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Vancomycin pharmacokinetics in infants: relationship to postconceptional age and serum creatinine.

Multidose pharmacokinetics of vancomycin were studied in 15 infants with gestational age less than 36 weeks and suspected or confirmed Staphylococcus epidermidis infections. Postconceptional age (PCA) at the time of the study ranged from 26 to 44 weeks. Vancomycin individual doses ranged from 6.7 to 10.6 mg/kg and were infused over 60 min. Five postinfusion samples were obtained in 13 infants, while 4 samples were obtained in 2 patients. Vancomycin pharmacokinetic parameters were determined by fitting the data to a two-compartment model using a weighted least-squares nonlinear regression method. Mean vancomycin body clearance (CL), volume of distribution (Vdss) and terminal elimination half-life were 1.37 ml/min, 0.58 liters and 5.6 h, respectively. When standardized for patient weight, the CL and Vdss values were 1.07 ml/min/kg and 0.48 liters/kg, respectively. The CL (ml/min/kg) was strongly inversely correlated with the serum creatinine (r = -0.82), while a weaker but significant association was noted with PCA (r = 0.41). These data suggest that in sick infants, in addition to the PCA, serum creatinine should be considered when determining the initial vancomycin dosing regimen.

Body Weight↗

[Effects of vancomycin and ofloxacin on rabbit ERG in vivo].

The retinal toxicity of vancomycin and ofloxacin was studied by electroretinogram (ERG) before and after intravitreal injection in rabbits. Vancomycin is known to be effective on methicillin-resistant Staphylococcus aureus. A dose of 1mg vancomycin caused no ERG change for at least eight weeks after injection. The feature that ERG became non-recordable during one to four weeks after an intravitreal injection of 10mg vancomycin, with recovery of only the c-wave was conspicuous. A dose of 200 micrograms ofloxacin did not cause deterioration of the b-wave, the c-wave or the oscillatory potentials throughout the follow-up period up to eight weeks. Judging from the susceptibility of each ERG component to antimicrobials and taking into account the difference of vitreous volume between rabbits and humans, clinical doses of intravitreal single-shot injection should be less than 1mg for vancomycin and 200 micrograms for ofloxacin.

Animals↗

Reduction of sternal infection by application of topical vancomycin.

Sternal or mediastinal infection after heart operations occurs infrequently but carries a high cost in money, morbidity, and mortality. At our hospital, Staphylococcus nonaureus causes most of these infections and is uniformly sensitive to vancomycin. In a prospective study of 416 patients having cardiac operations, randomized by hospital record number, topical vancomycin was applied to the cut sternal edges in 223 patients (group V) and was omitted in the control group (C) of 193 patients. The vancomycin was applied in a hemostatic paste of topical thrombin and powdered absorbable gelatin; in the control group only the hemostatic paste was applied. All patients received prophylactic systemic antibiotics for 2 days. Sternal infection occurred in one patient in group V (0.45%) and in seven patients in group C (3.6%) (p = 0.02). Infection also correlated with longer operative times (p = 0.027). By multivariate testing, vancomycin (p = 0.013) and shorter operative times (p = 0.014) independently predicted reduced infection rates. In the one patient with an infection in group V, Staphylococcus aureus was cultured; this organism was also cultured in two patients in group C, with Staphylococcus nonaureus being the culprit in the other five patients with sternal infections in group C. Topical vancomycin applied to the cut sternal edges reduces the risk of postoperative sternal infection.

Administration, Topical↗

Oral bacitracin vs vancomycin therapy for Clostridium difficile-induced diarrhea. A randomized double-blind trial.

The effectiveness of a ten-day course of either oral bacitracin or oral vancomycin hydrochloride for treatment of Clostridium difficile-induced antibiotic-associated diarrhea was compared in a randomized double-blind study. Bacitracin was as effective as vancomycin in resolving diarrhea; most patients responded within five days of therapy with either drug. Three patients receiving bacitracin worsened during therapy; two of these were considered treatment failures. Neither C difficile nor its toxin was detected in stool samples collected on the final day of therapy in 71% of patients (10/14) receiving vancomycin and in 30% (3/10) receiving bacitracin. Five patients receiving bacitracin and three receiving vancomycin had at least one recurrence. Low but nontoxic concentrations of bacitracin were detected in serum samples collected from 11 patients. Oral bacitracin at this dosage level was as effective as vancomycin in resolving the symptoms of C difficile-induced antibiotic-associated diarrhea in most patients but was less effective in eradicating C difficile and its toxin from patients' stools.

Aged↗

Vancomycin serum levels and toxicity in chronic hemodialysis patients with Staphylococcus aureus bacteremia.

The pharmacokinetics and toxicity of six week courses of vancomycin were assessed prospectively in 12 chronic hemodialysis patients who had 17 episodes of Staphylococcus aureus bacteremia. Patients were treated with 1 gram doses of vancomycin at weekly intervals for six weeks. Peak serum vancomycin concentrations ranged from 5.5-40.0 micrograms/ml and trough concentrations were 1.0-12.0 micrograms/ml at the time of the second dose. No patients demonstrated important drug accumulation at the time of the fifth dose. Pure tone audiometry demonstrated no auditory toxicity. Flushing and pruritus (two patients) were only adverse effects noted. In 16 episodes blood cultures were sterilized within 48 hours of therapy. This investigation demonstrates that in chronic hemodialysis patients with S. aureus bacteremia vancomycin is a safe and microbiologically effective antimicrobial agent. Peak and trough serum concentrations vary widely when 1 gram doses are given at one week intervals, and thus it is recommended that concentrations be measured for each patient, particularly if the minimum bactericidal concentration of vancomycin for the clinical isolate is greater than 1.0 microgram/ml.

Chronic Disease↗

Vancomycin therapy in severe staphylococcal infections.

Vancomycin was developed in the 1950s, when available therapy for severe staphylococcal infections was unsatisfactory. Early clinical experiences with vancomycin indicated a cure rate of 70%. The introduction of beta-lactamase-resistant penicillins and cephalosporins, which have a lower potential for toxicity, resulted in limited use of vancomycin. The current renewal of interest in vancomycin for treatment of severe staphylococcal infections stems primarily from the efficacy of this drug against methicillin-resistant pathogens and its utility in a number of unique clinical situations. In addition, the development of more purified preparations of vancomycin has lowered the frequency of adverse side effects.

Adult↗

[Continuous administration of vancomycin in patients with severe burns].

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.

Adult↗

[Intermittent mini-dose vancomycin intravenous administration and closed continuous irrigation technique applied to mediastinitis caused by MRSA following mitral valve replacement].

Mediastinitis caused by MRSA (Methicillin-Resistant Staphylococcus aureus) remains an intractable infection producing high mortality even in these days of advanced chemotherapy. The authors report a case of mediastinitis due to MRSA complicated with acute renal failure following mitral valve replacement. The patient's mediastinum had been thoroughly cleaned with physiological saline solution with 0.2% povidone iodine, and underwent a chemotherapy regimen of mini-dose vancomycin. The patient made favorable progress and recovered completely. Our patient's progress confirmed that when chemotherapy using vancomycin is administered in a patient whose condition is complicated with acute renal failure, closely monitoring the vancomycin serum concentration is essential. Intermittent mini-dose intravenous administration is sufficient to maintain an effective vancomycin serum concentration. In our case, vancomycin serum concentration measured before and at completion of dialysis revealed no appreciable decline.

Acute Kidney Injury↗

Treatment of shunt-related cerebral ventriculitis due to Corynebacterium jeikeium with vancomycin administered intraventricularly. Case report.

A 52-year-old female with subarachnoid haemorrhage and hydrocephalus was treated with external and later internal drainage. She developed ventriculoperitoneal shunt-related ventriculitis caused by Corynebacterium jeikeium. The infection was unsuccessfully treated with intravenous vancomycin. It was controlled only after shunt removal and administration of intraventricular vancomycin as well as systemic vancomycin, rifampicin and fusidic acid. A review of the literature confirmed our experience that vancomycin given intraventricularly is well tolerated and doses can be individualized by measuring vancomycin levels in cerebrospinal fluid.

Catheterization↗

Vancomycin dosing in haemodialysis patients and Bayesian estimate of individual pharmacokinetic parameters.

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)

Acute Kidney Injury↗

[Effect of antibiotic prophylaxis with vancomycin on methicillin-resistant Staphylococcus aureus infection following liver transplantation].

An epidemic outbreak of Methicillin-resistant Staphylococcus Aureus (MRSA) infections affecting liver transplantation patients was detected in our hospital. In this study we describe the special characteristics of the infections and the results of prophylactic treatment with Vancomycin. Between april 1990 and december 1991, 47 patients with mean age of 54.4 +/- 10 years underwent liver transplantation. The patients were included in two chronological groups: 1) Group I: 20 patients not treated prophylactically with Vancomycin; 2) Group II: 27 consecutive patients treated with Vancomycin. Systematical cultures of body fluids for bacteria and fungi were done in every patient, and were repeated after 24 hours. The cultures were repeated again in case of sepsis. Group I patients had a significantly higher frequency of MRSA infections than group II patients. Furthermore, in patients with MRSA infection, independently of the group, duration of transplantation (p < 0.01), reoperations (p < 0.001) and prophylactic treatment with Vancomycin (p < 0.001) were significative factors. In conclusion, Vancomycin appears to be an elective prophylactic antibiotic in case of high risk of MRSA sepsis after liver transplantation.

Adult↗

[Evaluation of susceptibility of methicillin resistant Staphylococcus aureus strains to vancomycin].

Susceptibility to vancomycin and teicoplanin was studied in the most frequently isolated Staphylococcus species isolated in the State Hospital Clinic Nr 1 in Warsaw in 1994. No strains resistant to vancomycin were found in two Staphylococci most frequently isolated from clinical material: S. aureus and S. epidermidis. Occurrence of this resistance is very rare and is restricted only to coagulase-negative Staphylococci such as S. xylosus, S. capitis, S. lentus and S. cohni. Resistance to teicoplanin was observed more often (1.4% in S. aureus and from 11.8% to 39.3% in 9 species of coagulase-negative Staphylococci). For the majority of methicillin-susceptible clinical strains (80%), the MBC value did not exceed 4.0 mcg/ml of vancomycin while for almost half of the strains in the population of methicillin-resistant strains MBC values ranged from 32.0 to 128 mcg/ml of vancomycin. Moreover, vancomycin-tolerant strains were found eight times more often in the studied MRSA (26.7%) population than in MSSA strains (3.3%).

Anti-Bacterial Agents↗

Validity of Bayesian forecasting programme in therapeutic drug monitoring of vancomycin in a surgical intensive care unit: a prospective evaluation.

The objectives of this study were: (a) to assess the predictive performance of a 2-compartment Bayesian vancomycin forecasting programme in critically ill patients in the surgical intensive care unit, and (b) to show the applicability of the programme, which is based on parameters derived from Western population, in our local Asian population. Twenty critically ill patients were enrolled into the study programme. All patients received multiple-dose vancomycin for infections due to methicillin-resistant staphylococcus aureus (MRSA). The patients dosage regimen were optimised by entering a set of peak and trough vancomycin serum levels into a clinical computer program (MB; USC*PACK PC collection; University of Southern California, USA) by utilising a 2-compartment Bayesian population model. The correlation between observed and predicted serum peak and trough concentrations were evaluated for both the non-fitted and fitted models by linear regression analysis. There was a significant correlation between observed and predicted concentrations using the fitted model (r = 0.97, P < 0.05). There was no significant correlation of these concentrations in the non-fitted model (r = 0.8). This study shows that the Bayesian programme is able to accurately predict future vancomycin concentrations in our local Asian population. It is possible to optimise patients dosage regimens with the knowledge of two concentrations of vancomycin in order to achieve targeted therapeutic goals.

Aged↗

Effects of dialysis membrane on intradialytic vancomycin administration.

STUDY OBJECTIVE: To quantify the influence of hemodialyzers on vancomycin removal when the drug was infused during hemodialysis. DESIGN: Prospective, controlled, crossover study with three arms. SETTING: A university-affiliated medical center. PATIENTS: Eight subjects receiving outpatient hemodialysis. INTERVENTIONS: The three treatment arms were vancomycin 1000 mg infused after dialysis was completed (control), and the same dosages infused during the last hour of hemodialysis with a cellulose triacetate (CT) and a cellulose acetate (CA) hemodialyzer. MEASUREMENTS AND MAIN RESULTS: The areas under the curve from time zero to 44 hours (AUC0-44 hrs) for the three study arms were significantly different (p < 0.05), with the mean vancomycin AUC0-44 hrs being significantly lower when administered during CT and CA dialysis (73.7% and 87.2% of control; p < 0.05 vs control). The mean vancomycin peak concentration achieved during CT dialysis was significantly lower than for the CA and control arms (20.5, 23.9, 27.0 mg/L, respectively). Forty-four-hour postinfusion concentrations were similarly lower. CONCLUSION: Clinicians should recognize that the composition of the hemodialyzer significantly influences vancomycin serum concentrations when the drug is administered during hemodialysis.

Anti-Bacterial Agents↗

[Study of the susceptibility of Staphylococcus sp. and Enterococcus sp. to teicoplanin and vancomycin].

PURPOSE: The study was performed in order to evaluate the susceptibility of Enterococcus and Staphylococcus to teicoplanin and vancomycin. METHODS: 150 Enterococcus strains and 450 Staphylococcus strains (298 Staphylococcus aureus and 152 negative coagulase strains) isolated in three Brazilian hospitals were studied. The MICs were determined using teicoplanin and vancomycin E Test strips. The range of the antimicrobial concentration in each strip went from 256 mcg/mL to 0.016 mcg/mL. Diffusion tests using disks impregnated with 10 mcg of teicoplanin and 30 mcg of vancomycin were also performed. RESULTS: All the 298 Staphylococcus aureus strains were susceptible to the two antimicrobials. Three of the 152 negative coagulase strains presented intermediate susceptibility to teicoplanin (MICs between 8 and 16 mcg/mL). Four of the 150 Enterococcus strains presented intermediate susceptibility to vancomycin but were totally susceptible to teicoplanin. CONCLUSION: According to these results teicoplanin and vancomycin are good therapeutical options in the treatment of staphylococcal and enterococcal infections.

Anti-Bacterial Agents↗

Pharmacokinetics and tissue residues of netilmicin and vancomycin in chickens.

Following a single intravenous injection of 10 mg netilmicin or 30 mg vancomycin/kg b.w. to normal chickens, the tested drugs obeyed a two or three compartments open model, with half-lives of distribution of 0.30 and 0.20 hours, respectively. The elimination half-lives following intravenous injection were 0.41 and 4.85 hours, respectively. Following a single intramuscular injection of 10 mg netilmicin or 30 mg vancomycin/kg b.w. to normal chickens, the serum drug concentrations peaked 2 hours post-injection with half-lives of absorption equal to 0.63 and 0.56 hours, respectively. The mean systemic bioavailability of netilmicin and vancomycin following a single intramuscular administration in normal chickens was 27.29 and 43.61%, respectively. These values indicated a limited and moderate absorption for netilmicin and vancomycin from intramuscular site, respectively. During repeated intramuscular administrations of both antibiotics for five consecutive days in normal chickens, the serum drug concentrations peaked two hours post each dose. The drugs concentrations during multiple dosage regimens were significantly increased in 2nd, 3rd, 4th and 5th days in comparison to the 1st day. Netilmicin and vancomycin persisted in liver and kidney for 96 and 120 hours, respectively, after the last intramuscular administration. The withdrawal time of netilmicin and vancomycin could be considered as five and six days, respectively. The in-vitro protein binding percents of netilmicin and vancomycin were 7.45 and 5.81%, respectively.

Animals↗

[Vancomycin resistant enterococci in Austria].

This study reports pheno- and genotypical analysis of 9 isolates of vancomycin-resistant enterococci (VRE) and 5 vancomycin-sensitive enterococci (VSE) in Austria: 5 E, faecium isolates of 4 patients (the sole patients demonstrating VRE at the University Hospital of Innsbruck in 1994 and 1995), 3 glycopeptide-sensitive isolates collected in Innsbruck in February 1996 for epidemiological analysis, and 6 enterococcus isolates from the University Hospitals of Vienna and Graz. The pheno- and genotypical analyses of all glycopeptide highly resistant E. faecium and E. faecalis isolates indicated the presence of VanA type resistance. One E. casseliflavus strain with intrinsic VanC-1 resistance showed a characteristic constitutive low-level resistance to vancomycin and susceptibility to teicoplanin. Genotyping with macro-restriction analysis demonstrated that 3 VRE isolates of the 5 E. faecium specimens were identical; the same applied to 2 VSE isolates. The two patients with VRE had been cared for at the same time in a surgical ICU and likewise, the two patients with VSE were simultaneously treated at a neurological ICU. The genotyping of E. faecalis strains showed that two strains of the three VRE isolates exhibited identical patterns. Epidemiological investigation did not reveal a mode of transmission for this cluster. Two of the 8 patients with VRE died within 60 days after isolation of the bacteria; the doctors in charge did not consider that the enterococci had been the cause of death. The results of our study indicate that oral vancomycin administration to humans is a primary cause of VRE in Austrian hospitals. In Austria approximately 66 kg vancomycin, 20% of it given orally, are administered to patients per year. Approx. 18-20 tons Avotan (active ingredient Avoparcin-10%)/year were used in Austria; as of April 1, 1997 the use of this animal foodstuff supplement is prohibited by the European Commission.

Administration, Oral↗

[Mechanism of vancomycin resistance in MRSA strain Mu50].

The mechanism of vancomycin resistance in methicillin-resistant Staphylococcus aureus (MRSA) Mu50 was investigated. More than 3 times increase of the incorporation of 14C-GluNAc into the cell wall of Mu50 was observed compared to those of vancomycin-susceptible strains FDA209P, H-1, LR5P1. The amount of cytoplasmic murein-monomer precursor increased more than 3 times in Mu50 compared to those of control strains. There was an increased production of PBP1, PBP2, and PBP2', which were 1.51, 17.2, and 7.06 times greater, respectively, in Mu50 than those in H-1, and 2.38, 4.46, and 1.96 times greater respectively, than those in LR5P1. By transmission electromicrograph, it was shown that the cell wall of Mu50 was twice thicker than that of LR5P1. Increase of tightly-bound vancomycin to the cell wall fraction was observed in Mu50 when compared to those in FDA209P and H-1 strains. From these results, the increase of the vancomycin targets, free D-Ala-D-Ala residues in the cell wall, in number, due to the activated cell wall synthesis, and/or decrease of the cross-linkage of the cell wall was suggested to be the mechanism of vancomycin resistance in the Mu50 strain.

Anti-Bacterial Agents↗