Vancomycin

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 testing of either drug is rarely necessary, and zone size standards are tentative.

Pharmacotherapy, 1985 Nov-Dec, 5(6), 340 - 4
A simplified dosing method for initiating vancomycin therapy; Lake KD et al.; Vancomycin dosing regimens should be individualized for each patient . The routine use of standard doses 500 mg every 6 hours or 1.0 g every 12 hours regardless of patients' age, weight or kidney function is no longer appropriate . A simplified method for initiating vancomycin therapy was developed and evaluated prospectively in 30 patients . Average doses of 8.3 +/- 0.6 mg/kg lean body weight (rounded to the nearest 50 mg) were administered to patients with varying degrees of renal function (estimated creatinine clearances 19-113 ml/min) . The dosing interval was predicted by the patient's estimated creatinine clearance . Our simplified schedule resulted in desired serum levels and required no modification in 25 of 30 patients . Only slight dosage changes were needed in the remaining five patients . Mean peak and trough serum concentrations of vancomycin were 26.9 +/- 5.8 micrograms/ml (range 18.8-39.7 micrograms/ml) and 7.7 +/- 2.0 micrograms/ml (range 4.5-11.8 micrograms/ml) respectively . Our regimen is practical and simple and requires limited patient information.

J Clin Microbiol, 1985 Sep, 22(3), 375 - 8
Isolation of Capnocytophaga species with a new selective medium; Rummens JL et al.; A selective medium (CAP) composed of a GC agar base supplemented with 1% hemoglobin, 1% Polyvitex, and an antibiotic mixture of polymyxin B (15 U/ml), vancomycin (5 micrograms/ml), trimethoprim (2.5 micrograms/ml), and amphotericin B (2.5 micrograms/ml) was compared with another selective medium (TBBP) and two nonselective media--a blood agar and a chocolate agar--to isolate Capnocytophaga species from 725 clinical specimens . These included sputa (467 specimens), throat swabs (116 specimens), oral ulcerations (35 specimens), and periodontal pockets (107 specimens) . The recovery rate of Capnocytophaga species was significantly higher with the CAP medium (96%) than with the selective TBBP medium (52.2%), the nonselective blood agar (6.2%), and the chocolate agar (4.6%) . Growth of the normal flora was best inhibited on CAP medium . Colony size and yellow-brown pigment formation were maximally expressed on chocolate agar and CAP medium, but gliding motility was mostly absent . We conclude that the CAP medium is an excellent medium for the recovery of Capnocytophaga species from contaminated clinical specimens.

J Antimicrob Chemother, 1985 Aug, 16(2), 235 - 41
A prospective study of adverse reactions associated with vancomycin therapy; Sorrell TC et al.; A prospective evaluation of the efficacy and safety of vancomycin was conducted in 54 consecutive patients over a 16-month period . Vancomycin was curative in 95% of 43 patients with proven infection . Drugs were ceased in six patients because of adverse reactions; in three of these vancomycin was considered the likely cause . Reactions included thrombophlebitis (20 of 54 patients), rash (4 of 54), nephrotoxicity (4 of 50), proteinuria (1 of 50) and ototoxicity (1 of 11 patients tested by audiometry) . Thrombophlebitis occurred only with infusion through peripheral cannulae; nephrotoxicity and ototoxicity were confined to patients receiving an aminoglycoside plus vancomycin . We conclude that vancomycin, administered appropriately, constitutes safe, effective therapy for infections caused by susceptible bacteria.

Appl Environ Microbiol, 1985 Jul, 50(1), 21 - 6
Enhanced chlorine resistance of tap water-adapted Legionella pneumophila as compared with agar medium-passaged strains; Kuchta JM et al.; Previous studies have shown that bacteria maintained in a low-nutrient "natural" environment such as swimming pool water are much more resistant to disinfection by various chemical agents than strains maintained on rich media . In the present study a comparison was made of the chlorine (Cl2) susceptibility of hot-water tank isolates of Legionella pneumophila maintained in tap water and strains passaged on either nonselective buffered charcoal-yeast extract or selective differential glycine-vancomycin-polymyxin agar medium . Our earlier work has shown that environmental and clinical isolates of L . pneumophila maintained on agar medium are much more resistant to Cl2 than coliforms are . Under the present experimental conditions (21 degrees C, pH 7.6 to 8.0, and 0.25 mg of free residual Cl2 per liter, we found the tap water-maintained L . pneumophila strains to be even more resistant than the agar-passaged isolates . Under these conditions, 99% kill of tap water-maintained strains of L . pneumophila was usually achieved within 60 to 90 min compared with 10 min for agar-passaged strains . Samples from plumbing fixtures in a hospital yielded legionellae which were "super"-chlorine resistant when assayed under natural conditions . After one agar passage their resistance dropped to levels of comparable strains which had not been previously exposed to additional chlorination . These studies more closely approximate natural conditions than our previous work and show that tap water-maintained L . pneumophila is even more resistant to Cl2 than its already resistant agar medium-passaged counterpart.

J Antimicrob Chemother, 1985 Jun, 15(6), 773 - 80
Vancomycin toxicity: a prospective study; Mellor JA et al.; A prospective study of 34 patients treated with 39 courses of intravenous vancomycin, was undertaken in order to assess toxicity . Six patients received vancomycin alone and 27 courses were associated with aminoglycoside administration either concurrently or within two weeks of the first dose of vancomycin . Hearing loss was slight and uncommon; patients were unaware of its occurrence . Tinnitus and dizziness was noted by two patients and resolved on withdrawal of vancomycin . Diminution of renal function was seen both during (7%) and after (9%) vancomycin therapy . A striking feature of these patients with renal deterioration was the severity of their underlying disease . No evidence of synergistic toxicity between vancomycin and aminoglycosides was seen.

Tokai J Exp Clin Med, 1985 Jun, 10(2-3), 139 - 46
Present status of bone marrow transplantation in Japan; Masaoka T et al.; One hundred and seventy three bone marrow transplantations (BMT) including 133 allogeneic, 17 syngeneic and 23 autologous BMT were recorded in Japan during the period between September, 1975 and March, 1984 . The number of cases of BMT increased rapidly over the years, i.e., 16 cases in 1980, 27 in 1981, 39 in 1982 and 57 in 1983 . All cases were treated in clean rooms, many of them receiving intensive gut decontamination containing vancomycin . In 110 cases with acute leukemia, the main causes of death were interstitial pneumonitis, relapse of leukemia, infection and GvHD . Favorable factors determined from 180-day survival were remission, no infection, low dose rate and fractionated total body irradiation (TBI), ABO minor mismatch and positive graft versus host reaction . Long-term survival of patients who received BMT during remission and were without infection amounted to 70% of acute lymphocytic leukemia (ALL) and 40% of acute myelogenous leukemia (AML) patients . Cyclosporin A (Cy-A) administered in 21 cases was compared with methotrexate (MTX) given in 20 cases . A statistically significant decrease of stomatitis was observed, while no difference in GvHD or survival was seen . There were seven cases giving a more than good response out of 11 cases treated with cyclosporin because methotrexate or immuran was ineffective or could not be administered due to toxicity . Such data suggest that allogeneic BMT is acceptable as a very promising form of treatment for acute leukemia in Japan.

Pathol Biol (Paris), 1985 Jun, 33(5 Pt 2), 511 - 6
{HPLC, RIA, FPIA . Evaluation of 3 methods for the assay of vancomycin}; Jehl F et al.; We describe a rapid and accurate high performance liquid chromatographic (HPLC) method for vancomycin quantitation . This method is then compared with two immunoassays, RIA and FPIA . The chemical extraction step needed for HPLC is simple and rapid . Both conventional reversed phase HPLC and high speed reversed phase HPLC were tested . The mobile phase was a mixture of aqueous ammonium acetate and acetonitrile . Specificity of the HPLC assay was good . Serum levels in 112 clinical specimens assayed by HPLC were regressed against the levels obtained for the same samples by both RIA and FPIA . The correlation was good (RIA : r = 0.945; FPIA : r = 0.967) . Considering the disadvantages of RIA, HPLC and FPIA emerge as the methods of choice.

Clin Pharm, 1985 May-Jun, 4(3), 311 - 5
Evaluation of the vancomycin-clearance:creatinine-clearance relationship for predicting vancomycin dosage; Matzke GR et al.; Four methods of predicting vancomycin maintenance doses on the basis of the relationship between total-body or renal clearance of the drug and creatinine clearance were evaluated retrospectively using data from 24 patients who received vancomycin hydrochloride . Data for 18 men and 6 women with creatinine clearances of 10-130 mL/min were used; the mean (+/- S.D.) vancomycin maintenance dose was 22.0 +/- 11.2 mg/kg/day . The actual vancomycin maintenance dose needed to sustain an average steady-state vancomycin concentration of 15 mg/L was determined based on individual pharmacokinetic values . Predicted vancomycin maintenance doses were generated using the vancomycin-clearance:creatinine-clearance relationships derived separately by Nielsen, Moellering, Rotschafer, and Matzke . Orthogonal regression analysis was used to determine relationships between actual and predicted maintenance doses . Predictive ability of each method was assessed for bias (mean error) and precision (root mean squared error) . Mean error and root mean squared error (+/- S.D.), respectively, for the four methods were as follows: Nielsen -262 +/- 451, 522 +/- 718; Moellering -91 +/- 439, 448 +/- 547; Rotschafer 192 +/- 602, 632 +/- 682; and Matzke -76 +/- 101, 408 +/- 517 . Doses predicted by the Nielsen relationship were significantly lower than the actual vancomycin maintenance doses . Use of the Rotschafer relationship resulted in substantial overprediction, which increased as creatinine clearance declined . Doses predicted by the Moellering and Matzke relationships were slightly less than but not significantly different from the actual dose . The Matzke method demonstrated the least bias and was the most precise.(ABSTRACT TRUNCATED AT 250 WORDS)

Am J Gastroenterol, 1985 May, 80(5), 381 - 3
Chlorpropamide-induced cholestatic jaundice and pseudomembranous colitis; Gupta R et al.; A previously healthy 59-year-old man received chlorpropamide 250 mg/day for adult-onset diabetes . Within 1 month of starting the drug, he developed cholestatic jaundice and pseudomembranous colitis . The colitis worsened during subsequent treatment with multiple antibiotics and sulfasalazine . Oral vancomycin produced a prompt and total remission . One similar case of chlorpropamide toxicity manifested by jaundice and colitis has been previously reported . It is possible that the sulfonamide moiety of the chlorpropamide was implicated in the development of the colitis.

Antimicrob Agents Chemother, 1985 Apr, 27(4), 578 - 82
Vancomycin disposition during continuous ambulatory peritoneal dialysis: a pharmacokinetic analysis of peritoneal drug transport; Rogge MC et al.; Expressions are presented to describe the absorption and also clearance of drugs administered into the peritoneal cavity of patients undergoing continuous ambulatory peritoneal dialysis (CAPD) . Application of the expressions to vancomycin kinetics in five male CAPD patients showed that therapeutic levels of vancomycin can readily be achieved and maintained in the systemic circulation by administering the appropriate loading and maintenance doses . The intrinsic peritoneal clearance of vancomycin reported here is higher than the apparent clearances reported previously, averaging 300 to 500 ml/min under the conditions used in this study . The low apparent clearances previously reported are useful clinically although they do not represent the true efficiency of vancomycin removal by CAPD . The degree to which apparent clearance underestimates the true intrinsic clearance is exponentially related to the dwell time of dialysate in the peritoneum . Intraperitoneal administration is a practical alternative to other routes for CAPD patients needing antibiotic or other therapy.

Antimicrob Agents Chemother, 1985 Apr, 27(4), 503 - 7
Determination of vancomycin in human serum by high-pressure liquid chromatography; Jehl F et al.; A rapid, accurate, reverse-phase high-pressure liquid chromatographic procedure for vancomycin quantitation in human serum, cerebrospinal fluid, and peritoneal fluid was developed . This procedure involves a simple chemical extraction of the antibiotic and is suitable for each of these body fluids . The column and mobile phase used provided a good resolution of the vancomycin peak with a retention time of 6.1 min . The precision of the assay was within the requirement for a daily routine clinical application . Coefficients of variation for within-day reproducibility were 5.80 and 6.28%, respectively, for samples at 50 and 25 micrograms/ml, and for between-day reproducibility they were 11.4 and 11.1%, respectively . No interference was found with respect to beta-lactam and aminoglycoside antibiotics and many other currently used drugs, indicating a good specificity for the procedure . The detection limit of 100 ng/ml has proven to be sufficient for monitoring drug levels in serum obtained after usual dosages . Drug levels in 112 clinical serum specimens assayed by high-pressure liquid chromatography were regressed against the levels obtained for the same samples by radioimmunoassay and fluorescent polarization immunoassay . Correlation coefficients were 0.945 and 0.967, respectively, and were highly significant (alpha less than 0.001).

Hosp Pharm, 1985 Apr, 20(4), 235 - 7, 240-1
Warfarin: a quality assurance model for concurrent drug monitoring; Mattei TJ et al.; Until recently, the mechanism to gain the attention of hospital decision makers on the potential implication of pharmacists' involvement in the drug use review process was missing . However, integrating clinical pharmacy services with quality assurance activities appears to provide a mechanism to reduce patient risk and cost while maintaining the quality of patient care services provided . The department of pharmacy at The Mercy Hospital of Pittsburgh, through the hospital-wide quality assurance committee (QAC) and pharmacy evaluation committee (PEC), has developed concurrent drug the reviews . The concurrent warfarin review conducted by the department of pharmacy is described in detail to illustrate the process that is followed in the development and implementation of a concurrent drug use review . The concurrent review of warfarin was initiated and, in general, criteria were met and few variations occurred . Interventions by staff pharmacists were effective in further improving compliance with certain criteria . Although it was not proven that the incidence of hemorrhage was actually decreased, the QAC felt that such an approach would serve to decrease the likelihood of hemorrhage as warfarin therapy is initiated in the hospital . Similar drug use reviews have been developed for aminoglycosides, third-generation cephalosporins, piperacillin, cefoxitin, cefazolin, vancomycin, phenytoin, and the digoxin-quinidine interaction . The objective of these reviews is also to reduce patient risk and costs associated with drug use . Therefore, in today's hospital environment, a mechanism to improve the visibility of the pharmacist's involvement in the health care process is to integrate clinical pharmacy services with quality assurance activities.

Am J Kidney Dis, 1985 Feb, 5(2), 120 - 3
Vancomycin prevents polytetrafluoroethylene graft infections in pediatric patients receiving chronic hemodialysis; Fivush BA et al.; Polytetrafluoroethylene (PTFE) grafts have been a useful addition to the pediatric hemodialysis vascular access armamentarium . In this study, 17 pediatric patients underwent 331 total months of hemodialysis via PTFE grafts . There was a statistically significant (P less than .025) decrease in the incidence of graft infections in 12 patients (235 patient-months) while receiving prophylactic parenteral vancomycin compared with 9 patients (96 patient-months) while receiving no vancomycin (0% v 44%) . Vancomycin side effects were uncommon and mild . Vancomycin is a safe and effective agent for the prevention of PTFE graft infections in pediatric patients receiving chronic hemodialysis.

Pediatr Pharmacol (New York), 1985, 5(1), 17 - 22
Vancomycin pharmacokinetics in premature infants; Gross JR et al.; Vancomycin pharmacokinetics were studied in nine premature infants . Infants weighing less than 1,000 gm had significantly larger volumes of drug distribution and consequently longer drug half-lives than larger premature infants, regardless of postconceptual or actual age . These differences alter the vancomycin dosing recommendations in these two groups of premature infants . We recommend initial dosage regimens consisting of a loading dose of vancomycin of 25 mg/kg followed by doses of 15 mg/kg every 12 hours for infants with weights less than 1,000 gm . Infants weighing over 1,000 gm should receive 10 mg/kg every 12 hours, with a loading dose of 12.5 mg/kg . Serum vancomycin concentration should be monitored, however, for final optimization of therapy.

J Antibiot (Tokyo), 1985 Jan, 38(1), 51 - 7
The stabilization of vancomycin by peptidoglycan analogs; Harris CM et al.; The glycopeptide antibiotic vancomycin is unstable in solution . It undergoes a rearrangement involving the conversion of an asparagine residue to isoaspartate to give an antibiotically inactive species, CDP-I . Peptide analogs of bacterial peptidoglycan, such as Ac-D-Ala-D-Ala and di-Ac-L-Lys-D-Ala-D-Ala bind to vancomycin and stabilize the antibiotic against degradation and consequent loss of activity . Protection by peptide is effective even under prolonged heating at 80 degrees C or steam sterilization (30 minutes, 10(4) kg/m2).

Can Anaesth Soc J, 1985 Jan, 32(1), 65 - 6
Cardiac arrest following administration of vancomycin; Mayhew JF et al.; A two-year-old female child status post-bilateral nephrectomies sustained a cardiac arrest following the central intravenous administration of vancomycin chloride . This report reviews the literature concerning the problems associated with the use of vancomycin chloride in the perioperative period.

Sex Transm Dis, 1985 Jan-Mar, 12(1), 44 - 8
Establishing Chlamydia trachomatis isolation capability in a local laboratory; Smeltzer MP et al.; A system for the culture and identification of Chlamydia trachomatis was established in a local health department laboratory . The McCoy cell-cycloheximide procedure was adopted with use of on-site monolayer production and iodine staining . Several procedural modifications were analyzed for sensitivity, including two-vial vs . one-vial inoculation, overnight refrigeration vs . immediate inoculation of the monolayer, and use of transport media with vancomycin (100 micrograms/ml) vs . transport media without vancomycin . Costs associated with establishing and maintaining this procedure over a one-year period were documented . Inoculation of two monolayers improved sensitivity only slightly (87/292 vs . 85/292) . Loss in sensitivity following overnight refrigeration of the sample was approximately 7%; 42 of 45 positive cultures were detected . Addition of 100 micrograms of vancomycin/ml to the transport media increased apparent sensitivity from 27.4% to 29.6% among females with gonorrhea . The cost was $.06 per culture . On the basis of this information, cultures for isolation of C . trachomatis are now offered to our clinic for sexually transmitted diseases as well as to some private physicians and clinics . We are using one-vial inoculation of a specimen transported in sucrose-phosphate buffer containing 100 micrograms vancomycin/ml . The specimen is either cultured immediately or snap frozen at -77 C.

Folia Haematol Int Mag Klin Morphol Blutforsch, 1985, 112(4), 629 - 35
Aggristin (ristomycin) precipitation test: a new tool for the detection of fibrin monomer and fibrin degradation products; Pfliegler G et al.; The specific detection of fibrin monomer and fibrin degradation products is of high importance in the laboratory diagnosis of intravascular clotting (disseminated intravascular coagulation, deep vein thrombosis) . The methods proposed until now are partly time-consuming, needing special laboratories or insensitive and poorly specific . Applying ristomycin instead of ristocetin (another member of the vancomycin antibiotics) a new simple, specific and sensitive method has been elaborated and recommended for the laboratory diagnosis of intravascular coagulation and its differentiation from primary fibrinogenolysis . The results obtained from in vitro and animal experiments and from human studies are presented.

J Antimicrob Chemother, 1984 Dec, 14 Suppl D, 53 - 7
Vancomycin pharmacokinetics in critically ill patients; Garaud JJ et al.; Peak and trough vancomycin serum levels were measured in 37 severely ill patients following dosing using the Moellering nomogram . The peak and trough serum concentrations were 61.2 +/- 23 and 22.6 +/- 16.5 mg/l, respectively, and higher than expected . Vancomycin pharmacokinetics obtained from 10 other patients were also studied . In five patients with a creatinine clearance greater than 1 ml min-1 kg-1, a mean plasma elimination half-life of 7.8 +/- 2.8 h was calculated . In the five other patients with markedly reduced renal function (creatinine clearance less than or equal to 1 ml min-1 kg-1), the mean elimination half-life was 18.3 +/- 10.2 h . A correlation was observed between the vancomycin and creatinine clearance . Important inter-patient variations of vancomycin clearance for the same creatinine clearance was also noted . Tubular damage in critically ill patients with severe sepsis may explain our results of the decreased vancomycin elimination.

J Antimicrob Chemother, 1984 Dec, 14 Suppl D, 43 - 52
Pharmacokinetics of vancomycin; Moellering RC Jr; Vancomycin is poorly absorbed when administered by mouth and, for systemic infections, must be given intravenously . The pharmacokinetics of vancomycin have been well defined in a number of recent studies in man . Since the drug is excreted primarily via the kidneys, dosage modification is imperative in patients with impaired renal function . With the possible exception of aqueous humour and cerebrospinal fluid, vancomycin penetrates well into most body fluids . It appears that excessively high serum concentrations of vancomycin may be associated with ototoxicity . It has not been possible to relate the development of nephrotoxicity to determined previously serum concentrations of vancomycin.

Gan To Kagaku Ryoho, 1984 Oct, 11(10), 2099 - 105
{Bone marrow transplantation}; Masaoka T; One hundred seventy-one of cases bone marrow transplantation (BMT), including 132 allogeneic, 16 syngeneic and 23 autologous, were recorded in Japan during the period from September 1975 through March 1984 . The number of BMT cases increase showed a rapid chronological i.e., 16 cases in 1980, 27 in 1981, 39 in 1982 and 57 in 1983 . All cases were treated in clean rooms, and many of them received intensive gut decontamination using Vancomycin.

J Clin Microbiol, 1984 Sep, 20(3), 311 - 6
Laboratory evaluation of five assay methods for vancomycin: bioassay, high-pressure liquid chromatography, fluorescence polarization immunoassay, radioimmunoassay, and fluorescence immunoassay; Pfaller MA et al.; We compared the precision and accuracy of five methods used to measure the concentration of vancomycin in serum: bioassay, high-pressure liquid chromatography, fluorescence polarization immunoassay (FPIA {TDX; Abbott Laboratories, North Chicago, Ill.}), radioimmunoassay (RIA), and fluorescence immunoassay . Based on an analysis of seven standards and of 106 patient samples, all five methods were accurate, and four (bioassay, high-pressure liquid chromatography, FPIA, and RIA) were also precise . The FPIA was the most precise and the fluorescence immunoassay was the least precise of the methods tested; intrarun coefficients of variation for these two methods were 0.9 to 3.0% versus 8.9 to 14.5%, and interrun coefficients of variation were 2.8 to 8.1% versus 12.2 to 16.2%, respectively . The RIA was inconvenient because it required an extra dilution of the specimen being tested and an additional (64 micrograms/ml) vancomycin standard for specimens with 32 to 64 micrograms of vancomycin per ml . Based on its rapid turnaround time and the stability of its standard curve, we believe that the FPIA is the best method currently available to quantitate vancomycin in the clinical laboratory.

Br J Audiol, 1984 Aug, 18(3), 179 - 80
Vancomycin ototoxicity in patients with normal renal function; Mellor JA et al.; Three patients with normal renal function developed ototoxicity during vancomycin therapy . This is an uncommon occurrence and the literature is reviewed . Assumptions on "safe' levels of vancomycin are questioned.

J Clin Microbiol, 1984 Aug, 20(2), 159 - 61
Comparison of fluorescence polarization immunoassay and bioassay of vancomycin; Pohlod DJ et al.; Human serum samples were analyzed for vancomycin concentrations by two different methods: the fluorescence polarization immunoassay and the disk plate bioassay . Each assay method offered acceptable precision . The correlation between both assay methods was excellent (correlation coefficient = 0.985) . Excluding technical time, the bioassay was the least expensive method to perform but was more labor intensive than the fluorescence polarization immunoassay.

Arch Intern Med, 1984 Jul, 144(7), 1373 - 5
The natural history of intravenous catheter-associated phlebitis; Hershey CO et al.; During a controlled evaluation of an intravenous therapy (IVT) team, we had the opportunity to follow up 202 episodes of catheter-associated phlebitis . While the IVT team had a considerable effect on the incidence of phlebitis, the clinical course of this complication was not influenced . More than 40% of catheter-associated phlebitis occurred more than 24 hours after withdrawal of the catheter . Premonitory symptoms were not useful in predicting the development of phlebitis . Factors that influenced the duration of phlebitis included the patient's diagnosis and the administration of vancomycin hydrochloride . The duration of phlebitis was prolonged by delayed removal of the catheter after the development of phlebitis.

Antibiotiki, 1984 Jul, 29(7), 495 - 500
{Regeneration of Nocardia orientalis protoplasts}; Trenin AS et al.; A method for effective regeneration of the protoplasts of N . orientalis, a vancomycin-producing organism into viable cells on a rich organic medium was developed . The dependence of the regeneration on the conditions of the protoplast plating out and the level of the regeneration medium dehydration was studied . The highest positive effect was observed when the protoplasts were suspended in the agarized medium and then plated out on the regeneration medium dehydrated by 2.5 per cent . The frequency of the protoplast regeneration increased on addition of bovine serum albumin to the regeneration medium . The effect of bovine serum albumin depended on its concentration . When the albumin concentration was optimal (0.01 per cent) the regeneration amounted to 100 per cent.

South Med J, 1984 May, 77(5), 664 - 5
Delayed appearance of vancomycin-induced neutropenia in a patient with chronic renal failure; Farwell AP et al.; A patient receiving hemodialysis for chronic renal failure had neutropenia six weeks after administration of his last dose of intravenous vancomycin and in the absence of other drug therapy . This case provides confirmation that neutropenia can be seen with vancomycin therapy; suggests an immunologic basis for the reaction, since the patient exhibited a concomitant hypersensitivity rash; and points out that delayed clearance of vancomycin in patients with chronic renal failure can produce late onset of side effects in such patients.

Ann Microbiol (Paris), 1984 May-Jun, 135A(3), 367 - 74
Evidence for the synthesis of peptidoglycan by spheroplasts of Mycobacterium smegmatis ATCC-14468; Murty MV et al.; Evidence for the synthesis of insoluble peptidoglycan by spheroplasts of Mycobacterium smegmatis ATCC-14468 was obtained by inhibition of synthesis by vancomycin and cycloserine and no inhibition of synthesis by tetracycline . Radioactivity in the peptidoglycan fraction decreased when treated with lysozyme . The ability of spheroplasts to synthesize macromolecular peptidoglycan was half that of whole cells . A relationship was obtained between the amount of intact cell wall present and peptidoglycan synthesized: as the amount of intact cell wall decreased, the ability to synthesize macromolecular peptidoglycan also decreased.

Br J Haematol, 1984 May, 57(1), 25 - 35
The agglutination of human platelets by botrocetin: evidence that botrocetin and ristocetin act at different sites on the factor VIII molecule and platelet membrane; Howard MA et al.; Botrocetin caused a factor VIII (FVIII) dependent platelet agglutination which was associated with a reduction in the plasma levels of all FVIII parameters as a result of specific binding of FVIII to the platelets . The site of binding of FVIII to the platelet in response to ristocetin or botrocetin involves the glycoprotein I complex . This is suggested by the inability of chymotrypsin treated platelets or platelets from patients with the Bernard-Soulier syndrome to agglutinate in response to ristocetin . These platelets responded to botrocetin , but this was greatly reduced compared to normal . Crossed immunoelectrophoretic analysis indicated that in the presence of botrocetin most multimetric forms of FVIII bound to the platelet, whereas ristocetin caused binding of high and intermediate molecular weight forms . The antibiotic vancomycin inhibited platelet agglutination by ristocetin but had no effect on that caused by botrocetin . Assays of FVIII von Willebrand factor (VIII:vWf) using botrocetin compared well with those obtained using ristocetin in plasmas from normal individuals and from patients with classical von Willebrand disease (vWd) . However, a patient with variant vWd demonstrated 100% botrocetin cofactor activity and 0% ristocetin cofactor activity . This suggested that the site of interaction on the FVIII molecule for botrocetin and ristocetin are different . Therefore the diagnosis of some von Willebrand variants cannot be excluded on the basis of a normal botrocetin cofactor assay.

Antimicrob Agents Chemother, 1984 Apr, 25(4), 433 - 7
Pharmacokinetics of vancomycin in patients with various degrees of renal function; Matzke GR et al.; The pharmacokinetics of vancomycin were characterized in 56 patients with different degrees of renal function after an intravenous dose of 18.4 +/- 4.7 mg kg-1 (mean +/- standard deviation) . Seven subjects had a creatinine clearance (CLCR) of greater than 60 ml min-1 (group I), 13 had a CLCR of 10 to 60 ml min-1 (group II), and 36 had a CLCR of less than 10 ml min-1 (group III) . Serial serum samples (range, 3 to 8) were collected during the 168 h after drug administration . The serum concentration-time profile in all patients demonstrated monoexponential decay . The mean half-lives were 9.1, 32.3, and 146.7 h in groups I, II, and III, respectively . A significant decline in serum clearance (CLS) was also noted (62.7 to 28.3 to 4.87 ml min-1 in groups I, II, and III, respectively) . The steady-state volume of distribution varied from 0.72 to 0.90 liter kg-1 . There was no significant relationship between the steady-state volume of distribution and CLCR . The observed relationship between CLS and CLCR (CLS = 3.66 + 0.689 CLCR; r = 0.8807) can be utilized to devise dosage schedules for patients with any degree of renal impairment . This relationship was utilized to develop a nomogram for initial and maintenance dosing of vancomycin.

Am J Hosp Pharm, 1984 Mar, 41(3), 473 - 7
Collaborative clinical pharmacokinetics service in a community hospital; Rietscha WJ et al.; A clinical pharmacokinetics service (CPS) operated through the collaborative efforts of the pharmacy and laboratory in a community hospital is described . Pharmacokinetic interpretations of aminoglycoside, vancomycin, chloramphenicol, digoxin, and theophylline concentrations are provided routinely by the CPS; other drug assays are interpreted upon physician request . The CPS is operated by two pharmacokinetics pharmacists and a clinical pharmacy coordinator during the week; pharmacy residents and staff pharmacists in decentralized areas assist on the weekends . Pharmacists assign sampling times to all assay requests unless otherwise specified by the physician . Pharmacy, nursing, laboratory, and medical staffs are involved in an ongoing quality-assurance monitoring program . During a recent one-year period, more than 100 pharmacokinetic consultations each were provided monthly for theophylline, digoxin, and antibiotic assays . Through the cooperation of the pharmacy and laboratory departments, the clinical pharmacokinetics service in this community hospital provides a valuable service to patients and serves as an educational forum for pharmacy and medical staffs.

Eur J Biochem, 1984 Jan 16, 138(2), 345 - 8
Hydrophobic interactions affect hydrogen bond strengths in complexes between peptides and vancomycin or ristocetin; Williamson MP et al.; A study on complexes of the glycopeptide antibiotics vancomycin and ristocetin with various dipeptides and tripeptides shows that the intermolecular hydrogen bond strengths of the complexes are reasonably well correlated with their free energy of formation . Such correlation is not anticipated on the basis of a purely hydrophobic interaction of the peptide side-chains with the antibiotics . It is also shown that the free energy changes observed are very different from those expected as a result of hydrophobic forces . These facts suggest that addition of a hydrophobic group not only allows hydrophobic bonding but also strengthens existing hydrogen bonds . The increased hydrogen bond strength can be an important factor in determining the overall binding energy.

Am J Dis Child, 1984 Jan, 138(1), 20 - 2
Vancomycin dosage in pediatrics reconsidered; Alpert G et al.; Vancomycin hydrochloride levels were studied in 44 children (age range, 10 days to 10 years) . These children received doses of vancomycin within current recommendations . Major variations in vancomycin levels were demonstrated in similar age groups and dosage regimens . For patients in the first month of life, second month of life, and older ages, respectively, 70%, 39%, and 30% of the peak determinations and 53%, 50%, and 23% of the trough determinations were greater than the desired level . Potentially toxic levels were found in eight patients.

J Thorac Cardiovasc Surg, 1984 Jan, 87(1), 145 - 6
Profound hypotension from rapid vancomycin administration during cardiac operation; Dajee H et al.; Profound hypotension from rapid vancomycin administration resulted in cardiac arrest . Successful resuscitation was performed with inotropic support.

Ther Drug Monit, 1984, 6(2), 238 - 42
Comparison of bioassay, high-performance liquid chromatography, and fluorescence polarization immunoassay for quantitative determination of vancomycin in serum; Ristuccia PA et al.; This investigation was designed to compare three assay techniques, the traditional bioassay (agar diffusion), and two more recent techniques, high-performance liquid chromatography (HPLC) and fluorescence polarization immunoassay (FPIA), for the determination of vancomycin concentrations in serum . One hundred clinical samples obtained from patients receiving vancomycin were assayed by each method . The results from each assay were compared using linear regression analysis . The resultant correlation coefficients were as follows: 0.9996 for the HPLC versus FPIA, 0.7773 for the FPIA versus bioassay, and 0.7779 for HPLC versus bioassay . The FPIA technique was the easiest and fastest of the three methods; FPIA and HPLC were the most accurate.

Vet Rec, 1983 Dec 3, 113(23), 535 - 6
Simple transport medium for the isolation of Chlamydia psittaci from clinical material; Spencer WN et al.; Infectious elementary bodies of Chlamydia psittaci in tissue samples from field cases of enzootic abortion were placed in five different transport media (A to E) . In one medium, in the absence of refrigerative storage, the organism remained viable for 30 days and at 4 degrees C for 34 days . This was medium D; it consisted of sucrose (74.6 g/litre), K2HPO4 (1.237 g/litre), L-glutamic acid (0.721 g/litre), fetal calf serum (10 per cent v/v), vancomycin and streptomycin (100 micrograms/ml) and nystatin and gentamicin (50 micrograms/ml) . Samples of this transport medium were supplied to veterinary investigation centres throughout the UK . Of 1862 samples submitted for diagnosis of enzootic abortion only 1.55 per cent were so contaminated that chlamydiae could not be detected . This transport medium permits the isolation of C psittaci from clinical material for up to about one month, even in the absence of conventional storage facilities.

South Med J, 1983 Dec, 76(12), 1554 - 5
Accumulation of vancomycin after intraventricular infusions; Arroyo JC et al.; A 50-year-old man with an infected intracerebral hematoma was treated with daily intraventricular infusions containing 10 mg of vancomycin (half the dose suggested by others) . A vancomycin level in the ventricular CSF of 606 micrograms/ml after nine days of therapy indicates a potential for accumulation of this drug in patients with extensive brain damage.

Can J Microbiol, 1983 Oct, 29(10), 1412 - 23
Cell division in Deinococcus radiodurans and a method for displaying septa; Murray RG et al.; The study of sections, freeze-cleaved, and whole-cell preparations of Deinococcus radiodurans supported the contention that septa close assymmetrically and originate from discrete opposing locations on the cell surface . Tetrads and the larger associations (sheets) of cells in some strains were formed by alternate and synchronized divisions in two planes . The polarity initiating the second division in cells of the Sark strain, in particular, was often expressed in slower growing cells before completion of the first division so that the advancing margins of the first septum were diverted towards the nearest new pole; the resulting gap was closed later on, and consequently, the cell compartments of this coccus were in communication for some time after two rounds of nuclear segregation . Freeze cleaving showed that the initial generation of septa involved a short sulcus in the plasma membrane and not a circumferential infolding . The shape and form of the developing septum was inferred from sections but was displayed in whole-cell preparations by a technique which selectively and positively stained a septal component . Positive staining of the septum with uranyl salts was appreciable when the relative stainability of the peripheral wall (mainly peptidoglycan) was reduced by pretreatment with salts of low atomic weight metals (0.01-1.0%, w/v) such as cobalt, copper, iron, or zinc . Examination of these whole-cell preparations by stereoscopy showed that the septal diaphragm closes as a slit or long oval, and the advancing margin shows curvature towards the next axis of division . The mechanism and exact site of this positive staining was not elucidated; vancomycin blocking of the uncross-linked peptides of peptidoglycan was almost as effective as the transition metal salts as a foretreatment for staining septa.

J Clin Microbiol, 1983 Oct, 18(4), 994 - 5
Comparison of radioimmunoassay and fluorescent polarization immunoassay for quantitative determination of vancomycin concentrations in serum; Ackerman BH et al.; A new fluorescent polarization immunoassay (Abbott Laboratories, Diagnostics Division, North Chicago, Ill.) was compared with a standard radioimmunoassay (American Diagnostics Corp., Newport Beach, Calif.) in 34 patients being treated with vancomycin . A total of 123 serum samples were divided and quantitatively analyzed for vancomycin by both assay methods . The results obtained indicated that the two assay methods are comparable (y = 1.01x - 0.81; r = 0.99).

Antimicrob Agents Chemother, 1983 Aug, 24(2), 216 - 20
Evaluation of an automated fluorescence polarization immunoassay for vancomycin; Filburn BH et al.; An automated fluorescence polarization immunoassay for the determination of vancomycin levels in serum was evaluated . The vancomycin assay is a homogeneous competitive inhibition immunoassay based on changes in fluorescence polarization that occur with antibody binding . This assay was compared with a liquid chromatographic assay and an agar well diffusion bioassay method by using clinical serum specimens and controls . Linear regression analysis of the data obtained on clinical specimens by the three methods resulted in correlation coefficients of 0.97 for the fluorescence polarization immunoassay versus the liquid chromatographic assay (n = 60), 0.90 for the fluorescence polarization immunoassay versus the bioassay (n = 57), and 0.90 for the liquid chromatographic assay versus the bioassay (n = 57) . Repetitive analysis of control sera containing 7, 35, and 75 micrograms of vancomycin per ml by the fluorescence polarization immunoassay yielded coefficients of variation of 3.0, 1.7, and 2.3, respectively . No interference was demonstrated in spiked hemolytic, lipemic, or icteric sera, and the assay was free of matrix effects . The automated fluorescence polarization immunoassay system offers a rapid, efficient, and accurate method for monitoring vancomycin serum levels for both toxicity and efficacy.

Antimicrob Agents Chemother, 1983 May, 23(5), 710 - 4
Vancomycin pharmacokinetics in patients with peritonitis on peritoneal dialysis; Magera BE et al.; Vancomycin pharmacokinetics were studied in four patients with peritonitis undergoing chronic intermittent peritoneal dialysis . Serum levels exceeding 4.0 micrograms/ml were maintained for 8 and 13 days after a single 1-g intravenous dose . Vancomycin serum concentrations measured before, during, and upon completion of dialysis revealed no appreciable decline . Peritoneal fluid concentrations in two patients exceeded 4.0 micrograms/ml for more than 12 days.

Laryngoscope, 1983 May, 93(5), 649 - 53
Ototoxicity of oral neomycin and vancomycin; Kavanagh KT et al.; In contrast to parenteral neomycin, which may result in severe and progressive ototoxicity, oral neomycin has been widely used for 25 years, and its index of safety has been regarded as high . Ototoxicity is viewed as an uncommon complication of oral neomycin most likely to occur in patients with renal failure or gastrointestinal inflammation . Two cases of ototoxicity resulting from oral neomycin are presented . Serial audiometric and neomycin blood level testing are suggested as a means of auditory monitoring in patients receiving the drug . A review of experience with oral vancomycin indicates that this drug has not been shown to cause ototoxicity.

Antimicrob Agents Chemother, 1983 Apr, 23(4), 603 - 9
Effects of hepatic function on vancomycin clinical pharmacology; Brown N et al.; Using a recently developed radioimmunoassay, we performed 15 vancomycin pharmacology studies in cancer patients with infections . Vancomycin (500 mg) was infused intravenously for 30 min every 6 h for up to 7 days . The plasma disappearance curve was biphasic, with an initial half-life of less than 30 min . The second half-life (t1/2 beta), not dose related, varied from 1.4 to 231 h among the patients . In six studies of patients with normal hepatic functions, the t1/2 beta was 2.6 h; the rate of total clearance was 162 ml/min . In contrast, nine studies of patients with impaired liver function had a much longer t1/2 beta (37 h) and a decrease in the rate of total clearance to 48 ml/min . These factors resulted in an increase in the value of area under the concentration-time curve from 59 to 3,434 micrograms X h/ml . These results have demonstrated the importance of the effects of liver function on vancomycin disposition . The vancomycin dose and schedule should be adjusted for patients with liver impairment.

Ther Drug Monit, 1983, 5(3), 341 - 5
Automated fluorescence polarization immunoassay for monitoring vancomycin; Schwenzer KS et al.; We have extended fluorescence polarization immunoassay (FPIA) technology for the measurement of drugs to include the complex amphoteric glycopeptide antibiotic vancomycin (molecular weight, 1,449) . Fluorescein-labeled vancomycin was employed as a tracer, and antisera specific for vancomycin were raised in rabbits by conventional procedures . Tracer, sample, and diluted antiserum were combined, and the polarization of tracer fluorescence is determined in a specially designed fluorometer (Abbott TDx) . Because of instrument design, the possibility of fluorescent interferences is minimized . The assay can measure as little as 0.6 mg/L of vancomycin and is free of interferences from hemolysis, lipemia, bilirubin, and changes in protein concentration . The coefficient of variation within assay was 3% (n = 5) and between assays was 5% (n = 5) . The FPIA assay (TDx Vancomycin) was compared to a liquid chromatographic (LC) assay for vancomycin and to a commercially available radioimmunoassay (RIA) for 98 clinical specimens . A linear least-squares regression analysis gave a correlation coefficient for LC of 0.980 from the equation FPIA = 1.09 LC + 3.04, and a correlation coefficient for RIA of 0.957 from the equation FPIA = 1.036 RIA + 1.66.

Dis Colon Rectum, 1982 Jul-Aug, 25(5), 478 - 82
Toxic megacolon secondary to pseudomembranous colitis; Cone JB et al.; Toxic megacolon has rarely been reported in the course of antibiotic-induced pseudomembranous colitis . We have been able to collect 20 cases from the literature and add one new case . The mortality in the collected series was 33 per cent . The critical factor in improving survival is early recognition of the pseudomembranous colitis . Most patients can be managed medically by removal of the offending antibiotic, bowel rest, vancomycin, and steroids . If toxic megacolon develops in the face of appropriate medical management, an aggressive surgical approach is indicated, as with ulcerative colitis . Subtotal colectomy appears to be the procedure of choice.

Antimicrob Agents Chemother, 1982 Apr, 21(4), 575 - 80
Vancomycin pharmacokinetics in normal and morbidly obese subjects; Blouin RA et al.; In an uncontrolled study, vancomycin pharmacokinetics were determined in four normal (total body weight {TBW}, 65.9 to 89.1 kg) and six morbidly obese (TBW, 111.4 to 226.4 kg) subjects . The morbidly obese subjects were investigated 3 to 4 h after gastric bypass surgery . Mean terminal half-lives, volumes of distribution, and total body clearances for the normal controls and the morbidly obese (TBW, 111.4 to 226.4 kg) subjects . The morbidly obese subjects were investigated 3 to 4 h after gastric bypass surgery . Mean terminal half-lives, volumes of distribution, and total body clearances for the normal controls and the morbidly obese subjects were 4.8 h, 0.39 liter/kg, and 1.085 ml/min per kg versus 3.2 h, 0.26 liter/kg TBW, and 1.112 ml/min per kg TBW . The mean terminal half-life and volume of distribution values were significantly different between the two groups . Strong correlations were found between TBW and both volume of distribution (correlation coefficient, 0.943) and total body clearance (correlation coefficient, 0.981) . There results implied that TBW should be used to calculate vancomycin doses for morbidly obese patients . This was supported by the finding that there was no significant difference in the daily dose (in milligrams per kilogram per day) required to produce an average steady-state concentration of 15 micrograms/ml in the two groups (23.4 +/- 1.5 mg/kg per day for normal weight subjects and 24.0 +/- 3.4 mg/kg per day TBW for the postsurgery morbidly obese subjects) . Therefore, the morbidly obese required higher total doses (in milligrams per day) than did normal weight subjects to achieve the same mean steady-state concentrations . In addition, normal weight and morbidly obese subjects had similar volumes of the central compartment (7.7 and 6.4 liters, respectively) . To avoid high transient peak concentrations which would occur when obese patients are given larger total doses (in milligrams per day), maintenance doses may be given at more frequent intervals . The shorter mean terminal half-lives observed in morbidly obese patients allows more frequent dosing without excessive accumulation.

Nephron, 1982, 31(1), 37 - 9
Peritoneal transport of vancomycin in 4 patients undergoing continuous ambulatory peritoneal dialysis; Pancorbo S et al.; The pharmacokinetics of vancomycin have been studied in 4 chronic renal failure patients undergoing continuous ambulatory peritoneal dialysis . Patients received 1 g of vancomycin in 2 liters of dialysate during an initial phase, and serum and dialysate samples were collected for vancomycin determination . 54% of the amount introduced into the peritoneal cavity were absorbed systemically during a 6-hour cycle . Peak serum concentrations averaged 23.7 microgram/ml . Mean elimination half-life was calculated to be 66.9 h, and dialysis clearance averaged 2.4 ml/min.

Med Clin North Am, 1982 Jan, 66(1), 175 - 181
Vancomycin; Fekety R; While vancomycin is thus not as nephrotoxic as once feared, its use by the parenteral route should be avoided if possible when other nephrotoxic drugs are being given . Used properly, vancomycin appears efficacious and can be given with safety to infants, children, and adults . Vancomycin is incompatible with many other drugs in intravenous solutions, especially chloramphenicol, adrenocorticosteroids, and methicillin.

Rev Infect Dis, 1981 Nov-Dec, 3 suppl, S269 - 72
Pharmacokinetics of vancomycin in anuria; Cunha BA et al.; After a single 1-g intravenous dose of vancomycin, the mean peak concentration in the serum of 29 anephric patients was 48.3 micrograms/ml . An initial rapid decline to 15 micrograms/ml within 3-5 hr was followed by slow elimination, with 3.5 micrograms/ml present after 18 days . Intermittent dialysis had no appreciable effect on drug levels in serum . The biphasic decline in serum concentrations of vancomycin indicates at least two-compartment pharmacokinetics in both anephric and normal patients . In anephric patients the elimination half-life was 7.5 days and the elimination rate constant was 0.32; these values were 8 hr and 10.25, respectively, in normal patients . On the basis of these results, the vancomycin regimen recommended for anephric patients is an initial 1-g intravenous dose followed by 500 mg every eight days . With these dosages peak concentrations are 49 micrograms/ml (well below reported toxic levels) and trough concentrations are 7 micrograms/ml (well above the minimal inhibitory concentrations for susceptible pathogens causing shunt infections).

Rev Infect Dis, 1981 Nov-Dec, 3 suppl, S224 - 9
Toxicology of vancomycin in laboratory animals; Wold JS et al.; The 50% lethal dose (LD50) of vancomycin for rodents was higher than that of tobramycin but much lower than that of cefamandole nafate . The rodents died in clonic convulsions immediately after receiving vancomycin . The LD50 for dogs similar to that for rodents; however, deaths occurred several days after administration of vancomycin and resulted from renal failure . Rapid intravenous administration of vancomycin to dogs produced a significant decrease in blood pressure that was prevented by pretreatment with the antihistamine methapyrilene . Subchronic administration of vancomycin to laboratory animals in doses of 12.5-400 mg/kg caused no systemic toxicity . Concomitant administration of vancomycin and tobramycin to rats resulted in significantly increased nephrotoxicity compared to that caused by either agent alone . The nephrotoxic response of rats receiving vancomycin was only partially reversed by large volumes of water given orally before and after the drug.

Rev Infect Dis, 1981 Nov-Dec, 3 suppl, S205 - 9
Structural features of vancomycin; Pfeiffer RR; Recent analytical methods have advanced knowledge of the structure of vancomycin from a description of only several molecular fragments to a complete understanding of the intact molecule . The molecular weight is 1,448 . The molecule consists of a seven-membered peptide chain that is formed by parts of three phenylglycine systems, two chlorinated tyrosine units, aspartic acid, and N-methylleucine . Two ether bonds and a carbon-carbon bond join the various substituents on the peptide chain into three large rings . A disaccharide, composed of glucose and vancosamine, is also present but is not part of the cyclic structure . Details of the vancomycin structure have been related to hydrogen bonding between the antibiotic and bacterial cell-wall precursors that have a D-alanyl-D-alanine carboxyl terminus; such bonding would provide a molecular basis for the cell-wall mode of action for vancomycin . With one carboxyl, two amino, and three phenolic groups, vancomycin undergoes a variety of ionic interactions in solutions of different pH and composition.

Appl Environ Microbiol, 1981 Nov, 42(5), 768 - 72
Glycine-containing selective medium for isolation of Legionellaceae from environmental specimens; Wadowsky RM et al.; Glycine, at a final concentration of 0.3%, has been shown to be an excellent selective agent for the isolation of Legionellaceae . Stock cultures of Legionella pneumophila were not inhibited on buffered charcoal-yeast extract agar containing the amino acid . Among the other Legionellaceae tested, only one of two strains of L . dumoffii and two of six strains of L . micdadei were appreciably inhibited . This medium permitted the isolation of L . pneumophila from environmental specimens with marked inhibition of many non-Legionellaceae bacteria . The selectivity of the medium was subsequently improved by the incorporation of vancomycin (5 microgram/ml) and polymyxin B (100 U/ml) . This selective medium, glycine-vancomycin-polymyxin B agar, should facilitate the recovery of Legionellaceae from environmental sources.

Antibiotiki, 1981 Aug, 26(8), 581 - 5
{Revision of the structure of ristomycinic and actinoidinic amino acids}; Lomakina NN et al.; The structures of ristomycin and actinoidine amino acids described earlier were revised . Crystalline derivatives of the amino acids and the products of their oxidation were prepared . The study on the spectral properties of the compounds showed that ristomycin and actinoidine amino acids had the structures of 3-(2'-hydroxy-5'-glycyl-phenoxy)-4-methyl-5-hydroxyphenylglycine and 2-(2'-hydroxy-5'-glycyl-phenyl)-3,5-dioxyphenylglycine respectively . They did not differ from deaminodicarboxylic acids prepared with ristocetin, vancomycin and actionoidine.

J Clin Microbiol, 1981 Apr, 13(4), 714 - 9
Isolation of Legionella spp . from environmental water samples by low-pH treatment and use of a selective medium; Bopp CA et al.; A selective medium was developed and used successfully to isolate Legionella pneumophila and Legionella-like organisms from environmental specimens previously positive by animal inoculation methods . This medium consists of charcoal-yeast extract agar to which have been added cephalothin (4 micrograms/ml), colistin (16 micrograms/ml), vancomycin (0.5 microgram/ml), and cycloheximide (80 micrograms/ml) . Pretreating of the environmental water samples with an acid buffer (pH 2.2), followed by plating on the selective medium, improved the rate of recovery of both Legionella and Legionella-like organisms relative to that with direct plating on selective media.

J Clin Microbiol, 1981 Apr, 13(4), 666 - 9
New medium selective for Fusobacterium species and differential for Fusobacterium necrophorum; Morgenstein AA et al.; Fusobacterium egg yolk agar is a new medium selective for Fusobacterium species and differential for Fusobacterium necrophorum . The medium is a Brucella Agar base (Difco Laboratories, Detroit, Mich.) containing vancomycin, neomycin, josamycin, and egg yolk . All species of fusobacteria grew with only minimal inhibition . The mean log difference in counts between Fusobacterium egg yolk agar and control media for 30 strains of seven species of fusobacteria was 0.1922 . F . necrophorum typically showed a strong lipase reaction . Most other organisms were significantly inhibited by the medium.

Ann Intern Med, 1981 Mar, 94(3), 343 - 6
Vancomycin therapy in patients with impaired renal function: a nomogram for dosage; Moellering RC Jr et al.; The relation between vancomycin clearance and renal function was studied in 22 patients with various degrees of renal functional impairment and in four normal volunteers . Clearance of vancomycin and creatinine were highly correlated (r = 0.92) among 17 persons not on dialysis . In five dialysis patients vancomycin clearance averaged 0.086 mL/min . kg of body weight (+/- SEM = 0.025) . These relations enabled us to construct a nomogram for vancomycin dosage adjustment (based on a mean steady-state serum vancomycin concentration of 15 micrograms/mL) in patients with various degrees of renal functional impairment.

Folia Microbiol (Praha), 1981, 26(1), 59 - 61
The completion of the replication map of the Mycobacterium phlei chromosome; Konickova-Radochova M et al.; New facts about the replication map of Mycobacterium phlei chromosome are summarized . Replication positions of two genes located in marginal regions of the replication map, ile close to the origin and ser near the terminus, were determined . Known positions of replication of some genes were defined with more precision within 2.5--5-min intervals using the method of sequential mutagenesis in synchronized cultures (leu, met, bac, pyr, stm, tet, cyc, his) . Replication positions of genes responsible for the biosynthesis of thiamine and resistance to tetracycline and vancomycin were further identified . The contemporary replication map contains replication positions of 24 genes.

Scott Med J, 1980 Oct, 25(4), 278 - 80
Pseudomembranous colitis; Ritchie PH et al.; Nine patients with pseudomembranous colitis (PMC) are described . Eight patients received prior therapy with antibiotics . Pyrexia and polymorph leukocytosis were common features . Six relapses occurred in four of the six patients who were treated with vancomycin . Two patients who did not receive vancomycin died.

J Lab Clin Med, 1980 Jul, 96(1), 168 - 84
Interaction of platelets, von Willebrand factor, and ristocetin during platelet agglutination; Moake JL et al.; Ristocetin induces platelet agglutination in the presence of human factor VIII-associated ristocetin cofactor (vWF) . The specificity, extent, and tenacity of binding among these reactants during agglutination and deagglutination were examined . Purified human vWF polymers were radioiodinated and reisolated . Radioiodinated vWF, a disulfide-linked polymer of 230,000 dalton subunits, attached to formalinized human platelets only in the presence of ristocetin . This binding reached equilibrium within 30 sec, and as ristocetin concentrations were raised from 0.2 mg/ml, the extent of attachment increased progressively to reach maximum at 0.5 to 0.6 mg/ml ristocetin . Ristocetin-induced binding was inhibited by vancomycin, unlabeled-purified vWF polymers, normal and hemophilia A plasma, and rabbit anti-human vWF . Binding was not impaired by plasma without detectable vWF or by naturally occurring human IgG antibodies to factor VIII coagulant activity . When formalinized platelets were pelleted from suspensions containing 125I-ristocetin, small quantities of radiolabeled ristocetin associated with platelets both in the presence or absence of vWF . About 95% of the attached 125I-ristocetin was removed by subsequent washes in buffered saline . The attachment of unmodified ristocetin or 125I-ristocetin to platelets, or the formation of complexes with vWF, could not be detected by agarose column chromatography, sucrose cushion ultracentrifugation, or equilibrium dialysis . These results indicate that (1) the initial binding of human vWF polymers to platelets is a specific interaction which requires the presence of ristocetin; (2) ristocetin and human vWF do not form persistent complexes in solution; and (3) the association of ristocetin and platelets is of low affinity.

J Clin Pharmacol, 1980 Apr, 20(4 Pt 1), 197 - 201
Single-dose kinetics of intravenous vancomycin; Krogstad DJ et al.; The pharmacokinetic properties of intravenously administered vancomycin were studied in four healthy volunteers . Reversible adverse effects (flushing, tachycardia, pruritus) occurred in two subjects who received high-dose rapid intravenous infusions . Distribution of vancomycin proceeded as a biphasic process in all four subjects . The initial distribution half-life (t1/2 alpha) was less than 8 minutes in all cases, with intermediate half-lives (t1/2 pi) varying from 0.43 to 1.48 hour and elimination half-lives (t1/2 beta) varying from 4.7 to 11.2 hours . Vancomycin clearance was less than creatinine clearance, probably because of serum protein binding, which was determined to be 55 per cent.

Antimicrob Agents Chemother, 1980 Apr, 17(4), 730 - 1
Bioassay for determination of vancomycin in the presence of rifampin or aminoglycosides; Walker CN; Vancomycin determinations were performed in the presence of an aminoglycoside or rifampin . A previously reported bioassay method was modified by using a rifampin-resistant strain and increasing the NaCl concentration in the minimal salts-glucose assay agar from 0.2 to 6.0%.

Blood, 1980 Feb, 55(2), 276 - 81
Polybrene-induced platelet agglutination and reduction in electrophoretic mobility: enhancement by von Willebrand factor and inhibition by vancomycin; Coller BS; It has recently been reported that the polycation Polybrene (hexadimethrine bromide), like ristocetin, agglutinates platelets more extensively in the presence of normal plasma than von Willebrand plasma . Since we have previously proposed that ristocetin may initiate agglutination by reducing platelet surface charge, I investigated the correlation between Polybrene's ability to induce agglutination and alter platelet electrophoretic mobility . In the absence of plasma, low concentrations of Polybrene produced small platelet aggregates and reduced the electrophoretic mobility . Higher concentrations were needed to produce small platelet aggregates in the presence of von Willebrand plasma; these same concentrations produced more rapid agglutination and much larger aggregates in the presence of normal plasma . The reductions in electrophoretic mobility were also greater in the presence of normal than von Willebrand plasma . Both agglutination and the reduction in mobility could be partially reversed with citrate . Vancomycin, an antibiotic that inhibits ristocetin-induced agglutination with some specificity, inhibited both Polybrene-induced agglutination and the reductions in platelet mobility . These data are consistent with our electrostatic model and support the view that reductions of platelet surface charge may be necessary (but perhaps not sufficient) to initiate the interaction between platelets and von Willebrand factor.

Acta Pathol Microbiol Scand {B}, 1979 Dec, 87(6), 391 - 2
Comparison of two selective media in the cultural diagnosis of Gonorrhoea; Svarva PL et al.; A "chocolate" agar medium (CA-NCV) containing nystatin, colistin and vancomycin, was compared with the MNYC medium which contain lincomycin, colistin, amphotericin and trimethoprim . A total of 277 clinical specimens were cultured for gonococci, and 120 of these showed positive cultures on either or both of the media . The MNYC medium detected 96.6 per cent of the total number of positive cultures and 92.5 per cent of the patients and the CA-NCV medium after 80 and 79 per cent, respectively . Nearly half the positive cultures were detected on the MNYC medium after 24 hours of incubation . It is concluded that the MNYC medium is superior to the CA-NCV medium in the diagnosis of gonorrhoea.

J Clin Microbiol, 1979 Aug, 10(2), 141 - 3
Use of a semiselective medium to culture Legionella pneumophila from contaminated lung specimens; Edelstein PH et al.; Legionella pneumophila was successfully isolated, using a semiselective medium, from two of three lung specimens heavily contaminated with other organisms . This medium is composed of charcoal yeast extract agar, supplemented with vancomycin and polymyxin B . L . pneumophila was observed at 8 days on plates containing less than or equal to 40 units of polymyxin B and less than or equal to 1 microgram of vancomycin per ml.

Oral Surg Oral Med Oral Pathol, 1979 Feb, 47(2), 136 - 41
A review of chemotherapeutic plaque control; Johnson RH et al.; Of the plaque-control agents studied, it would appear that chlorhexidine is the most suitable agent to prevent plaque accumulation and the development of gingivitis . It also is attractive to speculate on the possibilities of a commercially available mouthwash . A trio of antibiotics--kanamycin, spiramycin, and vancomycin--may prove of value in the treatment of severe gingival and periodontal disease . The ultimate role of xylitol has yet to be determined . Regardless of the agent selected, access to the gingival sulcus region seems critical.

Ther Drug Monit, 1979, 1(1), 75 - 83
High performance liquid chromatographic assay of vancomycin in serum; Uhl JR et al.; A liquid chromatographic procedure is described for rapid and accurate quantitation of vancomycin in serum . Vancomycin is extracted from serum by using a CM-Sephadex column and is measured by reversed-phase chromatography with detection by UV absorption . Ristocetin is used as an internal standard . Concentration and instrument response are linearly related in the range of therapeutically useful concentrations . Results correlate well with those obtained by bioassay . The between-day coefficient of variation (n = 8) was less than 4% . Recovery of vancomycin from serum is nearly complete, and no substances that interfere with the procedure have been detected in clinical specimens.

J Infect Dis, 1978 Jul, 138(1), 81 - 6
Comparison of five regimens for treatment of experimental clindamycin-associated colitis; Bartlett JG et al.; The hamster model of clindamycin-induced enterocolitis was studied to determine the natural course of the disease and the response to five therapeutic regimens . Tissue culture assays of stools from untreated animals showed that colitis toxin is present at low titers within 24--36 hr after challenge with clindamycin; titers of toxin in subsequent specimens of stool increased progressively until the animals died on days 2--4 after challenge . Therapeutic regimens tested in this model were initiated 24 hr after clindamycin challenge when the majority of the animals had evidence of colitis toxin . Methylprednisilone, an anion exchange resin, and gas gangrene polyvalent antitoxin had a minimal effect on toxin titers in stool and failed to delay substantially death due to enterocolitis . Vancomycin and tetracycline eliminated toxin in stools and delayed death . However, the salutary effects of these antibiotics were noted only during the course of their administration since all animals died of enterocolitis and had high titers of toxin when treatment was discontinued.

Nature, 1978 Jan 19, 271(5642), 223 - 5
Structure of vancomycin and its complex with acetyl-D-alanyl-D-alanine; Sheldrick GM et al.; Vancomycin, a broad-spectrum antibiotic, inhibits the growth of cell walls by complex formation with peptides terminating in D-alanyl-D-alanine . The structure of vancomycin was determined by X-ray analysis of the degradation product CDP-I . A model of the complex is proposed based on this study and spectroscopic data.

Health Lab Sci, 1978 Jan, 15(1), 22 - 7
The selectivity of vancomycin and lincomycin in NYC medium for the recovery of N . gonorrhoeae from clinical specimens; Faur YC et al.; Varying concentrations of vancomycin and lincomycin were tested separately in NYC medium to determine the degree of their selectivity and sensitivity for isolation of N . gonorrhoeae from clinical specimens . Results indicate that 2 microgram/ml of vancomycin used in conjunction with colymycin, amphotericin B, and trimethoprim lactate provide adequate selectivity and reduce the possibility of losses of vancomycin-sensitive strains of gonococci seen with 3 microgram/ml of vancomycin . The same medium with concentrations of from 1 to 4 microgram/ml of lincomycin substituted for vancomycin permitted more contamination and fewer recoveries of gonococci as compared with 2 microgram/ml of vancomycin.

Gastroenterology, 1977 Oct, 73(4 Pt 1), 772 - 6
Clindamycin-associated colitis in hamsters: protection with vancomycin; Bartlett JG et al.; Clindamycin and lincomycin produced a lethal enterocolitis in 65 of 67 Syrian hamsters . The administration of oral or parenteral vancomycin to recipients of clindamycin or lincomycin was uniformly protective in 49 patients . These results suggest that certain bacteria play a role in the pathogenesis of enterocolitis in this model.

Blood, 1977 Sep, 50(3), 397 - 406
Inhibition of ristocetin-induced platelet agglutination by vancomycin; Moake JL et al.; Ristocetin and vancomycin are structurally similar glycopeptide antibiotics . Both vancomycin and ristocetin in high concentrations (3.0 mg/ml) cause the precipitation of fibrinogen, plasminogen, and IgG from platelet-poor plasma (PPP) . In contrast to ristocetin, vanomycin (0.5-1.5 mg/ml) does not agglutinate platelets in normal platelet-rich plasma (PRP) or formalin-treated platelets in the presence of normal PPP . Preincubation of vancomycin (0.5-1.25 mg/ml) with normal PRP, von Willebrand platelets in normal PPP, or formalinized platelets results in inhibition of platelet agglutination induced by ristocetin (0.7-1.25 mg/ml) or ristocetin and normal PPP . This inhibition can be overcome by increasing the final concentration of ristocetin in the platelet suspension . Preincubation of formalin-treated platelets with the major fraction obtained by carboxymethyl-Sephadex C-50 chromatography of commercial vancomycin also results in inhibition of agglutination induced by ristocetin and normal PPP . Incubation with vancomycin (1.25 mg/ml) does not interfere with von Willebrand factor (vWF) or factor VIII coagulant activities in normal PPP or in Sepharose 4B void volume fractions of PPP . These results indicate that vancomycin interacts with normal, von Willebrand, and formalin-treated platelets and inhibits the binding of ristocetin (or ristocetin-vWF complexes).

Biochemistry, 1977 Apr 5, 16(7), 1251 - 7
Biosynthesis of spin-labeled peptidoglycan: spin-spin interactions; Johnston LS et al.; Membrane preparations from Gaffkya homari catalyzed the in vitro biosynthesis of soluble uncross-linked spin-labeled peptidoglycan, a uniformly labeled polynitroxide, from the spin-labeled nucleotide UDP-MurNAc-Ala-DGlu-Lys(Nepsilon-2,2,5,5-tetramethyl-1-pyrrolin-1-oxyl-3-carbonyl)-DAla-DAla (I) and UDP-GlcNAc . Soluble spin-labeled peptidoglycan was separated from membrane fragments and its spin-labeled precursor by centrifugation and gel filtration . The molecular weight distribution of the polymer was examined by agarose gel filtration . Spin-labeled {14C}peptidoglycan was polydisperse with a peak of radioactivity corresponding to a molecular weight of 5.0 X 10(5) . The electron spin resonance spectrum of spin-labeled peptidoglycan was extensively broadened by spin-spin exchange interactions . These interactions were modified by changes in temperature, reduction by ascorbate, hydrolysis by lysozyme, and complexation with the antibiotic, vancomycin . Spin-spin exchange was reduced or eliminated in spin-labeled peptidoglycan by the random reduction of free radicals by ascorbate . A rotational correlation time of 0.37 ns was calculated for the probe in partially reduced spin-labeled peptidoglycan . This compares to a correlation time of 0.13 ns for the substrate (I) . Raising the temperature increases spin-spin exchange line broadening . No transition points were observed for spin-labeled peptidoglycan as measured by this method . Degradati on of spin-labeled peptidoglycan by lysozyme eliminated the observed spin-spin exchange and yielded products with a mobility similar to I . Complexation of spin-labeled peptidoglycan with vancomycin resulted in both pronounced free-radical immobilization and a decrease in spin-spin exchange . The exchange effects are consistent with distance measurements in molecular models for peptidoglycan.

Thromb Diath Haemorrh, 1975 Sep 30, 34(1), 83 - 93
Effects of vancomycin on platelets, plasma proteins and hepatitis B surface antigen; Coller BS et al.; The antibiotic vancomycin shares many similarities with ristocetin, an agent noted for its effects on platelets and plasma fibrinogen . Vancomycin did not aggregate platelets as ristocetin, but platelets were incorporated into precipitates induced by vancomycin . Fibrinogen and factor VIII were precipitated from plasma at low concentrations of vancomycin . The precipitated fibrinogen remained clottable . Hepatitis B surface antigen was selectively precipitated from serum and could be recovered from the precipitate . Rabbits receiving bolus intravenous injections of high doses of vancomycin developed hypofibrinogenemia and thrombocytopenia within minutes and often went on to die . Studies with 125I-vancomycin revealed little stable binding of the antibiotic to platelets or fibrinogen . A relationship is suggested between the potent protein precipitating effects and phlebitis at the infusion site commonly associated with vancomycin therapy.

Br J Ophthalmol, 1975 Aug, 59(8), 435 - 8
Trachoma in the Sudan . A laboratory study; Salim AR et al.; Out of 46 patients in the Sudan who had been diagnosed clinically as having trachoma 25 strains of the trachoma agent were isolated . Bacterial contamination was easily controlled by streptomycin and vancomycin . On repeated passaging, chick embryos lost their susceptibility to the trachoma agent during the summer.

Int J Lepr Other Mycobact Dis, 1975 Jul-Sep, 43(3), 234 - 8
A radiometric method for predicting effectiveness of chemotherapeutic agents in murine leprosy; Camargo EE et al.; A simple radiometric method has been developed for evaluating the effect of drugs on the metabolism of M . lepraemurium . The method is based on the measurement of the 14CO2 produced through bacterial metabolism of acetate-U-14C . Seventeen drugs were tested: bacitracin, cephaloridine, chloramphenicol, cycloserine, dactinomycin, DDS, ethionamide, INH, kanamycin, methenamine mandelate, nitrofurantoin, oxacillin, polymyxin B, rifampicin, streptomycin, sulfadimethoxine and vancomycin . The drugs which caused most marked inhibition were chloramphenicol, INH, ethionamide and nitrofurantoin in order of increasing effectiveness . The radiometric study which is completed in 15 days permits direct study of the drug effect on the metabolism of M . lepraemurium and a more rapid screening of antileprosy drugs than has previously been possible . Currently, these observations are being extended to studies of the structure-activity relationships of antileprosy drugs and the metabolism and drug susceptibility of M . leprae in vitro.

Biochemistry, 1975 Jun 17, 14(12), 2754 - 60
Initial membrane reaction in the biosynthesis of peptidoglycan . Spin-labeled intermediates as receptors for vancomycin and ristocetin; Johnston LS et al.; Phospho-N-acetylmuramyl-pentapeptide translocase (UDP-MurNAc-Ala-DGlu-Lys-DAla-DAla:undecaprenyl phosphate, phospho-MurNAc-pentapeptide transferase) catalyzes the initial membrane reaction in the biosynthesis of peptidoglycan . The spin-labeled nucleotide, UDP-MurNAc-Ala-DGlu-Lys (Nepsilon-2,2,5,5-tetramethyl-N-oxyl-pyrroline-3-carbonyl)-DAla-DAla, was used as a substrate by this enzyme for the synthesis of membrane-associated undecaprenyl-diphosphate-MurNAc-Ala-DGlu-Lys(Nepsilon-Tempyo)-DAla-DAla . The spin-labeled substrate and product complex with the antibiotics vancomycin and ristocetin . The association constants for the spin-labeled nucleotide are 6.2 times 10(5) and 6.2 times 10(4) M-1 for vancomycin and ristocetin, respectively . The association constants for the spin-labeled lipid intermediate are 3.0 times 10(4) and 2.1 times 10(4) M-1 for vancomycin and ristocetin, respectively . These results indicate that the acyl-DAla termini of membranes-associated spin-labeled undecaprenyl-diphosphate-MurNAc-pentapeptide are accessible to vancomycin and ristocetin and that the association constants are smaller than those determined for the corresponding antibiotic spin-labeled UDP-MurNAc-pentapeptide complexes.

Can J Microbiol, 1975 May, 21(5), 606 - 12
Differential isolatoion of Pythium species from soil by means of selective media,temperature, and pH; Lunsden RD et al.; Pythium aphanidermatum, with an optimum temperature for growth at 35C, grew welland was readily isolated from soil on pimaricin-vancomycin medium (MPVM) when incubated for 24h at 38-40C . The pH of the medium affected recovery; maximum numbers developed above pH 6.0 . Other Pythium spp . were recovered on MPVM at 20-25C, but were excluded by incubation at 38-40C . These Pythium spp . included P . ultimun, P . paroecandrum, P . irregular, P . mamillatum, and an unidentified Pythium sp . These species grew well and were readily siolated from soil on gallic acid medium (GAM) when incubated for 24-8h at 20 C.P . aphanidermatum and P . myriotylum grew from mycelium on GAM, but their oospores did not germinate nor could they be isolated from soilon this medium . P . myriotylum grew well on MPVM, but was only rarely isolated, evenfrom soils with known high potential for disease caused by P . myriotylum . Propagules of Pythium were enumerated by a plate-dilution frequency method or by a smearplateethod is valuable for studies on the ecology, survival, and inoculum potential in soils with mixed populations of P . aphanidermatum and other Pythium spp.

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