Group II intraperitoneal vancomycin (1 g) and gentamicin (80 mg loading dose, followed by 15 mg/2 L) . Treatment duration was 14 days . Despite randomization, Group I had significantly more patients with primary Candida peritonitis . When fungal peritonitis was excluded from analysis, there were no significant differences in the treatment success rate (Group I, 73.3% vs Group II, 80.0%, p = NS), number of relapses (Group I, 0 vs Group II, 1), and Tenckhoff catheter removal rates (Group I, 26.6% vs Group II, 16.6%, p = NS) between the two groups . The patients treated with pefloxacin had an increased incidence of nausea and vomiting . In selected situations oral pefloxacin may be a suitable substitute for intraperitoneal gentamicin as out-patient therapy for CAPD peritonitis.

Drugs Exp Clin Res, 1993, 19(1), 19 - 24
Effect of oral activated charcoal on vancomycin clearance in rabbits with acute renal failure; el-Sayed YM et al.; The effect of oral administration of activated charcoal on total body clearance of vancomycin administered intravenously (7.5 mg/kg) has been studied in normal rabbits and rabbits with induced renal failure . Gastric intubation of a single dose (10 g) of activated charcoal to normal rabbits did not produce a statistically significant effect on any pharmacokinetic parameter for vancomycin . The mean vancomycin clearances were (mean +/- s.d.) 80.82 +/- 6.8 and 75.24 +/- 9.61 ml/h/kg with and without activated charcoal administration, respectively . To examine whether renal failure would influence the effect of activated charcoal and enhance the systemic clearance of vancomycin, uranyl nitrate was used (0.75 mg/kg, i.v.) to induce acute renal failure in rabbits . The derived pharmacokinetic parameters of vancomycin were consistent with renal failure . No significant differences were observed in any of the calculated pharmacokinetic parameters between the control and charcoal treated rabbits . The lack of effect may be attributed to the large molecular weight of vancomycin.

Adv Perit Dial, 1993, 9, 217 - 22
A retrospective view of factors that affect catheter healing: four years of experience; Newman LN et al.; To determine factors that lead to successful healing, the results of catheter placement were collected by retrospective chart review in 103 peritoneal dialysis patients between January 1988 and March 1992 . There were a total of 112 catheter insertions . A healing time of less than 2 weeks was defined as an optimal outcome . Data were analyzed using contingency tables . Strong predictors of early and effective healing were the following: exit site size less than 0.7 cm, the use of a tunneler to create the exit site, the use of Swan neck catheters, immobilization using Viasorb dressings, and postoperative prophylaxis with intravenous vancomycin . Dialysate leak and the development of hematomas significantly delayed healing . Leaking was associated with early use of the catheter for peritoneal dialysis . Hematoma formation was associated with the use of a tunneler . Uremic or nutritional status, diabetes, immunosuppressive agents, or HIV-positive did not affect catheter healing . Careful attention to intraoperative and postoperative factors optimizes healing independent of complications of primary disease processes in peritoneal dialysis patients.

Adv Perit Dial, 1993, 9, 173 - 6
Pregnancy and birth control in CAPD patients; Hou S; This report summarizes the experience with 17 pregnancies in 16 continuous ambulatory peritoneal dialysis (CAPD) patients . Early experience suggests that the outcome of pregnancy in CAPD patients may be better than in hemodialysis patients . Catheter placement can be undertaken during pregnancy with little increased risk . Peritonitis can precipitate premature labor . Blood-tinged dialysate may herald serious obstetric problems . Hypertension, anemia, and prematurity are serious problems in CAPD patients . Cesarean section can be done, with only a brief interruption in CAPD . The major modification of the usual regimen is the need for smaller exchange volumes and increased frequencyPIP: Clinicians should counsel continuous ambulatory peritoneal dialysis (CAPD) patients about contraceptive use . Hypertension contraindicates the pill . CAPD patients should not use IUDs, since they increase the risk of peritonitis . They can use barrier methods . Pregnancy is often not detected until late . The literature shows that 16 CAPD patients have had 17 pregnancies . 65% of the pregnancies resulted in surviving infants . Pregnancies of all women who conceived before starting dialysis were successful, compared to just 4 of 10 women who conceived after starting dialysis . CAPD patients have a more successful pregnancy rate than do hemodialysis patients, but the numbers are too small to be significant and selection bias may exist . Clinicians placed 11 catheters in 8 of the 16 CAPD patients between 4-29 weeks gestation . Fetal position contributed to outflow obstruction . Just 1 patient had dialysate leak . 3 peritonitis episodes occurred . Cephradine, gentamicin, cefadyl, and vancomycin were used to treat peritonitis . 2 women went into labor and delivered shortly after the onset of peritonitis . The infant delivered at 34 weeks survived, while the one delivered at 24 weeks was stillborn . Bloody dialysate was present in 3 pregnancies . It signaled abruptio placentae and subsequent fetal loss in 1 case, severe subserosal hemorrhage of the uterine wall in another case, and laceration of uterine vessels by the catheter . Hypertension complicated 9 pregnancies, but physicians managed it well and it did not cause premature delivery . 6 women had serum hemoglobin levels between 5.4 and 9 g/L . Just 2 received erythropoietin during pregnancy . Premature labor occurred in 9 pregnancies . CAPD infants are small for their gestational age . Cesarean section with no need for catheter removal was the delivery mode for 6 live born infants . Physicians had to hold dialysis for 24-72 hours after surgery . Smaller exchange volumes and increased frequency of dialysis are major changes in the usual regimen for pregnant CAPD patients .

J Hosp Infect, 1993 Jan, 23(1), 17 - 26
The duration of placement as a predictor of peripheral and pulmonary arterial catheter infections; Raad I et al.; To determine the appropriate time for removal or replacement of peripheral and pulmonary arterial catheters in critically ill cancer patients, we prospectively studied 71 peripheral arterial catheters and 71 pulmonary artery (Swan-Ganz) catheters from 110 consecutive cancer patients . All catheters were cultured semiquantitatively, by the roll-plate culture technique . Of the 71 peripheral arterial catheters, 11 (15%) produced local infections (> or = 15 colonies) and four (5.5%) produced catheter-related septicaemia . Ten of the 11 local infections and all four septicaemias occurred after 4 days of catheter placement (P < 0.05) . Likewise, of the 71 Swan-Ganz catheters, 12 (17%) produced local infection and four (5.6%) led to septicaemia . Swan-Ganz catheter-related septicaemia occurred at rates of 2% and 16%, before and after 7 days of catheter placement, respectively (P = 0.056) . Duration of placement was a risk factor for the development of catheter infections, independent of the patient's neutropenic status, administration of antibiotics such as vancomycin during catheterization, and the presence of concurrent central venous catheters . Life-table analysis showed that the cumulative risks of developing a catheter infection increased from 7% to 17% after 6 days of peripheral arterial catheter placement and from 9% to 18% after 4 days of placement of the Swan-Ganz catheter . We conclude that in the critically ill cancer patient in our unit, peripheral arterial catheters should be changed to a new site every 4-6 days and pulmonary artery catheters every 4-7 days.

Dev Pharmacol Ther, 1993, 20(3-4), 174 - 9
Overestimation of serum vancomycin concentrations using a fluorescence polarization immunoassay (Tdx) in preterm neonates; Paap CM et al.; Serum vancomycin concentrations determined by fluorescence polarization immunoassay (FPIA) with a specific high-performance liquid chromatography (HPLC) method in preterm neonates were compared . Preterm neonates (< 38 weeks gestational age) requiring vancomycin therapy and serum vancomycin concentration monitoring were enrolled . Peak serum vancomycin concentration samples were collected and independently analyzed by FPIA and HPLC . Multivariate and stratified data analysis was done with mean absolute error and mean percent error as dependent variables and independent variables as postconceptional age, postnatal age, gestational age, weight, and duration of therapy to characterize the findings . A total of 15 paired vancomycin concentrations were analyzed from neonates with a mean gestational age of 30 +/- 4 weeks . The mean percentage error of FPIA versus HPLC vancomycin concentrations was 18.1 +/- 11.1% and the mean absolute error was 3.7 +/- 2.0 mg/l . Postconceptional age, weight, and time from initiation of therapy to sample collection were independent variables which best characterized the overestimation of FPIA vancomycin concentrations . The FPIA vancomycin assay method overestimated actual vancomycin concentrations in preterm neonates . Preterm neonates less than 30 weeks postconceptional age, less than 1,200 g body weight, and duration of therapy greater than 48 h prior to concentration determination had the greatest difference in FPIA and HPLC results . Significant error in pharmacokinetic parameter estimations and dosage adjustments is possible when vancomycin concentrations are determined by FPIA.

Ann Pharmacother, 1992 Dec, 26(12), 1520 - 1
Stevens-Johnson-type reaction with vancomycin treatment; Laurencin CT et al.; OBJECTIVE: To report a case of Stevens-Johnson syndrome caused by vancomycin . CASE SUMMARY: Stevens-Johnson syndrome is an acute mucocutaneous process characterized by epidermal and mucosal desquamation . Its pathogenesis is poorly understood . Mortality rates have ranged from 30 to 100 percent . We describe a case of Stevens-Johnson syndrome related to the use of vancomycin in a 71-year-old woman with rheumatoid arthritis receiving treatment for an infected cervical fusion site . Classic "target" lesions distributed throughout the trunk and extremities along with erosive lesions involving the oral and vaginal mucosae were observed in this patient . DISCUSSION: A number of agents have been implicated in the etiology of Stevens-Johnson syndrome . Serious cutaneous reactions to vancomycin, however, have been uncommon . Cessation of vancomycin treatment in our patient led to eventual resolution of her symptoms . CONCLUSIONS: Vancomycin is a potential causative agent of Stevens-Johnson syndrome.

Pol Arch Med Wewn, 1992 Dec, 88(6), 441 - 50
{Personal experiences in the treatment of peritonitis with a complicated extended program of peritoneal dialysis}; Wankowicz Z et al.; In 37 pts treated with peritoneal dialysis (PD) in years 1980-1990 results of peritonitis (P) treatment were compared between years 1986-90 (cycle II) and years 1980-85 (cycle I) . In I cycle 47 episodes of P occurred in 9 of 21 pts treated with PD, and in cycle II 15 episodes of P in 7 of 16 dialysed pts . Treatment of P was as follows: in cycle I, daily standard PD with gentamicin and cephradine added to 2.01 dialysing exchanges; in cycle II, after initial lavage of peritoneum with a few litres of dialysing solution, 1.0 g vancomycin was given iv and continuous PD started using 1.0 litre prolonged exchanges and aminoglycosides added to dialysis solution . Treatment protocol used in cycle II was more effective than the first one: all episodes of P were immediately cured (only 32 of 47 in cycle I), there was only 1 relapse (in cycle I 6/32 cured P), duration of P was shorter (mean 6.5 days/9.8 days in cycle I) and morphological changes of peritoneum were less expressed than in cycle I . Practically important indicator of cure was decline of polynuclear cells in smear of peritoneal effluent sediment (less than 50% of cells) . All 9 pts suffering from P in cycle I had to be transferred to HD (43% of all dialysed pts) and only 2 in cycle II (12% of all dialysed pts).

Ann Pharmacother, 1992 Nov, 26(11), 1409 - 20
Continuous ambulatory peritoneal dialysis: a review of its mechanics, advantages, complications, and areas of controversy; Bailie GR et al.; OBJECTIVE: The primary objective of this article is to review the mechanics, advantages, complications, pharmacokinetics, and future trends of continuous ambulatory peritoneal dialysis (CAPD) as they pertain to pharmacotherapy . DATA SOURCES: Pertinent articles were obtained from an English-language literature search using MEDLINE (1980-1991), Index Medicus (1987-1990), and bibliographic reviews of review articles . Indexing terms included peritoneal dialysis, pharmacokinetics, peritonitis, vancomycin, and fluoroquinolones . DATA SYNTHESIS: All clinical studies comparing organism recovery methods and treatment of peritonitis have methodologic limitations (e.g., comparison of disparate patient groups, different definitions of peritonitis, lack of follow-up, lack of control for sterile cultures) that may affect the reported results . CONCLUSIONS: CAPD is an alternative to hemodialysis for the treatment of endstage renal disease and has many complications, leading to significant morbidity . This indicates that CAPD is not appropriate for all patients . Using blood-culturing techniques to culture for dialysate is most productive, but also the most costly . There are few data to indicate exactly the drugs, doses, and durations of choice for peritonitis . Both intraperitoneal and oral administration appear to be appropriate.

Antimicrob Agents Chemother, 1992 Oct, 36(10), 2204 - 10
Subcellular localization of tobramycin and vancomycin given alone and in combination in proximal tubular cells, determined by immunogold labeling; Beauchamp D et al.; The subcellular localization of tobramycin and vancomycin in the renal cortices of rats was determined with ultrathin sections by immunogold labeling . Four groups of four rats each were treated for 10 days with saline (NaCl, 0.9%), tobramycin at dosages of 20 mg/kg of body weight per 12 h intraperitoneally, vancomycin at dosages of 25 mg/kg/12 h subcutaneously, or the combination tobramycin-vancomycin . On day 11, the animals were killed, and cubes of renal cortex were fixed overnight in phosphate-buffered glutaraldehyde (0.5%), dehydrated in ethanol, and embedded in Araldite 502 resin . Ultrathin sections were made and incubated with sheep antitobramycin antibody followed by protein A-gold (15-nm diameter) complex or rabbit antivancomycin antibody followed by gold (30-nm diameter)-labeled goat anti-rabbit antibody . For the double labeling, incubations were made on opposite sides of the grid . Tobramycin was detected over the lysosomes of proximal tubular cells, but the labeling was concentrated into small areas in the matrix of the lysosomes . Vancomycin was seen over the lysosomes of proximal tubular cells and was distributed uniformly throughout the matrix of the lysosomes . In rats treated with tobramycin-vancomycin, both drugs were still detected in lysosomes of proximal tubular cells . It is concluded that tobramycin and vancomycin accumulate in lysosomes of proximal tubular cells throughout 10 days of treatment and that vancomycin has no effect on the subcellular distribution of tobramycin.

Am J Kidney Dis, 1992 Oct, 20(4), 354 - 60
Vancomycin elimination during high-flux hemodialysis: kinetic model and comparison of four membranes; DeSoi CA et al.; Vancomycin clearance was measured in five patients during dialysis with cuprophane (CU), polysulfone (PS), cellulose triacetate (CT), and polyacrylonitrile (PAN) dialyzers . Vancomycin was significantly cleared during routine high-flux (HF) hemodialysis (HD) with the latter three membranes, but not by CU . Postdialytic rebound of serum vancomycin concentrations was noted following HF dialysis, necessitating use of a two-compartment pharmacokinetic model . Measurement of serum vancomycin concentration immediately postdialysis significantly overestimates intradialytic removal, possibly resulting in inappropriate dose adjustment . Vancomycin infusion during HF HD results in significant drug removal during its administration to the patient, complicating the calculation of an adequate dose.

J Pharmacol Toxicol Methods, 1992 Aug, 28(1), 57 - 60
The influence of vancomycin concentration and the pH of plasma on vancomycin protein binding; Chen Y et al.; A review of numerous studies of the protein binding of vancomycin suggests major discrepancies among their results . The reported percent protein binding of vancomycin varies from 0% to 98% . The influence of pH and concentration on the protein binding of vancomycin was investigated in this study . There was a significant difference (p < 0.001) in percent protein binding in vancomycin-spiked plasma samples across the pH range of 7.0-8.0 . There was no significant difference (p > 0.05) in percent protein binding in vancomycin-spiked plasma samples across the concentration range of 2-80 mg/L . It is likely that some of the variation reported to date may be due to a lack of control of pH during the measurement of protein binding of vancomycin.

J Clin Microbiol, 1992 Jul, 30(7), 1891 - 2
Selective buffered charcoal-yeast extract medium for isolation of nocardiae from mixed cultures; Garrett MA et al.; The recovery of Nocardia species from mixed cultures is facilitated by use of a selective medium . We show that buffered charcoal-yeast extract medium with polymyxin, anisomycin, and vancomycin can be used for the selective isolation of nocardiae from contaminated specimens.

Antimicrob Agents Chemother, 1992 Jul, 36(7), 1424 - 6
Removal of vancomycin by high-flux hemodialysis membranes; Quale JM et al.; Levels of vancomycin in serum are traditionally believed to be unaffected by hemodialysis . By both in vivo and in vitro techniques, the effects of a newer, more permeable dialyzer membrane on vancomycin concentrations were investigated . Six patients who were receiving vancomycin and undergoing maintenance hemodialysis with polyacrylonitrile dialyzer membranes had postdialysis levels in serum that were 63% of predialysis levels; the intradialytic half-life was 5.7 h . Vancomycin concentrations in serum exiting the dialyzer were 68% of those simultaneously entering the dialyzer at the beginning of dialysis . When polyacrylonitrile and conventional cellulose membranes were perfused in vitro with a recirculating solution of vancomycin, vancomycin concentrations fell to 39 and 91%, respectively, of the original concentration . The vancomycin concentration in the ultrafiltrate collected from the polyacrylonitrile membranes was only 23% of the original perfusate concentration . A significant decrease in the serum vancomycin concentration may occur during hemodialysis with newer high-flux dialyzer membranes . It appears that vancomycin binds to polyacrylonitrile membranes; this binding does not require the presence of protein and is affected by the pH of the perfusate.

Rev Invest Clin, 1992 Jul-Sep, 44(3), 383 - 6
{Bone marrow transplantation in Mexico . Report of the 1st successful case in acute myeloblastic leukemia . Grupo de Trasplante Medular Oseo del INNSZ}; Leon E et al.; The first case of allogeneic bone marrow transplantation in acute myelogenous leukemia (AML) done in Mexico is reported . The patient was a 26 year old Mexican woman who in October 1987 was diagnosed of having AML of the M2 subtype . After three cycles of the TADOP regimen (6-thioguanine, cytosine-arabinoside, doxorubicin, vincristine & prednisone), the patient entered complete remission . Unfortunately, after a seven month period of remission she suffered a relapse which was refractory to a new chemotherapy cycle . On 9/14/88 an allogeneic BMT from her HLA identical brother was performed . The conditioning regimen consisted of busulfan and cyclophosphamide . Prophylaxis for GVHD consisted of cyclosporine and methylprednisolone . The posttransplantation course was satisfactory, reaching > 500 neutrophils x 10(9)/L on day 14 and > 50,000 platelets x 10(9)/L without support on day 23 posttransplant . The patient developed fever of unknown etiology, which was satisfactorily resolved with ceftazidime, vancomycin and metronidazole . She also presented a grade II oral and esophageal mucositis . As a late complication, on day 90 posttransplant, she developed a bilateral pneumonia which was resolved with sulfamethoxazole-trimethoprim administration . Up to the time of this report (40 months posttransplant) the patient is completely asymptomatic, is under no immunosuppression, and shows no evidence of graft versus host disease or recurrent leukemia.

Sangre (Barc), 1992 Jun, 37(3), 181 - 4
{Initial dosage of vancomycin in neutropenic hematologic patients}; Soto J et al.; PURPOSE: To evaluate the percentage of neutropenic patients who reach the therapeutic threshold when vancomycin is given at standard initial doses of 500 mg/6 hr, and to assess the creatinine clearance and body vancomycin clearance in such patients . MATERIAL AND METHODS: The study was performed on 37 haematological patients with normal renal function . They received intravenous vancomycin at an initial 500 mg/6 hr doses . The plasma concentration of the drug was assessed 48-72 hr later, pharmacokinetic parameters being calculated . Creatinine clearance was estimated by two different methods . RESULTS: The concentration attained was beyond the therapeutic threshold in 100% of the patients . The correlations between vancomycin and creatinine clearance were r = 0.42 and r = 0.47 when the Cockroft-Gault's and the Jellife's methods, respectively, were used . Administration of vancomycin at initial doses of 500 mg/6 hr renders a very high percentage of patients with plasma concentration of the drug beyond the therapeutic margin . CONCLUSIONS: 1) The poor correlation between creatinine and vancomycin clearance in the patients with normal renal function does not allow using nomograms based on such values for estimation of the initial doses . 2) The estimation of initial doses based on the patient's weight (20-25 mg/kg) may render a higher percentage of patients with therapeutic concentrations from the beginning of treatment . The maintenance doses can be adjusted at 48-72 hr, after measuring the plasma concentrations . 3) Therefore, it seems advisable to perform further clinical assays on different groups in order to verify an increase of the drug's efficacy with no higher toxicity when the initial vancomycin doses is adjusted according to the patient's weight, as recommended here.

J Clin Microbiol, 1992 May, 30(5), 1351 - 3
New plate medium for growth and detection of urease activity of Helicobacter pylori; Cellini L et al.; A new medium for detection of urease activity and isolation of Helicobacter pylori is proposed . This medium, containing Columbia Agar Base, was supplemented with IsoVitaleX, hemin, urea, and phenol red (nonselective medium {NSM}) . Both bacterial growth and color change were evaluated and compared with growth in the same medium supplemented with cefsulodin, vancomycin, polymyxin B sulfate, and amphotericin B (selective medium {SM}) . Twenty-five recent clinical isolates and antral biopsy specimens from 33 patients who underwent endoscopy were examined . The isolates showed a rapid color change and good growth at 5 days of incubation with NSM and SM . H . pylori-positive biopsies revealed a color change within 36 h, and bacterial growth was better appreciated in NSM, but with more contaminating flora than in SM.

Nippon Rinsho, 1992 May, 50(5), 1054 - 9
{Vancomycin and arbekacin, drugs of treatment for MRSA infections}; Kobayashi Y; In Japan, the Ministry of Health and Welfare has permitted recently that vancomycin is given parenterally . Therefore, this drug will be useful for the treatment for MRSA infections . Arbekacin, a newly developed aminoglycoside antibiotic, showed more active than vancomycin to MRSA in vitro . Therefore this drug will be also useful for the treatment for MRSA infections . Combined activity of arbekacin and vancomycin against 27 MRSA strains was evaluated by checkerboard technique . No synergistic effects were detected against these strains . Antagonistic effects were observed against 2 strains . "Vancomycin-arbekacin combined therapy" should be done, therefore, to restricted cases.

Clin Pharmacokinet, 1992 Apr, 22(4), 298 - 307
Prediction of serum vancomycin concentrations following intraperitoneal loading doses in continuous ambulatory peritoneal dialysis patients with peritonitis; Bailie GR et al.; The pharmacokinetics of vancomycin were studied in continuous ambulatory peritoneal dialysis patients with peritonitis . Six patients received an intraperitoneal loading dose of 15 mg/kg and 4 received an intraperitoneal dose of 25 mg/L . The ability of 2 methods to predict serum concentrations during the loading dose exchange was determined . The mean serum concentration after the exchange was 17.8 +/- 2.2 mg/L in patients receiving the loading dose . The mean dialysis clearance in all patients was 0.94 +/- 0.34 L/h . 66.6 +/- 13.4% of a dose was absorbed into the circulation in 4 h . The volume of distribution was 0.61 +/- 0.46 L/kg, and the half-life for equilibration of vancomycin into the circulation from dialysate was 2.76 +/- 0.94 h . Two methods of predicting serum vancomycin concentrations were tested, with 1 method predicting values significantly different from measured concentrations while the other did not . Serum vancomycin concentrations can be accurately predicted during a loading dose exchange.

Neurosurgery, 1992 Apr, 30(4), 630 - 4; discussion 634-5
Intraventricular vancomycin-induced cerebrospinal fluid eosinophilia: report of two patients; Grabb PA et al.; Pediatric neurosurgeons commonly instill vancomycin into the ventricles to treat shunt infections . This use for vancomycin, however, has not been studied in the laboratory to evaluate possible toxicities and side effects . We report two cases of cerebrospinal fluid eosinophilia (CSFE) secondary to the intraventricular administration of vancomycin . Two other cases of shunt infection during the same time period were treated for only 2 days with intraventricular vancomycin and did not manifest CSFE . We address the clinical problems and possible detrimental effects of CSFE in the setting of shunt infection . We propose a mechanism of vancomycin-induced mast cell degranulation and subsequent release of eosinophil chemotactic factor as a cause of CSFE . An initial dose of intraventricular vancomycin should take into account volume of distribution (ventricular size) to obtain a peak cerebrospinal fluid concentration of 20 to 30 micrograms/mL . We recommend following daily cell counts and vancomycin peak and trough levels to calculate the amount and frequency of intraventricular vancomycin required to maintain safe and effective concentrations and to monitor for CSFE.

J Clin Microbiol, 1992 Mar, 30(3), 537 - 9
Cefamandole-susceptible strains of Legionella pneumophila serogroup 1: implications for diagnosis and utility as an epidemiological marker; Vickers RM et al.; The standard selective Legionella medium that contains cefamandole failed to grow legionella pneumophila serogroup 1, subtype Bellingham, from a sputum sample from a patient with nosocomial Legionnaires' disease; the isolate did grow on a similar selective medium that substitutes vancomycin for cefamandole . Two Bellingham isolates from this patient's hospital environment also failed to grow when tested on the cefamandole medium . We tested 106 additional L . pneumophila serogroup 1 isolates that belonged to nine different monoclonal antibody subtypes and demonstrated that susceptibility to cefamandole was rare (10%) and limited to the Bellingham subtype . The diagnosis of Legionnaires' disease may be missed unless the culture protocol includes both a nonselective medium and a selective medium that does not contain cefamandole . In vitro susceptibility to cefamandole also provided an epidemiologic marker that linked a water source for a patient to nosocomial Legionnaires' disease.

Eur J Clin Pharmacol, 1992, 42(6), 635 - 9
Rebound of plasma vancomycin levels after haemodialysis with highly permeable membranes; Bohler J et al.; Vancomycin is usually given only once a week to haemodialysis (HD) patients . If highly permeable dialysis membranes are used, however, high clearance values have been reported, so the aim of the study was to determine whether high clearance of vancomycin resulted in sufficient drug elimination to induce subtherapeutic plasma levels after one week . In 18 chronic HD patients, treated with polysulfone dialyzers (1.2 m2), the pharmacokinetics of vancomycin were studied after administration of 1 g . Concentrations were determined by fluorescence polarisation immunoassay . At a blood flow of 219 ml.min-1, HD clearance of vancomycin was 62.3 ml.min-1 . Immediately after dialysis plasma concentrations were 38% lower than predialysis levels . However, marked rebound in the vancomycin level was observed 5 h later, resulting in plasma levels only 16% lower than prior to dialysis . 3 HD treatments in 1 week removed about one third of the initial dose . After one week 15 of 18 patients still had a therapeutic plasma level (greater than 4 micrograms.ml-1) . In conclusion, polysulfone membranes show high clearance of vancomycin . However, transfer of drug from blood to dialysate appears to be faster than from tissues to blood . Because of a marked rebound in plasma level after treatment, therapeutic drug concentrations will still be present in most patients after one week.

Dev Biol Stand, 1992, 74, 165 - 77; discussion 177-9
Moisture transfer from stopper to product and resulting stability implications; Pikal MJ et al.; Since the stability of a freeze-dried product is often sensitive to the level of moisture, control of residual moisture by attention to the secondary drying phase of the freeze-drying process is of considerable importance . However, several reports in the literature as well as our own experience suggest that low residual moisture immediately after manufacture does not ensure low moisture throughout the shelf life of the product . Equilibration of the product with moisture in the stopper can lead to significant increases in product water content . This research is a study of the kinetic and equilibrium aspects of moisture transfer from stopper to product at 5 degrees C, 25 degrees C, and 40 degrees C for two amorphous materials: vancomycin (highly hygroscopic) and lactose (moderately hygroscopic) . Stoppers are 13 mm butyl rubber (#1816, West Co.) slotted freeze-drying stoppers which were studied: (a) "U"-with no treatment; (b) "SV1"-steam-sterilized followed by 1 hr vacuum drying; and (c) "SV8"-steam sterilized followed by 8 hrs vacuum drying . No evidence was found for moisture transmission through the stopper . Rather, the product moisture content increases with time and reaches an apparent equilibrium value characteristic of the product, amount of product, and stopper treatment method ("SV1" much greater than "U" greater than "SV1") . As a first approximation, the rate of approach to "equilibrium" depends only on temperature (t1/2 approximately 10 months at 5 degrees C to approximately 4 days at 40 degrees C) with the "equilibrium" water content being independent of temperature . The "equilibrium" moisture content increases as the dose decreases and is larger for vancomycin than for lactose . The "equilibrium" moisture contents range from 5.0% (25 mg vancomycin, "SV1" stoppers) to 0.68% (100 mg lactose, "SV8" stoppers).

J Toxicol Clin Toxicol, 1992, 30(2), 285 - 94
Exchange transfusion and multidose activated charcoal following vancomycin overdose; Burkhart KK et al.; The inadvertent administration of a concentrated vancomycin solution to a 47 day-old premature male twin resulted in extremely high vancomycin levels and altered renal function . A 1.5 volume exchange transfusion did not change the measured vancomycin level . Multiple doses of oral activated charcoal, 1 g/kg, were administered beginning 5 h after the exchange transfusion . A calculated half-life of vancomycin before the exchange transfusion was 35 h . The half-life after the exchange transfusion and during charcoal administration was calculated to be 12 h . The only apparent adverse effect of this vancomycin overdose was reversible nephrotoxicity . The infant's hearing, tested by brainstem auditory responses, was normal . The higher volume of distribution of vancomycin in infants may preclude removing significant amounts of this drug by exchange transfusion . Gastrointestinal dialysis with activated charcoal warrants consideration in cases of vancomycin overdose in neonates.

Perit Dial Int, 1992, 12(1), 57 - 60
Chemical peritonitis following the intraperitoneal administration of vancomycin; Freiman JP et al.; The Food and Drug Administration has received 51 reports of cases in the United States in which chemical peritonitis was associated with the intraperitoneal administration of sterile vancomycin hydrochloride, USP intravenous . The clinical presentation of the cases ranged from mild (cloudy dialysate alone) to more severe (severe abdominal pain and fever) . The temporal circumstances suggest that intraperitoneal vancomycin may be associated with chemical peritonitis . A positive rechallenge was reported in 9 cases . The underlying mechanism responsible for this adverse reaction has not yet been identified.

J Am Acad Dermatol, 1992 Jan, 26(1), 45 - 8
Vancomycin-associated linear IgA dermatosis . A report of three cases; Carpenter S et al.; BACKGROUND: Linear IgA dermatosis is an autoantibody-mediated, subepidermal blistering disease that is rarely associated with drug exposure . OBJECTIVE: We report the development of linear IgA dermatosis in three patients associated with the administration of vancomycin and further characterize the immunopathology . METHODS: Direct and indirect immunofluorescence assays were performed to characterize the immunoreactants, determine the subclass of the IgA deposits, and map the site of antibody deposition . RESULTS: A subepidermal blistering disease developed in all patients shortly after vancomycin was initiated, which resolved on discontinuation of the drug . Immunofluorescence studies revealed linear deposits of IgA1 only at the basement membrane zone, below the lamina lucida . Circulating IgA anti-basement membrane zone antibodies were not detected . CONCLUSION: Three patients had linear IgA dermatosis in association with the administration of vancomycin . All patients had linear deposits of IgA1 localized to the sublamina densa zone . Immunophenotypically, the disease in these patients mimics the pattern of IgA deposits seen in the majority of patients with idiopathic linear IgA dermatosis.

Ren Fail, 1992, 14(4), 579 - 85
Evaluation and first validation study on a simplified drug dosage algorithm for multiple organ failure patients; Kroh UF et al.; As reported previously, drug concentrations during continuous hemofiltration (HF) and extracorporeal lung assist (ELA) follow certain rules, which can be expressed by a simplified algorithm for dosage adjustment: Drug sieving (S, fu) depends on the protein free fraction with small limitations, while the extrarenal elimination rate is not a constant but correlates inversely with the clinical state, r = -0.34, p = 0.00067, n = 96 . Up to now, more than 218 cases of drug dosage adjustments have been performed, following the described regimen: The expected concentration is obtained in 79-84% already from the first estimation for drugs such as aminoglycosides, vancomycin, teicoplanin, beta-lactam antibiotics, heart glycosides, and theophylline . Skilled therapeutic drug monitoring (TDM) with elaborated pharmacokinetic programs fails to improve these results significantly . Nevertheless, sporadic TDM is essential in these patients according to their rapidly changing clinical states.

Scand J Infect Dis, 1992, 24(3), 395 - 6
IgE-mediated reaction to vancomycin and teicoplanin after treatment with vancomycin; Knudsen JD et al.; A 38-year-old male patient developed severe signs of type 1 allergy after treatment with vancomycin . By the basophil histamine release test, the patient's isolated basophil leucocytes were shown to react IgE dependent after challenge with vancomycin and teicoplanin . This indicates that the patient is type 1 allergic towards vancomycin and teicoplanin.

Adv Perit Dial, 1992, 8, 302 - 5
Treatment of relapsing peritonitis in pediatric patients on peritoneal dialysis; Klaus G et al.; Relapsing peritonitis is often due to bacterial colonization of the Tenckhoff catheter and may require removal of the catheter in patients on peritoneal dialysis . The efficacy of a Tenckhoff catheter decontamination procedure was examined in 9 pediatric patients aged 1.5-18 years and compared to the outcome of a historical control group . After repeated dialysate cultures had become negative and cell count was normalized (< 100/ul), intraluminal urokinase (5000 IU/ml) and intraluminal high concentrated antibiotics (vancomycin, fosfomycin, cefotaxim) were instilled sequentially for 3 h and 1 h respectively . This procedure was performed once daily for three days . In addition, the connector was exchanged on the last day . This regimen prevented relapsing peritonitis in all study patients, whereas in the control group in 75.8% of events further relapses occurred, necessitating removal of the Tenckhoff catheter in 7/19 (36.8%) episodes . No side effects of intraluminal urokinase were recorded in any of the patients . We conclude that intraluminal urokinase and intraluminal high concentrated antibiotics combined with connector device exchange are highly effective for prevention of further relapses of peritonitis and reduce the need for Tenckhoff catheter exchange.

Adv Perit Dial, 1992, 8, 150 - 2
Hearing thresholds in CAPD patients; Morton LP et al.; Ultra high frequency (UHF, 10-20 kHz) and conventional audiometric thresholds (0,25-8 kHz) were obtained from 42 stable CAPD patients . Twenty-one (50%) and 11 (25%) of the patients had UHF and conventional hearing loss respectively, when compared to age related control data . This was unrelated to length of chronic renal failure and number of treatments with ototoxic drugs . Sixteen of these patients were monitored audiometrically using UHF during a course of vancomycin therapy for peritonitis . There was no significant change in hearing thresholds . In conclusion there is high incidence of hearing loss in CAPD patients which is unrelated to ototoxic drugs.

Pediatr Neurosurg, 1992, 18(3), 139 - 43
Vancomycin: its effect on intracranial pressure; Gaskill SJ et al.; Vancomycin is a commonly used antibiotic in neurosurgical practice . It is, however, notorious for causing histamine release which has been associated experimentally with rises in intracranial pressure (ICP) . The observation that patients receiving vancomycin had an elevation in ICP during vancomycin infusion over 1 h, and that this elevation persisted for the hour following infusion led to a more formal evaluation . Presented here are data obtained from 6 patients who received vancomycin while on external ventricular drainage for a variety of reasons . The mean ICP for the hour prior to, during and following vancomycin administration was 8 mm Hg (SD 5.6), 13.8 mm Hg (SD 4.9), and 12.6 mm Hg (SD 4.3), respectively . The data were analyzed using a repeated measures analysis of variance between the preadministration values, during-administration values and postadministration values . The p value was significant at < 0.0001 . These observations led to experimentation in animals to further assess the effects of vancomycin on ICP . The mean ICP prior to, during and following vancomycin infusion was 1.95 mm Hg (SD 0.75), 8.4 mm Hg (SD 5.1) and 5.6 mm Hg (SD 2.5), respectively . The data were analyzed using a repeated measure analysis of variance for the preadministration, during-administration and postadministration values . The p value was significant at < 0.0001 . Based on these data the use of vancomycin should be tempered in the setting of intracranial pathology.

J Infect Dis, 1991 Dec, 164(6), 1180 - 5
Red man syndrome: incidence, etiology, and prophylaxis; Wallace MR et al.; The red man syndrome (RMS) is the most common toxicity of vancomycin therapy . A prospective trial to investigate the frequency, causation, and possible prophylaxis of this syndrome was conducted . Thirty-three patients were observed during their first two doses (1 g/60 min) of vancomycin . Before dose 1, they were randomized to double-blinded pretreatment with either diphenhydramine (50 mg) or placebo . Patients were examined frequently, and histamine levels were obtained at 0, 30, and 60 min during dose 1 . Those with first-dose reactions were rerandomized for pretreatment and had histamine levels drawn during a second infusion . Of 17 patients with placebo pretreatment, 8 (47%) had RMS . None of the 16 pretreated with diphenhydramine had a first-dose reaction (P = .003) . Three of the eight first-dose reactors had a second-dose RMS reaction; in one of these three, it was more severe than the dose 1 RMS despite diphenhydramine pretreatment . RMS events were associated with elevated plasma histamine; this was especially true of severe reactions.

Biopharm Drug Dispos, 1991 Dec, 12(9), 637 - 46
Factors influencing the protein binding of vancomycin; Shin WG et al.; Various factors influencing the protein binding of vancomycin were examined using equilibrium dialysis method . Four per cent human serum albumin (HSA) and/or 0.08 per cent alpha-1-acid glycoprotein (AAG), dissolved in isotonic phosphate buffer, were dialyzed against isotonic phosphate buffer of pH 7.4 using Spectrapor 2 membrane . The protein binding of vancomycin to 0.08 per cent AAG was dependent on vancomycin concentrations; the values ranged from 21.1 per cent at the vancomycin concentration of 20 micrograms ml-1 to 5.30 per cent at 2400 micrograms ml-1 . However, binding to 4 per cent HSA was relatively constant, 8.79 +/- 2.43 per cent over a vancomycin concentration range of 20-2400 micrograms ml-1 . The values to 4 per cent HSA alone and 0.08 per cent AAG alone did not predict the greater binding of vancomycin in the presence of both proteins, especially at higher concentrations of vancomycin; the values to 4 per cent HSA with 0.08 per cent AAG were constant, 26.3 +/- 3.74 per cent, at the vancomycin concentration range of 20-2400 micrograms ml-1 . This suggested an interaction between the proteins, which resulted in enhanced binding of vancomycin . The protein binding of vancomycin to 4 per cent HSA with 0.08 per cent AAG was not influenced by the different incubation temperatures (4 degrees, 22 degrees, and 37 degrees), quantities of heparin (up to 40 units ml-1) or AAG (up to 0.16 per cent), or buffers (isotonic phosphate buffer of pH 7.4, phosphate buffer of pH 7.4 and 0.9 per cent NaCl solution) at the vancomycin concentration of 80 micrograms ml-1 . Vancomycin was found to be stable in human serum albumin or in isotonic phosphate buffer of pH 7.4.

Clin Pharmacol Ther, 1991 Dec, 50(6), 688 - 94
Vancomycin pharmacokinetics in acute renal failure: preservation of nonrenal clearance; Macias WL et al.; INTRODUCTION: The normal nonrenal clearance of vancomycin is reduced in patients with chronic renal failure (40 versus 6 ml/min) . The nonrenal clearance of vancomycin in patients with acute renal failure has not been characterized extensively . PURPOSE: To prospectively determine the pharmacokinetic profile of vancomycin in anuric patients with acute renal failure who are receiving continuous venovenous hemofiltration . METHODS: Vancomycin serum samples were obtained in 10 patients immediately before and 1 and 12 hours after a 1-hour infusion . Thirteen sets of data were obtained . Vancomycin concentration data were incorporated into a first-order, single-compartment model . Determinations for the area under the serum concentration-time curve were made by the trapezoidal rule . RESULTS: Total vancomycin clearance was 28.5 +/- 6.4 ml/min (range, 17.1 to 36.6 ml/min . Hemofilter clearance was either 6.7 or 13.3 ml/min, depending on ultrafiltrate production rate (assuming a sieving coefficient of 0.8) . Nonrenal clearance, calculated as total clearance minus hemofilter clearance was 16.2 +/- 7.0 ml/min (range, 3.8 to 23.3 ml/min) . Total clearance did not correlate with hemofilter clearance (r = 0.1; p greater than 0.25) but correlated strongly with nonrenal clearance (r = 0.94; p less than 0.0005) . Nonrenal clearance decreased significantly as the days on continuous venovenous hemofiltration increased (range, 2 to 14 days; r = 0.68; p less than 0.025) . CONCLUSION: Early in the course of acute renal failure there is a substantial preservation of the normal nonrenal clearance of vancomycin . This nonrenal clearance appears to decrease with the duration of renal failure, eventually approaching the clearance observed in patients with chronic failure.

J Pharmacol Exp Ther, 1991 Dec, 259(3), 1283 - 7
Mechanism of vancomycin transport in the kidney: studies in rabbit renal brush border and basolateral membrane vesicles; Sokol PP; The effect of vancomycin, a putatively nephrotoxic amine glycopeptide antibiotic, on the transport of organic cations was examined in rabbit renal basolateral and brush border membrane vesicles . The studies were conducted using a rapid filtration technique and the prototypic organic cation tetraethylammonium . In basolateral membrane vesicles, vancomycin cis-inhibited the electrogenic transport of tetraethylammonium with an IC50 value of 260 microM . In contrast, gentamicin, an aminoglycoside, was without effect . Inhibition by mepiperphenidol, a classical organic cation transport inhibitor, was observed with an IC50 value of 24 microM . Countertransport, that is, trans-stimulation experiments, were initiated in order to determine whether or not vancomycin was capable of traversing the plasma membrane . Vancomycin caused trans-stimulation of tetraethylammonium uptake . The specificity of inhibition was assessed by determining the effect of vancomycin on the transport of p-aminohippurate, an organic anion . Vancomycin did not inhibit transport, whereas probenecid, a classical organic anion inhibitor, did . In the brush border membrane, vancomycin had no effect on the transport of tetraethylammonium . These data are consistent with mediated transport for vancomycin across the basolateral membrane, but not across the brush border membrane . This implies that the nephrotoxicity of vancomycin may be due to entry through the basolateral membrane and the absence of mediated egress at the brush border membrane.

J Antibiot (Tokyo), 1991 Nov, 44(11), 1208 - 21
An NMR study of eremomycin and its derivatives . Full 1H and 13C assignment, motional behavior, dimerization and complexation with Ac-D-Ala-D-Ala; Batta G et al.; Complete 1H and 13C NMR assignments are presented for eremomycin (1) and some of its desglycosylated derivatives 2, 3 and compared to the structurally closely related glycopeptide vancomycin . Primary structure and stereochemistry of eremomycin is corroborated by the present high field total correlation spectroscopy, NOESY and heteronuclear multiple-bond correlation NMR methods . A rough motional characterization of the title compound is attempted by 13C-T1 and 13C-{1H} NOE measurements . Dimerization of eremomycin is observed both in DMSO-d6-CCl4 and D2O solutions . Complexation with cell wall analogue dipeptide Ac-D-Ala-D-Ala is also demonstrated.

JPEN J Parenter Enteral Nutr, 1991 Sep-Oct, 15(5), 536 - 9
In vitro assessment of vancomycin HCl compatibility after coinfusion with a specialized amino acid formulation; Martins AM et al.; Vancomycin usage at British Columbia's Children's Hospital has increased substantially in the Special Care Nursery as a consequence of a study demonstrating a reduced morbidity and mortality in neonates with necrotizing enterocolitis when treated with vancomycin and cefotaxime . The inability to place more than one peripheral intravenous access necessitates interruption of parenteral nutrition to infuse vancomycin, resulting in a reduction of the planned daily intake of these neonates . This is clinically significant with the administration of vancomycin because of the long administration period required for this drug (60 minutes) . This study was designed to assess the physical and chemical stability of vancomycin with a standard neonatal parenteral nutrition solution, Vamin A, when coadministered through the same intravenous line . To simulate the actual clinical setting, the dose of vancomycin and the infusion rate of Vamin A were chosen to represent those commonly used in a 1-kg neonate . Physical compatibility was assessed using effluent obtained after coinfusion of vancomycin with parenteral nutrition solution . Duplicate samples were visually checked for color changes and precipitate . High-pressure liquid chromatography (HPLC) and pH testing were used to assess chemical compatibility of vancomycin . The results of physical compatibility revealed no color change or precipitate . No changes in pH were observed . HPLC determination confirmed that there were no significant time-dependent changes in vancomycin stability . The samples were studied over 24 hours to determine the rate of degradation of vancomycin, if any, under various temperature conditions . The concentrations were not significantly different from each other at the different temperatures studied . Thus, there was no apparent change in the concentration of vancomycin in the presence of Vamin A.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharm Weekbl Sci, 1991 Aug 23, 13(4), 153 - 60
Teicoplanin in perspective . A critical comparison with vancomycin; Janknegt R; Teicoplanin is a new glycopeptide antibiotic with a chemical structure related to vancomycin . The proposed advantages of teicoplanin over vancomycin are discussed . These include lower incidence of side-effects, lower toxicity (especially in combination with aminoglycosides), lower dosage frequency and the possibility of intramuscular administration . There is only a limited number of studies comparing both agents; more studies are still needed before firm conclusions can be drawn . Therapeutic drug monitoring is not usually necessary for teicoplanin; the situation is not clear for vancomycin . There is some doubt whether the incidence of resistance is as infrequent for teicoplanin as it is for vancomycin . Teicoplanin appears to be a promising alternative to vancomycin, but more data are needed on the relative clinical efficacy and the development of resistance to both drugs.

J Chemother, 1991 Aug, 3(4), 226 - 31
Effects of vancomycin, teicoplanin, daptomycin and coumermycin on normal immune capabilities; Tawfik AF; Vancomycin, teicoplanin, daptomycin, and coumermycin were investigated for immunomodulatory activity on both humoral and cell-mediated immune responses in Balb/c mice . All four antibiotics did not produce any interference with these responses as measured by hemolytic plaque assay and delayed-type hypersensitivity to sheep red blood cells . The administration of these antibiotics for seven days did not affect the peripheral blood leukocyte count or spleen weights . When these antibiotics were tested for their interaction with human polymorphonuclear phagocytic activity, no alteration in this activity was observed . These findings suggest that vancomycin, teicoplanin, daptomycin, and coumermycin may be safely used for the treatment of infections without altering host-defence mechanisms.

Orthop Rev, 1991 Jul, 20(7), 607 - 10
Total hip replacement after central fracture dislocation of the acetabulum; Pritchett JW et al.; We performed total hip replacement (THR) for traumatic arthritis following central fracture dislocation of the acetabulum in 19 patients (15 men and four women) . This situation is significantly challenging, as most patients have scarring, contractures, and unequal leg length . The average age was 49 years, and all patients were followed for a minimum of 2 years . A two-piece cementless acetabular component and a cemented or cementless femoral component were utilized . In each patient, prophylactic low-dose irradiation was administered to discourage heterotopic ossification, and gentamicin with either cefazolin or vancomycin were given as prophylaxis for infection . Overall, the results were excellent . The mean Harris hip score after surgery was 84 . No infections, dislocations, or significant heterotopic ossification occurred . Limb length was within 1 cm in each patient . No revision surgeries were performed, and no components were roentgenographically loose . There was one case of transient nerve palsy . We conclude that THR after central fracture dislocation of the acetabulum is a safe and effective procedure.

J Clin Pharmacol, 1991 Jul, 31(7), 618 - 23
The effect of tobramycin on the renal handling of vancomycin; Munar MY et al.; Studies in experimental animals and humans have suggested that enhanced renal and auditory toxicity occur with concurrent vancomycin and aminoglycoside treatment . In volunteers, systemic vancomycin clearance at steady-state was measured simultaneously with renal clearances of vancomycin, creatinine, inulin, and para-aminohippurate . Group 1 (n = 9) received vancomycin 5 mg/kg IV for 1 hour, then 1.1 mg/kg/hr for 3 hours . Group II (n = 7) received vancomycin plus tobramycin (2 mg/kg IV over 30 min) . Groups did not differ demographically . Audiograms were obtained before and after vancomycin . Plasma samples were collected serially for vancomycin and tobramycin pharmacokinetic studies . Serum concentration versus time data were fit to a two-compartment model for vancomycin and a one-compartment model for tobramycin . For all volunteers, creatinine, inulin and para-aminohippurate clearance, and audiograms were not altered from baseline and were not statistically different between groups . No significant effect of tobramycin on vancomycin pharmacokinetics was observed . conversely, vancomycin had no significant effect on tobramycin pharmacokinetics . The nephrotoxic synergism of vancomycin and tobramycin is not explained by short-term differences in renal handling.

Clin Nephrol, 1991 Jul, 36(1), 35 - 41
Pharmacokinetics of vancomycin in patients undergoing hemodialysis with polyacrylonitrile; Torras J et al.; The pharmacokinetics of vancomycin in patients undergoing dialysis with cuprophane membranes are well known, however little has been reported of the use of polyacrylonitrile membranes in dialysis . We studied, in a crossover design, eight dialysis patients (7 men, 1 woman) aged 30 to 66 years who prospectively received 1 gram of vancomycin i.v . before first dialysis and were subsequently hemodialyzed with cuprophane every second day for a total of three times . A month later trial was repeated using polyacrylonitrile . A mono-compartment model was used to calculated pharmacokinetic parameters . Mean +/- standard deviation of vancomycin clearance varied from 5.2 +/- 2.1 ml/min in the interdialysis period to 9.7 +/- 2.7 ml/min during dialysis with cuprophane and to 58.4 +/- 15.6 ml/min during dialysis with polyacrylonitrile (p less than 0.001) . Vancomycin half-life varied from 71.5 +/- 23.0 to 35.9 +/- 9.8 and to 6.1 +/- 1.4 hours, respectively (p less than 0.001) . Fractional removal of vancomycin increased from 4% using the cuprophane dialyzer to 34% using the polyacrylonitrile dialyzer (p less than 0.001) . Serum vancomycin levels at 100 and 168 hours were higher with cuprophane than with polyacrylonitrile (7.0 +/- 2.2 vs 3.9 +/- 1.2 micrograms/ml) (p less than 0.001) . Moreover, the mean levels at 100 hours were suboptimal on polyacrylonitrile . Approximately 208 +/- 53 mg of vancomycin were removed during one polyacrylonitrile dialysis . Thus, those patients who undergo dialysis with polyacrylonitrile and are treated with vancomycin may need supplementary doses post dialysis or to lessen dosage intervals than those traditionally used for dialysis patients since clearance of the drug is significantly higher than with cuprophane dialyzers . Continuous monitoring of vancomycin levels is also recommended.

Am J Hosp Pharm, 1991 Jul, 48(7), 1477 - 83
Influence of a decision analysis model on selection of drug therapy; Peterson AM et al.; The impact of a decision analysis model on pharmacists' preferences for a drug therapy was studied . Three hundred forty members of the American College of Clinical Pharmacy were randomly assigned to receive either a copy of a drug therapy review alone (control group) or the review plus a decision analysis of the same clinical problem (experimental group) . The disease selected was pseudomembranous colitis, and the drugs to be considered were vancomycin, metronidazole, and bacitracin . The review and the decision analysis recommended metronidazole as the best agent . Each subject completed a short questionnaire, read the review or the review plus the analysis, and completed a follow-up questionnaire . Both questionnaires asked the subjects to rank the agents in order of preference . There were 164 usable responses, 86 from the control group and 78 from the experimental group; the total response rate was 48.2% . The difference in the proportion of respondents in each group who chose metronidazole as the most preferred agent, both before and after the intervention, was not significant . Of the 40 experimental-group subjects who ranked metronidazole as their second or third choice in the pretest, 16 (40%) ranked it as the most preferred agent in the posttest . Ten of these 16 stated that the model influenced their decision . Decision analysis plus a drug therapy review had no greater impact on pharmacists' opinions on the selection of drug therapy for pseudomembranous colitis than did the review alone . The model did influence some of those who changed their opinion.

ASAIO Trans, 1991 Jul-Sep, 37(3), M375 - 7
The effect of ultrafiltration on dialysance . Mathematical theory and experimental verification; Hootkins R et al.; It is known that convective transport (ultrafiltration, QF) augments diffusive transport . This augmentation achieves great importance as solute molecular weight increases . Previous mathematical treatments of dialysance (D) have provided the relationship between D and blood flow rate (QB), dialysate flow rate (QD), and dialyzer membrane surface area permeability product (KoA), in the limit of QF = 0 . The authors derived the relationship between D (defined as D') and QB, QD, and KoA for the general case of QF greater than or equal to 0: D' = X-Y/In X/Y . {(1-o) QF + KoA} for X = X(D', QF, QD) = 1 - {D'/QD + QF} Y = Y(D', QF, QB) = D'-QB/QF-QB o = the Staverman reflection coefficient . This equation demonstrates an approximate linear increase in D' as QF increases . Experimental verification is provided by in vivo studies of dialysis patients in which the dialysance of vancomycin doubles as QF is increased from 0 to 50 . Because D' varies linearly with QF, this allows for the determination of KoA and o . Using the Cobe 500HG Hemophan membrane, KoA for vancomycin was determined to be 6.54 and o = 0.88.

Clin Pharmacokinet, 1991 Jun, 20(6), 463 - 76
An updated comparison of drug dosing methods . Part IV: Vancomycin; Pryka RD et al.; The resurgence of the use of and interest in vancomycin, in conjunction with the high degree of interpatient variability in its pharmacokinetic profile, has prompted the development of many and varied dosing methods . Several dosing nomograms have been proposed and evaluated, methods which are useful for initial dosing but do not allow for individualisation of dosage . Given these constraints, several investigators have attempted to apply conventional least-squares regression techniques and, more recently, Bayesian methodologies using either 1- or 2-compartment pharmacokinetic models . Comparative information evaluating algorithmic methods demonstrates that those of Moellering and Lake offer the least biased and most precise predictions of vancomycin dosage . Patient individualisation using conventional least-squares methodology offers some improvement over nomogram-based methods, both in predictive performance and in dosage adjustment once serum concentration data are available . Overall, the latest data indicate that regimens which incorporate Bayesian principles tend to give better results than nomogram-based or conventional least-squares dosing methods for this drug . Despite the advances in methods for dosing vancomycin, several questions remain to be answered . A lack of convincing evidence of a correlation between serum concentrations and therapeutic outcome has prompted debate over the need for serum concentration monitoring and, if it is needed, over which patient population would most benefit . Secondly, little comparative information is currently available as to the dosing of vancomycin in paediatric and neonatal patient populations . Several nomograms for initial dosing have been proposed, but only 2 have been subject to subsequent testing . Finally, information regarding cost-effectiveness and the quality of patient outcome is lacking from the current literature.

J Antimicrob Chemother, 1991 Jun, 27(6), 845 - 9
Nephrotoxicity in bone marrow transplant recipients receiving aminoglycoside plus cyclosporine or aminoglycoside alone; Chandrasekar PH et al.; We performed a retrospective analysis of the medical records of allogeneic bone marrow transplantation (BMT) patients receiving cyclosporine plus an aminoglycoside and autologous BMT patients receiving an aminoglycoside without concurrent cyclosporine in the immediate post-transplant period . Acute nephrotoxicity was not seen in any of the patients . Concomitantly used agents such as acyclovir, vancomycin and amphotericin did not worsen renal function . The present study suggests that aminoglycosides, if carefully monitored, can be safely combined with continuous infusion of cyclosporine without excessive nephrotoxicity.

J Infect, 1991 May, 22(3), 217 - 23
High incidence of vancomycin-associated leucopenia and neutropenia in a cardiothoracic surgical unit; Morris A et al.; A retrospective case record review was undertaken to determine the incidence of vancomycin-associated leucopenia in a cardiothoracic surgical unit . Forty-nine patients received 50 courses of vancomycin therapy . Nine patients (18%) developed reversible leucopenia (white cell count less than 4000 x 10(6)/l) or neutropenia (polymorphonuclear leucocyte count less than 1500 x 10(6)/l) . Four patients (8%) had severe neutropenia (less than 1000 x 10(6)/l) . The median total dosage associated with leucopenia and neutropenia was 30 g, range 22-56 g . The median duration of treatment in leucopenic and neutropenic patients was 22 days, range 6-28 days . The median recovery time to a normal white cell count was 4 days, range 1-11 days . Patients who developed leucopenia on vancomycin therapy did not differ from those who did not with respect to age, total vancomycin dose, length of therapy, underlying illness, incidence of cardiac surgery or use of concomitant medications . Vancomycin-associated leucopenia and neutropenia is common in patients with cardiothoracic infections, many of whom are on several other medications . White cell counts should be estimated regularly in such patients.

Neurosurgery, 1991 May, 28(5), 742 - 5; discussion 745-6
Brain stem abscess treated successfully by medical therapy; Ruelle A et al.; A case of a solitary brain stem abscess in a 55-year-old man is presented . The computed tomographic scan and clinical picture allowed the presumptive diagnosis to be made . The abscess resolved completely after treatment with chloramphenicol, vancomycin, and ceftazidime administered intravenously . Medical therapy should be considered as an effective treatment of a brain stem abscess, provided the antibiotic therapy is administered under close clinical and computed tomographic monitoring.

Infusionstherapie, 1991 Apr, 18(2), 96 - 100
{Decrease in the concentration of tobramycin, vancomycin and phenobarbital in administration with infusion filter}; Bohrer H et al.; To assess the loss of drugs to in-line filters, concentrations of tobramycin, vancomycin, and phenobarbitone were determined in vitro in samples recovered upstream and downstream of the filter . Binding of the drugs to new filters was higher than to used filters . With bolus administration, the concentrations of vancomycin and phenobarbitone were reduced by 1% when using old filters and by 4% when using new filters . Tobramycin concentrations were reduced by 7 and 12%, respectively . With continuous administration of the drugs, binding was highest during the first half hour . Differences between new and used filters were also seen with continuous administration: The cumulative loss was 5% higher with new than with old filters . This difference in binding between filters may stem from a saturation of free binding sites . Tobramycin showed the highest binding to the in-line filter . The extent of adsorption of tobramycin to intravenous filters may be considered moderately important in adult patients . The adsorption of vancomycin and phenobarbitone is not clinically relevant in adult patients.

J Antimicrob Chemother, 1991 Apr, 27 Suppl B, 69 - 73
A review of the safety profile of teicoplanin; Davey PG et al.; Safety of teicoplanin has been assessed in 3377 patients treated in Europe up to the end of June 1990 . One or more adverse events were experienced by 10% of patients . Age and teicoplanin dose had no significant effect on the incidence or type of adverse event . In comparative trials the incidence and profile of adverse events to teicoplanin have been similar to those seen with beta-lactam therapy . Impaired renal function occurred consistently more frequently with vancomycin therapy than with teicoplanin therapy, particularly when these drugs were co-administered with aminoglycosides . Severe skin reactions have not been reported with teicoplanin, which, unlike vancomycin, does not cause infusion rate-related release of histamine . These data provide further evidence that teicoplanin is safer than vancomycin and does not have dose-related adverse effects in the dose range 3-10 mg/kg.

Agents Actions, 1991 Mar, 32(3-4), 217 - 23
Vancomycin-induced release of histamine from rat peritoneal mast cells and a rat basophil cell line (RBL-1); Williams PD et al.; Rapid intravenous administration of the glycopeptide antibiotic, vancomycin, may cause a hypotensive reaction which can usually be prevented by infusing vancomycin in dilute solutions . The release of histamine from circulating cells such as basophils and tissue mast cells has been implicated in hypotensive reactions since the effects can be prevented by antihistamine pretreatment . The direct effects of vancomycin on histamine release were therefore investigated in rat peritoneal mast cells and rat leukemic basophils (RBL-1 cells) . Suspension cultures of mast cells or RBL-1 cells were exposed to vancomycin for 30-60 minutes at concentrations comparable to those infused clinically (2.28 or 4.56 mg/ml) . Vancomycin induced a time- and dose-dependent release of histamine into the culture media from both cell types . The reference degranulating agent, Compound 48/80 (CP 48/80), was also shown to induce histamine release from mast cells and RBL-1 cells . Mast cells were significantly more sensitive to vancomycin and CP 48/80 than RBL-1 cells and, unlike RBL-1 cells, were responsive to the inhibitory effects of cromolyn sodium on histamine release . Cromolyn sodium did not inhibit vancomycin-induced histamine release in RBL-1 or mast cells . Morphologically, mast cells exposed to either vancomycin or CP 48/80 exhibited dose-related degranulation . On the other hand, treatment-related degranulation effects of either vancomycin or CP 48/80 on RBL-1 cells could not be reliably distinguished from controls by qualitative evaluation . Based upon these findings it is concluded that mast cells may represent a more useful model to evaluate the potential of investigational agents to release histamine and to study mechanisms of histamine release than RBL-1 cells.

DICP, 1991 Feb, 25(2), 127 - 9
Gentamicin and vancomycin removal by continuous venovenous hemofiltration; Thomson AH et al.; The dispositions and dose requirements for vancomycin and gentamicin were investigated in a 58-year-old man who was receiving long-term continuous venovenous hemofiltration . Estimates of clearance were obtained using a Bayesian parameter estimation program and stayed remarkably consistent throughout the therapy . Single daily doses of both vancomycin and gentamicin generally maintained the profiles for both drugs around the target ranges of peak 5-10 mg/L (gentamicin) and 25-40 mg/L (vancomycin) and trough less than 2 mg/L (gentamicin) and less than 10 mg/L (vancomycin).

Pathol Biol (Paris), 1991 Feb, 39(2), 131 - 5
{Prevention of septicemia caused by gastrointestinal tract organisms in patients with granulopenia . Comparison of three gastrointestinal tract decontamination treatments}; Ramounau-Pigot A et al.; Three gastrointestinal tract decontamination regimens were tested in patients with granulopenia: vancomycin 250 mg, tobramycin 75 mg, and colistin 1 million international units (regimen A); vancomycin 125 mg, tobramycin 75 mg, and colistin 1 million IU (regimen B); and colistin 1 million IU (regimen C); nystatin was added to all three regimens . Effectiveness was evaluated by stool organism counts and blood cultures to detect bacterial translocation (passage of bacteria from the intestinal tract to the bloodstream) . Regimen C proved insufficiently effective . Regimen A was found to be poorly tolerated by the digestive mucosa . Regimen B was the best treatment since the low dosage of vancomycin proved effective . Nystatin satisfactorily eliminated yeasts.

Perit Dial Int, 1991, 11(1), 31 - 7
Initial treatment of dialysis associated peritonitis: a controlled trial of vancomycin versus cefazolin; Flanigan MJ et al.; OBJECTIVE: To determine if intraperitoneal administration of vancomycin (a slowly absorbed antibiotic) improves the management of dialysis-associated peritonitis over that obtained by using cefazolin, an equally potent, rapidly absorbed antibiotic . SETTING: A university operated teaching hospital, with patient treatment initiated at home . PATIENTS: One hundred thirty-one patients trained to perform peritoneal dialysis (CAPD and CCPD) and followed at the University of Iowa Hospitals and Clinics Home Dialysis Treatment Center . DESIGN: Patients were prospectively allocated into groups adding either vancomycin 25 mgm/L, or cefazolin 50 mgm/L to their dialysate when signs or symptoms of peritonitis developed . Treatment results were analysed using chi-square testing . FINDINGS: Compared to cefazolin, initial peritonitis therapy with vancomycin improved the peritonitis resolution rate {67% vs 81%; p = 0.008}, reduced the incidence of hospital admissions {68% vs 48%; p = 0.001}, and decreased the risk of superinfection {4% vs 0%; p = 0.039} . CONCLUSION: Vancomycin appeared to be superior to cefazolin in the treatment of peritoneal dialysis associated peritonitis.

Am J Kidney Dis, 1991 Jan, 17(1), 76 - 9
Chemical peritonitis secondary to intraperitoneal vancomycin; Charney DI et al.; Although previously reported in the literature, the existence of chemical peritonitis due to vancomycin in patients on peritoneal dialysis remains controversial . We report four similar episodes of sterile peritonitis in three patients receiving intraperitoneal (IP) vancomycin . The prior report implicated a change in the brand of vancomycin preparation, from Vancocin to Vancoled, as a contributing factor . We noted the occurrence of such episodes following a switch from Vancocin to a generic preparation from Abbott Laboratories . High-performance liquid chromatographic (HPLC) profiles of the three preparations show Vancocin to have a lower level of impurities than the other two; the presence of certain contaminants in the other brands may be contributing to the clinical difference observed . We conclude that chemical peritonitis due to IP vancomycin administration does occur, and that increased awareness of this entity could allow other cases to be identified.

J Infect Dis, 1991 Jan, 163(1), 197 - 200
Instillation of vancomycin into a cerebrospinal fluid reservoir to clear infection: pharmacokinetic considerations; Hirsch BE et al.; Vancomycin instilled in an Ommaya reservoir was used to treat a reservoir-associated infection . Vancomycin concentrations in cerebrospinal fluid (CSF) were measured, and derivation of pharmacokinetic parameters allowed tailoring of dosing . First-order kinetics were observed . The calculated half-life of 3.52 h was less than reported by others, and the apparent volume of distribution (60 ml) was less than anticipated . The elimination constant was 0.197 h-1 . Empiric dosing based on schedules suggested in the literature would have led to high peak and low mean concentrations of intrareservoir vancomycin . Patients with reservoir-associated infections have a variety of pathophysiologic conditions that can result in alteration of normal CSF dynamics . Pharmacokinetic analysis is useful to individualize dosing and to optimize therapy with intrareservoir vancomycin.

Lijec Vjesn, 1991 Jan-Feb, 113(1-2), 1 - 9
{Critical review of drugs in 1990}; Vrhovac B et al.; New chemical entities approved abroad (43) and in Yugoslavia (37) were presented . Discussions on several "old" drugs (41) open at the Yugoslav Federal Drug Committee for any reason (new formulation, new dose, new packaging, dosage regimen or indication) and renewal of registration (114) were also included . Special attention was given to the drugs which had been refused the renewal of registration (8) . Critical drug re-evaluation as an important element of the improvement of pharmacotherapy was emphasized . A total of 78 drugs was discussed or registered in 1990-1.28% of drugs from the group A (vancomycin), 10.2% from the group B (aclarubicin, dexfenfluramine, warfarin, alprazolam, colestipol, lovastatin, combination: cetrimonium + lidocain and estradiol vag.), 87.1% (the greatest number so far!) from the group C and 1.28% from the group D . Surveys of the most prescribed drugs in Zagreb, in Yugoslavia and in the world were also given having proved largely non-rational drug prescribing in this country . Further development of drug formulary concept was discussed, primarily for the drugs paid by the Health Insurance, as well as the unsatisfactory ADR reporting in Yugoslavia . Presented were also the activities of the Committee for Diagnosis, Pharmacotherapy and ADR of the Yugoslav Federal Institute for Health Protection . Publishing of Yugoslav daily defined doses is, according to the authors essential for further systematic monitoring of drug consumption on different levels in this country . It would be impossible to rationalize pharmacotherapy without these data.

Am J Nephrol, 1991, 11(5), 369 - 73
Early cannulation of plasma TFE and Gore-Tex grafts for hemodialysis: a prospective randomized study; Jaffers G et al.; Fifty-one consecutive vascular access procedures were randomized to either the Medtronic plasma TFE or Gore-Tex polytetrafluoroethylene (PTFE) conduits in patients requiring immediate dialysis from December 1989 to April 1990 . There were 49 forearm loop fistulas and 2 upper arm grafts . Fifty of these fistulas were cannulated within 48 h of placement to avoid use of subclavian venous catheters for hemodialysis . Complications related to the early cannulation of these fistulas included 2 hematomas in the plasma TFE group, and 3 hematomas in the Gore-Tex group (p = 1.00) . Two patients with Gore-Tex grafts were systemically heparinized prior to hematoma formation after thrombectomy of their accesses . There were no adverse sequelae in these 5 patients, and none of the hematomas interfered with further dialytic therapy . One patient in the plasma TFE group and 3 patients in the Gore-Tex group developed cellulitis within the first month of placement (p = 0.65) . All were treated with intravenous vancomycin with resolution of the erythema . None of the plasma TFE and 3 of the Gore-Tex fistulas thrombosed within 30 days of placement (p = 0.22) . All were salvaged by thrombectomy . Both the plasma TFE and Gore-Tex vascular conduits may be used after surgical placement for early dialytic therapy and are associated with minimal early complications . The early use of these fistulas may eliminate the need for subclavian venous cannulation in most patients with renal failure, thus diminishing the incidence of subclavian venous stenosis and thrombosis . Further observation of these grafts will be necessary to determine the effect of immediate cannulation on their long-term performance for hemodialysis.

Klin Wochenschr, 1991, 69 Suppl 26, 36 - 42
{Renal failure--concepts for drug therapy in intensive care}; Evers J et al.; This article describes concepts of drug treatment for patients with severe renal failure (creatinine clearance less than 10 ml/min), especially in intensive care . These subjects often develop multiorgan failure and require special considerations: 1 . Not only should the maintenance dose of digoxin be reduced to 0.05-0.1 mg/day, but the loading or digitalizing dose should also be diminished to 0.4-0.6 mg . 2 . Penicillins, cephalosporins, quinolones, and other antibiotics with a high therapeutic ratio can be given as recommended by the manufacturer or reference lists according to renal insufficiency . 3 . For drugs with a low therapeutic index, such as aminoglycosides, vancomycin, flucytosine, some antiarrhythmic agents, cardiac glycosides, and theophylline, therapeutic drug monitoring is mandatory . 4 . Steroids, insulin, atropine, catecholamines, anticoagulants, thrombolytic agents, antihypertensive drugs, and organic nitrates can be given according to their effect . However, nitroprusside should be discontinued after 2 days because its metabolites may be toxic . 5 . The dose of H2-receptor antagonists used for the control of gastric acidity and the treatment of peptic ulcers should be reduced to 20-50% of the normal . The administration of aluminum, magnesium, and bismuth compounds should be avoided . 6 . Loop diuretics (e.g., furosemide) can be effective at increased doses in patients with chronic renal failure and fluid overload, particularly when used in combination with a thiazide in refractory edema . Thiazides alone are useless, and potassium-sparing diuretics are contraindicated . 7 . Colloid-containing solutions should be infused cautiously at a maximal rate of 2 x 500 ml/week only when the plasma volume is contracted.(ABSTRACT TRUNCATED AT 250 WORDS)

Dev Pharmacol Ther, 1991, 17(1-2), 95 - 9
Effect of drug combinations on bilirubin-albumin binding; Robertson A et al.; Drugs which compete with bilirubin for albumin binding may increase the risk of kernicterus . Fortunately, few drugs are strong competitors . However, in neonatology, many drugs are used simultaneously . We have studied the effect of drug combinations on bilirubin binding using human serum albumin and the peroxidase method . Combinations of aminophylline with phenobarbital, cefotaxime and vancomycin were studied as well as the combination of vancomycin and cefotaxime . The results show that the bilirubin-displacing effect of the drug combinations cannot be predicted from each drug's individual effect . These results are consistent with a flexible model of albumin binding . Combinations of drugs which are both albumin-bound and reach high serum concentrations should be tested for their combined effect on bilirubin binding and this information used in deciding on treatment in sick, premature infants.

Arch Pathol Lab Med, 1990 Dec, 114(12), 1262 - 3
Zeta potential and vancomycin-red blood cell interactions; Williams L et al.; Vancomycin hydrochloride is a polycationic antibiotic that we have previously reported to cause spontaneous aggregation of red blood cells (RBCs) in vitro at concentrations of more than 3.0 mg/mL, and false-positive direct antiglobulin tests at concentrations of 2.0 and 2.5 mg/mL . These latter reactions were abolished when the RBCs were pretreated with the proteolytic enzyme ficin suggesting an interaction with sialoglycoproteins . In this study we show that prior addition of vancomycin did not block binding of antibodies to several blood group antigens, nor does vancomycin precipitate in an Ouchterlony assay with any of several sialic acid moieties . Finally, we show that vancomycin possesses fluorescent properties but fails to be detected on the RBC surface by flow cytometry . These data indicate that vancomycin may be acting through its polycationic properties . Our findings do not support protein binding of vancomycin to the RBC surface, but underline the importance of the zeta potential in RBC serologic reactions.

Ther Drug Monit, 1990 Nov, 12(6), 562 - 9
Measurement of vancomycin in renally impaired patient samples using a new high-performance liquid chromatography method with vitamin B12 internal standard: comparison of high-performance liquid chromatography, emit, and fluorescence polarization immunoassay methods; Hu MW et al.; A new reverse-phase high-performance liquid chromatographic (HPLC) procedure has been developed for the quantitation of vancomycin and its crystalline degradation product, CDP-1 . The new HPLC procedure involves a liquid-liquid extraction pretreatment procedure and an HPLC internal standard, vitamin B12 . The new HPLC procedure was used to measure 50 renally impaired patient samples . Samples were than analyzed by the monoclonal antibody Emit vancomycin assay, and the polyclonal antibody fluorescence polarization immunoassay (FPIA) vancomycin assay, and the results were compared . The Emit vancomycin assay correlated well with HPLC, but FPIA quantitated higher than Emit and HPLC . We conclude that the polyclonal antibody FPIA assay detects CDP-1 in the samples of renally impaired patients, accounting for an average of 10% of the FPIA/Emit bias, and should therefore be used with caution when monitoring vancomycin levels in renally impaired patients.

J Antimicrob Chemother, 1990 Nov, 26(5), 683 - 8
Influence of teicoplanin and vancomycin on degranulation by polymorphonuclear leucocytes stimulated by various agonists: an in-vitro study; Van der Auwera P et al.; The interaction between vancomycin and teicoplanin (50 and 100 mg/l) on human neutrophils was studied using fMLP- and A23187-induced degranulation of elastase, beta-glucuronidase and vitamin B12-binding-protein . Each of these proteins is a marker of a different population of granules . fMLP-induced degranulation of beta-glucuronidase was significantly impaired by pre-incubating the neutrophils with teicoplanin (without affecting cell viability) although the inhibition was at most 23% at 100 mg/l, a concentration not achieved in the serum of patients after normal doses . Calcium ionophore-induced degranulation of beta-glucuronidase and elastase were slightly impaired (Student two-tailed; P less than 0.1) by both glycopeptides (beta-glucuronidase) and teicoplanin only (elastase) . Again, inhibition remained below 25% . Vancomycin and teicoplanin at high concentrations, seldom achieved in patients, can moderately impair neutrophil degranulation.

Clin Pharm, 1990 Oct, 9(10), 788 - 96
Using population-based serum drug concentration cutoff values to predict toxicity: test performance and limitations compared with Bayesian interpretation; Schumacher GE et al.; The use of population-based serum drug concentration cutoff values for several commonly monitored drugs as tests to distinguish toxicity from nontoxicity was studied . Serum drug concentration and response data published in studies of theophylline, digoxin, aminoglycosides, vancomycin, and procainamide were analyzed to determine the prevalence of toxicity in each group of patients . Serum drug concentration cutoff values were then varied, and the following performance characteristics of the cutoffs as tests for predicting toxicity were calculated for each value: sensitivity, specificity, likelihood ratio, predictive value, and ratio of net consequences . At commonly accepted cutoff values, sensitivity was lower than desirable, positive predictive values were less than negative values, and the ratio of net consequences indicated that false-negative errors are implicitly weighted as more risky than false-positive errors . As the cutoff for each drug was increased, specificity increased but sensitivity decreased, positive predictive values increased but negative predictive values decreased, and the ratio of net consequences increased . Therapeutic drug monitoring would improve if practitioners and laboratorians collaborated to (1) conduct prospective studies of the test performance characteristics of drug concentrations, (2) estimate the pretest probability of toxicity for each patient, (3) combine the pretest estimate with the test characteristics to make a posttest estimate, and (4) develop a more patient-specific, Bayesian approach.

Anesth Analg, 1990 Oct, 71(4), 394 - 9
Hemodynamic effects of rapid vancomycin infusion in critically ill patients; Stier GR et al.; The rapid infusion of vancomycin produces histamine release resulting in rash ("red-man's" syndrome) and hypotension . Because this phenomenon has been described primarily in healthy subjects, we prospectively studied the rapid infusion of vancomycin in 16 critically ill patients after open heart surgery in an attempt to document histamine release with resulting hemodynamic changes, and to see if there is any correlation with vancomycin levels . After establishing baseline hemodynamic stability and histamine levels, 1 g vancomycin diluted in 50 mL of 5% dextrose was infused over 30 min . Cardiac index, heart rate, blood pressure, pulmonary venous pressures, and systemic and pulmonary vascular resistances remained unchanged during the infusion . Although the mean plasma vancomycin level increased to a peak of 69 +/- 20 micrograms/mL after 20 min of the infusion before declining, mean plasma histamine levels in 15 of the 16 patients remained within the normal range during the infusion . In one patient a baseline histamine level (2.8 ng/mL) more than three times the normal before the vancomycin infusion increased further during the infusion (3.0, 4.9, and 5.0 ng/mL at t = 10, 20, and 30 min, respectively), and remained elevated (2.9 ng/mL) 30 min after the infusion . This patient developed the red-man's syndrome, although there were no hemodynamic changes . There was no evidence of myocardial depression in any of the patients . In conclusion, we safely infused a concentrated solution of vancomycin into critically ill patients over 30 min without any adverse hemodynamic changes . One patient developed the red-man's syndrome . There was no correlation between peak vancomycin levels and the release of histamine in this patient population.

No Shinkei Geka, 1990 Sep, 18(9), 807 - 12
{Clinical study of pseudomembranous colitis: a neurosurgical viewpoint}; Sugawara A et al.; In many instances patients who have undergone neurosurgery are given antibiotics . Some of these patients, however, run the risk of developing pseudomembranous colitis . In our department over the past three years, 239 patients, whose hospitalization period exceeded two weeks, were given antibiotics . Of this total number, 6 patients (2.5%) contacted pseudomembranous colitis and a clinical study of these 6 cases was conducted from a neurosurgical viewpoint . This study concentrated on diarrhea, the primary symptom, and the 6 patients consisted of 1 male and 5 females whose ages ranged from 61 to 75 years . All had undergone surgery, and a breakdown of their diseases is as follows: 2 cases of a subarachnoid hemorrhage, 2 cases of an intracerebral hemorrhage, 1 case involving a glioblastoma multiforme, and a case of normal pressure hydrocephalus . Diarrhea was present in all 6 cases and, additionally, pyrexia, abdominal pains, and leukocytosis were seen . On colonoscopic examination, 5 patients were diagnosed as having developed pseudomembranous colitis, and were treated by oral administrations of Vancomycin . In the remaining cases, in which a colonoscopic examination had not been performed, a diagnosis of pseudomembranous colitis had not been achieved and, subsequently, one patient died of multiple organ failure . On autopsy, however, it was determined that the patient had had pseudomembranous colitis . Thus, if symptoms of diarrhea occur during or after administrations of antibiotics, the possibility of pseudomembranous colitis must be assumed, and a colonoscopic examination should be performed immediately, so as to detect the disease at an early stage . This condition can be transmitted within a hospital and, therefore, great emphasis must be placed on preventing secondary infections.

Antimicrob Agents Chemother, 1990 Jul, 34(7), 1459 - 61
Protein binding of vancomycin in a patient with immunoglobulin A myeloma; Cantu TG et al.; Atypical vancomycin pharmacokinetics were observed in an immunoglobulin A myeloma patient . Drug concentrations in serum were extremely elevated, the elimination half-life was prolonged despite normal renal function, and the vancomycin therapy was ineffective . Extensive binding of vancomycin, presumably by high concentrations of an aberrant immunoglobulin A protein, may have accounted for these observations.

Antimicrob Agents Chemother, 1990 Jul, 34(7), 1342 - 7
Different modes of vancomycin and D-alanyl-D-alanine peptidase binding to cell wall peptide and a possible role for the vancomycin resistance protein; Knox JR et al.; A comparison was made of the binding modes of the bacterial cell wall precursor L-lysyl-D-alanyl-D-alanine to the glycopeptide antibiotic vancomycin and to the D-alanyl-D-alanine-cleaving peptidase of Streptomyces sp . strain R61, a model for cell wall-synthesizing enzymes whose X-ray three-dimensional structure is established . In each of the two pairings (vancomycin with peptide and DD-peptidase with peptide), polypeptide backbones were antiparallel, and the antibiotic or enzyme enveloped the peptide substrate from opposite sides . Hydrogen-bonding groups on the substrate which are involved with the DD-peptidase were shown to be different from the ones reported from nuclear magnetic resonance studies to be involved with vancomycin . Because of steric hindrance, the binding of either molecule to the substrate prevents the binding of the other molecule . Binding to the substrate by a D-alanyl-D-alanine-recognizing protein in a manner similar to that used by the DD-peptidase could explain recent observations of vancomycin resistance, in which a new membrane-associated protein has been detected.

Biochem Pharmacol, 1990 Jul 1, 40(1), 27 - 34
Molecular recognition by secondary metabolites; Williams DH et al.; Aspects of molecular recognition based on the interaction between the vancomycin group of antibiotics and bacterial cell wall precursor analogues are discussed . The energetically unfavourable folding-in of the residue 1 sidechain in vancomycin and ristocetin A is discussed in terms of the favourable entropy associated with simultaneous release of solvent molecules . The effect of the sugar amino substituent on the strength of an adjacent hydrophobic interaction in the vancomycin/acetyl-D-Ala-D-Ala complex is rationalised as an intramolecular "salting-out" of hydrocarbon entities . The slow on-rate for dimerisation of the ristocetin A/N,N-diacetyl-L-Lys-D-Ala-D-Ala complex is attributed to the need for the relatively rigid peptide backbone of the antibiotic to be extensively desolvated before dimerisation can occur . Some of these concepts are then applied to understanding the interactions between antibiotics and the minor groove of double-helical DNA, the receptor site with which they have probably evolved to interact . Two structural motifs (pi-polarised aromatic rings and deoxy sugars) are postulated to be important in this recognition process . The possible roles of these structural features are discussed.

Antimicrob Agents Chemother, 1990 Jun, 34(6), 1165 - 71
Application of a Bayesian method to monitor and adjust vancomycin dosage regimens; Hurst AK et al.; A Bayesian method for monitoring vancomycin concentrations and adjusting regimens in patients with unstable renal function by using a two-compartment population model was evaluated with a personal computer . The population model was derived from data from 12 cardiac outpatients who received single doses of vancomycin . The performance of the method was then tested in 27 acutely ill patients who received multiple doses of vancomycin . Significant renal impairment was observed in 15 patients . Renal function changed in 15 patients . The vancomycin concentrations in the patients with changing renal function were not at steady state during the observation times . Two concentrations in serum (peak and then trough, or trough and then peak) were fitted along with the population model to individualize the parameter values for each patient . All the subsequent concentrations in serum for each patient were then predicted by using the parameter values for each patient . Future concentrations of 118 serum samples were predicted . The mean absolute prediction error was 3.6 +/- 4.5 micrograms/ml, and the mean prediction error was -0.7 +/- 5.3 micrograms/ml . These results confirm that a two-compartment pharmacokinetic model can be sufficiently individualized with the knowledge of just two concentrations of drug in patient serum; it is possible to predict closely subsequent concentrations in serum, and dosing regimens for individual patients can be well adjusted to achieve the chosen therapeutic goals.

South Med J, 1990 Jun, 83(6), 720 - 2
Vancomycin-induced toxic epidermal necrolysis; Hannah BA et al.; We have reported a patient who had had renal transplantation for end-stage renal disease; she was treated for fever and presumed sepsis with intravenous tobramycin and vancomycin, with subsequent development of persistent fever, eosinophilia, and a maculopapular rash that progressed to linear bullae . Findings on skin biopsy were consistent with a diagnosis of toxic epidermal necrolysis . Sustained measurable serum concentrations of vancomycin, the temporal response to drug exposure, and the response to steroid therapy suggest vancomycin as the causative agent.

Gut, 1990 Jun, 31(6), 702 - 6
Successful use of vancomycin hydrochloride in the treatment of lactulose resistant chronic hepatic encephalopathy; Tarao K et al.; Vancomycin hydrochloride (2 g daily) was administered to 12 patients with cirrhosis and lactulose resistant portal systemic encephalopathy in a double blind crossover trial . All 12 patients showed a remarkable clinical improvement after vancomycin treatment . The mean (SE) electroencephalographic (EEG) frequency changed from 6.3 (0.2) to 8.5 (0.2) cps (p less than 0.001) and the mean arterial ammonia concentration from 152 (4) micrograms/ml to 97 (8) micrograms/ml (p less than 0.001) . Their clinical condition deteriorated when treatment was switched to lactulose, returning to the previous slower EEG frequency and high arterial ammonia concentrations . Vancomycin seems to be effective in chronic portal systemic encephalopathy in patients who are not helped by lactulose alone.

Antimicrob Agents Chemother, 1990 May, 34(5), 792 - 5
Vancomycin pharmacokinetics in burn patients and intravenous drug abusers; Rybak MJ et al.; The pharmacokinetics of vancomycin were evaluated in 34 patients (10 burn patients, 14 intravenous drug abusers {IVDA}, and 10 controls) . Multiple serum samples were drawn following a 1-h vancomycin infusion at steady state over an 8- to 12-h dosing interval . Pharmacokinetic parameters were derived by noncompartmental analysis . There were no significant differences among the groups with respect to age, weight, serum creatinine, volume of distribution, or protein binding . Burn patients had a significantly higher creatinine clearance than did IVDA or controls . Vancomycin clearances averaged 142.8, 98.0, and 67.7 ml/min in burn patients, IVDA, and controls, respectively . The renal clearance of vancomycin was also higher in burn patients than in the other groups . IVDA tended to have a higher vancomycin clearance (31% higher) than did controls, but the difference was not statistically significant . Vancomycin clearance was much higher in burn patients requiring dosage individualization and close monitoring . A considerable amount of vancomycin was eliminated through renal tubular secretion, making dosage predictions based on creatinine clearance more difficult . Further work with IVDA will be needed to determine if they represent a group requiring aggressive vancomycin dosages.

Antimicrob Agents Chemother, 1990 May, 34(5), 765 - 9
Comparison of vancomycin- and teicoplanin-induced histamine release and "red man syndrome"; Sahai J et al.; Twelve healthy adult males participated in a double-blind, randomized, two-way crossover study to determine histamine release and the frequency and severity of "red man syndrome" (RMS) following intravenous administration of vancomycin (15 mg/kg of body weight over 60 min) and teicoplanin (15 mg/kg over 30 min) . Concentrations of vancomycin and teicoplanin in serum and concentrations of histamine in plasma were measured at baseline and during and after each infusion . Erythema and pruritus were classified a priori as mild, moderate, or severe . The extent of erythema was determined by the use of a burn chart, and pruritus was assessed by the subject with a rank scale . Global severity of RMS was determined by summation of the individual scores for pruritus and erythema . Baseline areas under the concentration-time curve for histamine were not significantly different for the vancomycin and teicoplanin treatments . Vancomycin caused RMS in 11 of 12 subjects (9 severe and 2 moderate cases) and was associated with a significant increase in plasma histamine (46.7 +/- 31.3 ng.min/ml, P less than 0.05) . In contrast, teicoplanin did not cause RMS or elicit significant histamine release (8.7 +/- 13.2 ng.min/ml) . Peak concentrations of vancomycin and teicoplanin in serum were 58.8 +/- 8.4 and 148.0 +/- 31.8 micrograms/ml, respectively (P less than 0.05) . Assuming equal efficacy, these data suggest that teicoplanin may be a safe alternative agent in subjects experiencing severe RMS due to vancomycin; however, further studies in the clinical setting are needed.

J Antimicrob Chemother, 1990 Apr, 25(4), 679 - 87
Nephrotoxicity of vancomycin, alone and with an aminoglycoside; Rybak MJ et al.; The incidence of nephrotoxicity in patients receiving vancomycin alone or in combination with an aminoglycoside was prospectively evaluated . A total of 231 courses of antibiotic therapy in 224 patients were consecutively monitored over 28-month period . One hundred and sixty-eight patients received vancomycin alone, 63 patients received vancomycin with an aminoglycoside, and 103 patients received gentamicin . Nephrotoxicity was defined as an increase in serum creatinine of 0.5 mg/dl or a 50% increase above baseline, whichever was greater . Eight patients (5%) receiving vancomycin alone, 14 patients (22%) receiving vancomycin with an aminoglycoside, and 11 patients (11%) receiving gentamicin alone were found to have nephrotoxicity . Factors found to be associated with increased risk of nephrotoxicity in patients receiving vancomycin were concurrent therapy with an aminoglycoside, length of treatment with vancomycin (greater than 21 days), and vancomycin trough serum concentration (greater than 10 mg/l) . Although the incidence of vancomycin nephrotoxicity is low, patients receiving vancomycin therapy with the above risk factors should be closely monitored.

J Infect Dis, 1990 Apr, 161(4), 721 - 7
Endotoxin increases the nephrotoxic potential of gentamicin and vancomycin plus gentamicin; Ngeleka M et al.; To assess the possible role of endotoxin as an amplification factor for experimental nephrotoxicity due to gentamicin plus vancomycin, rats were given continuous intravenous (iv) endotoxin or saline followed by twice-daily intraperitoneal (ip) saline, vancomycin (20 mg/kg ip), gentamicin (15 mg/kg subcutaneously), or both gentamicin and vancomycin . After 5 or 8 days of treatment, functional and histologic parameters of renal function were evaluated: cortical drug levels, tritiated thymidine incorporation into cellular DNA, creatinine clearance, and appearance by light and electron microscopy . In animals not given endotoxin, only rats that received gentamicin plus vancomycin developed measurable abnormalities . Endotoxin did not cause nephrotoxicity in vancomycin-treated rats . However, in endotoxin-infused rats treated with gentamicin or gentamicin plus vancomycin for 8 days, the increase in blood urea nitrogen, decrease in creatinine clearance, and rise in renal cortical DNA synthesis were more severe than those in non-endotoxin-infused rats (P less than .01) . In these studies, endotoxin amplified the nephrotoxic potential of gentamicin alone and gentamicin plus vancomycin.

Antimicrob Agents Chemother, 1990 Apr, 34(4), 550 - 4
Vancomycin-induced histamine release and "red man syndrome": comparison of 1- and 2-hour infusions; Healy DP et al.; Vancomycin-induced "red man syndrome" (RMS) is mediated in part by histamine release, and its severity is correlated with the area under the plasma histamine concentration-time curve . Ten adult male volunteers participated in a randomized, double-blind, two-way crossover trial (1-week washout interval between regimens) to determine the effect of 1- and 2-h infusions of vancomycin (1.0 g) on histamine release and on the frequency and severity of RMS . The severity of RMS was classified a priori as mild, moderate, or severe from a combined score of pruritus and extent of erythema . Serial concentrations of histamine in plasma and concentrations of vancomycin in serum were measured at baseline and during and after each infusion . Of 10 subjects, 8 had evidence of RMS during the 1-h infusion (3 mild, 3 moderate, and 2 severe), whereas only 3 of the 10 subjects (all mild) had RMS during the 2-h infusion (P less than 0.05) . The 1-h infusion was associated with a significantly greater peak concentration of histamine in plasma (1.8 +/- 0.7 versus 1.0 +/- 0.3 ng/ml, P = 0.004) and a greater total release of histamine (74.3 +/- 54.1 versus 36.4 +/- 22.6 ng.min/ml, P = 0.017) than was the 2-h infusion . These data suggest that administration of vancomycin over 2 h reduces the frequency and severity of RMS and the amount of histamine released compared with those after a 1-h infusion in healthy volunteers.

Biochemistry, 1990 Mar 6, 29(9), 2271 - 7
Structure of vancomycin and a vancomycin/D-Ala-D-Ala complex in solution; Molinari H et al.; Restrained molecular dynamics simulations were used to study the interactions between the glycopeptide antibiotic vancomycin and the dipeptide Ac-D-Ala-D-Ala . Restraints were obtained from a combination of homonuclear and heteronuclear two-dimensional NMR experiments (NOESY, ROESY, 1H-15N inverse correlation) . The comparison between the structures obtained for vancomycin alone and for the complex suggests a new hypothesis on the binding mode of this system . The numerical simulations were not straightforward because vancomycin is made of building blocks for which standard force-fields are not available . The representation of unusual chemical environments is also mandatory . We believe that our extension of the force-field parameters to our system could be of more general interest . Furthermore, we consider vancomycin and its complex a good example for exploring the more general problem of molecular recognition, a challenge that has been widely approached in the past few years but for which no unique and general methodology has, so far, been recognized.

Ther Drug Monit, 1990 Mar, 12(2), 206 - 9
Using clinical data to determine vancomycin dosing parameters; Birt JK et al.; The serum concentrations and pharmacokinetic parameters produced from standard doses of vancomycin were evaluated in 22 patients . The mean (+/- SD) half-life, clearance (Cl), and volume of distribution, respectively, were 6.2 (+/- 1.9) h, 79.2 (+/- 34.3) ml/min, and 0.54 (+/- 0.23) L/kg . Geometric regression analysis was used to determine significant correlations between Cl and creatinine clearance (CrCl) (p less than 0.001) . The dosing method developed is based on the pharmacokinetic parameters of vancomycin derived from our patient data and the relationship between Cl and CrCl described by the following equation, Cl = (0.674) (CrCl) + 13.45 (r = 0.703) . Predictive performance measures were used to compare our dosing method with that of the Matzke nomogram . Our method was found to be less biased and more precise in regards to predicted half-life and volume of distribution, while less biased with no difference in precision in regard to predicting clearance . We plan to use this dosing method at our institution to provide a more individualized initial dosing regimen for vancomycin . Other institutions may wish to use a similar approach to design a dosing nomogram specific for their patient population.

Crit Care Med, 1990 Feb, 18(2), 181 - 3
Clearance of vancomycin during continuous arteriovenous hemodiafiltration; Bellomo R et al.; The clearance of vancomycin during therapy with continuous arteriovenous hemodiafiltration (CAVHD) has been measured in vivo . Vancomycin clearances (n = 16) were 0.636 +/- 0.269 L/h (10.5 +/- 4.46 ml/min) . Effective drug clearances were proportional to ultrafiltrate volumes, reflecting convective clearance . Clearances of vancomycin on CAVHD were approximately twice the values seen with continuous arteriovenous hemofiltration . These data allow construction of a dosing schedule for vancomycin therapy in patients receiving renal support via CAVHD.

Clin Pharmacokinet, 1990 Feb, 18(2), 104 - 17
Drug therapy in patients undergoing continuous ambulatory peritoneal dialysis . Clinical pharmacokinetic considerations; Keller E et al.; Continuous ambulatory peritoneal dialysis (CAPD) is an accepted alternative to haemodialysis in the treatment of end-stage renal failure . The frequently used intraperitoneal administration of antibiotics to treat peritonitis and the possible role of CAPD in the elimination of drugs has stimulated pharmacokinetic research in this field . The 2 principal results derived from these studies are: (1) the elimination capacity of CAPD for drugs given systemically or orally is very low, and (2) drugs administered intraperitoneally rapidly enter the circulation, a significant amount of drug being absorbed from the peritoneal cavity . This pharmacokinetic behavior is easily understood considering some basic and simple pharmacokinetic principles: the higher the volume of distribution of a substance, the lower will be the percentage of drug present in the peritoneal cavity . Thus, a prerequisite for rapid drug elimination by CAPD is a low body volume of distribution of a particular drug . Only in such a case will the drug diffuse into the peritoneal space to a significant extent . For dosing regimens in CAPD patients, the fraction of the dose eliminated by the peritoneal route should be known or estimated . This fraction depends on the relation of the peritoneal clearance to the total body clearance, and on the protein binding of the drug . The low flow rate of the peritoneal effluent (approximately 10 L/day = 7 ml/min) appears to be the most important limiting factor for the low extraction capacity of CAPD . The list of drugs that have been found to be significantly eliminated by CAPD is short: particular mention should be made of the aminoglycosides and some cephalosporins . The data on the peritoneal elimination of vancomycin are inconsistent . Although the intravenous and oral routes have been successfully used for the treatment of peritonitis, the time course of antibiotic concentrations in the peritoneal space appears to favour the peritoneal route of drug administration . During peritonitis, intraperitoneally administered drugs enter the circulation more rapidly and completely, due to the increased permeability of the peritoneal membrane . As long as the dialysate outflow rate and protein binding of the drug are not extensively altered by peritoneal inflammation, however, the extraction capacity of CAPD appears to remain low.

DICP, 1990 Jan, 24(1), 11 - 8
Oral fluoroquinolone versus mono- or combination parenteral therapy in the management of bacterial infections: a critical appraisal; Guay DR; There has been a great deal of interest in the use of oral fluoroquinolone monotherapy rather than mono- or combination parenteral therapy in the management of serious bacterial infections . A review of the published comparative studies and abstracts indicates that, overall, oral fluoroquinolones were at least as effective as, and certainly less expensive than, the parenteral agents studied . However, the spectrum of infection types and the number of patients studied in comparative trials have been small . In addition, ofloxacin and enoxacin were underrepresented in the study material . Oral fluoroquinolones were devoid of the serious adverse effects associated with the aminoglycosides, vancomycin, and the methylthiotetrazole-containing cephalosporins . In general, the incidence of minor adverse effects were similar for the oral fluoroquinolones and comparison parenteral regimens . Meta-analysis of the published reports and abstracts revealed that the oral fluoroquinolones are as effective as parenteral mono- or combination regimens for the treatment of serious bacterial infections in selected patient populations.

J Antimicrob Chemother, 1990 Jan, 25(1), 141 - 7
Pharmacokinetics of once daily intra-peritoneal aztreonam and vancomycin in the treatment of CAPD peritonitis; Brown J et al.; The pharmacokinetics of aztreonam and vancomycin were studied in six adult patients who developed peritonitis during Continuous Ambulatory Peritoneal Dialysis . Aztreonam 3 g was added to the first exchange in each 24 h period with vancomycin 500 mg on the first day and 250 mg on each subsequent day (provided the pre-dose serum vancomycin concentration was less than 10 mg/l) for a total of ten days . Aztreonam and vancomycin concentrations were measured in the serum and dialysate at 1, 2, 6, 12, 18 and 24 h after the initial dose and pre-dose on days 5 and 10 . By the end of the ten day study all patients had recovered clinically and had a normal dialysate . For aztreonam, the mean peak serum concentration was 84.3 mg/l (range 59.6-102.8), the mean 24 h pre-dose serum concentration was 23.0 mg/l (range 8.6-39.2) and the mean 24 h pre-dose dialysate concentration was 15.5 mg/l (range 5.0-32.0) . For vancomycin, the mean peak serum concentration was 10.2 mg/l (range 8.1-12.6), the mean 24 h pre-dose concentration was 5.5 mg/l (range 3.6-6.4), and the mean 24 h pre-dose dialysate concentration was 3.4 mg/l (range 2.4-4.6) . In the treatment of CAPD peritonitis, once daily intra-peritoneal administration of aztreonam 3 g with vancomycin 500 mg initially and 250 mg on subsequent days (serum concentrations permitting) provides concentrations of antibiotic in both the serum and dialysate throughout the 24 h period in excess of the inhibitory concentrations of those organisms most frequently encountered in this condition.

Arch Otolaryngol Head Neck Surg, 1990 Jan, 116(1), 61 - 4
Augmented gentamicin ototoxicity induced by vancomycin in guinea pigs; Brummett RE et al.; Vancomycin has been reported to be an ototoxic drug in the clinical literature . At best, this literature is confusing . There are no reports of ototoxicity of vancomycin in experimental animals, even when it is administered concurrently with ethacrynic acid, a drug known to augment the ototoxic effect of most other ototoxic drugs . In most of the cases of permanent ototoxicity that have been reported, the patient was treated with an aminoglycoside antibiotic as well as vancomycin . This study found no evidence of vancomycin ototoxicity in guinea pigs, but found that vancomycin greatly enhanced the ototoxicity of gentamicin.

Antimicrob Agents Chemother, 1990 Jan, 34(1), 139 - 47
Effects of daptomycin and vancomycin on tobramycin nephrotoxicity in rats; Beauchamp D et al.; Daptomycin is a new biosynthetic antibiotic which belongs to a new class of drugs known as lipopeptides . The objective of this study was to evaluate the effects of daptomycin and vancomycin on tobramycin-induced nephrotoxicity . Female Sprague-Dawley rats were treated during 4 and 10 days with either saline (NaCl, 0.9%) or tobramycin at doses of 4 and 40 mg/kg per day (given every 12 h {q12h} intraperitoneally) . Each treatment was combined with saline, daptomycin at a dose of 20 mg/kg per day (given q12h subcutaneously), and ancomycin at a dose of 50 mg/kg per day (given q12h subcutaneously) . Daptomycin and vancomycin had no effect on the intracortical accumulation of tobramycin . Daptomycin did not accumulate in renal tissue even after 10 days of treatment . Tobramycin given at a dose of 40 mg/kg per day during 10 days induced a significant inhibition of sphingomyelinase activity in the renal cortex (P less than 0.01) and increased cellular regeneration (P less than 0.01), as measured by the incorporation of {3H}thymidine into DNA of the renal cortex . These changes were minimal when daptomycin was combined with tobramycin . Histologically, signs of tobramycin toxicity were also less severe in the presence of daptomycin . The intracortical accumulation of vancomycin was not modified by tobramycin . The sphingomyelinase activity was significantly more inhibited (P less than 0.01) when vancomycin was associated with tobramycin (4 and 40 mg/kg) without affecting the rate of {3H}thymidine incorporation into DNA . Histologically, signs of tobramycin toxicity were not affected by vancomuycin, but the cellular vacuolizations which were also observed in vancomycin-treated animals were still present in the proximal tubular cells of animals that were treated with the combination vancomycin-tobramycin . This study strongly suggests that daptomycin protects animals from tobramycin-induced nephrotoxicity but that vancomycin may enhance the effect of tobramycin . We conclude that daptomycin is safe and protects kidney cells from tobramycin-induced nephrotoxicity.

J Pharm Biomed Anal, 1990, 8(6), 513 - 20
Determination of EDTA in vancomycin by liquid chromatography with absorbance ratioing for peak identification; Inman EL et al.; An LC method is described for the determination of EDTA in vancomycin formulations . EDTA is complexed with iron and the Fe(EDTA)- complex is separated from vancomycin components on a reversed-phase column using an ion pair mobile phase . Quantitation is achieved using UV detection, with absorbance ratioing employed to discriminate between the analyte and vancomycin-related compounds . The complexity of the sample matrix and the trace levels of EDTA that are of interest dictate unique development considerations . This method offers good specificity and precision over the range 20-300 ppm EDTA in vancomycin formulations, while maintaining a degree of simplicity . Wavelength selection is optimized to demonstrate the potential application of absorbance ratioing to trace determinations . This method has been effectively applied to vancomycin formulations containing a wide range of chemical impurities and is not affected by vancomycin degradation products.

Perit Dial Int, 1990, 10(4), 283 - 5
Vancomycin absorption from the peritoneal cavity during dialysis-related peritonitis; Rubin J; The uptake of vancomycin from the peritoneal cavity during acute episodes of peritonitis was compared to noninfected patients in 14 patients, 7 of whom had dialysis-related peritonitis . Treatment consisted of 8 hourly dialysate exchanges, followed by 4-h dwells containing 37.5 mg/L of vancomycin . On day 4, serum vancomycin concentrations were 13.4 +/- 4.8 mg/L in the controls and 15.5 +/- 6.8 mg/L in the group with peritonitis . After 180 min in the peritoneal cavity, 61% +/- 13% of the infused vancomycin remained in controls and 30% +/- 15% in patients with peritonitis (p less than 0.05) . Uptake of vancomycin from the peritoneal cavity is enhanced during episodes of peritonitis.

Eur J Clin Pharmacol, 1990, 39(5), 457 - 61
Drug utilization review in a teaching hospital: experience with vancomycin; Misan GM et al.; A prospective, two-phase, drug utilization review (DUR) was performed at the Royal Adelaide Hospital (RAH) to determine the extent and pattern of vancomycin use . For all patients commencing oral or parenteral vancomycin, treatment indication, route of administration, duration of therapy, results of culture and sensitivity tests, adverse drug reactions and results of therapeutic drug level monitoring were recorded . Vancomycin courses were classified as being for therapy or prophylaxis and compared with predetermined audit criteria to assess appropriateness of use . During the 8 week initial phase, data on 62 treatment courses in 59 patients were recorded, 50% for therapy and 50% for prophylaxis . Sixty four percent were classified as inappropriate, occurring in 32% of therapeutic courses and 97% of those for prophylaxis . During the 10 week re-evaluation, conducted 10 months later, data for 43 treatment courses in 43 patients were reviewed, 42% for therapy and 58% for prophylaxis . Sixty five percent were inappropriate occurring in 17% of therapeutic courses and 100% of the prophylactic courses . When compared with the initial phase, the re-evaluation demonstrated a decrease in the empirical use of vancomycin in the combination treatment of neutropaenic fever and also in the duration of vancomycin use for surgical prophylaxis . During both study phases, criteria contraventions were mostly due to inappropriate indication or duration of therapy . The cost of inappropriate vancomycin use was reduced by over 50% between survey phases, from $Aus11,500 or 55% of total vancomycin cost during the initial phase to $Aus3,600 or 25.7% during the re-evaluation . The most effective of the remedial strategies implemented after the initial phase was direct consultation with prescriber groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Rev Med Univ Navarra, 1990 Jan-Mar, 34(1), 51 - 4
{Intensive chemotherapy with 1-3 drugs and support with autologous myelopoietic cells extracted from the peripheral blood: the preliminary results}; Sureda M et al.; Fourteen patients with different solid tumors have been treated with high-dose combination chemotherapy followed by autologous PBSC support . A total of 15 procedures have been done . 4,5-7 x 10(10) mononuclear cells were obtained through 1-4 leukapheresis using a CS-3.000 continuous flow blood cell separator . Cells were maintained in standard culture conditions for 3-5 days prior to infusion . Chemotherapy consisted in the administration of 1-3 agents: CPA 80 mg/kg; VP-16, 800 mg/m2; BCNU 700-800 mg/m2, CBDCA 1.000 mg/m2 . APBSC were infused 48 hours after the last chemotherapy was given . Patients were maintained in single-bed rooms with standard prophylactic antibiotics, including gentamycin, piperacillin, vancomycin and amphotericin B during the period of aplasia . Currently 5 procedures are available for response and all patients are evaluable for toxicity . Responses have been: 2 complete responses and 3 partial response . All patients entered in aplasia, with 12 infections (73%), 8 bleeding (53%), 4 diarrhea (27%), 2 stomatitis (13%) and 3 renal failure (16%) . Conclusions: 1 . Bone marrow recovery after high dose chemotherapy can be shortened with APBSC support . 2 . APBSC can be safely maintained using standard culture techniques, thus avoiding the freezing procedure.

Adv Perit Dial, 1990, 6, 123 - 5
Efficacy of vancomycin plus tobramycin as antiperitonitis regimen for patients on CAPD; Vargemezis V et al.; From October 1985 to August 1989, 55 episodes of peritonitis were treated with intraperitoneal (i.p.) use of Vancomycin (V) and Tobramycin (T), in 35 patients (18 males, 17 females) . After three rapid IL peritoneal exchanges, the pts received i.p . loading dose of V500 mg/L and an intramuscular dose of T 1.7 mg/Kg, followed by four IL exchanges, with addition of V15 mg/L and T8 mg/L . The length of treatment was 10 days for all pts . The continued administration of V or T as the simple antibiotic regimen was based on the antibiogram, while the combination of both antibiotics was used in negative cultures . Recurrence of peritonitis was seen in 3 episodes (5.4%) . No side effects were seen during the therapy . These results indicate that the i.p . use of Vancomycin plus Tobramycin are an appropriate antiperitonitis regimen in the treatment of CAPD peritonitis.

Appl Environ Microbiol, 1990 Jan, 56(1), 49 - 53
Isolation of Legionella longbeachae serogroup 1 from potting mixes; Steele TW et al.; Following a statewide outbreak of legionellosis due to Legionella longbeachae serogroup 1 in South Australia in 1988 and 1989, studies were performed to find a source of the organism . A number of water and soil samples with and without acid decontamination were examined for L . longbeachae by using a selective medium containing vancomycin, aztreonam, and pimafucin . There were no isolations of L . longbeachae from water samples . Organisms resembling L . longbeachae were isolated from a number of samples of potting mixes and from soil surrounding plants in pots collected from the homes of four patients . The organisms were found to persist for 7 months in two potting mixes stored at room temperature . Legionellae were isolated with difficulty from potting mixes which were allowed to dry out . Identification of isolates as L . longbeachae serogroup 1 was confirmed by quantitative DNA hybridization and serological tests . Restriction-fragment-length-polymorphism studies showed minor differences between patient and environmental isolates but differentiated these readily from L . longbeachae serogroup 2 and other antigenically related legionellae . The isolation of L . longbeachae from some potting mixes and the prolonged survival of the organisms in this medium suggest that soil rather than water is the natural habitat of this species and may be the source of human infections.

J Hosp Infect, 1990 Jan, 15(1), 95 - 102
Double-blind placebo controlled study of vancomycin prophylaxis for central venous catheter insertion in cancer patients; Ranson MR et al.; To assess whether vancomycin administration at the time of central venous catheter insertion would prevent catheter-related sepsis (CRS) in immunocompromised patients, 98 cancer patients were entered into a randomized placebo-controlled trial . Patients were stratified according to whether they were having therapy for acute leukaemia or undergoing bone-marrow transplantation (group A) or required chemotherapy for a solid tumour (group B) . Eligible patients were randomized to receive either 500 mg vancomycin in 250 ml of 0.9% saline prior to catheter insertion followed by a further 500 mg infused via the established catheter, or the same regimen with 0.9% saline alone . In group A, there were 32 instances of CRS occurring in 20 of the 35 evaluable catheters (57%) . Six catheters were removed because of CRS . No significant difference was found in the incidence of CRS between the two arms . Of the 37 evaluable catheters in group B, CRS occurred in 6 (16%), and none of the catheters required removal because of CRS . Again, no significant differences were found in the incidence of CRS between the patients given vancomycin or placebo . These findings indicate that the incidence of CRS is greater in patients who have more severe and prolonged immunosuppression and that vancomycin prophylaxis fails to reduce CRS in patients undergoing chemotherapy for malignant disease.

Ann Otol Rhinol Laryngol, 1989 Dec, 98(12 Pt 1), 950 - 4
Audiologic threshold monitoring of patients receiving ototoxic drugs . Preliminary report; Meyerhoff WL et al.; An effort was made to determine the efficacy of auditory threshold monitoring of patients receiving ototoxic drugs . Forty-four patients treated with either tobramycin or vancomycin for osteomyelitis were tested at the beginning of treatment, following treatment, and twice weekly during treatment when possible . All patients had renal function carefully monitored . Peak and trough drug levels were kept out of the toxic range throughout the study . In no patient did indisputable ototoxicity occur, and therefore, no conclusion about the most efficacious schedule for auditory monitoring of patients receiving ototoxic drugs was made, and what constitutes a significant intratherapeutic threshold shift is still in question . Until further data are collected, monitoring of renal function and peak and trough drug levels, as well as patient counseling, is recommended . Pretherapy and posttherapy auditory monitoring and intratherapeutic monitoring of high-risk patients and those who develop aural symptoms may prove beneficial.

Am J Med Sci, 1989 Nov, 298(5), 299 - 304
Sodium protects against nephrotoxicity in patients receiving amphotericin B; Stein RS et al.; Neutropenic patients receiving amphotericin B, frequently in combination with aminoglycosides and vancomycin, were prospectively monitored for the development of nephrotoxicity . Based on previous studies, the authors recommended that these patients receive greater than or equal to 90 meq of sodium/day on each day of amphotericin B administration . Patients who received this amount of sodium on every day of amphotericin B therapy were classified as adequate sodium . The adequate sodium group was further subdivided on the basis of whether or not the adequate sodium was in the form of sodium ticarcillin . Patients not receiving this amount of sodium on every day of amphotericin B therapy were classified as inadequate sodium; overall, these patients received greater than or equal to 90 meq of sodium/day on 74% of days on which they received amphotericin B . The inadequate sodium and adequate sodium groups did not differ significantly with respect to age, gender, diagnoses, or baseline creatinine . The incidence of nephrotoxicity (creatinine greater than or equal to 2.0 mg/dl) was significantly higher, 4 of 14 (29%), in the inadequate sodium group, as compared to the adequate sodium, adequate ticarcillin group, 1 of 35 (3%), or the adequate sodium only group, 1 of 24 (4%), p = .008 . To adjust for total amphotericin dose, the risk of nephrotoxicity as a function of time on study was evaluated by the life table method; the risk of nephrotoxicity was significantly greater in the inadequate sodium group, p = .019.(ABSTRACT TRUNCATED AT 250 WORDS)

J Antimicrob Chemother, 1989 Nov, 24(5), 797 - 803
Long-term accuracy of fluorescence polarization immunoassays for gentamicin, tobramycin, netilmicin and vancomycin; Joos B et al.; External quality control was performed during six years to determine the accuracy over time of the Abbott TDx fluorescence polarization system for assaying antibiotics . Unknown spiked serum samples of gentamicin, tobramycin, netilmicin and vancomycin were provided monthly by the British national external quality assessment scheme . Comparison of the 209 assay results with the target concentrations showed good correlations in all four assays . No significant deviations from linearity, from slope 1.0, and from intercept 0.0 were detected by regression analysis . Relative deviations were less than 10% and less than 15% for 78% and 90% of all specimens, respectively . On an average the same calibration curves could be used over a period of 19 weeks . Fluorescence polarization immunoassays provided rapid and reliable results over the entire study period.

J Infect Dis, 1989 Nov, 160(5), 876 - 81
Influence of antihistamine pretreatment on vancomycin-induced red-man syndrome; Sahai J et al.; Twelve adult male volunteers participated in a double-blind study to determine the effect of pretreatment with histamine and/or histamine2 receptor antagonists on the incidence and severity of vancomycin-induced "red-man syndrome." Subjects received hydroxyzine, 50 mg, ranitidine, 300 mg, hydroxyzine plus ranitidine, or placebo at weekly intervals 2 h before a l-h infusion of vancomycin, 1,000 mg . The extent of erythema was evaluated by burn chart and pruritus was assessed by each subject using a rank scale; symptoms were thus classified a priori as mild, moderate, or severe and their summation determined a global severity score for red-man syndrome . There was no significant intrasubject variation between area under the concentration-time curves for histamine and vancomycin (P greater than .05) . Pretreatment with hydroxyzine alone provided significant protection against vancomycin-induced erythema and pruritus (P less than .05) whereas the effect of ranitidine did not differ significantly from placebo . The combination of hydroxyzine and ranitidine offered no advantage over hydroxyzine alone . Similar results were observed for global severity scores . Thus in normal volunteers prior administration of a histamine antagonist (hydroxyzine) provided significant protection against vancomycin-induced red-man syndrome compared to that afforded by placebo . There was no significant benefit from the histamine antagonist alone or by its addition to a histamine antagonist.

J Burn Care Rehabil, 1989 Sep-Oct, 10(5), 425 - 8
The influence of serum albumin and alpha 1-acid glycoprotein on vancomycin protein binding in patients with burn injuries; Zokufa HZ et al.; Ten patients with burn injuries (mean total body surface area burn = 29% +/- 16) were studied at various points in the course of their burn therapy . Alpha 1-Acid glycoprotein, albumin, and vancomycin concentrations were determined with either a trough or peak vancomycin quantitative determination . Alpha 1-Acid glycoprotein concentrations ranged from 125 to 333 mg/dl and albumin concentrations ranged from 1.7 to 4.2 gm/dl . Vancomycin protein binding, as determined by ultrafiltration, averaged 29% +/- 6% . There was a strong (r = 0.92) relationship between percent protein-bound vancomycin and albumin . There was a poor statistical relationship between percent protein-bound vancomycin and alpha 1-acid glycoprotein (r = 0.28) . Alpha 1-Acid glycoprotein appeared to have virtually no effect on the protein-binding characteristics of vancomycin over the range of concentrations studied.

Ther Drug Monit, 1989 Sep, 11(5), 585 - 91
Potential problem with fluorescence polarization immunoassay cross-reactivity to vancomycin degradation product CDP-1: its detection in sera of renally impaired patients; Anne L et al.; During the development of a homogeneous immunoassay for the antibiotic vancomycin, we observed in certain patient samples a quantitation difference between the enzyme multiplied immunoassay technique (EMIT) method and the comparison method, fluorescence polarization immunoassay (FPIA) . This prompted us to evaluate the integrity of vancomycin in samples from renally impaired patients . Since it has been reported in the scientific literature that vancomycin degrades into an antibiotically inactive crystalline degradation product (CDP-1) in vitro, we developed high-performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS) methods to determine whether CDP-1 is present in patient sera . HPLC and LC/MS analysis on samples from renally impaired patients positively identified CDP-1 in fresh samples . Next, we tested the cross-reactivity of three currently available vancomycin immunoassays, radioimmunoassay (RIA) FPIA, and EMIT, to CDP-1 prepared in our laboratory . Our data suggest that CDP-1 is recognized by FPIA and RIA, both polyclonal antibody-based methods, but not by EMIT, which uses a monoclonal antibody.

Arch Intern Med, 1989 Aug, 149(8), 1777 - 81
Mild nephrotoxicity associated with vancomycin use; Downs NJ et al.; Nephrotoxicity related to vancomycin hydrochloride therapy has been reported at overall rates of 7% to 16% and as high as 35% when combined with an aminoglycoside antibiotic . We conducted a prospective study in older men . A group that received vancomycin was compared with a control group to determine the incidence of nephrotoxicity secondary to vancomycin therapy alone and in combination with aminoglycosides, to identify possible risk factors associated with nephrotoxicity, and to determine the incidence of other adverse effects associated with vancomycin use . Nephrotoxicity occurred in 11 (17%) of 66 patients receiving vancomycin and in 3 (5%) of 57 controls overall . Stepwise logistic-regression analysis failed to identify underlying illnesses or concurrent risks that may have contributed to the development of nephrotoxicity associated with vancomycin . Adverse effects, including phlebitis (14%), neutropenia (1%), rash (0%), and red neck syndrome (0%), occurred at rates similar to previous reports.

Clin Chem, 1989 Aug, 35(8), 1766 - 70
Estimation of reference intervals for total protein in cerebrospinal fluid; Lott JA et al.; Protein in cerebrospinal fluid (CSF) was measured by a modified biuret procedure and in two automated instruments, the Du Pont aca and the Kodak Ektachem . The latter's dry-slide reagent was also evaluated for precision, linearity, and effect of potential interferents . In vitro, ampicillin and vancomycin increase the apparent value for CSF protein as measured with the Ektachem slides . We excluded patients with disorders of the central nervous system, and we estimated the central 95% percentile reference intervals for CSF protein for each of the three methods . We found no age or gender dependence of values . By the biuret procedure, the reference interval is 140 to 620 mg/L.

Can J Hosp Pharm, 1989 Aug, 42(4), 153 - 6
Intravenous vancomycin usage in a tertiary care hospital; Madsen M et al.; Intravenous vancomycin usage at our institution was examined by a five-month retrospective chart review . Cardiovascular surgery, neurosurgery, and intensive care units accounted for the most use . Sixty courses in 48 patients were reviewed; 42 percent was considered inappropriate, which extrapolated to an annual drug acquisition cost of $51,338 . Inappropriate use was categorized as mainly due to documented infection with a beta-lactam sensitive organism in a patient with no history of an allergy (40 percent of inappropriate use) and excessive duration of empiric therapy (28 percent of inappropriate use) . Concurrent monitoring by pharmacy staff was felt to be the approach most likely to be effective in modifying this problem.

Clin Chem, 1989 Jul, 35(7), 1504 - 7
Clinical performance of the EMIT vancomycin assay; Yeo KT et al.; In evaluating the EMIT system for vancomycin used in the Cobas Bio centrifugal analyzer, we found two potential problems, each of which may have important clinical ramifications . First, precision, though acceptable in concentrations up to 30 mg/L, was marginal in the range above 30 mg/L . Second, when EMIT values were compared with those by fluorescent polarization immunoassay (TDx), we found a good correlation but a significant proportional bias: {EMIT} = (0.877){TDx} + 0.435 mg/L (r = 0.971) . The proportional bias was much more pronounced in specimens with high creatinine values than in specimens with normal values for creatinine . It remains to be determined which method is more nearly accurate . This imprecision and proportional bias in specimens with increased creatinines lead us to conclude that the EMIT vancomycin system should be used with caution.

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