Adv Perit Dial, 1995, 11, 179 - 81 A prospective randomized comparison of single versus multidose gentamicin in the treatment of CAPD peritonitis; Lye WC et al.; There is an increasing trend towards the use of aminoglycosides in a once-daily dose administration for the treatment of severe infections in nonrenal failure patients . The use of once-daily dose aminoglycoside therapy may be associated with a reduction in toxicity . We performed a prospective randomized study comparing once-daily versus multiple-dose gentamicin in the treatment of continuous ambulatory peritoneal dialysis (CAPD) peritonitis . Seventy-three patients with 100 new episodes of peritonitis were enrolled in the study . At presentation of peritonitis, the patients were alternately assigned to receive either intraperitoneal gentamicin at a dose of 40 mg/2 L dialysate administered as a once-daily dose or gentamicin at a dose of 10mg/2 L dialysate administered 4 times per day . All patients also received intraperitoneal vancomycin at a dose of 1 g per week . There were no significant differences in the treatment success (88% vs 82%, p = NS) and relapse (18% vs 20%, p = NS) rates between the once-daily dose and multiple-dose groups . The mean trough serum gentamicin level was higher in the once-daily dose group compared to the multiple-dose group (0.75 +/- 0.72 vs 1.50 +/- 1.40 mg/L) . In conclusion, gentamicin administered in a once-daily dose is as effective as multiple-dose administration in the treatment of CAPD peritonitis . The lower gentamicin level with once-daily dose administration may be associated with a reduction in aminoglycoside toxicity. ASAIO J, 1995 Jan-Mar, 41(1), 100 - 4 A comparison of solute clearance during continuous hemofiltration, hemodiafiltration, and hemodialysis using a polysulfone hemofilter; Reeves JH et al.; The clearance of urea, creatinine, amino acids, vancomycin, and phenytoin was measured in vivo in a small animal model during continuous venovenous (CVV) hemofiltration, CVV hemodiafiltration, and CVV hemodialysis using a 0.25 m2 polysulfone hemofilter . Six domestic piglets (weighing 6-11.8 kg) each received 1 hr of all three techniques in random order . Blood flow was 50 ml/min . During CVV hemofiltration, filtrate production was 500 ml/hr and dialysate flow was zero . During CVV hemodiafiltration, filtrate production was 250 ml/hr and dialysate flow was 250 ml/hr . During CVV hemodialysis, net filtrate production was zero and dialysate flow was 500 ml/hr . The ratio of concentration of solute in filter effluent to concentration in whole plasma was derived for each solute during each of the three techniques . Mean (SD) effluent:plasma ratio for urea during CVV hemofiltration was 0.957 (0.038), CVV hemodiafiltration 0.876 (0.109), and CVV hemodialysis 0.754 (0.123); creatinine 0.942 (0.05), 0.934 (0.056), and 0.814 (0.057); amino acids 0.996 (0.344), 0.904 (0.196), and 0.778 (0.18) . For small unbound solutes, there is a decrease in clearance of 6% from CVV hemofiltration to CVV hemodiafiltration and a further decrease of 14% from hemodiafiltration to hemodialysis . The effluent:plasma ratio for vancomycin during CVV hemofiltration was 0.739 (0.082), CVV hemodiafiltration 0.643(0.063), and CVV hemodialysis 0.509 (0.081), corresponding to a decrease of 30% from CVV hemofiltration to CVV hemodialysis . The effluent:plasma ratio for phenytoin was 0.302 (0.028) during CVV hemofiltration and was not significantly different during CVV hemodiafiltration or CVV hemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS) Biopharm Drug Dispos, 1995 Jan, 16(1), 23 - 35 An in vitro study of the influence of a drug's molecular weight on its overall (Clt), diffusive (Cld) and convective (Clc) clearance through dialysers; Mac-Kay MV et al.; The dialyser clearance of a drug is the sum of two components: one diffusive, arising from the concentration gradient across the membrane, and the other convective, arising from the ultrafiltration of plasma water, produced by the increases in hydraulic pressure that the membrane undergoes . To demonstrate the importance of these clearances during haemodialysis, this study analyses the influence of a drug's molecular weight on them . To this end, an experimental study of dialysis in vitro was carried out to determine the clearances, in aqueous solution, of five drugs of increasing molecular weights (theophylline, quinidine, tobramycin, digoxin, and vancomycin), using two series of dialysers with the same type of membrane (Cuprophan), differing in effective surface area and ultrafiltration coefficient . From the data obtained in this study, the importance of quantifying convective clearance during haemodialysis becomes apparent since if it is not taken into account errors of up to 20% and more may be made . This is particularly so if the drug is of high molecular weight and if a high filtration rate is being used. Ther Drug Monit, 1994 Dec, 16(6), 612 - 5 Effect of heating sera under conditions necessary for deactivation of human immunodeficiency virus on commonly monitored therapeutic drugs; Dasgupta A et al.; Minimizing the risk of infection of laboratory staff from contaminated blood samples is a major safety goal in a clinical laboratory . One dangerous pathogen, the human immunodeficiency virus (HIV) can be deactivated by heating sera at 56 degrees C for 30 min . We studied the effect of such heat treatment on serum concentrations of 11 commonly monitored therapeutic drugs . We used blood specimens collected in serum separator tubes (SSTs), which were routinely submitted for therapeutic drug monitoring in our laboratory for this study . Concentrations of digoxin in sera were measured using a fluorescence polarization immunoassay (FPIA), while concentrations of tobramycin, gentamicin, vancomycin, theophylline, valproic acid, procainamide, N-acetylprocainamide (NAPA), phenytoin, phenobarbital, and carbamazepine were measured by enzyme-multiplied immunoassay technique assays using a Monarch 2000 analyzer . We observed no significant change in the concentration of any drug except phenytoin and carbamazepine following heating at 60 degrees C . The decrease in concentration of phenytoin and carbamazepine after heating was related to absorption of the drug to the gel rather than the instability of the drug under heating conditions . We conclude that blood contaminated with HIV may be deactivated by heating prior to analysis for most of the routinely monitored therapeutic drugs. Ann Pharmacother, 1994 Dec, 28(12), 1335 - 9 Impact of vancomycin therapeutic drug monitoring on patient care; Welty TE et al.; OBJECTIVE: To document differences in the outcome of vancomycin therapy in patients managed through a therapeutic drug monitoring (TDM) service and patients managed empirically, without the participation of a TDM service . DESIGN: Prospective, cohort study . SETTING: An 1100-bed, tertiary-care, teaching hospital . PATIENTS: Those who received vancomycin for more than four days, were at least 18 years old, had an estimated creatinine clearance of more than 0.33 mL/s (20 mL/min), were not neutropenic at the start of vancomycin therapy, and were not treated in a critical care unit were enrolled in the study . A total of 116 patients (61 TDM; 55 non-TDM) were monitored prospectively from June 1990 through March 1991 . INTERVENTIONS: Patients in the TDM group had vancomycin drug therapy monitored daily by a pharmacist and vancomycin dosages adjusted following a pharmacokinetic analysis of vancomycin serum concentrations . For patients in the non-TDM group, the pharmacist only completed a data collection form . The patients and physicians were unaware of the monitoring . MAIN OUTCOME MEASURES: Duration of therapy, total vancomycin dosage, infection site, concomitant antibiotics, body temperature, and white blood cell counts were compared between the two groups . Length of stay data were also compared . Nephrotoxicity was evaluated by comparing serum creatinine concentration and estimated creatinine clearance . RESULTS: TDM of vancomycin appeared to reduce the incidence of vancomycin-related renal insufficiency (TDM 7 percent; non-TDM 24 percent) . Patients managed through the TDM service received an average of 5 g less of vancomycin than did the patients in the non-TDM group . The duration of vancomycin therapy was an average of 2 days less for patients in the TDM group . Mean length of stay was 38.0 days for the TDM group and 44.5 days for the non-TDM group . Other measures of efficacy, infection site, and concomitant antibiotics were the same for both groups . CONCLUSIONS: TDM of vancomycin was associated with fewer cases of vancomycin-related renal insufficiency . Vancomycin efficacy was not compromised by TDM . Provision of TDM for vancomycin therapy aided in patient management. Mol Gen Genet, 1994 Nov 15, 245(4), 431 - 40 Identification and preliminary characterization of temperature-sensitive mutations affecting HlyB, the translocator required for the secretion of haemolysin (HlyA) from Escherichia coli; Blight MA et al.; We have carried out a genetic analysis of Escherichia coli HlyB using in vitro(hydroxylamine) mutagenesis and regionally directed mutagenesis . From random mutagenesis, three mutants, temperature sensitive (Ts) for secretion, were isolated and the DNA sequenced: Gly10Arg close to the N-terminus, Gly408Asp in a highly conserved small periplasmic loop region PIV, and Pro624Leu in another highly conserved region, within the ATP-binding region . Despite the Ts character of the Gly10 substitution, a derivative of HlyB, in which the first 25 amino acids were replaced by 21 amino acids of the lambda Cro protein, was still active in secretion of HlyA . This indicates that this region of HlyB is dispensable for function . Interestingly, the Gly408Asp substitution was toxic at high temperature and this is the first reported example of a conditional lethal mutation in HlyB . We have isolated 4 additional mutations in PIV by directed mutagenesis, giving a total of 5 out of 12 residues substituted in this region, with 4 mutations rendering HlyB defective in secretion . The Pro624 mutation, close to the Walker B-site for ATP binding in the cytoplasmic domain is identical to a mutation in HisP that leads to uncoupling of ATP hydrolysis from the transport of histidine . The expression of a fully functional haemolysin translocation system comprising HlyC,A,B and D increases the sensitivity of E . coli to vancomycin 2.5-fold, compared with cells expressing HlyB and HlyD alone . Thus, active translocation of HlyA renders the cells hyperpermeable to the drug . Mutations in hlyB affecting secretion could be assigned to two classes: those that restore the level of vancomycin resistance to that of E . coli not secreting HlyA and those that still confer hypersensitivity to the drug in the presence of HlyA . We propose that mutations that promote vancomycin resistance will include mutations affecting initial recognition of the secretion signal and therefore activation of a functional transport channel . Mutations that do not alter HlyA-dependent vancomycin sensitivity may, in contrast, affect later steps in the transport process. Presse Med, 1994 Nov 5, 23(34), 1554 - 8 {Continuous administration of vancomycin in patients with severe burns}; Conil JM et al.; OBJECTIVES: In the severely burned patient, a marked, rapid fall in serum concentrations is often observed after intermittent infusion of vancomycin at the usual dose of 30 mg/kg . This specific "jagged" pharmokinetic course with inadequate residual concentrations raises the problem of the efficacy of this time-dependent antibiotic . Studies in patients in general resuscitation units have shown the interest of vancomycin administration in continuous infusion . METHODS: We analyzed variations in serum concentrations of vancomycin during continuous infusion in 18 patients with burns involving a mean of 40% total body surface and reported the doses necessary to maintain serum vancomycin at therapeutic levels; the possible correlations between serum vancomycin concentrations, burn parameters, age and renal function; and clinical and biological tolerance . RESULTS: Higher initial doses were required in burn patients (40 mg/kg in patients aged under 60) than in other patients . Impairment of renal function is a contra-indication of continuous infusion . CONCLUSION: This mode of administration has the advantage of ensuring greater efficacy by preventing fluctuations in serum concentrations. Ann Allergy, 1994 Nov, 73(5), 402 - 4 Vancomycin anaphylaxis and successful desensitization; Anne' S et al.; This report describes vancomycin anaphylaxis and successful desensitization . A 35-year-old woman who tolerated vancomycin initially, developed generalized urticaria and respiratory distress when the drug was readministered . Symptoms recurred following infusion of vancomycin at a lowered rate and dose despite premedication with antihistamines and corticosteroids . Intradermal skin tests with vancomycin were positive at a concentration of 0.1 micrograms/mL . Control subjects reacted at a concentration of 10 micrograms/mL or greater . A rapid 1-day desensitization protocol was unsuccessful . The patient then was "desensitized" by sequential increments in intravenous vancomycin doses over 13 days . After the full therapeutic dose was tolerated, there was a loss of skin test reactivity to vancomycin . We conclude that desensitization to vancomycin is possible and may be the only means to treat an allergic patient adequately when there are no viable therapeutic alternatives. Fundam Appl Toxicol, 1994 Nov, 23(4), 590 - 7 Developmental toxicology studies of vancomycin hydrochloride administered intravenously to rats and rabbits; Byrd RA et al.; Pregnant CD rats were given vancomycin intravenously in doses of 0, 40, 120, or 200 mg/kg on Gestation Days (GD) 6-15; pregnant New Zealand white rabbits were given 0, 40, 80, or 120 mg/kg intravenously on GD 6-18 . Cesarean sections were performed on rats and rabbits on GD 20 and 28, respectively . In rats, maternal toxicity was indicated in the 120- and 200-mg/kg treatment groups by cortical tubular nephrosis . Maternal body weight gain and food consumption and fetal viability, weight, and morphology were not adversely affected by vancomycin . Maternal and developmental no observed adverse effect levels (NOAELs) in the rat were 40 and 200 mg/kg, respectively . In rabbits, maternal toxicity was indicated by cortical tubular nephrosis in the 80- and 120-mg/kg treatment groups; a single death and depression of body weight gain and food consumption occurred in the 120-mg/kg treatment group . Developmental toxicity was indicated by depression of fetal weight in the 120-mg/kg treatment group; fetal viability and morphology were not adversely affected by vancomycin . Maternal and developmental NOAELs in the rabbit were 40 and 80 mg/kg, respectively . Based on these data, vancomycin did not exhibit selective toxicity toward the developing rat or rabbit conceptus. Pediatr Infect Dis J, 1994 Nov, 13(11), 969 - 74 A prospective study of vancomycin pharmacokinetics and dosage requirements in pediatric cancer patients; Chang D et al.; Pharmacokinetics of vancomycin and dosage requirements were evaluated prospectively in 28 pediatric cancer patients 9 months to 13 years of age . The predictive performance of a two-compartment Bayesian forecasting program was also evaluated . A mean (+/- SD) daily dosage of 75 +/- 22 mg/kg/day was necessary to attain a mean peak serum vancomycin concentration (SVC) of 23.1 +/- 5.8 mg/liter and a mean trough SVC of 6.2 +/- 2.3 mg/liter . Mean vancomycin clearance, volume of distribution and serum half-life were 0.153 +/- 0.033 liter/hour/kg, 0.63 +/- 0.08 liter/kg and 2.95 +/- 0.48 hours . Final peak SVCs, which reflected the last dosage regimens received, were predicted with minimal bias (mean prediction error, -1.2 mg/liter) and accurate precision (root mean-squared prediction error, 2.0 mg/liter) whereas trough SVCs were predicted with even smaller bias (mean prediction error, -0.1 mg/liter) and greater precision (root mean-squared prediction error, 0.8 mg/liter) . This study showed that pediatric cancer patients with normal renal function required vancomycin dosage regimens substantially greater than the standard 40 mg/kg/day to attain the desired SVCs. Ther Drug Monit, 1994 Oct, 16(5), 513 - 8 Vancomycin pharmacokinetics in a patient population: effect of age, gender, and body weight; Ducharme MP et al.; The effects of age, gender, and body weight on the pharmacokinetics of vancomycin were examined using data collected as part of routine therapeutic drug monitoring in patients . One thousand eighty-five sets of steady-state peak and trough serum concentrations obtained from 704 different patients were used to calculate elimination rate constant (k), volume of distribution (V), and clearance (Cl) using a one-compartment model . The median half-life of vancomycin was 6.5 h . Clearance was significantly correlated with creatinine clearance as estimated using the Cockcroft-Gault equation {Cl = 0.771 (Clcr) + 18.9; r = 0.63} . V averaged 0.69 L/kg ideal body weight (IBW) with increased values in females, patients over age 60, and obese patients . V ranged from 0.58 L/kg IBW in normal weight males under age 40 to 1.17 L/kg IBW in obese females over age 60 . V was not different in underweight patients and those of normal weight (43.8 vs . 44.4 L) . Regression analysis indicated that V was more predictable in women than in men and that vancomycin distributed into excess body weight (EBW) to a greater extent in women . However, the correlation coefficients from multiple regression analysis of V with IBW, EBW, and age did not exceed 0.60, and the high root mean square error values of 11-15 L suggest considerable variability in V is not accounted for by these factors alone . Despite these limitations, dosing of vancomycin may be improved by adjusting initial estimates of V for patient age, gender, and obesity. Biotechnol Prog, 1994 Sep-Oct, 10(5), 503 - 12 Partitioning of vancomycin using poly(ethylene glycol)-coupled ligands in aqueous two-phase systems; Singh M et al.; Affinity partitioning describes a process in which a biospecific ligand is used to manipulate the partitioning behavior of a biomolecule by coupling a ligand to one of the phase-forming polymers . It combines the high selectivity of affinity chromatography with the scalability of aqueous two-phase extractions . Fundamental studies have been made on the factors affecting affinity partitioning of the antibiotic vancomycin using a series of polymer-ligands composed of the D-Ala-D-Ala peptide coupled to poly(ethylene glycol) in methoxypoly(ethylene glycol)/dextran aqueous two-phase systems . The effects of varying the ligand molecular weight, the ligand binding interaction, the number of binding sites, the tie-line length, and the aggregation of vancomycin have been measured . A modification of the Flanagan and Barondes model for affinity partitioning has been suggested to explain the results . The modified model accounts for the changes in the surface properties of the biomaterial on complex formation. Epidemiol Infect, 1994 Aug, 113(1), 31 - 9 Immunomagnetic separation as a sensitive method for isolating Escherichia coli O157 from food samples; Wright DJ et al.; Minced beef samples inoculated with Escherichia coli O157 were cultured in buffered peptone water supplemented with vancomycin, cefsulodin and cefixime (BPW-VCC) and subcultured to cefixime tellurite sorbitol MacConkey (CT-SMAC) agar both directly and after immunomagnetic separation (IMS) of the organism with magnetic beads coated with an antibody against E . coli O157 (Dynabeads anti-E . coli O157, Dynal, Oslo) . E . coli O157 was recovered from initial inocula of 200 organisms/g by direct subculture and 2 organisms/g by IMS . Twelve strains of E . coli O157 of different combinations of phage type, H antigen and toxin genotype were all recovered from initial inocula of two organisms/g by IMS . Non-specific binding of other organisms to the magnetic beads could be reduced by washing of the beads in PBS with Tween-20 0.002-0.005% E . coli O157 was not bound by magnetic coated with an unrelated antibody . During investigation of a dairy herd that was possibly linked to a small outbreak of infection with E . coli O157, the organism was isolated from 2 of 279 forestream milk samples from individual cattle; both isolates were made only by the IMS technique . IMS is rapid, technically simple, and a specific method for isolation of E . coli O157 and will be useful in epidemiological studies. Clin Pharmacol Ther, 1994 Aug, 56(2), 169 - 75 Population pharmacokinetics of vancomycin in neonates; Seay RE et al.; OBJECTIVE: To determine population pharmacokinetic parameters of vancomycin in neonates . METHODS: This was a retrospective design, with prospective validation . Two hundred ten sequential neonates were evaluated at the neonatal intensive care units of Minneapolis Children's Medical Center and Children's Hospital of St . Paul . Five hundred twenty serum concentrations from 192 patients were included . A mean +/- SD gestational age of 29.5 +/- 5.1 weeks, postnatal age of 16.5 +/- 19.6 days, and dosing weight of 1492 +/- 1053 gm described the population . Thirty additional patients were studied for validation . Dosing, serum concentrations, and 28 covariates were collected . Data were evaluated with NONMEM . Forward selection and backward elimination regression identified significant covariates . One- and two-compartment population pharmacokinetic parameters and predictive performance of the models were measured . RESULTS: Two-compartment final regression equations were as follows: Clearance (CL) = 0.0590 L/kg/hr (multiplied by 0.460 if exposed to dopamine and 0.643 if gestational age was < or = 32 weeks), central volume (VC) = 0.440 L/kg, intercompartmental clearance (Q) = 0.0313 L/hr/kg, and steady-state volume of distribution (Vss) = 0.764 L/kg . Interindividual variability was 40.6% for CL, 54.1% for Vss, and 16.8% for VC . Residual variability was 3.3 micrograms/ml . One-compartment final regression equations were: CL = 0.0626 L/kg/hr (multiplied by 0.455 if exposed to dopamine and 0.656 if gestational age was < or = 32 weeks), and Vd = 0.496 L/kg . Differences in relative performance were insignificant by use of one- or two-compartment parameters . CONCLUSIONS: Gestational age < or = 32 weeks and concurrent use of dopamine were significant factors in prediction of vancomycin clearance . alpha Half-lives of 2.8 to 3.7 hours and beta half-lives of 13.4 to 33.7 hours suggest that some individuals in this neonatal population have considerably longer half-lives than those previously reported. Foot Ankle Int, 1994 Jul, 15(7), 354 - 9 Tibiocalcaneal arthrodesis for nonbraceable neuropathic ankle deformity; Alvarez RG et al.; Seven patients with nonbraceable, neuropathic ankle joints have been successfully treated by tibiocalcaneal arthrodesis utilizing an adolescent condylar blade plate, large cannulated AO screws, and a special cancellous allograft mixture . All patients had fragmentation and partial resorption of the talus . This procedure was considered as an alternative to below-knee amputation . Goals were limb salvage and limited community ambulation . Criteria for proceeding with the fusion were a commitment by the patient to 6 to 8 months of nonweightbearing ambulation, a biopsy and culture of the talus revealing no evidence of infection, and a nonbraceable deformity of the foot and ankle that would otherwise require amputation . A toe-level Doppler index or a transcutaneous oxygen index of greater than 0.45 was required . All patients were treated initially in a total contact cast or bivalved total contact ankle-foot orthosis (AFO) until wounds and swelling were controlled and there was no erythema . Presence of an ulcer did not preclude surgery . The arthrodesis used a combination of 7.0-mm AO cannulated screws and an adolescent condylar blade plate . A special preparation of fresh-frozen, irradiated, cancellous allograft mixed with tobramycin and vancomycin powder was used . All ankles fused solidly in an average of 5.2 months . No infectious complications were encountered . Two patients developed a stress fracture of the tibia at the proximal aspect of the blade plate before use of a bivalved AFO . These healed with nonoperative treatment in 6 weeks . All patients were satisfied with their result at their latest follow-up (average 26.9 months).(ABSTRACT TRUNCATED AT 250 WORDS) Am J Hosp Pharm, 1994 Jul 1, 51(13), 1672 - 5 Pharmacokinetics services in Department of Veterans Affairs medical centers; Howard CE et al.; The provision of pharmacokinetics services in Veterans Affairs (VA) medical centers was studied . In October 1992 a questionnaire was mailed to the chief of pharmacy at each of the nation's 160 VA medical centers . The survey was designed to determine the percentage of centers providing pharmacokinetics services, the general characteristics of pharmacokinetics services provided, and whether the presence of these services was associated with specific characteristics of the medical centers . Of the 160 questionnaires mailed, 148 (93%) were returned and analyzed . Pharmacokinetics services were provided by 104 (70%) of the respondents . Of the 104 services, 58 (56%) had existed for less than five years . Of the 44 VA medical centers without a pharmacokinetics service, almost two thirds planned to start one in the future . Aminoglycosides, vancomycin, and theophylline were the drugs most frequently monitored . Fifty-four percent of the pharmacokinetics services evaluated 1-24 patients per month, and another 24% evaluated 25-49 patients monthly . VA medical centers with a pharmacy residency program were more likely to have a pharmacokinetics service than centers without such a program; an association with geographic region was also identified . Nearly three fourths of responding VA medical centers indicated that they provided pharmacokinetics services. Jpn J Antibiot, 1994 Jun, 47(6), 731 - 5 {Clinical efficacy of arbekacin on MRSA infections}; Ichiyama S et al.; Clinical efficacy of arbekacin (ABK) was examined on patients with MRSA infection during hospitalization in Nagoya University Hospital . A total of 15 analysed cases of 5 sepsis, 3 pneumonias, 6 wound infections and one abdominal abscess . ABK was administered intravenously by drip infusion of 200 mg per day divided into 2 doses with or without other antibiotics . Overall clinical efficacy rate was 76.9%, and eradication rate for the MRSA was 54.5% . Adverse effects were noted in 3 cases (one each case of urticaria, disorder of liver function, and renal disorder) . The renal disorder was found in the case where ABK was used in combination with vancomycin. Jpn J Antibiot, 1994 Jun, 47(6), 664 - 75 {A study on nephrotoxicity of arbekacin and vancomycin in rats}; Niizato T et al.; Nephrotoxicities of arbekacin (ABK) and/or vancomycin (VCM) were examined by administrating rats intravenously with single doses or 10 times repeated daily doses . ABK was found less toxic to kidney than VCM, and the toxicity was strengthened by combined treatment with VCM and ABK . Fosfomycin decreased the nephrotoxicity when added to the single or combined treatment with ABK and VCM. Artif Organs, 1994 Jun, 18(6), 425 - 8 A comparison of molecular clearance rates during continuous hemofiltration and hemodialysis with a novel volumetric continuous renal replacement system; Jeffrey RF et al.; We developed a continuous, volumetrically controlled veno-venous renal replacement system that can be operated in filtration or dialysis modes . We compared the clearances of substances with a range of molecular weights (MW) in each mode . Ten patients with acute renal failure underwent serial postdilutional hemofiltration and hemodialysis, for 30 min each, in sequence and in randomized order . All were receiving vancomycin for concurrent sepsis . The system incorporated a Filtral 10 AN69 artificial kidney; blood flow rate was 200 ml/min, and dialysate/filtrate flow rate was 25 ml/min . Sieving (SC) and diffusion (DC) co-efficients, for hemofiltration and hemodialysis, respectively, were identical for urea (MW 60; 1.01 +/- 0.05 vs 1.01 +/- 0.07) and creatinine (MW 113; 1.00 +/- 0.09 vs 1.01 +/- 0.06), and clearance equated with dialysate/filtrate flow . There was a modest difference in uric acid clearance (MW 168; SC 1.01 +/- 0.04 vs DC 0.97 +/- 0.04; p < 0.05) . Vancomycin (MW 1,800) removal was 19% greater during filtration compared with dialysis (SC 0.87 +/- 0.10 vs DC 0.74 +/- 0.06; p < 0.01) . For small solutes, the two modalities were equivalent . Vancomycin clearance was appreciably greater with hemofiltration, which is consistent with a greater potential for convection-based therapy in the removal of uremic and other middle molecules. Ann Pharmacother, 1994 Jun, 28(6), 723 - 6 Vancomycin-induced neutropenia during treatment of endocarditis in a pediatric patient; Shinohara YT et al.; OBJECTIVE: To report a case of reversible vancomycin-associated neutropenia occurring during long-term therapy with vancomycin using weight and age-adjusted dosing . CASE SUMMARY: A 2-year-old boy was started on vancomycin therapy for presumed endocarditis resulting from his ventriculoseptal defect . After 18 days of treatment, neutropenia with an absolute neutrophil count (ANC) of 990 x 10(6) cells/L was noted . The neutropenia progressed over the next 3 days and reached a nadir concentration of 459 x 10(6) cells/L . Vancomycin therapy was discontinued after 17 days (antibiotic day 20) . A rise in the ANC occurred within 2 days of discontinuation . An improved ANC of 1672 x 10(6) cells/L occurred within 5 days . Vancomycin serum concentrations remained within an acceptable range: a peak of 30 micrograms/mL and a trough of 9 micrograms/mL . DISCUSSION: Case reports in the literature of vancomycin-associated neutropenia in adults were briefly reviewed and compared . The onset and resolution and mechanism of vancomycin-induced neutropenia were studied . The potential relationship between vancomycin, weight-, and age-adjusted dosing and the occurrence of neutropenia in our pediatric patient was postulated . CONCLUSIONS: Vancomycin is identified as a possible cause of drug-induced neutropenia . More data are needed that clearly indicate vancomycin as the offending agent in children . The vancomycin-induced neutropenia is believed to be immunologically based and independent of drug concentrations. Ann Pharmacother, 1994 May, 28(5), 572 - 6 Stability of ceftazidime and vancomycin alone and in combination in heparinized and nonheparinized peritoneal dialysis solution; Vaughan LM et al.; OBJECTIVE: To examine the stability of ceftazidime, vancomycin, and heparin, alone and in combination, in dialysis solution over six days at three temperatures . DESIGN: Nine 250-mL Dianeal PD-2 dextrose 1.5% bags were prepared with ceftazidime, vancomycin, and heparin alone and in combination at set concentrations of 100 micrograms/mL, 50 micrograms/mL, and 1 unit/mL, respectively . Three bags of each mixture were stored at 4, 25, and 37 degrees C . Duplicate samples for analysis were removed from each bag at the following time points: premix, 0, 12, 24, 48, 72, 96, 120, and 144 hours . MAIN OUTCOME MEASURES: Each sample was examined visually for signs of cloudiness and precipitation . Each sample was analyzed by stability-indicating HPLC assay for ceftazidime and vancomycin, with stability defined as less than 10 percent degradation of drug over time . RESULTS: No color change or precipitation was observed in any bag . Vancomycin with or without heparin was stable for 5-6 days at 4, 25, and 37 degrees C . Ceftazidime with and without heparin was stable for 6 days at 4 degrees C, 4 days at 25 degrees C, and less than 12 hours at 37 degrees C . Vancomycin plus ceftazidime with and without heparin was stable for 6 days at 4 degrees C and 25 degrees C, and 4-5 days at 37 degrees C . Ceftazidime plus vancomycin with or without heparin was stable for 6 days at 4 degrees C, 2-3 days at 25 degrees C, and 12 hours at 37 degrees C . CONCLUSIONS: Bulk preparations of ceftazidime and vancomycin, alone and in combination and with or without heparin in Dianeal PD dextrose 1.5% solution, are sufficiently stable for use up to 6 days under refrigeration or 48 hours at room temperature. J Antimicrob Chemother, 1994 Apr, 33(4), 811 - 21 A comparative assessment of vancomycin-associated nephrotoxicity in the young versus the elderly hospitalized patient; Vance-Bryan K et al.; The incidence of vancomycin-associated nephrotoxicity was determined in a younger (age < 60 y) versus elderly (age > or = 60 y) hospitalized adult population to identify associated drug- and nondrug-related risk factors . Nephrotoxicity was defined as an acute increase in serum creatinine of > or = 44.2 mumol/L if baseline serum creatinine was < or = 221 mumol/L or an increase in serum creatinine of > or = 88.4 mumol/L if baseline serum creatinine > 221 mumol/L . A total of 289 patients, 141 younger (mean age, +/- S.D . 37.9 +/- 12.4 y) and 148 elderly (73.6 +/- 8.5 years), was retrospectively reviewed . Nephrotoxicity occurred in 7.8% younger vs 18.9% elderly patients (P = 0.003) . Using multivariate logistic regression models for the pooled patient population, concurrent loop diuretic use was significantly associated with vancomycin-associated nephrotoxicity (relative risk (R.R.) = 5.06); for the younger population, only concurrent amphotericin B use was significantly associated with vancomycin-associated nephrotoxicity (R.R . = 6.65); and for the elderly population, only concurrent loop diuretic use was significantly associated with vancomycin-associated nephrotoxicity (R.R . = 9.70) . These data suggest that elderly patients are at significantly greater risk of vancomycin-associated nephrotoxicity than are younger patients . However, because age was not a significant risk factor for nephrotoxicity in comparing the pooled vancomycin-associated nephrotoxicity group compared to the non-nephrotoxicity group, the differences observed between age groups probably reflect differences in risk factor prevalence. Clin Infect Dis, 1994 Apr, 18(4), 533 - 43 Serum vancomycin concentrations: reappraisal of their clinical value; Cantu TG et al.; Although monitoring serum vancomycin concentrations in clinical practice is commonplace, the data supporting this practice are meager . The rationale for monitoring these concentrations is to improve the effectiveness and/or reduce the toxicity of the drug . However, there are no data to suggest that monitoring serum vancomycin concentrations improves the effectiveness of therapy . In addition, despite many case reports of vancomycin-associated nephrotoxicity and ototoxicity, it is unclear whether this agent truly causes such conditions . Moreover, there is no evidence that adherence to specific ranges of vancomycin concentrations will preclude these events . Finally, vancomycin pharmacokinetics are sufficiently predictable that adequate serum drug concentrations can be obtained with dosing methods that take into account the patient's age, weight, and renal function . Safe and effective vancomycin dosage regimens can be constructed with these empirical dosing methods, whereas monitoring vancomycin levels increases the cost of therapy without improving the safety or efficacy of treatment. Am J Hosp Pharm, 1994 Mar 15, 51(6), 798 - 800 Vancomycin pharmacokinetics in middle-aged and elderly men; Leonard AE et al.; A study was conducted to establish new values for vancomycin volume of distribution (V) and clearance (CL) that would result in more accurate predictions of serum vancomycin concentrations (SVCs) . All patients who had received vancomycin at a Veterans Affairs medical center were divided into two groups: those for whom SVCs had been measured between August 13, 1990, and February 12, 1991 (group 1), and those for whom SVCs had been measured between February 13, 1991, and October 4, 1991 (group 2) . Data for group 1 were used to derive new values for V and CL by means of Bayesian analysis . SVCs for each patient in group 2 were calculated by using the new pharmacokinetic values, and the predictive performance of these values was compared with that of accepted population values (V = 0.70 L/kg, CL = 0.65 times creatinine clearance {CLcr}) . Forty-four men with 95 SVCs were entered into group 1, and 69 men with 171 SVCs were entered into group 2 . The mean +/- S.D . ages for groups 1 and 2 were 61.6 +/- 12.9 and 64.3 +/- 11.3 years, respectively . There were no significant differences between the groups . V could not be evaluated because of inadequate sample size . Compared with the method employing the conventional CL value, the method that assumed a CL of 0.90CLcr was more precise and less biased in estimating group 2 SVCs . In middle-aged and elderly men, use of a CL value of 0.90CLcr produced estimates of serum vancomycin concentration that were more precise and less biased than did use of a CL value of 0.65CLcr. Pharmacotherapy, 1994 Mar-Apr, 14(2), 196 - 201 Individualizing vancomycin dosing regimens: an evaluation of two pharmacokinetic dosing programs in critically ill patients; Fernandez de Gatta MM et al.; We evaluated the predictive performance of two commercial computer programs (Abbott and Simkin) for pharmacokinetic dosing of vancomycin in 50 critically ill patients, 40 with hematologic malignancies and 10 in intensive care . Predictive performance was assessed for both pharmacokinetics and forecasting vancomycin serum levels by using a set of peak and trough drug levels per patient . The effect of renal function and serum sampling (steady state, nonsteady state) on predictive performance of both programs was also analyzed . No statistically significant differences were found between the programs for predicting either pharmacokinetics or serum levels, regardless of a patient's renal function or serum sampling . The Abbott and Simkin programs were similar for individualizing vancomycin dosage regimens. Am J Hosp Pharm, 1994 Feb 1, 51(3), 321 - 7 Bayesian and threshold probabilities in therapeutic drug monitoring: when can serum drug concentrations alter clinical decisions? Schumacher GE, Barr JT. The use of Bayesian and threshold probabilities is examined with respect to the range of probabilities of toxicity for which obtaining a patient's serum drug concentration leads to information that is potentially useful in altering a clinical decision . For the situation of potential drug-induced toxicity, three threshold probabilities are needed to characterize the decision process: the decision threshold for deciding between continuing and discontinuing the drug regimen, the testing threshold that separates the decision to continue the regimen without testing the serum drug concentration from the decision to test before deciding, and the companion testing threshold that separates the decision to discontinue the regimen without testing from the decision to test before deciding . For digoxin, theophylline, aminoglycosides, vancomycin, and phenytoin, three prototypical decision threshold probabilities, 0.33, 0.2, and 0.1, are used, along with published true-positive and false-positive rates, to calculate serum concentration testing thresholds for each drug . Practitioners can be more effective in their use of serum drug concentration data when a Bayesian approach to probability assessment is used in conjunction with testing thresholds. Ther Drug Monit, 1994 Feb, 16(1), 37 - 41 Bayesian forecasting of serum vancomycin concentrations with non-steady-state sampling strategies; Rodvold KA et al.; The application of three non-steady-state sampling strategies and the fitting of either three or five pharmacokinetic parameter estimates by a two-compartment Bayesian forecasting program was evaluated retrospectively in 27 adult patients with stable renal function . Sampling strategies included a single midpoint concentration, a set of peak and trough concentrations, and three serial vancomycin concentrations . The most precise and least-bias predictions of steady-state peak vancomycin concentrations were observed by using population-based parameter estimates {mean prediction error (ME) = -0.40 and mean absolute error = 5.77} . The addition of non-steady-state feedback concentration(s) did not provide additional information for predictions of future steady-state peak concentrations . The least-bias prediction of steady-state trough vancomycin concentrations was seen when a single midpoint non-steady-state concentration was used (ME = 0.92 and -0.17 for five and three fitted parameter estimates, respectively) . The MEs of serial and peak and trough feedback strategies were similar in magnitude to those obtained using population parameters, but in opposite directions (underprediction vs . overprediction, respectively) . The fitting of only three parameters produced results similar to those using five parameters . The results from this study confirm our previous evaluation that non-steady-state concentrations provide very minimal information to Bayesian forecasting of future steady-state concentrations. Int J Artif Organs, 1994 Jan, 17(1), 19 - 26 Vancomycin dosing in haemodialysis patients and Bayesian estimate of individual pharmacokinetic parameters; Keller F et al.; A dose reduction of vancomycin to 1000 mg once a week usually is recommended for haemodialysis patients . Our modified dosing schedule consists of a loading dose of 1000 mg and a maintenance dose of 500 mg administered 3 times a week after haemodialysis . Different vancomycin regimens were retrospectively evaluated by therapeutic drug monitoring and bayesian parameter estimates in 39 dialysis patients . The mean (+/- SD) trough level in 7 patients receiving only the conventional dosage regimen was significantly lower than in 17 patients strictly treated by the modified schedule (7 +/- 4 versus 17 +/- 8 mg/L; p = 0.001) . The corresponding peaks were low in both groups and no different (23 +/- 10 versus 27 +/- 12 mg/L) . The one week average vancomycin clearance was significantly lower in the conventional dosage group compared to the modified dosage group (6 +/- 3 versus 10 +/- 3 ml/min; p = 0.001) . High-flux dialysers were not used in the conventional dosage group but for 30 percent of the procedures in the modified dosage group, where the vancomycin one week average elimination half-life was 66 hours (+/- 18) and the volume of distribution 50 litres (+/- 5) . As compared to the bayesian programme, NONMEM calculated comparable pharmacokinetic parameters but could be applied only in 5 cases with a sufficient number of concentration measurements . Ototoxicity occurred in 1 patient, whereas vancomycin treatment was judged as ineffective against infection in 5 of the 39 patients . Their troughs were below 15 mg/L.(ABSTRACT TRUNCATED AT 250 WORDS) Pathology, 1994 Jan, 26(1), 56 - 8 Catheter-related septicemia caused by a vancomycin-resistant Coryneform CDC group A-5; Campbell PB et al.; A case of catheter-related septicemia, due to Coryneform CDC group A-5, in an 11 yr old boy with acute myelomonocytic leukemia is discussed . The child failed to respond to initial antibiotic therapy, even following the addition of vancomycin . Laboratory studies later showed the organism to be vancomycin resistant but cefotaxime susceptible. Kidney Int, 1994 Jan, 45(1), 232 - 7 Vancomycin redistribution: dosing recommendations following high-flux hemodialysis; Pollard TA et al.; Although increased vancomycin clearance has been reported with highly permeable hemodialysis membranes (such as polysulfone), failure to consider post-dialysis redistribution could lead to unnecessary dosage supplementation . In protocol 1, twelve hemodialysis patients admitted for vascular access thrombectomy received 15 mg/kg of vancomycin as surgical prophylaxis . Post-operatively, patients underwent high-flux hemodialysis (HFHD) for two hours using a Fresenius F-80 polysulfone dialyzer (QB = 417 +/- 49, QD = 800 ml/min) . Vancomycin's intradialytic clearance increased 13-fold compared to the patient's endogenous clearance (120 +/- 59 vs . 9 +/- 8 ml/min, respectively) yet dialysate recovery indicated that only 17% of body stores were removed (179 +/- 70 mg) . Although serum vancomycin levels decreased 33% during HFHD, vancomycin levels increased in all patients following dialysis and the post-rebound values reached 87% of the pre-dialysis concentration . In protocol 2, eight outpatients receiving maintenance HFHD with a F-80 dialyzer (Kt/V = 1.29 +/- 0.08) were given 20 mg/kg of vancomycin immediately following dialysis on Monday; pre- and post-levels were measured during the next three dialysis treatments . The predialysis serum vancomycin levels were > 7.5 micrograms/ml (9.7 +/- 1.0 micrograms/ml; range 8.0 to 11.0) in all patients the following Monday . Thus, vancomycin clearance is increased during HFHD, but redistribution post-HD minimizes changes in serum levels . We recommend a 20 mg/kg i.v . loading dose and subsequent doses of 15 mg/kg every seven days; to account for individual variability, weekly vancomycin levels should be drawn before dialysis. Int Urol Nephrol, 1994, 26(2), 223 - 8 Comparison of the effects of three haemodialysis membranes on vancomycin disposition; Alwakeel J et al.; Polysulfone (PSF) and polyacrylonitrile (PAN) were recently introduced haemodialysis (HD) membranes . The effect of each on vancomycin disposition was compared with cuprophan (SCE) in 12 chronic HD patients who received 14 infusions . Vancomycin (1 g) was infused over 1 hour, followed by three 4-hour HD sessions over 5 days, beginning 1 hour after the end of infusion . The intradialytic clearances of vancomycin were 73, 54 and 15 ml/min for PSF, PAN and SCE, respectively . At the end of the third HD session, vancomycin concentration dropped to subtherapeutic level (< 7.5 micrograms/ml) only in patients dialysed with PSF and PAN . The corresponding elimination half-lives (t1/2 beta) were 61, 60 and 86 hours for the three membranes, respectively . According to these findings, vancomycin should be given every three HD sessions for PSF and PAN . The dosage interval should be extended up to every 5 HD sessions for patients on SCE . The peak (mean +/- S.D.) obtained one hour after the end of infusion was 34.2 +/- 11.4 micrograms/ml, which is within the therapeutic range. Proc Annu Symp Comput Appl Med Care . 1994;:972. Pharmaco-informatics: more precise drug therapy from "multiple model" (MM) stochastic adaptive control regimens: evaluation with simulated vancomycin therapy; Jelliffe RW et al.; MM stochastic control of dosage regimens permits essentially full use of information, either in a population pharmacokinetic model or a Bayesian updated MM parameter set, to achieve and maintain selected therapeutic goals with optimal precision . The regimens are visibly more precise than those developed using mean parameter values . Bayesian MM feedback has now also been implemented. J Basic Microbiol, 1994, 34(6), 387 - 99 Effect of inhibitors of cell envelope synthesis on beta-sitosterol side chain degradation by Mycobacterium sp . NRRL MB 3683; Sedlaczek L et al.; The role of the lipid bilayer and the peptidoglycan of the mycobacterial cell wall in the permeation of beta-sitosterol into the cell and its transformation to androst-1-ene-3,17-dione (AD) and androsta-1,4-diene-3,17-dione (ADD) was studied . Specific inhibitors were used at concentrations affecting the biosynthesis of the assumed target structures, but causing only partial cell growth inhibition or exerting no effect on growth . m-Fluorophenylalanine and DL-norleucine which are known to disorganize the biosynthesis of amphipatic components of the outer layer of the lipid bilayer, used at concentrations 250 micrograms/ml and 400 micrograms/ml, respectively, increased the formation rate of AD+ADD from 0.3 (control) to 0.7 and 0.8 mg products/g dry weight/h . The disorganization of the underlying mycolyl-arabinogalactan structure by the action of the ethambutol at the concentration 40 micrograms/ml, at which the cell growth was apparently not affected, caused the decrease of the product formation from 135 mg/l to 70 mg/l . In the presence of isoniazid (350 micrograms/ml) only trace amounts of AD accumulated during 48 hours of transformation indicating much lower activity than that of the intact cells . The most effective among the tested inhibitors of peptidoglycan synthesis were glycine (15 mg/ml) and vancomycin (150 micrograms/ml) which enhanced the transformation activity of the treated cells nearly three times . Increased transformation rate was also obtained by the action of colistin at concentrations ranging from 10 micrograms/ml to 15 micrograms/ml. Ophthalmic Res, 1994, 26(4), 202 - 6 Previous ocular compression increases intraocular penetration of systemic drugs; Murube J et al.; Intraocular drug penetration is dependent upon the physical and chemical characteristics of the drug, the manner of drug administration and the drug's ability to pass through the blood/aqueous barrier . Most systemically administered drugs do not achieve intraocular therapeutic levels . The authors present a new method to increase the intraocular concentration of intravenously administered drugs based on the premise that ocular hypotony by ocular compression produces a temporary break in the blood/aqueous barrier during the period of hypersecretion that follows to regain normal intraocular pressure levels . Vancomycin introduced parenterally was used as the drug model . The right eye of 22 rabbits served as experimental eye, while the left eye served as control . The concentrations of vancomycin in the aqueous humor half an hour after intravenous injection of 40 mg/kg vancomycin in 50 ml of lactated Ringer's solution were as follows: 30.17 +/- 20.68 micrograms/ml in the right (hypotonized) eyes and 4.92 +/- 3.33 micrograms/ml in the left (control) eyes . The difference in drug levels between the two sets of eyes had a high statistical significance at p = 0.001. Eur J Pediatr Surg, 1993 Dec, 3 Suppl 1, 17 - 8 Control of hydrocephalus by endoscopic choroid plexus coagulation--long-term results and complications; Pople IK et al.; Endoscopic choroid plexus coagulation has been used for the control of hydrocephalus regularly at this unit for the past 20 years . 156 of these operations have been performed on 116 patients and the aim of this study was to assess the rate of long-term control of hydrocephalus and the complications of the procedure . Data have so far been found for 98 patients with a median age at operation of 5 months (range 1 week-30 years) . After a mean follow-up period of 10.5 years there were 32 (33%) patients continuing without a ventricular shunt . One patient developed papilloedema and required ventricular shunting 16 years after choroid plexus coagulation . There were no deaths resulting from operation . 5 patients developed post-operative meningitis and 3 patients had post-operative infections of implants (2 shunts and 1 reservoir) . No cases of post-operative meningitis have occurred since vancomycin and gentamicin have been added to the solution used to perfuse the ventricles after operation (28 cases) . Other complications included post-operative fits (2), respiratory arrest in a premature baby (10, low-pressure state (1), blocked or leaking external ventricular drain (4), drain displacement (4), subdural effusion (1) and per-operative minor ventricular bleeding forcing abandonment of the procedure (2). Neonatal Netw, 1993 Dec, 12(8), 27 - 30 Safety of vancomycin with or without gentamicin in neonates; Linder N et al.; Short- and long-term side effects of vancomycin, or the combination of vancomycin and gentamicin, were retrospectively evaluated for 65 treatment courses in 47 premature infants who were exposed to high vancomycin serum concentrations . Thirty-five treatment courses involved treatment with the combination; 30 courses involved treatment with vancomycin alone . No immediate side effects were noted . Nephrotoxicity, defined as an increase in serum creatinine 0.5 mg/dl or more above baseline, was found in only 1 patient receiving vancomycin as the only antibiotic; that patient had pre-existing renal dysfunction . Three treatment courses involving the vancomycin-gentamicin combination resulted in nephrotoxicity; renal function returned to normal by 14 days after treatment . Thrombocytopenia was noted in 5 patients, but none exhibited clinical bleeding . Low platelet counts persisted throughout treatment, but by two weeks after treatment, this was resolved . In conclusion, the use of vancomycin or the combination of vancomycin and gentamicin in seriously ill premature infants is usually safe . The adverse effects noted were reversible, and monitoring creatinine and platelet counts during treatment is recommended. Ann Pharmacother, 1993 Nov, 27(11), 1383 - 8 Drug disposition in neonates with patent ductus arteriosus; Gal P et al.; OBJECTIVE: To review the literature on the physiologic changes created by neonatal patent ductus arteriosus (PDA) and the potential impact on drug disposition in these infants . DATA SOURCES: An Index Medicus and bibliographic search of the English-language literature pertaining to neonatal PDA and drug usage in newborns . DATA SYNTHESIS: PDA in premature infants is associated with a variety of physiologic changes that could alter drug disposition . Perfusion of drug-elimination organs (i.e., liver and kidney) may be diminished, resulting in decreased drug elimination . Further, the general fluid overload state associated with PDA may result in larger volumes of distribution (Vd), and dilutional effects for many drugs . Drug absorption, Vd, tissue penetration, and clearance may be affected by the physiologic changes incurred by a PDA . Although the pharmacokinetics of several categories of therapeutic agents may be affected by a PDA, disposition changes with the aminoglycosides and indomethacin have been the best documented . The most reliable pharmacokinetic change appears to be related to drug Vd . The interpretation of many of these studies is confounded by a potential drug interaction with the concurrent administration of indomethacin for PDA closure . CONCLUSIONS: Close therapeutic drug monitoring is indicated in newborns with PDAs as abrupt changes in drug disposition can occur with PDA closure . PDA-induced changes in specific pharmacokinetic parameters of agents such as the aminoglycosides, indomethacin, and perhaps vancomycin may prove to be a valuable diagnostic adjunct for the identification of babies with undiagnosed PDA . More research into this pharmacophysiologic aspect of pharmacokinetics is warranted. Ann Pharmacother, 1993 Nov, 27(11), 1346 - 8 Correlation of aminoglycoside and vancomycin pharmacokinetic parameters; Wragge TM et al.; OBJECTIVE: To investigate a correlation between the elimination rate constants (Ke) of aminoglycosides (AG) and vancomycin; to investigate the correlation between actual Ke and creatinine clearance (Clcr) for AG versus vancomycin; to investigate the calculated versus actual Ke for AG and vancomycin; and to investigate a correlation between volumes of distribution (Vd) between AG and vancomycin . DESIGN: Retrospective data collection . METHODS: Patients in our institution who received AGs or vancomycin concomitantly or within six weeks of each other were identified retrospectively . Patient subpopulations were identified and analyzed collectively as well as individually . Steady-state serum concentrations of AG and vancomycin (more than four half-lives) were obtained and kinetic parameters (Ke, Vd) were calculated using first-order pharmacokinetic equations . Linear regression was used to determine correlation coefficients . RESULTS: In the total population and all subpopulations, the correlation between Ke of AG and vancomycin was superior to the correlation between Ke and Clcr . The correlations (r2) between Ke for AG and vancomycin in the total, general medicine, oncology, and intensive care units (ICU) populations were 0.572, 0.878, 0.349, and 0.561, respectively . The correlations (r2) between Ke and Clcr for AG in the total, general medicine, oncology, and ICU populations were 0.235, 0.430, 0.005, and 0.238, respectively . The correlations (r2) between Ke and Clcr for vancomycin in the total, general medicine, oncology, and ICU populations were 0.300, 0.407, 0.055, and 0.309, respectively . CONCLUSIONS: The correlation between Ke of AG and vancomycin may be beneficial for predicting Ke of vancomycin when AG concentrations have already been obtained or vice versa, and may give more accurate estimations of dosing intervals and require less time adjusting, ordering, and interpreting concentrations and dosages. J Pediatr Gastroenterol Nutr, 1993 Oct, 17(3), 291 - 7 Development of lipolytic activity in gastric aspirates from premature infants; Lee PC et al.; Neonates, having little or no pancreatic lipase, would have a compromised ability to digest lipids if not for lingual and gastric lipases . To document the postnatal developmental profile of preduodenal lipase activity, 350 premature infants who were at various gestational ages and who had an orogastric tube had their gastric aspirates collected . Two hundred one infants had their gastric aspirates collected within 12 h after delivery . Serial collections were performed in 25 infants at various postnatal ages . Gastric aspirates collected from premature infants had a pH activity profile similar to that of lingual and gastric lipase but different from that of pancreatic lipase, indicating that their origin was from the tongue and/or stomach . Lipolytic activity and pH of these aspirates were quite variable, but no correlation was found between pH and enzyme activity . At birth, lipase activity was lower in the younger infants (< or = 26 weeks, n = 13) . It increased to a peak at 30-32 weeks of gestational age and then declined to a lower level at term (> or = 40 weeks, n = 40) . Postnatally, a composite plot of the serially collected aspirates also showed a predominant peak at 28-33 weeks of age . Comparison among siblings in twins (n = 12 pairs) and triplets (n = 3) showed great variations in their lipolytic activities, suggesting that the hereditary factor is not a major determinant . Various combinations of antibiotic medications (ampicillin, cefotaxime, gentamicin, and vancomycin) and drugs (dexamethasone, heparin, furosemide, phenobarbital, albumin, and vitamin K) apparently had no effect on the level and development of gastric lipolytic activities.(ABSTRACT TRUNCATED AT 250 WORDS) Antimicrob Agents Chemother, 1993 Oct, 37(10), 2139 - 43 Vancomycin skin tests and prediction of "red man syndrome" in healthy volunteers; Polk RE et al.; The purpose of the present study was to assess the cutaneous response to intradermally administered vancomycin in healthy adults and to determine whether the magnitude of the cutaneous response correlated to the severity of "red man syndrome" (RMS) following intravenous administration of vancomycin to the same subjects . Eleven healthy males were skin tested with intradermally administered histamine and saline controls and intradermally administered vancomycin at different concentrations . Vancomycin caused a dose-dependent area of flare in all subjects . The sigmoidal maximal flare model was used to fit each dose-response curve, and cutaneous responsiveness to vancomycin was quantified by various methods, including the flare area at each dose, maximum flare area (maximal flare), dose required to produce 50% of maximum flare, dose required to produce a flare area of 400 mm2, and the slope of the dose-response curve . One week after skin testing, subjects received an infusion of vancomycin, 15 mg/kg of body weight over 60 min . For the assessment of the severity of RMS, we used previously described methods . Although all subjects experienced erythema from the intravenously administered vancomycin and 10 subjects had pruritus, there was no significant correlation between vancomycin skin test results and the severity of RMS . We conclude that vancomycin skin tests do not predict the severity of RMS . In addition, vancomycin skin tests may be of no benefit for assessing immunoglobulin E-mediated allergy to vancomycin, since all subjects had a positive reaction at concentrations of > or = 10 micrograms/ml. J Clin Microbiol, 1993 Oct, 31(10), 2764 - 8 Growth of 28 Legionella species on selective culture media: a comparative study; Lee TC et al.; We compared the growth of 28 Legionella spp . on four manufacturers' buffered charcoal-yeast extract (BCYE) agar media and selective BCYE media that contained polymyxin B, anisomycin, and vancomycin or cefamandole . With BCYE as a "gold standard," growth for Legionella pneumophila was significantly better than for the nonpneumophila species on all media tested . L . pneumophila and 24 other Legionella spp . grew on vancomycin-containing media, while L . santicrucis, L . rubrilucens, and L . erythra grew poorly . In contrast, 11 of 28 species (notably L . micdadei and L . bozemanii) did not grow on cefamandole-containing media and 8 of 28 species only grew marginally . We demonstrated that selective BCYE media that contain vancomycin or cefamandole may not support the growth of all Legionella spp . One commercial manufacturer's media were consistently suboptimal . Laboratories should not rely on a manufacturer's quality control testing in lieu of their own. Ann Pharmacother, 1993 Oct, 27(10), 1187 - 9 Inadvertent intravenous administration of an elemental enteral nutrition formula; Malone M et al.; OBJECTIVE: To report a case of intravenous infusion of an elemental enteral nutrition formula . CASE SUMMARY: A 65-year-old woman with a high-output jejunostomy required fluid and electrolyte replacement via a central line and enteral nutrition support via a gastrostomy tube . She inadvertently received 160 mL of half-strength elemental enteral nutrition formula (Vivonex TEN) via her central venous catheter . After four hours of the infusion, the patient felt ill and was found to by hypotensive and pyrexic . Over the next 24 hours she developed severe back pain and diffuse muscle tenderness . Her creatine kinase concentration was mildly elevated and there were no electrocardiographic changes . There was no rise in serum amylase concentration . Her renal function deteriorated markedly over the following three hours but responded to hydration and diuretic therapy . Liver enzymes, slightly elevated prior to this event, remained unchanged . Blood cultures were negative, but prophylactic therapy with vancomycin and ceftazidime was instituted . The patient recovered and was discharged eight days later . DISCUSSION: Previous reports of inadvertent intravenous administration of enteral feedings have described such complications as osmolarity, microembolism, hypersensitivity, and septicemia . This patient's nonfatal outcome may have been related to the infusion of the enteral formula via the central rather than the peripheral route, the infusion of an elemental rather than a whole protein formula, and the use of sterile water to reconstitute the formula . CONCLUSIONS: Particular care should be taken when a patient has more than one catheter implanted on the chest or abdomen (e.g., central venous or peritoneal dialysis catheter) . It is important that inservice training is provided and written protocols are available for the safe infusion of enteral formulas. Int J Syst Bacteriol, 1993 Oct, 43(4), 715 - 20 Amycolatopsis alba sp . nov., isolated from soil; Mertz FP et al.; A new Amycolatopsis species isolated from soil produces a new glycopeptide antibiotic related to vancomycin . Traditional taxonomic methods and contemporary fatty acid analysis techniques were used to establish the position of this species . The hyphae fragment extensively when the organism is cultured in liquid media . The organism is characterized by white aerial hyphae that bear long chains of cylindrical conidia . The reverse side is yellowish brown; a faint light brown soluble pigment is occasionally produced . The organism has a type IV cell wall (meso-diaminopimelic acid), a type A whole-cell sugar pattern, and a type PII phospholipid pattern . Mycolic acids are not present in whole-cell hydrolysates . The major menaquinone is MK-9(H4); there is also a minor amount of MK-8(H4) . The name proposed for this new species is Amycolatopsis alba . The type strain is strain A83850 (= NRRL 18532). Otolaryngol Clin North Am, 1993 Oct, 26(5), 821 - 8 Ototoxicity of vancomycin and analogues; Brummett RE; This article details clinical reports and animal studies of ototoxicity associated with vancomycin and its analogues . From these studies, the ototoxicity of these agents is still not clear . In the author's opinion, vancomycin must affect the auditory system in a manner that results in augmentation of the usual ototoxicity of aminoglycoside antibiotics . This postulated effect may manifest as a temporary hearing loss in humans . More studies are needed, however, before a definitive conclusion can be made. J Clin Pharmacol, 1993 Oct, 33(10), 918 - 22 Comparison of vancomycin pharmacokinetics in hospitalized elderly and young patients using a Bayesian forecaster; Guay DR et al.; Limited data have been published that compare the pharmacokinetic parameters of vancomycin in elderly versus young patients . This study was designed to assess vancomycin pharmacokinetics in 148 elderly (> or = 60 years of age) and 140 young (18-59 years of age) hospitalized infected patients . Serum vancomycin concentrations were determined using fluorescence polarization immunoassay . Serum concentration-versus-time data were fitted to a two-compartment Bayesian forecasting program . Elderly versus young vancomycin pharmacokinetic parameters derived were as follows (patients with serum creatinine < or = 1.5 mg/dL); mean +/- standard deviation terminal disposition half-life (t1/2) of 17.8 +/- 11.8 versus 7.5 +/- 6.7 hours, respectively, P < .05; volume of distribution (Vz) of 74.2 +/- 32.3 versus 67.0 +/- 30.7 L, respectively, P = .16; and total body clearance (CL) of 0.71 +/- 0.41 versus 1.22 +/- 0.50 mL/min/kg, respectively, P < .05 . Comparing subjects with normal serum creatinine values (< or = 1.5 mg/dL), the elderly required smaller daily doses as compared with the young group to maintain target peak and trough vancomycin serum concentrations (18.2 +/- 5.8 verus 25.2 +/- 7.8 mg/kg/day, P < .05) . Stepwise multiple regression models for the pharmacokinetic parameters were developed to assess the predictive power of age, controlling for the effects of gender, total body weight, serum creatinine, and creatinine clearance . Age was consistently an independent and significant predictor of t1/2, Vz, and CL . These data demonstrate that elderly patients exhibit significant differences in vancomycin pharmacokinetic parameters compared with young patients and constitute a patient population in need of individualized vancomycin dosing due to substantial heterogeneity in physiologic and pharmacokinetic parameters. J Infect Dis, 1993 Sep, 168(3), 773 - 6 Prospective evaluation of red man syndrome in patients receiving vancomycin; O'Sullivan TL et al.; The incidence of red man syndrome (RMS) and its relationship to histamine were investigated in patients receiving vancomycin or an aminoglycoside (control) . During the 60-min infusions, patients were observed for signs or symptoms consistent with RMS, including pruritus, erythema, angioedema, and cardiovascular depression . Four blood samples were obtained at 30-min intervals for determination of histamine concentrations . One (3.4%) of 29 vancomycin- and none of 8 aminoglycoside-treated patients had documented RMS . The mean maximum changes in blood pressure and heart rate were not significant and were similar between groups . Increases in histamine concentrations to > 1 ng/mL occurred only in 25% (2/8) of the aminoglycoside patients . Vancomycin induced minimal changes in histamine concentrations despite the occurrence of RMS . From these observations, it appears that RMS is not closely associated with histamine release, and elevated histamine concentrations do not predict RMS . Further investigation is needed to elucidate other mediators of RMS. Clin Pharmacokinet, 1993 Sep, 25(3), 243 - 57 Drug dosage in end-stage renal disease (ESRD) patients undergoing haemodialysis . A predictive study based on a microcomputer program; Mac-Kay MV et al.; Drug dosage in end-stage renal disease (ESRD) patients undergoing haemodialysis is a very complex problem because of numerous variables relating to the patient, the type of drug administered and the type of dialysis and dialyser . We carried out a multifactorial study of these parameters using a microcomputer program written in BASIC . Three sets of data were fed into the computer: those relating to the biophysical characteristics of the patient, the type of dialysis and dialyser to be used, and others relating to the chemical and pharmacokinetic characteristics of the drug . From these, a predictive intravenous dosage regimen (bolus and infusion) was compiled for each ESRD patient . To check the program we used 2 drugs (tobramycin and vancomycin) and several types of dialyser . The findings were that, with tobramycin, an ESRD patient should be given different postdialytic doses, depending on the type of dialyser used . The maintenance doses calculated by the program were similar to those usually administered to patients receiving clinical treatment with this drug . In the case of vancomycin, the program calculated the clearance value in vivo through the 'Hemoflow F60' dialyser with a polysulphone membrane . The computer program calculated the maintenance dosage of vancomycin that should be given after each dialysis cycle so that its concentration did not fall below its minimum therapeutic concentration. Agents Actions, 1993 Sep, 40(1-2), 28 - 36 Mechanisms of vancomycin-induced histamine release from rat peritoneal mast cells; Horinouchi Y et al.; The mechanisms of vancomycin (VCM)-induced histamine release were studied with rat peritoneal mast cells . VCM (> 1 x 10(-3) M) released histamine from the isolated mast cells in a dose-dependent and noncytotoxic manner . In the absence of extracellular Ca2+, the histamine release was reduced markedly . When the intracellular Ca2+ was depleted, it was further decreased . The Fura-2-loaded single mast cells showed a biphasic increase in the intracellular Ca2+ concentration ({Ca2+}i) by VCM: the first transient and the second sustained components . In the absence of extracellular Ca2+, the transient component was unchanged, while the sustained component was eliminated completely . The IP3 content in the mast cells increased within 10 s after the application of VCM . These results suggest that VCM release histamine from rat peritoneal mast cells via an IP3 production and increase in {Ca2+}i. Ther Drug Monit, 1993 Aug, 15(4), 263 - 6 Preliminary studies of the effects of extracorporeal membrane oxygenator on the disposition of common pediatric drugs; Dagan O et al.; There is an increased use of extracorporeal membrane oxygenation (ECMO) in the last 15 years for critically ill neonates . While receiving ECMO therapy, the critically ill infant needs various medications . We performed an in vitro study to evaluate the potential effect of the membrane oxygenator on drug extraction . Two closed ECMO circuits were set up at rates of 320 ml/min . One circuit was new and the other was used clinically for 5 days . Morphine at 8 ng/ml, gentamicin 10 micrograms/ml, vancomycin 40 micrograms/ml, phenobarbital 20 micrograms/ml, and phenytoin 20 micrograms/ml were injected into the circuit at 1-h intervals . Blood samples were drawn from the circuit at 10, 30, 60, and 240 minutes after injection . In the new circuit, drugs were eliminated as follows: vancomycin 36%, gentamicin 10%, phenobarbital 17%, phenytoin 43%, morphine 36% . In the used system, levels fell to a much smaller extent: vancomycin 11%, phenobarbital 6%, gentamicin 0%, phenytoin 0%, and morphine 16% . In a child receiving 20 micrograms/kg/h infusion of morphine, steady-state concentrations of 68.2 ng/ml fell to 11.6 ng/ml after changing the membrane . Our data indicate that the ECMO is associated with lowering of the concentrations of commonly used medications and that this process may depend partially on how new the membrane is . Before these changes may lead to new dosing guidelines for small children receiving ECMO, more experiments with new and used systems are warranted, as well as with different types of ECMO. Curr Opin Ophthalmol, 1993 Aug, 4(4), 75 - 83 Storage, surgery, outcome, and complications of corneal and conjunctival grafts; Williams KA et al.; Corneal transplantation is still limited by a shortage of donor material, but the type of storage medium used once a cornea has been acquired is probably irrelevant to graft outcome . Vancomycin HCl shows promise as a supplement to gentamicin sulfate in storage media . New methods of HLA typing using donor ocular tissue have largely helped to overcome the problems associated with typing of cadaveric blood, but the value of HLA typing in improving corneal graft survival is now in doubt . Alternative regimens of immunosuppression are being tested in animal models, but there is still no consensus on the best ways to use existing agents such as corticosteroids . Rejection remains the most common cause of unsuccessful corneal grafting in large cohorts, but glaucoma and astigmatism also limit postoperative graft function . Limbal stem cell grafts are promising for the management of many ocular surface diseases and conjunctival limbal autografts for pterygia may be the most successful surgical method for preventing recurrence. Ann Pharmacother, 1993 Jul-Aug, 27(7-8), 912 - 21 Vancomycin administration into the cerebrospinal fluid: a review; Luer MS et al.; OBJECTIVE: To discuss administering vancomycin directly into the cerebrospinal fluid (CSF) to treat serious central nervous system (CNS) infections . DATA SOURCES: References were obtained through an online search of MEDLINE, limited to material published in English . In addition, information was extracted from clinical trials, review articles, abstracts, and textbooks . STUDY SELECTION: Systematic evaluation of this topic in humans has not been done in a prospective manner . Related research articles describing the pathophysiology of CNS infections, intrathecal drug administration, and case reports of CSF vancomycin administration were reviewed . DATA EXTRACTION: Case reports regarding CSF vancomycin dosing were evaluated and included: drug dosing, infecting organism, infectious disease state, infectious outcome, CSF dynamics/flow abnormalities, methods of drug administration, drug monitoring, and toxicities . DATA SYNTHESIS: The results of this review are based on qualitative evaluations of anecdotal case reports and a basic understanding of intrathecal and intraventricular drug dosing principles . CSF administration of vancomycin is an effective means of bypassing the blood-brain barrier to achieve greater drug concentrations within the CSF . Current limitations to the CSF administration of vancomycin include a lack of data describing its safety, efficacy, and pharmacokinetics . CONCLUSIONS: CNS infections may require the CSF administration of vancomycin for successful eradication . Recommendations for dosing in the literature vary . Because of the potential toxicities associated with elevated CSF concentrations of vancomycin, dosing should be conservative. Antimicrob Agents Chemother, 1993 May, 37(5), 1132 - 6 Serum protein-binding characteristics of vancomycin; Sun H et al.; A synthesis of studies of serum protein binding of vancomycin and its reported abnormal binding in serum with very high concentrations of immunoglobulin A (IgA) suggests that this antibiotic may be bound to more than one serum protein . Using an ultrafiltration method for separating free from bound drug and high-performance liquid chromatography to measure drug concentration, we studied the binding characteristics of vancomycin for alpha-1 acid glycoprotein, IgG, IgM, IgA, and albumin . The results showed that vancomycin does not bind to alpha-1 acid glycoprotein, IgG, or IgM . Major binding to albumin and IgA occurs, and total drug binding to serum proteins can be fully explained by binding to these two proteins . We calculated an N (number of binding sites per molecule) of 1.3 +/- 0.4 and a K (association constant) of 3.3 x 10(5) +/- 6.3 x 10(4) M-1 (NK = 4.3 x 10(5) M-1) for binding to IgA, whereas the corresponding NK value for albumin was only 527.5 M-1, indicating that vancomycin preferentially binds to IgA . Very high concentrations of IgA in serum (i.e., grams per deciliter), such as in patients with IgA myeloma, may result in the paradox of high (total) concentrations of vancomycin in serum that may be clinically ineffective. Clin Pharmacokinet, 1993 May, 24(5), 362 - 79 Drug dosage in patients during continuous renal replacement therapy . Pharmacokinetic and therapeutic considerations; Reetze-Bonorden P et al.; The advantages of continuous haemofiltration and haemodialysis over intermittent haemodialysis for the treatment of acute renal failure are well recognised . In intensive care patients, 4 different continuous procedures, arteriovenous and venovenous haemofiltration (CAVH and CVVH) or haemodialysis (CAVHD and CVVHD), are employed . These effective detoxification treatments require knowledge of their influence on drug disposition . Data on kinetics of drugs during continuous treatment are scarce and limited almost exclusively to the oldest and least effective procedure (CAVH) . Selected dialysis membranes may adsorb drugs, as in the case of aminoglycosides . In addition, elimination of substances with large molecular weights may vary depending on the pore size of the membrane, as in the case of vancomycin . Thus, even if drug dosages can be based on pharmacokinetic studies, selection of a dialysis membrane not studied may cause unpredictable drug concentrations . With these limitations in mind and considering the available literature on pharmacokinetics in patients with renal failure, general guidelines for drug dosage during continuous renal replacement therapy can be given . In haemofiltration, drug protein binding is the major factor determining sieving, i.e . the appearance of the drug in the ultrafiltrate . In haemodialysis, diffusion is added to ultrafiltration, and therefore the saturation of the combined dialysate and ultrafiltrate will decrease further with increasing dialysate flow rate . In continuous haemofiltration or haemodialysis the extracorporeal clearance can be calculated by multiplying the saturation value (estimated or, better, measured) with the ultrafiltrate and dialysate flow rate . Dividing the extracorporeal clearance by the total clearance (including the nonrenal clearance) gives the fraction of the dose removed due to extracorporeal elimination . Whether dosage recommendations available for anuric patients have to be modified or not can be decided on the basis of this value . In case of high nonrenal clearance, the degree of saturation is without clinical significance . Based on these considerations guidelines have been constructed for the effect of extracorporeal elimination on more than 120 different drugs commonly used in intensive care patients. Cornea, 1993 May, 12(3), 222 - 7 Stability and activity of vancomycin in corneal storage media; Lindquist TD et al.; Gentamicin is the only antibiotic currently added to commercially available corneal storage media . To reduce the potential for bacterial dissemination from donor corneal tissue to the recipient eye, we evaluated the addition of vancomycin to corneal storage media . When added to Dexsol at a concentration of 200 micrograms/ml, vancomycin levels were maintained, showing a 7% decrease in vancomycin concentration per month, measured < or = 90 days after its addition . Human corneas were stored in gentamicin-free Dexsol (Chiron Ophthalmics, Inc., Irvine, CA, U.S.A.) containing 150 micrograms/ml vancomycin . Corneal tissue levels of vancomycin determined by agar diffusion bioassay were 201, 226, 292 micrograms/ml at 1, 3, and 7 days of storage respectively, suggesting that corneal tissue concentrates vancomycin with time . No differences in endothelial cell count or cell death were seen in corneas stored in Dexsol (containing gentamicin) or Dexsol plus vancomycin when followed for < or = 14 days . Vancomycin added to corneal storage media should reduce the potential for endophthalmitis due to gentamicin-resistant organisms. Pediatr Infect Dis J, 1993 Apr, 12(4), 300 - 4 Pharmacokinetics of intravenous vancomycin in pediatric cardiopulmonary bypass surgery; Hatzopoulos FK et al.; The purposes of this investigation were to characterize the disposition of vancomycin in children undergoing cardiopulmonary bypass (CPB) surgery and to determine whether a 15-mg/kg intravenous dose provides adequate serum concentrations during and after CPB . Six children (age range, 0.8 to 4.8 years) received intravenous vancomycin 15 mg/kg 1 to 2 hours before CPB surgery . Serial blood samples (mean, 10/patient) were collected before, during and after CPB surgery . The mean (+/- SD) vancomycin concentrations at the end of the infusion and 5 hours after the infusion were 27.3 +/- 5.7 and 5.9 +/- 3.0 mg/liter, respectively . The initiation of CPB resulted in an abrupt decrease (44.5%) in serum vancomycin concentrations; however, concentrations remained constant (range, 6.2 to 14.1 mg/liter) throughout the rest of the CPB procedure . The mean (+/- SD) values for the apparent volume of distribution, total body clearance and elimination half-life were 0.59 +/- 0.15 liter/kg, 2.94 +/- 0.93 ml/min/kg and 2.4 +/- 0.8 hours, respectively . These values were similar to those reported in the literature for children not undergoing CPB surgery . A single vancomycin dose of 15 mg/kg before pediatric CPB surgery provides serum concentrations greater than 5 mg/liter throughout the duration of the CPB procedure . To sustain these concentrations subsequent dosing of vancomycin is necessary within 6 hours after the initial vancomycin dose. Arch Ophthalmol, 1993 Apr, 111(4), 492 - 4 Ocular penetration of ceftriaxone, ceftazidime, and vancomycin after subconjunctival injection in humans; Barza M et al.; Vancomycin (25 mg), ceftriaxone (125 mg), and ceftazidime (100 mg) were given by subconjunctival injection before vitrectomy to patients with uninfected eyes . Most of the patients had diabetic vitreous hemorrhage with or without traction retinal detachments, and some had rhegmatogenous retinal detachments with proliferative vitreoretinopathy . Samples of vitreous were obtained by pars plana vitrectomy at intervals from 46 minutes to 4 hours 13 minutes after the subconjunctival injection . The median vitreous concentrations of all three drugs were below the limit of detection . Vitreous concentrations of these drugs after a single subconjunctival injection are exceedingly low. Anesth Analg, 1993 Apr, 76(4), 809 - 11 Vancomycin does not enhance hypotension under anesthesia; von Kaenel WE et al.; The rapid administration of vancomycin is associated with flushing and hypotension, a consequence of histamine release . The manufacturer discourages administering vancomycin to anesthetized patients, stating that vancomycin aggravates the hypotensive effects of anesthetics . To test this, we randomly assigned 36 adults (ASA classes I through III) to one of two groups: preinduction (Preind, n = 19) and postinduction (Postind, n = 17) . Both groups received two different infusions: vancomycin (1 g/250 mL normal saline) and saline (250 mL normal saline) over 30-60 min . The Preind group received vancomycin before anesthesia was induced and saline was administered immediately after anesthesia was induced; for the Postind group, this order was reversed . This was done in a double-blind fashion . The anesthetic induction was standardized by the intravenous administration of thiopental and vecuronium and anesthetic maintenance by inhalation of nitrous oxide and enflurane . End-tidal enflurane, heart rate (HR), and blood pressure (BP) were measured every 3 min . Independent (unpaired) t-test was used in data analysis . The groups did not differ significantly . We conclude that vancomycin infusion may be given under anesthesia without significant adverse hemodynamic consequences if administered over a 30-60 min period of time. Int Ophthalmol, 1993 Apr, 17(2), 85 - 8 Use of vancomycin in vitrectomy infusion solution and evaluation of retinal toxicity; Borhani H et al.; The retinal toxicity of vancomycin in infusion solution used in vitrectomy and lensectomy was investigated in rabbit eyes by means of electroretinography and histologic study (light microscopy) . Concentrations of 8 micrograms/ml, 16 micrograms/ml, and 32 micrograms/ml of vancomycin in balanced salt solution caused no abnormal ERG or histologic changes . However, ERG amplitude depression and abnormal histologic changes occurred when the concentration of 100 micrograms/ml of vancomycin was used. Antimicrob Agents Chemother, 1993 Mar, 37(3), 436 - 40 Effect of obesity on vancomycin pharmacokinetic parameters as determined by using a Bayesian forecasting technique; Vance-Bryan K et al.; Few data exist concerning the effect of obesity on the pharmacokinetic parameters of vancomycin . The purpose of this investigation was to assess the effect of obesity on vancomycin pharmacokinetic parameters in 95 nonobese and 135 obese adult patients (age range, 18 to 92 years) receiving vancomycin . All subjects had normal renal function as defined by a creatinine concentration in serum of < or = 1.5 mg/dl (mean estimated creatinine clearance +/- 1 standard deviation, 76 +/- 34; range, 23 to 215 ml/min) . Vancomycin concentrations in serum were determined by the fluorescence polarization immunoassay . All data for vancomycin concentration in serum versus time for each course of therapy were fitted by using a two-compartment Bayesian forecasting program . Subjects were stratified into nine groups on the basis of the percent difference between actual body weight (ABW) and lean body weight (LBW) (> -10%, -10 to 0%, > 0 to 10%, > 10 to 20%, > 20 to 30%, > 30 to 40%, > 40 to 50%, > 50 to 60%, > 60%) . Analysis of variance with post hoc Scheffe's testing revealed that statistically significant differences occurred in terminal disposition half-life (t1/2 beta) between the extremes of modestly obese (group 4) and morbidly obese (group 9, P < 0.05) patients . Similar analysis with distribution volume (V) identified significant differences in patients at or near their LBW (groups 2 to 4) and patients who were morbidly obese (groups 8 and 9, P < 0.05) . Multiple regression models for the pharmacokinetic parameters V, t1/2beta, and vancomycin total body clearance were developed to assess the joint predictive power of LBW, ABW, and percent over LBW, controlling for the effects of age, initial creatinine concentration in serum, initial creatinine clearance, and gender . In the final model for V, both ABW and percent over LBW were independent and significant predictors . For total body clearance, only ABW was significant and predictive . Percent over LBW was a significant and independent predictor of t1/2beta . LBW is not predictive of these pharmacokinetic parameters and should not be used for initial dosing . On the basis of these data, ABW appears to be superior to LBW for calculating initial dose requirements for vancomycin. Ann Intern Med, 1993 Feb 15, 118(4), 255 - 67 Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients; McDonald GB et al.; OBJECTIVE: To determine the incidence and clinical course of veno-occlusive disease of the liver (VOD) after bone marrow transplantation and to analyze risk factors for severe VOD . DESIGN: Cohort study of 355 consecutive patients . SETTING: A bone marrow transplantation center . MEASUREMENTS: Each patient was prospectively evaluated for VOD, and many risk factors for severe VOD were analyzed using logistic regression models . The relation of VOD to renal and cardiopulmonary failure was analyzed using time-dependent proportional hazards models . RESULTS: Veno-occlusive disease developed in 190 of 355 patients (54%; 95% CI, 48% to 59%): Fifty-four patients had severe VOD and 136 had mild or moderate VOD . Independent variables derived from a multivariate model for predicting severe VOD included elevated transaminase values before transplantation (relative risk, 4.6; P < 0.0001); vancomycin therapy during cytoreductive therapy (relative risk, 2.9; P = 0.003); cytoreductive therapy with a high-dose regimen (relative risk, 2.8; P = 0.01); acyclovir therapy before transplantation (relative risk, 4.8; P = 0.02); mismatched or unrelated donor marrow (relative risk, 2.4; P = 0.02); and previous radiation therapy to the abdomen (relative risk, 2.2; P = 0.04) . Vancomycin therapy was a marker for persistent fever . Multiorgan failure was more frequent among patients with VOD and usually followed the onset of liver disease . CONCLUSIONS: Veno-occlusive disease, which developed in 54% of bone marrow transplant recipients, is frequently associated with renal and cardiopulmonary failure . Pretransplant transaminase elevations, use of high-dose cytoreductive therapy, and persistent fever during cytoreductive therapy are independent predictors of severe VOD. Clin Pharm, 1993 Feb, 12(2), 126 - 30 Computer dosing program for the initiation of vancomycin therapy; Ito MK et al.; The predictive performance of a computer dosing program used for initiating vancomycin therapy was studied . Initial serum vancomycin concentrations in 31 adult patients receiving vancomycin were estimated by using a computer program (T.D.M.S.) incorporating a two-compartment open model . Sixty-two serum vancomycin concentrations at steady state (Css) were obtained before and after one-hour infusions and compared with estimated Css values . Bias and precision were evaluated by calculating median error (ME) and median absolute error (MAE), respectively . Population-based estimates of volume of distribution (V) and clearance (CL) were compared with those obtained by fitting each patient's data set by using Bayesian analysis (BA) and non-linear least-squares regression (NLLS) . Median (mean +/- S.D.) bias and precision for peak Css were 7.7 (10.2 +/- 10.8) and 7.7 (10.6 +/- 10.5) mg/L, and for trough Css were 7.4 (7.7 +/- 7.6) and 7.4 (8.8 +/- 6.2) mg/L . The medians were significantly different from zero . Estimated median (mean +/- S.D.) V, CL, and half-life were 0.72 L/kg, 0.60 (0.67 +/- 0.21) mL/min/kg, and 11.59 (12.87 +/- 3.91) hours . Median (mean +/- S.D.) CL values determined by BA and NLLS were 0.86 (0.89 +/- 0.32) and 0.85 (0.92 +/- 0.34) mL/min/kg, respectively . Both CL values were significantly greater than the population-based estimate . However, median V values determined by BA and NLLS did not differ from the population-based estimate . A revised clearance model derived from Bayesian analysis of data for the first 21 patients was tested in the 10 other patients and appeared to improve the predictive performance of the a priori model.(ABSTRACT TRUNCATED AT 250 WORDS) Ann Pharmacother, 1993 Feb, 27(2), 224 - 7 Vancomycin and tobramycin clearance in an infant during continuous hemofiltration; Armstrong DK et al.; OBJECTIVE: To report a case of vancomycin and tobramycin clearance by continuous veno-venous hemofiltration in an infant . Hemofiltration clearance (ClHF) was calculated by two methods and compared for ease and reliability . METHODOLOGY: Case report of a hospitalized four-month-old infant . With method A, ClHF calculation for vancomycin and tobramycin was determined by accurate collection of ultrafiltrate in five 24-hour periods and a midpoint serum sample . With method B, ClHF calculation was determined by obtaining prefilter sample, postfilter sample, and blood flow through filter (Fick principle) over three study periods, correlating to three of five study periods in method A . RESULTS: The infant received continuous veno-venous hemofiltration . With method A, vancomycin ClHF ranged from 0.27 to 0.80 mL/min; tobramycin ClHF ranged from 0.32 to 0.91 mL/min . With method B, ClHF for vancomycin ranged from 0 to 2.08 mL/min . Tobramycin ClHF ranged from 0 to 1.6 mL/min when calculated with method B . CONCLUSIONS: Continuous veno-venous hemofiltration increased the clearance of vancomycin and tobramycin requiring dosage modifications . It appears that method A, which uses the ultrafiltration concentration compared with the serum concentration is more accurate than method B, as it averages fluctuations in ultrafiltrate flow rates . Method B compares a single pre- to postfilter drug concentration and relies on an accurate measurement of ultrafiltration flow rate . Determining ClHF based upon one point in time may overestimate ClHF when the ultrafiltration flow rate varies, as it does in the critically ill . Daily serum concentrations for vancomycin and tobramycin are recommended during continuous veno-venous hemofiltration. Ann Pharmacother, 1993 Feb, 27(2), 174 - 7 Hypersensitivity reactions associated with parenteral nutrition: case report and review of the literature; Nagata MJ; OBJECTIVE: To report a case of hypersensitivity reaction to total parenteral nutrition (TPN) and to review the available literature on this rare adverse effect . CASE SUMMARY: The reaction occurred in a 52-year-old woman with pancreatic carcinoma who received intravenous metronidazole, tobramycin, vancomycin, ranitidine, morphine, TPN, and lipid emulsion postoperatively . Within 30 minutes of starting the TPN and lipid emulsion, the patient complained of dyspnea and pruritus . She began hyperventilating and was hypoxic . The reaction resolved after discontinuation of the TPN and lipid emulsion . The reaction recurred when lipid-free TPN was initiated on two subsequent occasions, and resolved spontaneously following the discontinuation of the lipid-free TPN . The antibiotics, ranitidine, and morphine therapy were continued with no further adverse effects and the patient was discharged on postoperative day 17 . DISCUSSION: Case reports in the literature on TPN-related hypersensitivity reactions were reviewed . It was speculated that the multivitamin preparation (MVI) may have been the causative agent in our patient; however, this was not confirmed by MVI-free TPN administration or by epicutaneous allergy testing . CONCLUSIONS: Hypersensitivity reactions to TPN can be managed by withholding the TPN and treating with antihistamines if needed until the reaction resolves . Identification, possibly by epicutaneous allergy testing, and removal of the offending agent(s) from the TPN is necessary if TPN therapy must be restarted. Perit Dial Int, 1993, 13 Suppl 2, S355 - 6 Single daily dose of aminoglycosides in the treatment of continuous ambulatory peritoneal dialysis peritonitis; Vas SI; Toxicity of aminoglycosides is a major concern in the treatment of continuous ambulatory peritoneal dialysis (CAPD) peritonitis . The relatively high blood levels and prolonged and repeated usage may all be contributory . The recognition of the so-called postantibiotic effect, together with the increased phagocytosis of antibiotic-treated cells, may introduce a new mode of therapy with once-daily dosage . Intermittent therapy with vancomycin is already generally accepted . The extension of this modality to antibiotic therapy is discussed. Perit Dial Int, 1993, 13 Suppl 2, S348 - 50 Intraperitoneal vancomycin/oral pefloxacin versus intraperitoneal vancomycin/gentamicin in the treatment of continuous ambulatory peritoneal dialysis peritonitis; Lye WC et al.; Sixty patients were enrolled in a prospective, randomized study to evaluate the efficacy of two different regimens for the empirical treatment of continuous ambulatory peritoneal dialysis (CAPD) peritonitis . At presentation, Group I received intraperitoneal vancomycin (1 g) and oral pefloxacin (400 mg b.i.d.), and Group II intraperitoneal vancomycin (1 g) and gentamicin (80 mg loading dose, followed by 15 mg/2 L) . Treatment duration was 14 days . Despite randomization, Group I had significantly more patients with primary Candida peritonitis . When fungal peritonitis was excluded from analysis, there were no significant differences in the treatment success rate (Group I, 73.3% vs Group II, 80.0%, p = NS), number of relapses (Group I, 0 vs Group II, 1), and Tenckhoff catheter removal rates (Group I, 26.6% vs Group II, 16.6%, p = NS) between the two groups . The patients treated with pefloxacin had an increased incidence of nausea and vomiting . In selected situations oral pefloxacin may be a suitable substitute for intraperitoneal gentamicin as out-patient therapy for CAPD peritonitis. Drugs Exp Clin Res, 1993, 19(1), 19 - 24 Effect of oral activated charcoal on vancomycin clearance in rabbits with acute renal failure; el-Sayed YM et al.; The effect of oral administration of activated charcoal on total body clearance of vancomycin administered intravenously (7.5 mg/kg) has been studied in normal rabbits and rabbits with induced renal failure . Gastric intubation of a single dose (10 g) of activated charcoal to normal rabbits did not produce a statistically significant effect on any pharmacokinetic parameter for vancomycin . The mean vancomycin clearances were (mean +/- s.d.) 80.82 +/- 6.8 and 75.24 +/- 9.61 ml/h/kg with and without activated charcoal administration, respectively . To examine whether renal failure would influence the effect of activated charcoal and enhance the systemic clearance of vancomycin, uranyl nitrate was used (0.75 mg/kg, i.v.) to induce acute renal failure in rabbits . The derived pharmacokinetic parameters of vancomycin were consistent with renal failure . No significant differences were observed in any of the calculated pharmacokinetic parameters between the control and charcoal treated rabbits . The lack of effect may be attributed to the large molecular weight of vancomycin. Adv Perit Dial, 1993, 9, 217 - 22 A retrospective view of factors that affect catheter healing: four years of experience; Newman LN et al.; To determine factors that lead to successful healing, the results of catheter placement were collected by retrospective chart review in 103 peritoneal dialysis patients between January 1988 and March 1992 . There were a total of 112 catheter insertions . A healing time of less than 2 weeks was defined as an optimal outcome . Data were analyzed using contingency tables . Strong predictors of early and effective healing were the following: exit site size less than 0.7 cm, the use of a tunneler to create the exit site, the use of Swan neck catheters, immobilization using Viasorb dressings, and postoperative prophylaxis with intravenous vancomycin . Dialysate leak and the development of hematomas significantly delayed healing . Leaking was associated with early use of the catheter for peritoneal dialysis . Hematoma formation was associated with the use of a tunneler . Uremic or nutritional status, diabetes, immunosuppressive agents, or HIV-positive did not affect catheter healing . Careful attention to intraoperative and postoperative factors optimizes healing independent of complications of primary disease processes in peritoneal dialysis patients. Adv Perit Dial, 1993, 9, 173 - 6 Pregnancy and birth control in CAPD patients; Hou S; This report summarizes the experience with 17 pregnancies in 16 continuous ambulatory peritoneal dialysis (CAPD) patients . Early experience suggests that the outcome of pregnancy in CAPD patients may be better than in hemodialysis patients . Catheter placement can be undertaken during pregnancy with little increased risk . Peritonitis can precipitate premature labor . Blood-tinged dialysate may herald serious obstetric problems . Hypertension, anemia, and prematurity are serious problems in CAPD patients . Cesarean section can be done, with only a brief interruption in CAPD . The major modification of the usual regimen is the need for smaller exchange volumes and increased frequencyPIP: Clinicians should counsel continuous ambulatory peritoneal dialysis (CAPD) patients about contraceptive use . Hypertension contraindicates the pill . CAPD patients should not use IUDs, since they increase the risk of peritonitis . They can use barrier methods . Pregnancy is often not detected until late . The literature shows that 16 CAPD patients have had 17 pregnancies . 65% of the pregnancies resulted in surviving infants . Pregnancies of all women who conceived before starting dialysis were successful, compared to just 4 of 10 women who conceived after starting dialysis . CAPD patients have a more successful pregnancy rate than do hemodialysis patients, but the numbers are too small to be significant and selection bias may exist . Clinicians placed 11 catheters in 8 of the 16 CAPD patients between 4-29 weeks gestation . Fetal position contributed to outflow obstruction . Just 1 patient had dialysate leak . 3 peritonitis episodes occurred . Cephradine, gentamicin, cefadyl, and vancomycin were used to treat peritonitis . 2 women went into labor and delivered shortly after the onset of peritonitis . The infant delivered at 34 weeks survived, while the one delivered at 24 weeks was stillborn . Bloody dialysate was present in 3 pregnancies . It signaled abruptio placentae and subsequent fetal loss in 1 case, severe subserosal hemorrhage of the uterine wall in another case, and laceration of uterine vessels by the catheter . Hypertension complicated 9 pregnancies, but physicians managed it well and it did not cause premature delivery . 6 women had serum hemoglobin levels between 5.4 and 9 g/L . Just 2 received erythropoietin during pregnancy . Premature labor occurred in 9 pregnancies . CAPD infants are small for their gestational age . Cesarean section with no need for catheter removal was the delivery mode for 6 live born infants . Physicians had to hold dialysis for 24-72 hours after surgery . Smaller exchange volumes and increased frequency of dialysis are major changes in the usual regimen for pregnant CAPD patients . J Hosp Infect, 1993 Jan, 23(1), 17 - 26 The duration of placement as a predictor of peripheral and pulmonary arterial catheter infections; Raad I et al.; To determine the appropriate time for removal or replacement of peripheral and pulmonary arterial catheters in critically ill cancer patients, we prospectively studied 71 peripheral arterial catheters and 71 pulmonary artery (Swan-Ganz) catheters from 110 consecutive cancer patients . All catheters were cultured semiquantitatively, by the roll-plate culture technique . Of the 71 peripheral arterial catheters, 11 (15%) produced local infections (> or = 15 colonies) and four (5.5%) produced catheter-related septicaemia . Ten of the 11 local infections and all four septicaemias occurred after 4 days of catheter placement (P < 0.05) . Likewise, of the 71 Swan-Ganz catheters, 12 (17%) produced local infection and four (5.6%) led to septicaemia . Swan-Ganz catheter-related septicaemia occurred at rates of 2% and 16%, before and after 7 days of catheter placement, respectively (P = 0.056) . Duration of placement was a risk factor for the development of catheter infections, independent of the patient's neutropenic status, administration of antibiotics such as vancomycin during catheterization, and the presence of concurrent central venous catheters . Life-table analysis showed that the cumulative risks of developing a catheter infection increased from 7% to 17% after 6 days of peripheral arterial catheter placement and from 9% to 18% after 4 days of placement of the Swan-Ganz catheter . We conclude that in the critically ill cancer patient in our unit, peripheral arterial catheters should be changed to a new site every 4-6 days and pulmonary artery catheters every 4-7 days. Dev Pharmacol Ther, 1993, 20(3-4), 174 - 9 Overestimation of serum vancomycin concentrations using a fluorescence polarization immunoassay (Tdx) in preterm neonates; Paap CM et al.; Serum vancomycin concentrations determined by fluorescence polarization immunoassay (FPIA) with a specific high-performance liquid chromatography (HPLC) method in preterm neonates were compared . Preterm neonates (< 38 weeks gestational age) requiring vancomycin therapy and serum vancomycin concentration monitoring were enrolled . Peak serum vancomycin concentration samples were collected and independently analyzed by FPIA and HPLC . Multivariate and stratified data analysis was done with mean absolute error and mean percent error as dependent variables and independent variables as postconceptional age, postnatal age, gestational age, weight, and duration of therapy to characterize the findings . A total of 15 paired vancomycin concentrations were analyzed from neonates with a mean gestational age of 30 +/- 4 weeks . The mean percentage error of FPIA versus HPLC vancomycin concentrations was 18.1 +/- 11.1% and the mean absolute error was 3.7 +/- 2.0 mg/l . Postconceptional age, weight, and time from initiation of therapy to sample collection were independent variables which best characterized the overestimation of FPIA vancomycin concentrations . The FPIA vancomycin assay method overestimated actual vancomycin concentrations in preterm neonates . Preterm neonates less than 30 weeks postconceptional age, less than 1,200 g body weight, and duration of therapy greater than 48 h prior to concentration determination had the greatest difference in FPIA and HPLC results . Significant error in pharmacokinetic parameter estimation