Arch Intern Med, 1989 Jun, 149(6), 1425 - 6 Vancomycin allergy presenting as fever of unknown origin; Clayman MD et al.; A 37-year-old woman receiving long-term hemodialysis was admitted to the hospital with a fever of unknown origin (6 weeks of unexplained, persistent, low-grade fever) . Although she had received vancomycin hydrochloride 5 days before the onset of fever, the drug was not suspected as the cause because of the duration of fever, the administration of vancomycin on prior occasions without incident, and the lack of allergic stigmata . After hospitalization, vancomycin and gentamicin sulfate were administered empirically . Immediately thereafter, her temperature rose to 40 degrees C, and over the ensuing 24 hours, eosinophilia and a maculopapular rash developed that resolved entirely when antibiotic therapy was stopped and low-dose steroid therapy was instituted . The prolonged hypersensitivity reaction after a single dose of vancomycin is consistent with the greatly extended half-life of this drug in the population with end-stage renal disease and should alert physicians to the possibility of such persistent idiosyncratic reactions in this group. Pediatr Infect Dis J, 1989 Jun, 8(6), 354 - 7 Use of aminoglycosides during cyclosporine A immunosuppression after liver transplantation in children; Leach CT et al.; To determine the frequency of renal dysfunction associated with the use of aminoglycosides with cyclosporine A (CyA) in children, the records of 26 consecutive children receiving CyA after liver transplantation were reviewed . Fourteen patients with normal baseline serum creatinine concentrations received an aminoglycoside postoperatively . These children received CyA and an aminoglycoside for 249 days (average, 17.8 days/patient) . Forty of the 249 days included treatment with vancomycin or amphotericin B . Twelve children (86%) showed no evidence of renal dysfunction after aminoglycoside therapy . Two children developed renal dysfunction and eventually succumbed . In neither case could aminoglycoside nephrotoxicity be identified as the main cause of renal dysfunction . Multiple other factors, including ischemia and high CyA concentrations, probably contributed to renal deterioration . We conclude that aminoglycosides can be used safely in children receiving CyA following liver transplantation, provided serum CyA concentrations are followed closely and other risk factors for renal dysfunction are minimized. Toxicol Appl Pharmacol, 1989 Jun 1, 99(1), 61 - 71 Gentamicin-induced renal metabolic alterations in newborn rat kidney: lack of potentiation by vancomycin; Kacew S et al.; Daily subcutaneous administration of 20 or 100 mg/kg gentamicin for 4 days significantly decreased pyridoxal-5'-phosphate and lysosomal specific phosphatidylinositol-phospholipase C (PI-PLC) in newborn rat kidney . The fall in PI-PLC was associated with an elevation in renal phosphatidylinositol, phosphatidylserine, and phosphatidylcholine . The 100 mg/kg gentamicin dose also produced a rise in renal sphingomyelin, phosphatidylethanolamine, phosphatidylglycerol, and total phospholipid (TPL) accompanied by inhibition in the activities of Na+,K+-ATPase and alkaline phosphatase . In contrast, daily intraperitoneal injection of 100 mg/kg vancomycin for 4 days failed to markedly alter renal metabolic parameters . However, the 500 mg/kg vancomycin dose increased kidney weight, TPL, and all individual phospholipid class concentrations accompanied by inhibition of lysosomal specific PI-PLC activity and reduced pyridoxal-5'-phosphate levels . Simultaneous administration of 20 mg/kg gentamicin with either vancomycin dose resulted in renal alterations similar to those produced by gentamicin alone . Concurrent treatment with 100 mg/kg aminoglycoside and either vancomycin dose produced changes in kidney which were similar to those produced by gentamicin alone, except for a synergistic rise in PI as well as a greater fall in alkaline phosphatase and pyridoxal-5'-phosphate . Surprisingly, the concentration of gentamicin and vancomycin was less in newborn kidneys of rats receiving a simultaneous high dose of vancomycin and aminoglycoside treatment compared to levels found in animals given either antibiotic separately . The lack of potentiation of nephrotoxicity in newborns administered a combination of vancomycin and gentamicin may be due to decreased accumulation of either antibiotic in kidney. Eur J Clin Microbiol Infect Dis, 1989 Jun, 8(6), 529 - 31 Elimination of vancomycin during hemofiltration; Rawer P et al.; The study was designed to establish guidelines for vancomycin treatment of patients with acute renal failure undergoing hemofiltration . During 27 hemofiltration treatments in four anuric patients requiring daily consecutive hemofiltration therapy, plasma levels and elimination rates of vancomycin were measured . Regression analysis of the initial vancomycin concentration versus the total amount of vancomycin eliminated showed a clear linear relationship (r = 0.91), thus permitting prediction of the total elimination via hemofiltration by measurement of the initial plasma concentration . Applying these calculations the dosage in patients undergoing hemofiltration can be determined by monitoring the initial plasma concentration . The findings also indicate that hemofiltration is an effective method for treatment of vancomycin intoxication. Br J Anaesth, 1989 May, 62(5), 576 - 7 Perioperative complications following the use of vancomycin in children: a report of two cases; Best CJ et al.; We describe two patients in whom rapid administration of vancomycin caused severe hypotension . Possible mechanisms for this effect are discussed, with reference to the role of the anaesthetist as administrator of drugs prescribed by others . Recommendations are made on safe administration of vancomycin with respect to rate of infusion and possible interactions. Anaesthesist, 1989 May, 38(5), 225 - 32 {Dosage adjustment of drugs during continuous hemofiltration . Results and practical consequences of a prospective clinical study}; Kroh U et al.; In 43 ICU patients undergoing continuous volume constant hemofiltration (CVHF), the pharmacokinetics of 12 drugs were investigated to ensure correct dosage adjustments . Under conditions of CVHF, maximum doses were defined for cefotaxime, ceftazidime, digoxin, digitoxin, imipenem, metronidazole++, netilmicin, phenobarbital, phenytoin, theophylline, tobramycin, and vancomycin . For the estimation of sufficient doses without blood level measurements, sieving coefficients (S) were calculated by a new method . In addition, S was integrated as a CVHF-specific factor into a common equation for drug dose adjustment in patients with renal insufficiency . The regression of dosage received from kinetics on blood-level-independent equation adjustment was r = 0.9923 . Since the volumes of distribution in ICU patients are variable, it is suggested that further drug monitoring is necessary for toxic drugs. Pediatr Infect Dis J, 1989 May, 8(5), 282 - 6 Vancomycin pharmacokinetics in very low birth weight neonates; Leonard MB et al.; The pharmacokinetics of vancomycin hydrochloride was studied in 12 very low birth weight infants . The gestational age (mean +/- SD) was 25.9 +/- 1.3 weeks and body weight was 769.2 +/- 151.5 g at the time of initiation of the study . Vancomycin was infused over a period of 60 minutes in a dosage of 14.2 +/- 3.2 mg/kg once daily in 10 patients, twice daily in 1 patient and every 36 hours in 1 patient for a mean of 10.5 +/- 4.9 days . Serial blood samples were obtained and the concentration time data were fitted to a one-compartment open model using the ADAPT computer program . A significant positive correlation was found between postconceptional age and vancomycin clearance (P less than 0.005) and between vancomycin elimination half-life and plasma creatinine (P less than 0.01) . A negative correlation existed between plasma creatinine and vancomycin clearance (P less than 0.005), between postconceptional age and plasma creatinine (P less than 0.005) and between vancomycin half-life and postconceptional age (P less than 0.01) . On the basis of these findings a vancomycin dosage of 15 mg/kg every 24 hours for infants less than 1000 g should yield concentrations within the accepted therapeutic range . This susceptible population requires frequent monitoring of vancomycin concentrations because of the high degree of interpatient variability and the continuous maturation of renal function. Pathol Biol (Paris), 1989 May, 37(5), 455 - 8 {Effect of teicoplanin and vancomycin on cerebrospinal fluid proteins of non-infected rabbits after suboccipital injection}; Manquat G et al.; The IC inoculation of antibiotics into the CSF for therapeutic use could produce biological effects we should consider when analysing samples . To corroborate this assumption, we observed the effect of ICI T and V on the PL of the CSF of non infected rabbits . T and V were ICI as dosage of 1 mg/kg diluted in 0.2 ml of isotonic saline solution (ISS) . ISS was also ICI alone . CSF samples were obtained before inoculation from 41 animals (T0) setting the normal PL . Other samples were obtained 2 (T2) and 4 hours (T4) after inoculation . PL were assayed in an Analyser Clinic Automatic (Du Pont) . The statistical analysis was performed by the Kolomogorov-Smirnov Test, for comparison of samples from unknown and not necessarily similar distributions . Results were (mg/l) = PL at T0 = 0.20 +/- 0.08 . At T2, levels were 0.6 +/- 0.41 (ISS), 0.73 +/- 0.27 (V) and 0.87 +/- 0.44 (T) . At T4 they were 0.3 +/- 0.15 (ISS), 0.55 +/- 0.25 (V) and 0.78 +/- (T) . Statistical differences (p less than 0.05) were demonstrated at T2 (T, V and ISS vs control at T0), at T4 = V, vs control at T0 but not between the two antibiotics nor between the two antibiotics and ISS, at any time . We conclude that IC inoculation of T and V and ISS increased significantly the CSF PL. DICP, 1989 Apr, 23(4), 294 - 300 Evaluation of a Bayesian method for predicting vancomycin dosing; Burton ME et al.; The purpose of this study is to evaluate the performance of a vancomycin dosing program in predicting dosages necessary to achieve desired serum vancomycin concentrations in a relatively large patient population . With the completion of initial performance evaluation, revised pharmacokinetic parameter estimates derived in the initial evaluation are used to reevaluate program performance . The program uses population estimates of vancomycin's volume of distribution (Vd) and clearance (Cl) to initially predict dosing, then individualizes those estimates by a Bayesian algorithm (iterations) which uses dosing and the resulting serum vancomycin concentration data . Use of the Bayesian forecaster with one iteration significantly increases the calculated Cl value as compared with population estimates; two and three iterations significantly increase both Vd and Cl when compared with population estimates . Absolute values of the predicted minus observed peak serum vancomycin concentrations (accuracy) are 17.7 +/- 14.0, 6.1 +/- 3.6, and 3.4 +/- 2.1 mg/L for dosing using population estimates, Bayesian with one iteration, and Bayesian with two iterations, respectively . Similarly, accuracy of predictions for trough concentrations is 13.8 +/- 12.4, 3.5 +/- 3.2, and 3.2 +/- 2.6 mg/L for each method, respectively . Bias of dosing predictions in achieving desired peak and trough serum vancomycin concentrations is also significantly reduced by using the Bayesian algorithm . Use of the mean Vd and Cl values from three iterations as the starting parameters in a new group of 12 patients significantly improves program performance when compared with use of initial population parameters . Time of sampling for peak serum concentrations has no effect on program performance . In patients with impaired renal function, use of population estimates resulted in less accurate dosing prediction, but this less accurate performance was not observed with use of the Bayesian forecaster . These data demonstrate the accuracy and lack of bias in individualized dosing predictions using the Bayesian dosing method and the ability of revised pharmacokinetic parameter estimates to improve performance. Neonatal Netw, 1989 Apr, 7(5), 31 - 5 Vancomycin: current perspectives and guidelines for use in the NICU; Fogarty KA et al.; Vancomycin is an important antibiotic agent that is being used with increasing frequency in the NICU . The nurse administering this agent must have adequate knowledge of the indications and pharmacologic actions of this product . Appropriate drug administration and patient assessment are also essential in maximizing therapy and reducing the risk of toxicity. J Chromatogr, 1989 Feb 24, 487(2), 421 - 7 Rapid and specific method for the determination of vancomycin in plasma by high-performance liquid chromatography on an aminopropyl column; Hosotsubo H; A high-performance liquid chromatographic method has been developed for the quantitative analysis of vancomycin in plasma . The method involves protein precipitation with acetonitrile, followed by normal-phase chromatography on an aminopropyl column . The clear supernatant was injected after centrifugation, and the eluent was monitored at 240 nm . No interference was found either with endogenous substances or with many currently used drugs, indicating a good selectivity for the procedure . The standard curve was linear between 0.1 and 100 micrograms/ml, and the detection limit was 0.01 microgram/ml of plasma . The mean intra- and inter-assay coefficients of variation were 2.4 and 4.0%, respectively, in the 10-50 micrograms/ml range . Application of the method to the study of vancomycin pharmacokinetics in a rabbit after a single intravenous dose is also reported. DICP, 1989 Feb, 23(2), 123 - 8 Evaluation of three methods for determining initial vancomycin doses; Ackerman BH; Dosing methods proposed by Matzke et al., Moellering et al., and Lake and Peterson were used to predict initial doses of vancomycin for serum concentration simulation using a two-compartment open model . Previously reported pharmacokinetic data from 25 of 28 patients were used to simulate steady-state serum vancomycin concentrations for doses derived from the three methods . The Matzke method failed to provide simulated one-hour postinfusion levels less than 30 micrograms/mL in 48 percent and troughs greater than 5 micrograms/mL in more than 88 percent of the patients . The Moellering method succeeded in achieving this goal in 96 percent of the simulated one-hour levels, and in 72 percent of the troughs when a six-hour dosing interval was selected . For the 8 mg/kg Lake-Peterson doses, one-hour levels greater than 30 micrograms/mL occurred in 28 percent of the simulations, and for the 10 mg/kg doses this increased to 40 percent . The 8 mg/kg doses resulted in trough simulations less than 5 micrograms/mL in 28 percent and the 10 mg/kg reduced this to only 20 percent . These simulations indicated that the Moellering nomogram with the six-hour dosing interval was the most successful method for initial dose selection, but early serum concentration monitoring and adjustment of initial empirical and nomogram-derived doses is necessary to assure safe and effective vancomycin serum concentrations. Pharmacotherapy, 1989, 9(1), 10 - 6 Simulation of vancomycin peak and trough concentrations using five dosing methods in 37 patients; Zokufa HZ et al.; Five methods of dosing vancomycin (Matzke, Moellering, Nielsen, Lake-Peterson, and manufacturer's) were simulated in 37 patients . Ten serum samples were obtained after a 1-hour intravenous infusion of 6.2-20 mg/kg total body weight . A preinfusion serum sample was obtained from patients not studied on the first dose . Initial estimates of pharmacokinetic values were made using nonlinear iterative least squares regression and serum concentration-time data . These data were fitted to a two-compartment, open-infusion model . Simulations of the peak and trough serum concentrations at steady state for each patient were determined by multiple-dose simulated pharmacokinetics and each patient's pharmacokinetic values using the regimen suggested by each of the five methods . Steady-state serum concentrations, predicted systemic clearance by each method (except Lake-Peterson), and the daily dose for each patient recommended by each method were determined . All the methods underpredicted actual drug clearance, with the Nielsen method having the lowest prediction . The Matzke method recommended the largest dosage . Using each of the methods, only 3-16% of patients would have achieved recommended peak and trough serum concentrations . In the simulation model used, no method performed satisfactorily in attaining the desired vancomycin peak and trough concentrations . We suggest that the Lake-Peterson method could be used initially, provided that monitoring is also performed to adjust the dosage regimen further. Chemotherapy, 1989, 35(5), 320 - 5 Effect of intravenous vancomycin on renal function; Eng RH et al.; In the past, vancomycin has been reported to cause renal failure during intravenous administration; however, more recently, such renal toxicity is alleged not to occur because of increased purity of the vancomycin preparations . In this study, 23 patients were prospectively examined during intravenous vancomycin administration for changes in renal function . Vancomycin was administered for an average of 15 days . The blood urea nitrogen (BUN) changes averaged +1.7 mg/dl and the creatinine changes averaged +0.06 mg/dl . Since the accuracy of the serum creatinine determination was +/- 0.3 mg/dl, clinically significant deterioration of renal function occurred in 4 patients or 17% . Even among these 4 patients with documented worsening of renal function, we suspect that deterioration was related to the infection being treated . With close monitoring of dosing, the propensity of vancomycin to cause nephrotoxicity may be less than once thought. Arch Otorhinolaryngol, 1989, 246(2), 67 - 70 An experimental study of vancomycin-induced cochlear damage; Tange RA et al.; Vancomycin has been successfully used clinically for many years . Although early reports found ototoxicity to be a side effect of this antibiotic, later studies could not confirm this . For this reason we have started an experimental study in an animal model on the ototoxic effects of vancomycin . We now report the results of this study . Fourteen healthy Mongolian gerbils were treated with intraperitoneal injections of vancomycin (80 mg/kg per day) for a 2-week period . Before and after treatment each animal's hearing was evaluated by evoked response audiometry . Post mortem the cochleae were investigated by scanning electron microscopy in Amsterdam and by microdissection with surface preparations (hair cell counting) in Stockholm . The results of this study show that there is no clear evidence for the existence of ototoxicity due to vancomycin in this dosage. Ther Drug Monit, 1989, 11(3), 269 - 75 Evaluation of a two-compartment Bayesian forecasting program for predicting vancomycin concentrations; Rodvold KA et al.; The application of a two-compartment Bayesian forecasting program for vancomycin was tested retrospectively in 45 adult patients with stable renal function . Serial blood samples from 25 of these patients were used to determine population-based parameter estimates . The predictive performance of the Bayesian program was assessed by using both non-steady-state and steady-state vancomycin concentrations as feedback information . Overall, the program tended to underpredict peak and trough steady-state vancomycin serum concentrations . A larger mean prediction error (ME) was seen when non-steady-state feedback serum concentrations were used compared with using population-based parameter estimates (no feedback) . In contrast, a marked improvement in ME (peaks: -1.03 versus -2.61; troughs: -1.60 versus -2.07) was seen when steady-state feedback serum concentrations were used compared with no feedback data . Precision improved when either feedback serum concentrations were used to predict steady-state peak and trough vancomycin concentrations . The results from this clinical evaluation demonstrate that the initial pharmacokinetic parameter estimates for a two-compartment Bayesian model provided accurate prediction of steady-state vancomycin concentrations . Prediction bias and precision were improved when steady-state vancomycin concentrations were used to determine individualized pharmacokinetic parameters. Clin Pharm, 1989 Jan, 8(1), 34 - 9 Comparison of heparin and 0.9% sodium chloride injection in the maintenance of indwelling intermittent i.v . devices; Garrelts JC et al.; Heparin sodium 10 units/mL was compared with 0.9% sodium chloride injection as a flush solution for indwelling intermittent i.v . devices, or i.v . locks (IVLs), in a prospective, randomized, double-blind study . The heparin and 0.9% sodium chloride injections were prepared in the pharmacy using aseptic technique . Most of the IVLs were inserted by an i.v . therapy team member . Each patient's IVL site was evaluated for phlebitis and patency by one of three study nurses, and when a catheter was removed, its contents were flushed so that clots or fibrin strands could be detected . Nurses also collected information regarding disease states, surgical procedures, medications administered, and how long each site lasted . A total of 173 sites were studied in 76 patients in the heparin group, and 131 sites were studied in 71 patients in the sodium chloride group . The groups were well matched, except that the sodium chloride group received more vancomycin and dextrose-containing i.v . solutions, while the heparin group received more penicillins . There was no significant difference in the incidence of phlebitis or lost patency between the groups . When locks through which vancomycin, penicillins, and dextrose-containing i.v . solutions were administered were excluded, there was still no significant difference between the groups.(ABSTRACT TRUNCATED AT 250 WORDS) J Clin Anesth, 1989, 1(6), 426 - 30 Anaphylactic/anaphylactoid reactions during cardiac surgery; Levy JH; Over a 12-month period, 1,743 patients were retrospectively evaluated for anaphylactic/anaphylactoid reactions during cardiac surgery . Reactions to protamine, vancomycin, blood, and metocurine were observed in eight patients (0.46%) . Baseline to reaction mean arterial pressures decreased from 81 +/- 9 mmHg to 50 +/- 7 mmHg (mean +/- SD; p less than 0.001), cardiac output increased from 4.6 +/- 0.6 L/min to 6.5 +/- 1.2 L/min (p less than 0.005), stroke volume increased from 49 +/- 11 to 83 +/- 22 ml/beat (p less than 0.02), and systemic vascular resistance decreased from 1.294 +/- 137 to 563 +/- 127 dyne/sec/cm-5 (p less than 0.001) . Two patients developed pulmonary artery hypertension, while only one patient developed bronchospasm . Initial hypotension during anaphylactic/anaphylactoid reactions is due to decreased systemic vascular resistance, not myocardial depression. Adv Perit Dial, 1989, 5, 130 - 2 Intraperitoneal Vancoled does not cause chemical peritonitis; Johnson CA et al.; A prior report has suggested that loading doses of intraperitoneal Vancoled (vancomycin, Lederle) cause chemical peritonitis in patients with catheter infections . The present open-label study was conducted to determine the effects of a 30 mg/kg intraperitoneal loading dose of Vancoled given to five patients with a culture-positive, erythematous, draining exit-site infection . Prior to dosing, all dialysate was drained and sent for baseline cell count and culture . The loading dose was added to the dialysate and infused in the usual fashion . A sample of dialysate was drained at two hours and sent for cell count and culture . The entire exchange was drained at four hours and also sent for cell count and culture . Serum vancomycin concentrations wer measured at four hours . Baseline dialysate contained less than 9 white blood cells per microliter in all patients . Two and four hour samples contained less than 4 and less than 11 white blood cells per microliter, respectively . All fluid was sterile . WB C differential counts were unremarkable . No adverse effects occurred . The mean serum vancomycin concentration was 26.5 micrograms/ml . Intraperitoneal Vancoled did not cause chemical peritonitis and was well-tolerated by patients with exit-site infections. JPEN J Parenter Enteral Nutr, 1989 Jan-Feb, 13(1), 63 - 4 Stability and delivery of vancomycin hydrochloride when admixed in a total parenteral nutrition solution; Schilling CG et al.; Vancomycin hydrochloride, 400 mg/liter was mixed in six standard pediatric parenteral nutrition solutions with and without heparin added . The solutions were stored over a period of 8 days (192 hr) under refrigeration and at room temperature . Aliquots from all six solutions were assayed in duplicate for vancomycin at time 0, 24, 96, and 192 hr . All samples were run through an Ivex 0.22-micron filter, observed for physical incompatibilities, and frozen at -70 degrees C until assay . Our results indicate that vancomycin was stable and was delivered with loss in concentration of less than 5% with and without storage under refrigeration . This study suggests an alternative method for delivering vancomycin when treating a catheter-related infection . If vancomycin is delivered in this fashion, less manipulations of the line would be required . In addition, there may be a theoretical advantage of constantly bathing the catheter with vancomycin when the catheter is suspected of harboring the infecting organism. Ann Clin Lab Sci, 1988 Nov-Dec, 18(6), 440 - 3 Acute renal failure owing to inadvertent vancomycin overdose . Vancomycin removal by continuous arteriovenous hemofiltration; Walczyk MH et al.; Acute renal failure developed in a patient who received 56 grams of vancomycin intravenously over a 10 day period . The resulting serum vancomycin level was 284 micrograms per ml and declined to 140 micrograms per ml in a linear fashion with the institution of continuous arteriovenous hemofiltration (CAVH) . Our conclusion is that high blood vancomycin levels may be nephrotoxic and CAVH may be an effective means of vancomycin removal in patients with acute renal failure. Am J Hosp Pharm, 1988 Nov, 45(11), 2358 - 60 Accuracy of delivery of cefazolin, chloramphenicol, and vancomycin by a controlled-release membrane infusion device; Nahata MC et al.; The effects of flow rate and drug concentration on the accuracy of in vitro delivery of cefazolin, chloramphenicol, and vancomycin by a new controlled-release membrane infusion device, MICROS, were studied . Cefazolin, chloramphenicol, and vancomycin 1 g in sterile water for injection 10 mL were injected into the drug chamber of the device and delivered through an administration set with 0.9% sodium chloride injection from a primary line . Drug delivery was studied at four flow rates (0.5, 1.0, 1.5, and 2.0 mL/min) . In addition, three concentrations of each drug (25, 50, and 100 mg/mL for cefazolin and vancomycin, and 50, 100, and 200 mg/mL for chloramphenicol) were studied at a fixed flow rate of 1 mL/min . Samples were collected in triplicate every 2.5-5.0 minutes using a fraction collector over a 90-minute period for cefazolin and a 120-minute period for chloramphenicol and vancomycin . The concentration of each drug was measured by high-performance liquid chromatography . At various flow rates, the time for delivery of greater than or equal to 95% of each dose ranged from 30 to 55 minutes for cefazolin, 45 to 70 minutes for chloramphenicol, and 50 to 65 minutes for vancomycin . At various concentrations, greater than or equal to 95% of each dose was delivered in 40 to 55 minutes for cefazolin, 40 to 70 minutes for chloramphenicol, and 50 to 60 minutes for vancomycin . The desired delivery times were 30-60 minutes for cefazolin and chloramphenicol and 50-70 minutes for vancomycin . Delivery of cefazolin and vancomycin by the MICROS membrane infusion system was accurate . Some delay was encountered in the delivery of chloramphenicol.(ABSTRACT TRUNCATED AT 250 WORDS) Arch Dis Child, 1988 Nov, 63(11), 1390 - 3 Oral vancomycin in prevention of necrotising enterocolitis; Ng PC et al.; Eighty four very low birthweight babies (considered high risk for developing necrotising enterocolitis) were given vancomycin orally for 48 hours before introduction of oral feeds; one developed necrotising enterocolitis . One hundred and twenty very low birthweight babies (not considered such high risk) were fed without first receiving vancomycin; 17 developed necrotising enterocolitis . Although this was not a randomised control trial, results indicate a role for vancomycin in prophylaxis of necrotising enterocolitis. Arch Ophthalmol, 1988 Nov, 106(11), 1599 - 604 Collagen-shield delivery of gentamicin and vancomycin; Phinney RB et al.; The ability of collagen-shield therapeutic contact lenses to release gentamicin sulfate and vancomycin hydrochloride individually and in combination was investigated using a fluorescent polarization immunoassay . In vitro studies showed that presoaked collagen shields released the majority of gentamicin within the first 30 minutes of elution, while vancomycin was released gradually over six hours of elution . Three experiments in rabbits compared the gentamicin and vancomycin levels produced at five time points in tears, cornea, and aqueous humor by collagen shields soaked in antibiotics vs frequent-drop therapy . The collagen shields soaked in gentamicin, vancomycin, or a combination of the two produced tear, cornea, and aqueous humor levels that were generally higher or at least comparable with those achieved by frequent-drop therapy. Drug Intell Clin Pharm, 1988 Nov, 22(11), 881 - 2 Vancomycin-associated exfoliative dermatitis during continuous ambulatory peritoneal dialysis; Gutfeld MB et al.; Vancomycin is commonly prescribed to patients undergoing continuous ambulatory peritoneal dialysis (CAPD) for catheter-related infections and acute episodes of peritonitis . Although adverse dermatological reactions have been reported secondary to the rapid intravenous infusion of vancomycin, the intraperitoneal route of administration has been used routinely during CAPD without these effects . This case report describes a CAPD patient with systemic lupus erythematosus who developed erythema multiforme that progressed to exfoliative dermatitis during intermittent intraperitoneal vancomycin therapy for a catheter-related exit-site/tunnel infection. Arch Intern Med, 1988 Oct, 148(10), 2139 - 40 Acute interstitial nephritis associated with vancomycin therapy; Bergman MM et al.; Nephrotoxicity due to vancomycin is relatively uncommon and usually occurs in patients receiving concomitant therapy with an aminoglycoside or in patients with preexisting renal disease receiving prolonged courses of therapy and who exhibited excessive serum levels . We treated a healthy young woman who developed acute interstitial nephritis and moderate reversible azotemia associated with intravenous vancomycin hydrochloride therapy. South Med J, 1988 Sep, 81(9), 1095 - 9 Nephrotoxicity in leukemic patients receiving empirical amphotericin B and aminoglycosides; Stein RS et al.; Twelve leukemic patients (19%) receiving amphotericin B and aminoglycosides had nephrotoxicity (creatinine value greater than 2.0 mg/dl) . Patients with nephrotoxicity tended to be older than patients without nephrotoxicity; gender and total amphotericin B dose were not related to nephrotoxicity . Sodium administration has previously been shown to reverse amphotericin B nephrotoxicity . In this series, among patients receiving ticarcillin at greater than or equal to 18 gm/day (93.6 mEq of sodium per day) the incidence of nephrotoxicity was significantly decreased (1/30, or 3.3%) . A multivariate analysis showed that this protective effect of ticarcillin was not dependent on the fact that patients receiving ticarcillin were less likely to receive vancomycin . There were insufficient patients receiving sodium in the absence of ticarcillin to study the effect of sodium alone . However, our observations are consistent with the hypothesis that sodium can prevent renal dysfunction in this clinical situation. Med Toxicol Adverse Drug Exp, 1988 Sep-Oct, 3(5), 376 - 86 Vancomycin ototoxicity and nephrotoxicity . A review; Bailie GR et al.; Vancomycin has been in clinical use as a potent antistaphylococcal antibiotic for over 30 years . Most reports of ototoxicity and nephrotoxicity have been associated with early, relatively impure, formulations of vancomycin . This paper reviews the literature concerning vancomycin ototoxocity and nephrotoxicity and the evidence for their correlation with the therapeutic serum concentration range . There have been 28 reports of vancomycin-associated ototoxicity published in the medical literature since 1958 . It remains unclear whether any diminution in hearing is permanent or reversible . Few patients in the literature had follow-up audiometry and the hearing impairment tends to be at higher frequencies . Several authors reported peak serum vancomycin concentrations, but the exact time these were drawn with respect to the last dose is mostly unclear . In other reports, the 'peak' concentrations noted 3 to 6 hours after the last dose are probably indicative of much higher concentrations because of vancomycin's rapid phase of distribution . More than half the 57 cases of reported nephrotoxicity due to vancomycin occurred within the first 6 years of the drug's use . Many of these patients also had pre-existing renal dysfunction or were concomitantly receiving other nephrotoxic agents . It is unclear whether the coadministration of aminoglycosides produces a synergistic toxicity . The exact incidence of nephrotoxicity is uncertain, but is probably less with the current, relatively pure, product . The correlation of nephrotoxicity with certain serum vancomycin concentrations remains to be clarified . Other aspects also require clarification, such as when to draw samples to determine peak serum concentrations and whether or not routine measurements are necessary at all . In the absence of better guidelines, efforts should be made to tailor individual patient's regimens to produce peak and trough serum vancomycin concentrations to within the widely accepted ranges of 30 to 40 and 5 to 10 mg/L, respectively . In addition, the concomitant use of other potentially nephrotoxic and ototoxic agents should be avoided. Drug Intell Clin Pharm, 1988 Jul-Aug, 22(7-8), 598 - 600 Survey of vancomycin monitoring guidelines in Illinois hospitals; Fitzsimmons WE et al.; Disparity exists in published recommendations for monitoring of vancomycin serum concentrations . To evaluate the degree of disparity of practice in Illinois, directors of pathology of 202 Illinois hospitals were surveyed to assess their vancomycin monitoring practices . Of the 202 surveys mailed, 82 were returned for a response rate of 41 percent . Most hospitals have 200-500 beds (60 percent) and are nonteaching institutions (72 percent) . Two thirds of the hospitals sent vancomycin to an outside laboratory for analysis . Timing of postinfusion (peak) concentrations ranged from 0 minutes following end of infusion to 360 minutes . Approximately one half of the institutions reported a peak therapeutic range of 30-40 mg/L at 30 minutes following end of infusion . A great majority of institutions were consistent in recommended trough range, with 48 of 55 reporting 5-10 mg/L . Although there is some consistency among at least half of the hospitals, there is a great deal of variability among the other half in peak monitoring guidelines. Am J Surg, 1988 Jul, 156(1), 68 - 76 Use of serum drug concentrations in surgical patients; Connors JE et al.; Surgical patients frequently require drug treatments that can be assessed with serum drug concentrations . Of the agents for which serum drug concentrations are routinely available, the aminoglycosides theophylline, vancomycin, digoxin, and phenytoin are used most frequently in surgical patients . When using serum drug concentrations, the clinician should have an understanding of the relationships (or lack of) between drug concentrations and therapeutic or toxic effects . When blood is collected for serum concentration determinations, the exact timing of the sample in relation to the dose must be considered . For some drugs, (such as the aminoglycosides, it is necessary to determine peak and trough concentrations, whereas for other agents, like theophylline, the average or mid-dose level may be more important to consider . There are many factors that affect serum drug concentrations . Among these are various disease states, obesity, fluid imbalances, the drug dosage form used, and concurrent drug use . Not all patients require serum drug concentration monitoring; however, with each drug there are high-risk patients who may benefit . When used properly, serum drug concentrations may be helpful in maximizing therapeutic benefits, minimizing or diagnosing drug toxicity, and assessing patient compliance with drug regimens. Clin Pharmacol Ther, 1988 Jul, 44(1), 9 - 13 Altered vancomycin dose vs . serum concentration relationship in burn patients; Garrelts JC et al.; Drug elimination in patients sustaining serious thermal injury may be altered, resulting in an increased clearance and shortened half-life . Nine burn and eight medical/surgical patients with normal renal function were studied prospectively . Doses were adjusted to achieve peak and trough vancomycin serum concentrations within a narrow range . No significant difference between the groups was noted in terms of demographic characteristics, creatinine clearance, or vancomycin serum concentrations . However, the difference in daily dose needed to maintain the specified serum concentrations was significantly greater for burn patients (p less than 0.02) . Burn patients also had to be dosed significantly more often than medical/surgical patients to achieve peak and trough vancomycin serum concentrations within the desired range (p less than 0.02) . The elimination half-life in burn patients was significantly shorter than that in control patients (p less than 0.001) . Because of the unusually high dosage requirements in burn patients, along with their poor predictability, individualization of therapy with vancomycin serum concentrations is recommended to ensure a successful therapeutic outcome. Antimicrob Agents Chemother, 1988 Jun, 32(6), 848 - 52 Vancomycin pharmacokinetics in patients with various degrees of renal function; Rodvold KA et al.; The influence of age, protein binding, and renal function on the pharmacokinetics of intravenous vancomycin was evaluated in 37 adult patients with various degrees of renal function . Patients were categorized into three groups based on measured creatinine clearance (CLCR): groups 1, 2, and 3 had 24-h CLCRs of greater than 70, 40 to 70, and 10 to 39 ml/min per 1.73 m2, respectively . After 1 h of intravenous infusion, concentrations of vancomycin in serum declined in a biexponential manner in all patients . Diminished renal function in groups 2 and 3 was accompanied by a lower total body vancomycin clearance (CL) (52.6 and 31.3, respectively, versus 98.4 ml/min per 1.73 m2) and a lower renal vancomycin clearance (CLR) (48.2 and 19.8, respectively, versus 88.0 ml/min per 1.73 m2) than in group 1 . No significant differences in apparent distribution volume of the central compartment or apparent distribution volume at steady state were observed . Mean serum protein binding of vancomycin was 30% and was not significantly affected by renal function . Stepwise multiple linear regression analysis revealed that CLCR was the strongest predictor of vancomycin CL (r = 0.77, P less than 0.001) and vancomycin CLR (r = 0.87, P less than 0.001) . Age did not significantly improve these correlations once CLCR was included . The relationship of vancomycin CL and CLCR was utilized to develop the following equation to dose vancomycin in the majority of renally impaired patients: dose (milligrams per kilogram per 24 h) = 0.227CLCR + 5.67, where CLCR is standardized to milliliters per minute per 70 kg . The practical dosing intervals that the calculated dose can be divided into and administered include 8, 12, 24, and 48 h based on the CLCR of the patient. Drug Intell Clin Pharm, 1988 Jun, 22(6), 480 - 3 Use of vancomycin and tobramycin polymethylmethacrylate impregnated beads in the management of chronic osteomyelitis; Scott DM et al.; Over the past several years there has been a growing interest in the use of locally implanted beads containing antibiotics for the treatment of chronic osteomyelitis . This method has been popularized in Europe and, with few exceptions, gentamicin has been the only antibiotic used . There have been only a few reports from the U.S . and there is little information regarding the pharmacokinetics of antibiotics used in this fashion . To our knowledge this is the first report using vancomycin . Three patients with chronic osteomyelitis were treated with vancomycin and/or tobramycin polymethylmethacrylate beads . These beads were extemporaneously compounded and implanted for up to six weeks . From the site of bead implantation local fluid aliquots were collected for the measurement of antibiotic concentrations . In two patients, initial tobramycin concentrations exceeded 400 mg/L . In one patient receiving vancomycin, initial localized concentrations were approximately 100 mg/L . In all three patients therapeutic concentrations of localized antibiotic were maintained with immeasurable systemic concentrations throughout the period of bead placement . Localized antibiotic therapy for the management of chronic osteomyelitis represents a potential therapeutic alternative to long-term parenteral therapy . Data presented here suggest that other antibiotics, such as vancomycin and tobramycin, can be used successfully in polymethylmethacrylate beads and provide preliminary facts for future investigations of such applications. Antimicrob Agents Chemother, 1988 May, 32(5), 631 - 5 Effect of cardiopulmonary bypass on vancomycin and netilmicin disposition; Klamerus KJ et al.; The effect of cardiopulmonary bypass (CPB) on the disposition of vancomycin (15 mg/kg) and of netilmicin (3 mg/kg) was studied in 10 adults . The concentration-time profile of the drug in serum and renal clearance were characterized pre-CPB, during CPB, and post-CPB . Vancomycin and netilmicin exhibited initial decreases in mean concentrations in serum of 4.0 mg/liter (16.8%) and 2.2 mg/liter (29.1%), respectively, upon initiation of CPB . Netilmicin concentrations in serum rebounded to a mean of 0.6 mg/liter (15.4%) within 90 min on CPB and then continuously decreased . Vancomycin concentrations in serum demonstrated a rebound increase of 2.3 mg/liter (23.5%) at the end of CPB when the aorta was unclamped . Mean renal clearance throughout CPB was decreased for vancomycin (58.4 to 43.4 ml/min per m2) and netilmicin (53.4 to 31.5 ml/min per m2) . The rebound in vancomycin concentration in serum strongly correlated with the length of time between unclamping the aorta and coming off CPB (r = 0.94), as well as with the increase in temperature upon rewarming (r = 0.92). Drug Intell Clin Pharm, 1988 Apr, 22(4), 300 - 3 Vancomycin serum protein binding determination by ultrafiltration; Ackerman BH et al.; Sixty-two serum concentrations were obtained from 12 infected patients enrolled in a vancomycin pharmacokinetic study . Both unbound and total serum vancomycin concentrations were measured using ultrafiltration and a commercial fluorescent polarization immunoassay . Ultrafiltrates were obtained by centrifugation at 1000 X g for ten minutes at room temperature and their assay indicated a range in protein binding from 7.9 to 71 percent . The mean protein binding (mean +/- SD) was 41.95 +/- 14.15 percent . No measurable adsorption of vancomycin onto the ultrafiltration membrane was noted . Orthogonal regression of unbound versus total vancomycin concentrations was described by the equation y = 0.597x-0.362 with a correlation coefficient of 0.948. J Comput Aided Mol Des, 1988 Apr, 2(1), 31 - 41 Forces in molecular recognition: comparison of experimental data and molecular mechanics calculations; Waltho JP et al.; NMR studies of the rotation barrier of the disaccharide of the glycopeptide antibiotic vancomycin have been used to test the performance of computer simulation techniques using molecular mechanics . In the absence of any solvated water, no correlation could be found between experiment and calculation . By introducing solvent water molecules into the binding region of the antibiotic, the NMR results could be simulated both qualitatively and quantitatively within experimental error without using massive computational resources. Clin Pharm, 1988 Mar, 7(3), 198 - 206 Drug dosing during continuous arteriovenous hemofiltration; Bickley SK; An overview of continuous arteriovenous hemofiltration (CAVH), which is an alternative to hemodialysis and peritoneal dialysis in the management of acute renal failure, is provided, and literature concerning drug clearance via hemofiltration is reviewed . CAVH is a slow, continuous process that removes, by convective mass transport, non-protein-bound solutes smaller than 10,000 daltons from blood diverted through an extracorporeal filter . The system provides a creatinine clearance of approximately 10 mL/min . The sieving coefficient of a particular compound reflects its ability to permeate the filter membrane and is primarily influenced by protein binding . Clearance of a compound depends on its sieving coefficient and the ultrafiltration rate . Methods for estimating drug clearance, the amount of drug removed per time interval, and appropriate drug dosages are discussed . Many drugs commonly used in an intensive-care setting, including aminoglycosides, cephalosporins, acyclovir, vancomycin, phenobarbital, ranitidine, and theophylline, can be expected to have a limited but clinically important clearance during CAVH . CAVH substantially enhances the current treatment of acute renal failure; although limited data for specific drugs are available in the literature, drug dosages may be adjusted based on the methods outlined in this review. Zentralbl Bakteriol Mikrobiol Hyg {B}, 1988 Mar, 186(1), 73 - 8 Experimental studies of detection and processing of Legionella spp . in public drinking water supplies; Muller HE; Studies were conducted to improve the detection and processing of Legionella spp . in public drinking water supplies . The survival of legionellas was the best in tap water samples, stored at 4 degrees C . Comparing investigations showed that the most cells could be recovered from glassware whereas plastics adsorbed legionellas up to 80-90 percent on their surfaces . A method of enrichment and isolation of legionellas from large volumes of tap water samples was developed using precipitation by Fe(OH)3 . Finally, a comparison of BCYE alpha-agar containing different mixtures of antibiotics revealed that the supplement of vancomycin, polymyxin, and glycine (VPG) gave better results than of cephalothin, colistin, vancomycin, and cycloheximide (CCVC), especially, because of the different growth of various serogroups of Legionella pneumophila on the CCVC medium. J Infect Dis, 1988 Mar, 157(3), 502 - 7 Vancomycin and the red-man syndrome: pharmacodynamics of histamine release; Polk RE et al.; Two regimens for infusing vancomycin over 1 h (500 mg every 6 h for five doses or 100 mg every 12 h for three doses) were used in 11 volunteers . Subjects received both regimens one week apart; the regimen used first for each subject was randomized . Nine receiving the 1000-mg dose experienced the "red-man (neck)" syndrome; none had the reaction while receiving the 500-mg dose (P = .002) . Plasma histamine concentration, measured every 10 min during the first infusion of each regimen, increased in most subjects given 1000-mg doses; there was only a slight change in histamine levels after 500-mg doses . There was a significant relation between histamine release and reaction severity; frequency and severity of the reaction declined with subsequent doses . We conclude that the red-man syndrome occurs frequently in normal adults who receive 1000 mg of vancomycin over 1 h, that vancomycin causes an infusion rate-dependent increase in plasma histamine concentration, and that the increase in plasma histamine concentration is correlated with the severity of the reaction. Clin Nephrol, 1988 Feb, 29(2), 86 - 7 An improved method of vancomycin administration to dialysis patients; Edell LS et al.; Vancomycin is a nondialyzable antibiotic frequently used by patients on hemodialysis . Traditionally, a 1-gram dose is administered at the conclusion of dialysis . Recent rate-related side effects have prompted the manufacturer to revise the package insert suggesting a maximum infusion rate of 500 mg/h; necessitating a two-hour infusion post-dialysis . We evaluated the safety and efficacy of vancomycin administered during dialysis in nine chronic hemodialysis patients in an open crossover study . All patients received vancomycin during and post-dialysis in consecutive weeks . Therapeutic peak and trough serum concentrations were achieved in all patients . No adverse reactions occurred. Am J Kidney Dis, 1988 Jan, 11(1), 15 - 9 Vancomycin dosing chart for use in patients with renal impairment; Brown DL et al.; A new vancomycin dosing chart for use in patients with impaired renal function is described . The chart has been adapted from a previously published nomogram, based on a linear relationship between vancomycin clearance and creatinine clearance . Doses are designed to achieve an average steady-state serum concentration of approximately 15 mg/L . Use of the chart necessitates first measuring or estimating the patient's body weight and creatinine clearance . The chart provides the advantages of generating an exact dose and dosing interval, as well as being somewhat easier to use than the original nomogram . Predicted average steady-state serum concentrations resulting from the dosing chart range from 12.1 to 18.2 mg/L, with a mean of 15.0 mg/L. Eur J Cancer Clin Oncol, 1988, 24 Suppl 1, S29 - 33 The tolerability profile of prophylactic norfloxacin in neutropenic patients; Corrado ML et al.; Norfloxacin has been compared to placebo (136 patients), sulfamethoxazole plus trimethoprim (SXT, 72 patients) and oral vancomycin plus colistin (V/C, 61 patients) for the prevention of alimentary tract-associated infections during and after induction chemotherapy . These patients were evaluated for the safety and tolerability of each regimen by clinical and laboratory means . Most neutropenics involved, regardless of the regimen, experienced at least one adverse experience . The majority were felt to be unrelated to prophylactic study drug therapy . Of 139 patients who received norfloxacin, only two had drug-related adverse experiences, compared to two of 35 receiving SXT, five of 28 for VC, and none of 67 receiving placebo . In evaluating adverse experiences considered possibly drug related, 19 occurred on norfloxacin compared to 13 for placebo . Among neurologic adverse experiences, only one possibly related to norfloxacin occurred (confusion), while three occurred on placebo (confusion, decreased auditory acuity and hallucinations) . Generally, no significant differences were seen between any of the regimens except for a higher frequency of diarrhea in those receiving V/C. Child Nephrol Urol, 1988-89, 9(4), 232 - 5 Elimination of vancomycin by continuous arteriovenous hemofiltration; Lau AH et al.; Continuous arteriovenous hemofiltration (CAVH) is being used increasingly in pediatric patients with acute renal failure and/or other fluid and electrolyte imbalances . At times, vancomycin may be concurrently given for sepsis therapy . We evaluated the removal of vancomycin by CAVH in a 15-month-old male child with renal failure who was receiving the drug for suspected infection of an arterial catheter . Two separate CAVH treatments were performed with polysulfone membranes . Serum samples and ultrafiltrate outflow (n = 6) were collected over 79 h for vancomycin concentration determination . The mean vancomycin concentration in the ultrafiltrate was 90.4 +/- 5.4% of those of the serum . 0.53-1.11 mg of the drug was removed per hour by CAVH at serum concentrations of 12.4-25.4 mg/l . CAVH vancomycin clearance was 0.039-0.050 liter/h . The CAVH drug clearances accounted for 66.2% of the total vancomycin clearance . CAVH is thus a major route of vancomycin elimination . Dosage adjustment and serum concentration monitoring are necessary in patients undergoing CAVH while receiving vancomycin therapy. Pharmacotherapy, 1988, 8(5), 284 - 6 Evaluation of a method for initiating vancomycin therapy: experience in 205 patients; Lake KD et al.; This study evaluated a dosing method for initiating vancomycin therapy in a large population based on patients' age, weight, and renal function . The aims were to determine the method's efficacy in achieving predetermined peak and trough serum concentrations, and to calculate the cost savings incurred by individualizing therapy . Average doses +/- 1 SD of 7.93 +/- 0.29 mg/kg corrected body weight (lean body weight + 40% excess weight) were administered at intervals predicted by the patients' estimated creatinine clearances (range 22-130 ml/min) . The calculated mean dose +/- SD was 558 +/- 83 mg (range 350-750 mg) and the calculated median interval was 12 hours (range 6-24 hr) . Peak and trough concentrations +/- SD measured at steady state averaged 26.0 +/- 5.4 and 7.3 +/- 2.3 micrograms/ml, respectively . Peak and trough serum concentrations fell within the predetermined therapeutic range in 311 (76%) of 410 samples . Peak concentrations were in the range of 20-30 micrograms/ml in 145 (71%) of 205 samples . Trough concentrations were in the range of 5-10 micrograms/ml in 166 (81%) of the 205 samples . This simplified dosing method successfully individualized therapy in most patients, and produced a significant savings to the pharmacy in reduced drug acquisition costs and to patients in reduced drug charges. J Ocul Pharmacol, 1988 Summer, 4(2), 153 - 64 Transscleral and transcorneal iontophoresis of vancomycin in rabbit eyes; Choi TB et al.; We examined the ability of transscleral and transcorneal iontophoresis to deliver vancomycin into the aqueous humor, the vitreous humor, and the cornea of rabbit eyes . Control eyes receiving subconjunctival injection (25 mg) attained peak aqueous, vitreous, and corneal concentrations (mean +/- S.E.M.) of 14.73 +/- 0.35 mcg/ml (at 4 hours after injection), 1.10 +/- 0.78 mcg/ml (2 hours), and 1167 +/- 63 mcg/g (1 hour), respectively . Eyes receiving transscleral iontophoresis (3.5 mA for 10 minutes) attained significantly higher vitreal levels than controls: 6.33 +/- 0.25 mcg/ml (p less than 0.001; 1 hour), 13.43 +/- 2.32 mcg/ml (p less than 0.01; 2 hours), 11.93 +/- 0.76 mcg/ml (p less than 0.001; 4 hours), 8.40 +/- 0.60 mcg/ml (p less than 0.001; 8 hours) . Eyes receiving transcorneal iontophoresis (0.5 mA for 5 minutes) attained earlier and significantly higher aqueous and corneal levels than controls . Aqueous humor levels were 16.20 +/- 3.19 mcg/ml (p less than 0.05; 1 hour) and 20.20 +/- 0.43 mcg/ml (p less than 0.001; 2 hours) . Corneal levels were 10799 +/- 755 mcg/g (p less than 0.001; 0.5 hour), 4856 +/- 606 mcg/g (p less than 0.005; 1.0 hour), 2185 +/- 71 mcg/g (p less than 0.001; 2 hours), and 710 +/- 112 mcg/g (p less than 0.025; 4 hours) . Corneal endothelial cell counts were decreased by 8.8% (p = 0.08) after transcorneal iontophoresis of vancomycin and 5.4% (p less than 0.02) following Balanced Salt Solution (BSS) . However, corneal thickness were not significantly increased by iontophoresis of either vancomycin or BSS . These experiments show that transscleral and transcorneal iontophoresis are efficacious in delivering high concentrations of vancomycin into the aqueous and vitreous humor and the cornea. J Chromatogr, 1987 Dec 11, 410(2), 373 - 82 Chromatographic methods for the analysis of vancomycin; Thomas AH et al.; Four thin-layer chromatographic systems were developed for the separation of vancomycin, related antibiotics and degradation products . Bioautography was suitable for detecting trace amounts of biologically active components . High-performance liquid chromatography was used to examine the composition of vancomycin and other glycopeptide antibiotics and to monitor the stability of vancomycin . Degradation of vancomycin lead to changes in the composition which were not matched by a similar loss of potency. Appl Environ Microbiol, 1987 Dec, 53(12), 2704 - 7 Relative sensitivities of environmental legionellae to selective isolation procedures; Roberts KP et al.; A survey of water samples to determine the efficacy of standard procedures for the isolation of environmental legionellae was conducted . Marked variations in intraspecies resistance to selective agents and treatments were observed, and in experiments with one of the isolates, the response was modified by culture conditions . Five selective procedures incorporating acid (pH 2.2) and heat (50 degrees C, 30 min) treatments, with and without plating on buffered charcoal-yeast extract agar supplemented with vancomycin (5 micrograms/ml), polymyxin B (60 U/ml), and cycloheximide (80 micrograms/ml), caused 5 to 99% decreases in viable counts of pure cultures in water suspensions . The differences in the responses of the cultures to the five treatments were statistically significant . Cells in retained samples of naturally contaminated water from which the original cultures had been isolated were significantly less sensitive than artificially grown isolates . The sensitivities of the laboratory-grown cells to the treatments were affected by the length of incubation on buffered charcoal-yeast extract agar . Whereas acid resistance increased after 24 h of incubation, resistance to the antibiotic mixture decreased. J Neurol Neurosurg Psychiatry, 1987 Nov, 50(11), 1419 - 23 Intraventricular vancomycin in the treatment of ventriculitis associated with cerebrospinal fluid shunting and drainage; Bayston R et al.; The results of treatment of 50 cases of ventriculitis associated with the use of cerebrospinal fluid shunts or external ventricular drains, and treated with intraventricular vancomycin, are reported . While the overall cure rate was 66% with four cases lost to follow-up, in those cases where treatment involved shunt removal, 20 mg vancomycin daily intraventricularly, and another appropriate systemic antibiotic, 22 of 24 cases were cured with two cases lost to follow-up . In those cases where the shunt was left in during treatment, results were poor and revision for blockage of the distal catheter of ventriculoperitoneal shunts was required in 44% of these . All five patients whose ventriculitis followed external ventricular drainage were cured . Despite relatively high trough levels of vancomycin in the cerebrospinal fluid, no evidence of toxicity was seen. Antimicrob Agents Chemother, 1987 Nov, 31(11), 1689 - 91 Vancomycin entry into lung lymph in sheep; May DG et al.; The distribution of antibiotics into target tissues is a crucial factor in therapeutic efficacy . To estimate the availability of systemically administered vancomycin to the interstitial fluid in the lung, we have used a sheep model with a chronic pulmonary lymph fistula to collect simultaneously series of plasma and pulmonary lymph specimens during a 6-h period after an intravenous dose of vancomycin (7 mg/kg) . After a minor delay in transit from blood to lymph, vancomycin was completely distributed to pulmonary lymph with a ratio of free drug in lymph to free drug in plasma of 0.9 . This suggests that vancomycin is an excellent choice for treating pulmonary infections by susceptible organisms. Pathol Biol (Paris), 1987 Nov, 35(9), 1235 - 8 {Diffusion of vancomycin in the cerebrospinal fluid, in the dog, in the absence of meningeal inflammation}; Chabenat C et al.; The diffusion of vancomycin into the cerebro-spinal fluid was studied in 5 healthy dogs . Its appears that vancomycin does diffuse across the blood-brain barrier . Though the concentrations reached in the CSF are low, they are of the same order of magnitude as the minimal inhibitory concentrations of this antibiotic towards the germs usually treated . The usual pharmacokinetic parameters were determined. Am J Med Sci, 1987 Aug, 294(2), 110 - 3 Prolonged vancomycin-associated neutropenia in a chronic hemodialysis patient; Milsteen S et al.; A chronic hemodialysis patient developed severe marrow granulocytic hypoplasia and peripheral blood neutropenia related to vancomycin therapy for an infected arteriovenous fistula . Neutropenia was prolonged and associated with sustained serum levels of vancomycin that persisted for more than 4 weeks following the last dose of vancomycin . No vancomycin-dependent leukoagglutinins were demonstrable in the patient's serum . Although a direct toxic effect on marrow granulocyte production seems likely, a vancomycin-dependent immune suppression of granulopoiesis cannot be ruled out. Am J Med Sci, 1987 Aug, 294(2), 100 - 4 Bayesian and least-squares methods for vancomycin dosing; Uaamnuichai M et al.; The authors assessed the performance of a Bayesian and a least squares method for predicting individual pharmacokinetic parameters for vancomycin . For clearance, the best performance of both methods was an absolute error of approximately 5% . This level of accuracy required 4 serum vancomycin concentrations with the least squares method but could be achieved with a peak and trough concentration with the Bayesian method . For volume of distribution, the best performance occurred with 3 or 4 levels with both methods and amounted to an error of about 15% . In conclusion, both methods of estimating vancomycin pharmacokinetics perform comparably, but the Bayesian method appears to require fewer data. Klin Wochenschr, 1987 Jul 15, 65(12), 562 - 70 {Treatment of peritonitis during continuous ambulatory peritoneal dialysis (CAPD) with co-trimoxazole, cefazolin or vancomycin}; Konig U et al.; Three initial treatment schedules of peritonitis during continuous ambulatory peritoneal dialysis are analysed . In 20 patients 56 episodes of peritonitis were treated by co-trimoxazole, 29 episodes in 20 patients by cefazolin, and 29 infections in 22 patients by vancomycin . The efficiency of the treatment modes was comparable . Vancomycin was found to be appropriate in particular because of the resistance characteristics of bacterial isolates. J Chromatogr, 1987 Jun 5, 417(1), 121 - 8 High-performance liquid chromatographic analysis of vancomycin in plasma, bone, atrial appendage tissue and pericardial fluid; Greene SV et al.; Solid-phase extraction coupled with reversed-phase high-performance liquid chromatography and UV detection was employed for the analysis of the antibiotic vancomycin in patient plasma, bone, atrial appendage, and pericardial fluid . Vancomycin was quantitated in samples from patients undergoing cardiac surgery . Calibrations were linear in the range 3-100 micrograms/ml vancomycin; the lower limit of detection was approximately 3 micrograms/ml in fluids with an absolute limit of detection in bone samples of 0.75 microgram per injection. Ther Drug Monit, 1987 Jun, 9(2), 212 - 5 Overestimation of vancomycin concentrations utilizing fluorescence polarization immunoassay in patients on peritoneal dialysis; Morse GD et al.; During a study of vancomycin pharmacokinetics in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), a discrepancy was noted when serum concentrations were determined by high performance liquid chromatography (HPLC) in comparison to a fluorescence polarization immunoassay (FPI) technique . Following three weekly intraperitoneal doses (30 mg/kg/2 L), peak serum concentrations (at the end of the 6-h dwell) by FPI were 42.1 +/- 9.1, 43.1 +/- 8.7, and 45.6 +/- 7.4 micrograms/ml . In comparison, the same samples when analyzed by HPLC yielded 36.3 +/- 9.4, 32.2 +/- 8.9, and 31.6 +/- 9.1 micrograms/ml, respectively . A subsequent in vitro study of vancomycin (40 micrograms/ml) in serum indicated a degradation half-life of 693 (FPI) compared with 210 (HPLC) h . These data suggest that vancomycin degradation products accumulate in CAPD patients and lead to an overestimation of vancomycin serum concentrations when measured by FPI. Antimicrob Agents Chemother, 1987 Apr, 31(4), 610 - 1 Instability of vancomycin in Infusaid drug pump model 100; Greenberg RN et al.; The implantable Infusaid drug pump model 100 (Shiley Infusaid, Norwood, Mass.) is undergoing trials as a drug delivery system in the treatment of osteomyelitis . This study evaluated the stability of vancomycin (1 mg/ml) incubated at 37 degrees C for 4 weeks in the pump . Both bioassay and high-pressure liquid chromatography data demonstrated a loss of at least 38% of activity over 4 weeks and colloidal precipitation of vancomycin in the pump at the end of the experiment . This study suggests that vancomycin is not stable enough for use in the Infusaid drug pump model 100. Am J Hosp Pharm, 1987 Apr, 44(4), 802 - 4 Stability of vancomycin hydrochloride in various concentrations of dextrose injection; Nahata MC et al.; The stability of vancomycin hydrochloride in plastic syringes containing high concentrations of dextrose injection after storage for 24 hours in a refrigerator followed by storage for two hours at room temperature was studied . Vancomycin hydrochloride was reconstituted with sterile water for injection to a concentration of 50 mg/mL . One-milliliter samples were added to 9 mL of various concentrations of dextrose injection (5, 10, 15, 20, 25, and 30%) in 10-mL plastic syringes . Ten syringes of each concentration were stored at 4 degrees C for 24 hours . At various storage times, samples were assayed in triplicate for vancomycin using high-performance liquid chromatography . After 24 hours, the syringes were removed from the refrigerator, and the vancomycin concentration was determined after storage for two hours at room temperature . Percent change in vancomycin concentration during storage for 24 hours was less than 6% in all cases except for 5% dextrose injection at 4 and 24 hours . Vancomycin concentration did not change (percent change 0.7-5%) during storage for two hours at room temperature . Vancomycin hydrochloride is stable in various concentrations of dextrose injection when stored in plastic syringes for 24 hours in the refrigerator followed by two hours at room temperature. Antimicrob Agents Chemother, 1987 Apr, 31(4), 612 - 3 Absence of ototoxicity of teichomycin A2 in guinea pigs; Brummett RE et al.; Teichomycin A2 is a new antibiotic that is similar to vancomycin . Because vancomycin is reported to be ototoxic, teichomycin A2 was tested for ototoxicity . No evidence of ototoxicity was found . Furthermore, ethacrynic acid, a diuretic that augments the ototoxicity of many drugs, did not enhance ototoxicity with teichomycin A2. Antimicrob Agents Chemother, 1987 Mar, 31(3), 393 - 7 Comparison of steady-state pharmacokinetics of two dosage regimens of vancomycin in normal volunteers; Healy DP et al.; A pharmacokinetic comparison of the two recommended dosages of vancomycin given as multiple doses has not been previously performed . Eleven adult subjects with normal renal function randomly received 500 mg every 6 h (five doses) and, later, 1,000 mg every 12 h (three doses) . Each dose was infused over 1 h, and regimens were separated by 1 week . Compared with the two-compartment fit, a three-compartment fit significantly reduced the residual weighted sums of squares . Accumulation occurred for both regimens after repeated dosing and was independent of dose . At steady state, concentrations in serum at 1 h showed little variation for the 1,000- or the 500-mg dose regimen (33.7 +/- 3.8 versus 22.6 +/- 3.2 micrograms/ml); trough concentrations were 7.9 +/- 1.7 versus 11.2 +/- 2.2 micrograms/ml, respectively . With the 1,000-mg dose, the terminal half-life was 7.7 +/- 1.8 h, steady-state area under the curve for the dose interval was 227 +/- 28.3 micrograms X h/ml, and total body clearance was 86.1 +/- 8.9 ml/min per 1.73 m2 . The red-man syndrome occurred in 9 of 11 volunteers who received 1,000-mg doses and in none of those who received 500-mg doses . We concluded that vancomycin disposition in healthy adults with normal renal function is best described by a three-compartment model, there is relatively little variation in vancomycin disposition in normal volunteers, significant accumulation occurs with multiple dosing, it is inappropriate to use the same therapeutic window for both regimens, and the pharmacokinetics of vancomycin justify a 12-h dose interval; however, a 1-g dose is associated with a significantly greater incidence of the red-man syndrome. J Antimicrob Chemother, 1987 Mar, 19(3), 351 - 7 Pharmacokinetics of single dose intravenous vancomycin in CAPD peritonitis; Whitby M et al.; The pharmacokinetics of single dose intravenous vancomycin (25 mg/kg) were studied in six patients with peritonitis complicating continuous ambulatory peritoneal dialysis . The volume of distribution after equilibration was 1.1 +/- 0.1 l/kg (mean +/- standard error) with a serum elimination half-life of 115 +/- 6 h . The peritoneal clearance was 1.4 +/- 0.5 ml/min and the serum clearance was 7.2 +/- 0.3 ml/min . Mean peak serum levels of 56.8 +/- 4.7 mg/l were detected . Initial mean overnight dialysate level was 12.3 +/- 0.8 mg/l . Vancomycin dialysate levels of 8 mg/l were achieved for a mean of 3.0 days and levels of 4 mg/l for a mean of 6.2 days . Single dose intravenous vancomycin may, therefore, have therapeutic value in selected patients. Antimicrob Agents Chemother, 1987 Feb, 31(2), 173 - 7 Comparative study of intraperitoneal and intravenous vancomycin pharmacokinetics during continuous ambulatory peritoneal dialysis; Morse GD et al.; The pharmacokinetic characteristics of vancomycin were investigated in eight patients undergoing continuous ambulatory peritoneal dialysis . A crossover design was used . Four noninfected patients received both a 15-mg/kg (body weight) intravenous dose and a 30-mg/kg intraperitoneal (i.p.) dose . Bioavailability ranged from 0.35 to 0.65 after i.p . administration . i.p . absorption was rapid, with concentrations in serum of 8.8 +/- 6 micrograms/ml noted at 1 h peak values of 30.4 +/- 7 micrograms/ml at 6 h . A slow distribution phase was apparent, with a terminal elimination phase emerging after 12 to 24 h . Vancomycin was eliminated slowly, with a mean total clearance of 5.0 +/- 1.3 ml/min, and concentrations in serum were 7.0 +/- 1.2 micrograms/ml at 168 h . The mean serum half-life was 91.7 +/- 28.1 h, and similar pharmacokinetics were noted after intravenous administration . Subsequently, four patients with catheter-related exit site or tunnel infections received a 30-mg/kg i.p . dose of vancomycin and displayed a similar kinetic pattern . This method of administering vancomycin achieved therapeutic serum and end-dwell dialysate concentrations over a 1-week period, represents a simple, cost-effective therapy which avoids the possibility of infusion-related toxicity, and deserves further investigation in patients with continuous ambulatory peritoneal dialysis-related peritonitis. Pharmacotherapy, 1987, 7(3), 69 - 72 Evaluation of a new vancomycin dosing method; Musa DM et al.; Thirty-one patients who were prescribed vancomycin therapy at our institution since January 1, 1986, were dosed using the guidelines as described by Lake and Peterson . Peak and trough vancomycin serum concentrations were measured at steady state: 24 (77%) peak serum concentrations were within the range of 20-30 mg/L, and 24 (77%) trough serum concentrations were within the range of 5-10 mg/L . We have found that the method of Lake and Peterson is satisfactory for initiating vancomycin therapy in most patients . Some, however, may not achieve optimal serum concentrations using these guidelines alone, and their regimens may have to be adjusted based upon actual serum concentration data. Chemotherapy, 1987, 33(4), 302 - 4 Lack of nephrotoxicity in pediatric patients receiving concurrent vancomycin and aminoglycoside therapy; Nahata MC; Based on retrospective studies, nephrotoxicity may occur in as many as 35% of adult patients receiving vancomycin and an aminoglycoside . Limited data are available about the incidence of nephrotoxicity in pediatric patients, especially when drug therapy is closely monitored . We prospectively evaluated the potential of nephrotoxicity in 90 infants and children (61 less than 1 year and 29 greater than 1 year of age) receiving concomitant vancomycin and gentamicin for a duration of 3 to 38 (mean 9) days . Vancomycin and gentamicin doses ranged from 20 to 60 (mean 35) mg/kg/day and 2.5 to 14 (mean 6.5) mg/kg/day . Peak and trough serum concentration of vancomycin ranged from 10 to 55 and 2 to 18 micrograms/ml, respectively . Gentamicin peak and trough serum concentration ranged from 4 to 9 and 0.5 to 2.0 micrograms/ml, respectively . Serum creatinine concentration prior to, during and at the end of therapy averaged 0.42, 0.40, and 0.43 mg/dl (p greater than 0.1), respectively . Clinical status and urinalysis results showed no evidence of renal toxicity . These data suggest that nephrotoxicity is uncommon in pediatric patients receiving a combined therapy with vancomycin and gentamicin, particularly when serum concentrations of gentamicin are within therapeutic range. Antimicrob Agents Chemother, 1987 Jan, 31(1), 52 - 4 Vancomycin pharmacokinetics and dose recommendations for preterm infants; James A et al.; The pharmacokinetics of intravenous vancomycin was studied in 20 preterm infants (gestational age, 26.5 weeks +/- 2.6 weeks {standard deviation}; birthweight, 880 +/- 340 g) . At the time of the studies their postconceptional age was 36.4 +/- 4.5 weeks . The drug was infused over 30 min in a dose between 9.2 and 18 mg/kg . A highly significant correlation existed between postconceptional age or body weight and vancomycin t1/2 and clearance . Serum creatinine concentrations correlated with vancomycin t1/2 and clearance . Serum creatinine tended to decrease with increasing postconceptional age . Based on the excellent correlation between age (or weight) and vancomycin pharmacokinetics, dose and dose-interval recommendations are presented. Am J Med, 1986 Dec, 81(6), 1059 - 61 Agranulocytosis related to vancomycin therapy; Adrouny A et al.; A patient with renal failure due to Goodpasture's syndrome was treated with vancomycin . After he had received 3 g of the drug, his white blood cell count fell to a level of 200/microliter . Bone marrow biopsy disclosed severe myeloid hypoplasia . The patient subsequently recovered fully from this episode of vancomycin-induced agranulocytosis, but he eventually died of other causes . Vancomycin-related leukopenia has been reported, but the severely depressed white blood cell count and myeloid hypoplasia observed in this patient have not previously been described . Vancomycin must be excluded as the cause of leukopenia in any patient who is receiving this drug. J Antibiot (Tokyo), 1986 Nov, 39(11), 1578 - 83 Thermochemistry of the interaction between peptides and vancomycin or ristocetin; Rodriguez-Tebar A et al.; The thermodynamics of the interaction between the glycopeptide antibiotics vancomycin and ristocetin and bacterial peptidoglycan peptide analogs have been studied by means of a microcalorimetric titration technique . From results of the calorimetric measurements, changes in Gibbs energies, enthalpies, entropies and heat capacities for the binding reactions have been calculated . The derived thermodynamic data have been discussed on the basis of stereochemical data available for the interaction of acetyl-D-alanyl-D-alanine with each of the two antibiotics . The significance of entropic factors connected with conformational changes of the antibiotics is stressed. J Clin Microbiol, 1986 Oct, 24(4), 636 - 8 Comparison of two selective media for Actinobacillus actinomycetemcomitans; Martijn van Steenbergen TJ et al.; Two selective media, malachite green-bacitracin (MGB) agar and tryptic soy-serum-bacitracin-vancomycin (TSBV) agar, were compared for the isolation of Actinobacillus actinomycetemcomitans . The highest recovery was found on TSBV agar plates cultured in air-5% CO2 both for plaque samples from periodontal pockets and for pure cultures. Drug Intell Clin Pharm, 1986 Oct, 20(10), 783 - 5 Vancomycin-induced neutropenia during treatment of osteomyelitis in an outpatient; Henry K et al.; A case of vancomycin-associated neutropenia occurring during long-term outpatient therapy with vancomycin is described . Pharmacokinetic studies demonstrated that the patient's vancomycin serum levels were within an acceptable range during treatment . Eighteen other reported cases of vancomycin-associated leukopenia are discussed in brief . An immunologic mechanism has been proposed but a clear understanding is lacking . Patients receiving long-term vancomycin therapy should have their white blood cell counts periodically monitored. Drug Intell Clin Pharm, 1986 Oct, 20(10), 780 - 2 Vancomycin-induced neutropenia; Koo KB et al.; A case of vancomycin-induced neutropenia is presented with a review of other reported cases in the literature . A 59-year-old white female was started on vancomycin therapy for a chronic infection of a total left hip replacement . After 38 days of treatment, the patient developed a severe leukopenia with a white blood cell count of 1700/mm3 and the presence of only occasional neutrophils . Upon discontinuation of vancomycin, the leukocyte and neutrophil counts promptly increased with full recovery in one week . Subsequently, the patient was restarted on a five-day course of vancomycin at a lower dose that proved uneventful with no recurrence of neutropenia . It is unclear whether the neutropenia would have recurred with a longer course of vancomycin . A review of the literature suggests that an immunologic mechanism may be responsible for the reaction . Physicians and other health professionals should be aware that neutropenia is a potential reaction of patients receiving prolonged vancomycin treatment. Drug Intell Clin Pharm, 1986 Oct, 20(10), 757 - 61 Monitoring vancomycin therapy; Rybak MJ et al.; Vancomycin is an effective and widely used antistaphylococcal antibiotic . Despite several decades of use, however, our knowledge of the toxicologic and pharmacokinetic properties of vancomycin remains incomplete . This review summarizes current information regarding the adverse reactions and pharmacokinetics of vancomycin . Although there have been reports of side effects with vancomycin, these effects tend to be infrequent, easily managed, and reversible . Several methods for adjustment of vancomycin therapy have been recommended . The relationship between serum concentrations of vancomycin and the occurrence of ototoxicity or nephrotoxicity has not been well established . However, because of large interpatient variations in pharmacokinetic parameters, it seems preferable to individualize vancomycin therapy based on serum concentration data. Clin Pharmacol Ther, 1986 Oct, 40(4), 425 - 30 Disposition of vancomycin during hemofiltration; Matzke GR et al.; The disposition of vancomycin was assessed in five patients receiving hemofiltration after intravenous dosing with an 18 mg/kg dose after a hemofiltration procedure . The serum concentration-time profile was characterized before, during, and after the next hemofiltration procedure . The t 1/2 of vancomycin was 136.0 +/- 27.2 hours (mean +/- SD) before hemofiltration and 4.1 +/- 1.2 during hemofiltration . Approximately 400 mg of vancomycin was recovered in the filtrate and the hemofiltration clearance was 152.6 +/- 21.5 ml/min . A significant relationship was observed between vancomycin clearance and ultrafiltration flow rate (r = 0.9914) . A marked rebound in vancomycin serum concentration (52.4% +/- 15.6%) was observed in all patients . Hemofiltration has a significant effect on the disposition of vancomycin . Because of the marked interpatient variability in elimination t 1/2 and the degree and time course of the rebound, an individualized approach to vancomycin therapy in this patient population is recommended. Am J Hosp Pharm, 1986 Sep, 43(9), 2198 - 201 Pharmacist interventions to improve prescribing of vancomycin and tobramycin; Fletcher CV et al.; The effect of clinical pharmacist interventions that promoted the use of nafcillin rather than vancomycin and of gentamicin rather than tobramycin, when appropriate, was evaluated . Physician information sheets and criteria describing appropriate use of the target drugs vancomycin and tobramycin were developed by a clinical pharmacist and infectious disease physicians . When drugs were prescribed for indications that did not meet the established criteria, the clinical pharmacist either contacted the prescribing physician or left the sheet in the patient's chart if the physician was not available . The average use of the target drugs and their alternatives was evaluated monthly during two six-month study periods and compared with the average use of these drugs during a three-month period before the target-drug programs were initiated . Throughout the 12-month study, on a per-patient basis, nafcillin use increased 31% while vancomycin use decreased 27% compared with the reference period; gentamicin use increased 21% while tobramycin use decreased 12% during the same period . These changes in use resulted in a net decrease in drug expenditures of $161,396 . Approximately 0.5 full-time equivalent was spent on the program, and the return on investment for the service was greater than 10 to 1 . Clinical pharmacist interventions through target-drug programs were effective in improving the appropriateness of vancomycin and tobramycin prescribing based on literature-derived criteria . The effects achieved by these interventions may decrease with time, and ongoing drug-use monitoring and physician education are necessary. Mayo Clin Proc, 1986 Sep, 61(9), 721 - 4 Adverse effects of vancomycin administered in the perioperative period; Southorn PA et al.; Indications for the administration of vancomycin in the perioperative period have expanded in recent years . Used in this situation, vancomycin has caused adverse reactions, the most serious of which is hypotension . We describe five patients who had adverse reactions to vancomycin perioperatively . Vancomycin-induced hypotension usually results from a negative inotropic and vasodilator effect produced in part by a histamine-release phenomenon, which occurs most commonly with rapid intravenous infusion of the drug . Such a release of histamine may also produce an acute urticarial flushing of the upper torso (the "red neck syndrome") and symptoms of pain and muscle spasm in the chest or paraspinal muscles, which may mimic myocardial infarction . These effects usually abate promptly when the infusion of vancomycin is discontinued, and their resolution may be expedited by administration of an antihistamine. Antimicrob Agents Chemother, 1986 Jul, 30(1), 20 - 4 Vancomycin enhancement of experimental tobramycin nephrotoxicity; Wood CA et al.; The influence of vancomycin on tobramycin nephrotoxicity was assessed in male Fischer rats . Treatment groups included controls receiving diluent and groups receiving vancomycin alone at a dosage of 200 mg/kg (body weight) per day, tobramycin alone at a dosage of 80 mg/kg per day, and a combination of vancomycin and tobramycin at the above dosages . All regimens were injected on a twice-a-day schedule . The animals were sacrificed on days 1, 3, 10, 14, 17, and 21 . When compared with controls, animals receiving vancomycin alone exhibited no detectable renal toxicity . Compared with the case with controls, tobramycin alone was toxic, as manifested by lower mean animal weights, increased blood urea nitrogen concentrations on days 14 and 17 (P less than 0.005), increased serum creatinine concentrations on days 17 and 21 (P less than 0.005), and the presence of renal cortical tubular necrosis and regeneration . When compared with tobramycin alone, the combination of vancomycin and tobramycin caused earlier and more severe toxicity . By day 10, the magnitude of weight loss, the rise in blood urea nitrogen, and the increase in serum creatinine concentration were all greater in the rats given the combination of vancomycin plus tobramycin than in the animals given tobramycin alone (P less than 0.005) . In addition, there was more proximal tubular necrosis and regeneration in rats given vancomycin plus tobramycin compared with those given tobramycin alone . In this animal model, vancomycin alone caused no detectable renal injury, tobramycin alone produced minimal proximal tubular damage, and the combination of vancomycin and tobramycin resulted in a greater degree of kidney injury than observed with tobramycin alone. Am J Hosp Pharm, 1986 Jul, 43(7), 1729 - 31 Stability of vancomycin hydrochloride in 5% dextrose and 0.9% sodium chloride injections; Das Gupta V et al.; The stability of vancomycin hydrochloride mixed with 5% dextrose and 0.9% sodium chloride injections was studied . Vancomycin hydrochloride powder was mixed with each of the two diluents in final concentrations of 5 mg/mL . Duplicate samples of each admixture were divided into four parts and stored at 24 degrees C in glass and in plastic i.v . bags for 17 days and at 5 degrees C and -10 degrees C in glass for 63 days . To additional samples, hydrochloric acid or phosphate buffer was added; these were stored at 24 degrees C for 17 days . At various storage times, clarity and pH of the samples were recorded and vancomycin concentrations were measured in triplicate by high-performance liquid chromatography . Except for the buffered samples, all solutions remained clear and pH was unchanged . Vancomycin concentrations decreased less than 6% during 17 days at room temperature . In the refrigerated and frozen samples, vancomycin concentrations decreased less than 1% throughout the study . Vancomycin hydrochloride is stable in admixtures with 5% dextrose injection and 0.9% sodium chloride injection for 17 days at 24 degrees C and for 63 days at 5 degrees C and -10 degrees C. Neurosurgery, 1986 Jun, 18(6), 725 - 9 Pharmacokinetics of intraventricular vancomycin in hydrocephalic rats; Howard MA et al.; An animal model was developed for studying the pharmacokinetics of antibiotics administered intraventricularly in hydrocephalus . Obstructive hydrocephalus was consistently produced in craniectomized adult rats by injecting kaolin into the cisterna magna . After induction of hydrocephalus, vancomycin was injected into the right lateral ventricle of each rat . Bilateral ventricular cerebrospinal fluid (CSF) and brain parenchymal samples were obtained at 0.5, 1, 2, 4, 8, and 12 hours and the concentration of vancomycin in these samples was determined . Brain tissue was also analyzed histologically . The results show: (a) vancomycin is rapidly distributed within the CSF, including the contralateral ventricle, within 30 minutes; (b) vancomycin concentrations were nearly identical in both ventricles at all time points; (c) mean peak CSF vancomycin concentrations occurred at 2 hours and were 23.8 and 21.3 micrograms/ml for the left and right lateral ventricles, respectively; (d) elimination from CSF was slow (T1/2 beta = 2.22 hours, T1/2 gamma = 19.65 hours); (e) no vancomycin was detected (less than or equal to 2 micrograms/g) in the samples of periventricular white matter; (f) histological changes observed were consistent with untreated obstructive hydrocephalus and did not seem to be related to vancomycin treatment . The clinical significance of these results and the usefulness of the experimental model are discussed. Clin Pharmacol Ther, 1986 Jun, 39(6), 631 - 4 Vancomycin elimination in patients with burn injury; Brater DC et al.; Patients with burns clinically appear to require considerably larger doses of vancomycin than normal to attain therapeutic serum concentrations . It has been presumed that this phenomenon is a result of increased renal elimination of this drug consequent to increased glomerular filtration rates in such patients, as has been documented with aminoglycoside antibiotics . We measured the serum clearance of vancomycin in 10 patients with burns and found this parameter to correlate closely with creatinine clearance (serum clearance = 12.5 + 0.695 creatinine clearance; r = 0.932; P less than 0.001) . The slope of this relationship was similar to that reported by other investigators in patients not suffering from thermal injury . We conclude that at all levels of renal function, patients with burns clear vancomycin in a manner similar to that of other patients . Consequently, renal function can be used to select a dosing regimen for vancomycin in such patients. Clin Chem, 1986 Jun, 32(6), 1016 - 9 Simplified liquid-chromatographic determination of vancomycin; Rosenthal AF et al.; We simplified determination of vancomycin in serum by using a direct and rapid solvent precipitation of protein and by using a simple organic compound as internal standard . Reproductibility of the vancomycin retention time was improved by modifying the mobile phase . Data obtained by fluorescence polarization immunoassay correlated well, and there was little bias between the two methods . The present method is sufficiently rapid to make this a practical choice for many laboratories. J Antibiot (Tokyo), 1986 May, 39(5), 694 - 8 A cryptic plasmid from Nocardia orientalis NRRL 2452, a vancomycin producer; Oh YK et al.; A plasmid was found in Nocardia orientalis (formerly Streptomyces orientalis) . Physical characterization of the plasmid DNA indicates a size of 33.5 kb and a single cleavage site for EcoR I . The presence of plasmid, and variation in its copy member, did not directly affect vancomycin resistance or production levels . The plasmid represents the first to be isolated and characterized from a glycopeptide-producing nocardia. Pediatr Infect Dis, 1986 May-Jun, 5(3), 304 - 8 Vancomycin pharmacokinetics in infants: relationships to indices of maturation; Schaible DH et al.; The relationships between steady state pharmacokinetics of vancomycin and various indices of maturation were examined in 11 infants (gestational ages, 27 to 40 weeks; postconceptional ages (PCA), 29 to 48 weeks) . Vancomycin was administered as a 10-mg/kg iv infusion over 30 minutes . Serial blood samples were obtained over a dosage interval and vancomycin serum concentrations were determined by fluorescence polarization immunoassay . Model-independent pharmacokinetic data analysis yielded values for vancomycin systemic clearance (CL), volume of distribution (Vdss) and half-life ranging from 0.032 to 0.484 liter/hour, 0.44 to 2.5 liters and 3.5 to 9.6 hours respectively . Stepwise multiple regression analysis indicated that PCA was the best single variable model to predict vancomycin clearance as described, namely: CL (liters/hour) = 0.0224 PCA (weeks) - 0.639 (r = 0.91; P less than 0.0001) . Other more complex models using a combination of patient variables only modestly improved the ability to explain the variability in vancomycin clearance . Vdss was strongly related to body weight (r = 0.93; P less than 0.0001) Vdss = 0.563 weight (kg) + 0.052) . Our results suggest that postnatal alterations in vancomycin disposition are related to maturational changes in body composition and renal function . These data also suggest that vancomycin doses smaller than those previously recommended may be used to achieve therapeutic steady state vancomycin serum concentrations during the first 2 months of life. Clin Pharmacokinet, 1986 May-Jun, 11(3), 199 - 213 Drug disposition in obese humans . An update; Abernethy DR et al.; Drug disposition for many drugs has now been studied in obese individuals and some general conclusions can be drawn . Absorption of drugs evaluated to date is unchanged due to obesity . Apparent volume of distribution is greatly increased for some drugs including most benzodiazepines, thiopentone, phenytoin, verapamil and lignocaine (lidocaine) . Modest increases in volume of distribution have been noted for methylxanthines, aminoglycosides, vancomycin, ibuprofen, prednisolone and heparin . Distribution of digoxin, cimetidine and procainamide is unchanged in obesity . The mechanism for the increased distribution of some drugs and unchanged distribution of others in obesity is unclear at present . It may be in part due to the lipophilic character of the drug molecule; however, other complex and as yet poorly understood factors contribute to the variability in drug distribution in obese patients . Protein binding of drugs bound to albumin is not dramatically changed in obesity . In contrast, some studies report that drugs bound to alpha 1-acid glycoprotein (AAG) may have increased binding that is related to increased serum AAG concentration; however, this is not a consistent finding . Oxidative drug biotransformation is minimally changed in obesity with the exceptions of ibuprofen and prednisolone, for which clearance increases as a highly correlated function of total bodyweight . Drug conjugation uniformly increases as a function of bodyweight in obesity, with paracetamol (acetaminophen), lorazepam and oxazepam having been studied . Drug acetylation may be unchanged in obesity, with only procainamide evaluated at this time . High clearance drugs, including lignocaine, verapamil and midazolam, have no change in clearance in obese individuals compared to normal bodyweight controls . Renal clearance of drugs is little changed for some drugs evaluated (digoxin, cimetidine), and increased for others (aminoglycosides, unmetabolised procainamide) . Characterisation of appropriate animal models of obesity is underway to clarify the mechanisms for these in vivo pharmacokinetic observations in obese man . Two models, the Zucker obese and the obese cafeteria-fed male Sprague-Dawley rat, have provided preliminary physiological pharmacokinetic data with evaluations of theophylline, phenobarbitone and verapamil.(ABSTRACT TRUNCATED AT 400 WORDS) J Pediatr Gastroenterol Nutr, 1986 Mar-Apr, 5(2), 314 - 5 Relapsing pseudomembranous colitis; Holmes R et al.; Pseudomembranous colitis secondary to C . difficile and its toxin(s) is a well-recognized disease in children and usually responds to treatment with oral vancomycin . There are well-documented reports of relapse in adults after initial successful treatment with vancomycin . This report documents relapse in a child who developed diarrhea following treatment of pseudomembranous colitis . Stool cultures were negative for C . difficile at the end of the initial course of treatment, but the organism was isolated from the stool when the diarrhea recurred . The symptoms improved following a second course of treatment with vancomycin and have not recurred during 8 months of follow-up monitoring. Ann Intern Med, 1986 Mar, 104(3), 419 - 23 Prophylaxis for infective endocarditis: an update; Kaye D; The American Heart Association has updated its recommendations for prevention of bacterial endocarditis . The major changes are less emphasis on administration of parenteral agents and a reduction of the period of prophylaxis . The simplified new recommendations should make compliance easier and should be assiduously implemented by dental and medical practitioners . However, several changes are suggested for possible consideration: Because of the relatively low risk, prophylaxis may not be needed for persons with mitral valve prolapse (unless there is a holosystolic murmur) or for most gastrointestinal endoscopic procedures . Consideration should be given to using a single oral 3-g dose of amoxicillin for dental procedures in all patients at risk and for genitourinary and gastrointestinal tract procedures in patients at risk who have natural cardiac valves . Vancomycin should probably be the agent of choice for prophylaxis in cardiac valve surgery. Am J Dis Child, 1986 Feb, 140(2), 107 - 10 Vancomycin pharmacokinetics in small, seriously ill infants; Naqvi SH et al.; Twenty vancomycin pharmacokinetic studies were performed on 17 small infants who were receiving the antibiotic for treatment of documented infections . Fourteen patients were less than or equal to 41 weeks' postconception . In this group there was no statistical difference in mean elimination rate, volume of distribution, or clearance between neonates and infants 4 to 8 weeks of age . However, they had significantly lower clearance and prolonged mean beta-half-life than infants who were 3 to 6 months old (greater than 43 weeks' postconception) . Vancomycin clearance was directly related to postconceptional age by linear regression analysis . beta-Half-life was influenced by the weight of the patient, volume of distribution, and gestational age . In view of the interpatient variability observed in the prematurely born infants, pharmacokinetic studies should be performed to determine the appropriate dose and intervals in vancomycin therapy. Am J Med, 1986 Feb, 80(2), 333 - 5 Vancomycin-induced neutropenia complicating bone marrow recovery in a patient with leukemia . Case report and review of the literature; Mordenti J et al.; Neutropenia associated with intravenous vancomycin therapy is reported in a patient with chronic myelogenous leukemia . The patient received 12 days of vancomycin therapy without incidence; however, a second course of vancomycin initiated on hospital day 14 produced severe neutropenia . This delayed onset is typical of vancomycin-induced neutropenia . The neutropenia reversed, without complications, as soon as the vancomycin was discontinued. Drug Intell Clin Pharm, 1986 Jan, 20(1), 64 - 8 Individualized adjustment of vancomycin dosage: comparison with two dosage nomograms; Rybak MJ et al.; An individualized method of vancomycin dosage adjustment using steady-state serum concentrations was assessed in 50 patients (86 sets of vancomycin serum concentrations) . The predictive accuracy of this method was compared with that of two published nomograms (Moellering, Matzke) . Peak and trough serum concentrations predicted from previously drawn vancomycin serum concentrations (individualized method) using a one-compartment pharmacokinetic model were compared with measured steady-state peak and trough serum concentrations . Predicted peak and trough serum concentrations were also generated for both the Moellering and Matzke nomograms by using the elimination rate constant derived from each of the respective nomograms and the fixed volume of distribution (0.9 L/kg) assumed by the nomograms, and the actual administered vancomycin dose and dosage interval . These predicted concentrations were also compared with the measured peak and trough concentrations . Statistical measures of bias and precision indicated that the individualized method of dosage adjustment more closely predicted vancomycin serum concentrations following a dosage change than did either of the nomograms . Overall, the Moellering nomogram was the least accurate of the three methods in predicting vancomycin serum concentrations, and this nomogram should not be used to titrate vancomycin dosages in a clinical setting . Adjustment of vancomycin dosages should be individualized based on pharmacokinetic data derived from measured serum concentrations . In situations where quantitative analysis of vancomycin concentrations is not available, the Matzke nomogram appears to be a reasonable method of adjusting vancomycin dosages. Tokai J Exp Clin Med, 1986, 11 Suppl, 23 - 8 Experience with protective isolation for infection prevention in the compromised host; Nagao T; Ten years of experience with protective isolation of compromised patients was analyzed . The total number of patients was 191 including 116 patients with leukemia . Isolation could significantly prevent exogenous infections such as pneumonia, and prophylactic antibiotic regimens consisting of vancomycin and other nonabsorbable antibiotics could reduce the onset of endogenous infections such as sepsis . Elimination of serious and fatal infections by isolation together with prophylactic antibiotics increased the chances of remission or long-term survival for cases of hematological malignancies, solid tumor and bone marrow transplantation. Am J Nephrol, 1986, 6(2), 132 - 4 Therapeutic drug monitoring in patients with chronic renal failure: evaluation of the Abbott TDx drug assay system; Sedman AJ et al.; Immunoassay techniques have been widely used for therapeutic drug monitoring, but lack of antibody specificity can lead to measurement of erroneous drug concentrations due to cross-reactivity with other drugs, metabolites, or endogenous substances, particularly in patients with excretory organ compromise such as renal dysfunction . The Abbott TDx system, a popular automated immunoassay method for therapeutic drug monitoring, was used to measure apparent serum concentrations of carbamazepine, digoxin, gentamicin, lidocaine, phenobarbital, phenytoin, quinidine, valproic acid, and vancomycin in patients with renal failure who were not receiving these drugs . Endogenous substances and other concomitantly administered drugs did not lead to spuriously elevated drug levels, and a previous report of cross-reactive digoxin-like substances was not confirmed . Pooled plasma samples from the patients were spiked with digoxin or phenytoin, each at two concentrations, and the samples were assayed for the drug concentration using the TDx system . No falsely elevated values were found . This work suggests that the TDx system may be better suited for the measurement of these drugs in patients with renal failure than some other immunoassay methods. J Clin Microbiol, 1986 Jan, 23(1), 100 - 3 Evaluation of teicoplanin and vancomycin disk susceptibility tests; Barry AL et al.; Disk tests with two glycopeptide antibiotics, teicoplanin and vancomycin, were evaluated, and MICs were compared with those of fusidic acid and coumermycin . For tests with 30-micrograms vancomycin disks, we recommend modification of the current zone size standards to less than or equal to 10 mm for resistant and greater than or equal 15 mm for susceptible . For teicoplanin disk tests, 30-micrograms disks are recommended, with zone size interpretive standards of less than or equal to 10 and greater than or equal 14 mm . Since no resistant clinical isolates are available at this time, susceptibility test