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PubMed2002

Preliminary analysis of the genetic basis for vancomycin resistance in Staphylococcus aureus strain Mu50.

Glycopeptides, such as vancomycin, are frequently the antibiotics of choice for treatment of infections caused by the now common methicillin-resistant Staphylococcus aureus (MRSA). Incidences of vancomycin resistance in S. aureus (VRSA) have been increasing worldwide for the last 5 years. Complex mechanisms producing changes in cell wall content and composition generate the VRSA phenotype, but the genetic basis of these changes has not yet been determined. To facilitate the genetic investigation, entire genome sequences of the archetypal VRSA (Mu50), and vancomycin-susceptible MRSA strains N315, EMRSA 16 and COL were compared. The in silico analysis revealed several loss-of-function mutations in Mu50, affecting important cell wall biosynthesis and intermediary metabolism genes, not previously reported. The new findings provide further evidence for the hypothesis that vancomycin resistance in Mu50 is due to fundamental changes, important to metabolic pathways that impinge on peptidoglycan biosynthesis. These observations will inform targeted experiments aimed at a complete understanding of the mechanism(s) of vancomycin resistance in S. aureus Mu50 and other VRSA strains.

Humans↗

PubMed1997

Risk factors for adverse cutaneous reactions associated with intravenous vancomycin.

We retrospectively studied adverse cutaneous reactions associated with intravenous vancomycin therapy over a 14-month period when two different brands of vancomycin were used. Of 224 adults, 12 (5.4%) had infusion-related reactions; ten of 174 patients who received more than one day of vancomycin (5.7%) had delayed cutaneous reactions. Age less than 40 years was a risk factor for both infusion-related and delayed reactions by both univariate and multivariate analysis. Duration of therapy greater than 7 days was a risk factor for delayed reactions. There was a significant increase in adverse cutaneous reactions associated with the use of a particular batch of vancomycin, although analytical testing of this batch failed to identify any difference from other batches associated with routine rates of adverse reactions. Awareness of vancomycin-associated infusion-related and delayed cutaneous reactions is necessary, and the risk factors associated with these reactions may have important clinical implications.

Adolescent↗

PubMedDate not supplied

Treatment of bacterial endocarditis with vancomycin.

Five patients with bacterial endocarditis who were allergic to penicillin were treated successfully with vancomycin. The causative microorganisms were Streptococcus bovis, S faecalis, S agalactiae, S intermedius, and Staphylococcus aureus. Except for the strain of S faecalis, vancomycin was bactericidal against these organisms at easily achievable serum concentrations. To insure a bactericidal serum titer of 1:8 or greater, streptomycin was added in the therapy of the case caused by S faecalis. There was no toxicity from vancomycin therapy in our patients except for mild phlebitis at the infusion site. Vancomycin appears to be an effective alternative to penicillin in individuals with endocarditis due to susceptible organisms. Vancomycin in combination with an aminoglycoside may be appropriate therapy for enterococcal endocarditis.

Adult↗

PubMed1987

Prolonged vancomycin-associated neutropenia in a chronic hemodialysis patient.

A chronic hemodialysis patient developed severe marrow granulocytic hypoplasia and peripheral blood neutropenia related to vancomycin therapy for an infected arteriovenous fistula. Neutropenia was prolonged and associated with sustained serum levels of vancomycin that persisted for more than 4 weeks following the last dose of vancomycin. No vancomycin-dependent leukoagglutinins were demonstrable in the patient's serum. Although a direct toxic effect on marrow granulocyte production seems likely, a vancomycin-dependent immune suppression of granulopoiesis cannot be ruled out.

Adult↗

PubMed2004

Approaches to vancomycin-resistant enterococci.

PURPOSE OF REVIEW: This article reviews recent publications regarding new antimicrobial drugs for the treatment of vancomycin-resistant enterococci. RECENT FINDINGS: Newer drugs against vancomycin-resistant enterococci are now available or will soon be available. Quinupristin-dalfopristin, a streptogramin, and linezolid, an oxazolidinone, are effective and safe but only bacteriostatic against enterococi. Bacterial isolates resistant to either antibiotic have been described. Daptomycin, a lipopeptide antimicrobial, has good in-vitro bactericidal activity against enterococci, but very limited clinical data exist regarding the treatment of serious enterococcal infection with this compound. Ramoplanin, the first glycolipodepsipeptide antimicrobial in clinical trials, is not systemically absorbed after oral administration, and is being evaluated for the prevention of bloodstream infection in patients colonized with vancomycin-resistant enterococci. Oritavancin and dalbavancin (both glycopeptides) and tigecycline (a monocycline derivative) are being evaluated in phase II and III trials and are not yet commercially available. SUMMARY: Treatment of vancomycin-resistant enterococci continues to be problematical although these new drugs offer some hope. The rational use of antibiotics, strict guidelines for the use of new compounds, and adherence to infection control practices continue to be essential components of the management of vancomycin-resistant enterococci colonization and infection.

Anti-Bacterial Agents↗

PubMed1988

Ceftazidime with or without vancomycin vs. cephalothin, carbenicillin and gentamicin as the initial therapy of the febrile neutropenic pediatric cancer patient.

In a 28-month randomized trial we compared ceftazidime (CAZ), an extended spectrum cephalosporin, with cephalothin, carbenicillin and gentamicin (KCG) as empiric therapy for febrile neutropenic pediatric cancer patients. Because of the occurrence of ceftazidime-resistant Gram-positive primary infections, vancomycin was added to CAZ after the first year of study. Of 206 evaluable episodes 76 (37%) were documented infections including 20 bacteremias; 130 (63%) episodes were caused by fever of unknown origin. The number of complete responses to initial therapy in patients with documented infections did not differ among regimens: 26 of 43 (61%) for KCG, 9 of 16 (56%) for ceftazidime and 8 of 16 (50%) for CAZ + vancomycin (not significant). In patients with fever of unknown origin, response without modification of the initial regimen was 52 of 62 (84%) in the KCG arm, 32 of 40 (80%) on CAZ and 23 of 29 (80%) in patients treated with CAZ + vancomycin (not significant). Modifications of the regimen were similar among all three groups and were due primarily to the use of empiric antifungal or antiviral therapy and to empiric treatment of interstitial pneumonia. Hypokalemia occurred in 25 of 105 patients treated with KCG and in 4 of 101 treated with CAZ or CAZ + vancomycin (P less than 0.001). No differences between the efficacy of KCG, CAZ and CAZ + vancomycin as initial empiric therapy were demonstrated.

Agranulocytosis↗

PubMed1990

Pharmacokinetics of intravenous vancomycin in patients with end-stage renal failure.

The pharmacokinetics of a 500-mg dose of i.v. vancomycin were studied in six Chinese patients with end-stage renal failure. Serum vancomycin concentrations were determined by high-performance liquid chromatography. Observed peak and trough (at 168 h postinfusion) concentrations were in the range of 14.2-35.0 micrograms/ml and 2.8-5.5 micrograms/ml, respectively. The data were analyzed using the PCNONLIN. In all six patients, the data could be fitted well by both the biexponential and triexponential models, but in three patients the latter model provided a better fit. Two-compartment pharmacokinetic parameters obtained from the six patients were t 1/2 alpha 1.13 +/- 0.25 h (mean +/- SEM), t 1/2 beta 121.3 +/- 8.2 h, Vc 0.45 +/- 0.09 L/kg, Vss 1.00 +/- 0.12 L/kg, ClT 5.90 +/- 0.69 ml/kg/h, and the calculated Cmax 25.0 +/- 6.1 micrograms/ml. The mean vancomycin serum protein binding was 18.5 +/- 12.0% as compared with a mean of 46.0% in pooled serum from normal controls. Hemodialysis had no significant effect on vancomycin protein binding or clearance. On the basis of our kinetic study, 500 mg of vancomycin given every seven days is probably adequate treatment for methicillin resistant Staphylococcus aureus infection in end-stage renal failure patients, but further clinical studies are necessary to confirm this.

Aged↗

PubMed1990

Measurement of vancomycin in renally impaired patient samples using a new high-performance liquid chromatography method with vitamin B12 internal standard: comparison of high-performance liquid chromatography, emit, and fluorescence polarization immunoassay methods.

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

Chromatography, High Pressure Liquid↗

PubMed1995

Bayesian forecasting of serum vancomycin concentrations in neonates and infants.

A dynamic pharmacokinetic model for i.v. vancomycin administration was developed and tested in 47 neonates and infants. Twenty-nine patients (Group 1), having two or more concentrations, were used to estimate population parameters by nonlinear least-squares analysis. Multiple stepwise linear regression techniques showed that estimated creatinine clearance, Clcr, and postnatal age were significant demographic factors related to vancomycin clearance (CL). No strong associations were found for the apparent volume of distribution. A one-compartment model was constructed using the associations of CLcr and postnatal age with vancomycin CL. Eighteen patients (Group 2), receiving 35 courses of vancomycin therapy, with both initial and subsequent sets of peak and trough concentrations, were used to test the predictive performance of the model with and without the use of Bayesian forecasting. Using only population-based parameters, the respective mean error (ME) (bias) and mean absolute error (MAE) (precision) for predicting subsequent peak concentrations were -1.20 and 3.89 mg/L and for trough concentrations, 0.83 and 2.23 mg/L, respectively. For the Bayesian method, these values were, respectively, 0.45 and 4.13 mg/L for peak concentrations and 1.55 and 2.40 mg/L for trough concentrations. When predicted concentrations occurred within 30 days of feedback concentrations, the Bayesian method tended to be slightly less biased and more precise than the population-based parameters. The opposite was true > 30 days of the initial set of feedback concentrations. The use of population-specific pharmacokinetic parameters and Bayesian forecasting should allow accurate dosage regimen design as well as minimize the need for monitoring serum vancomycin concentrations in neonates and young infants.

Bayes Theorem↗

PubMed1998

New modified fluorescence polarization immunoassay does not falsely elevate vancomycin concentrations in patients with end-stage renal disease.

Recent literature has urged caution in the interpretation of vancomycin serum concentrations in patients with end-stage renal disease (ESRD), because falsely elevated levels in excess of 70% have been reported with the most commonly used fluorescence polarization immunoassay (FPIA). The purpose of this study was to evaluate the performance of a recently modified FPIA assay for use in patients with ESRD, in comparison to high-performance liquid chromatography (HPLC) and an enzyme-mediated immunoassay technique (EMIT). Serum vancomycin samples were prospectively collected from adults with ESRD undergoing chronic hemodialysis. Each sample was stored at -70 degrees C until analyzed in duplicate by FPIA, EMIT, and HPLC. In an in vitro experiment, blank serum samples with 15 microg/ml vancomycin were spiked with increasing amounts of CDP and analyzed in duplicate with the modified FPIA assay. When compared to HPLC, no statistically significant difference was found in patients with ESRD with the use of the modified FPIA assay (mean concentrations, HPLC 14.92 microg/ml, FPIA 15.96 microg/ml), with FPIA exhibiting a positive bias of 0.64 microg/ml and a precision of +/-3.49 microg/ml (n = 18, p = 0.44). The mean EMIT concentration was 18.34 microg/ml, with a positive bias of 3.43 microg/ml and a precision of +/-5.17 microg/ml (p < 0.01). The addition of increasing amounts of CDP to vancomycin in vitro resulted in concentrations similar to those expected in the absence of significant cross-reactivity with the modified FPIA assay. The modified FPIA assay is a satisfactory tool for monitoring vancomycin serum concentrations in patients with ESRD undergoing hemodialysis. Results obtained with EMIT were not as precise as with FPIA.

Adolescent↗

PubMed2004

Linezolid for treatment of ventilator-associated pneumonia: a cost-effective alternative to vancomycin.

OBJECTIVES: To determine the incremental cost-effectiveness of linezolid compared with vancomycin for treatment of ventilator-associated pneumonia due to Staphylococcus aureus. DESIGN: Decision model analysis of the cost and efficacy of linezolid vs. vancomycin for treatment of ventilator-associated pneumonia. The primary outcome was the incremental cost-effectiveness of linezolid in terms of cost per added quality-adjusted life-year gained. Other outcomes were the marginal costs per hospital survivor and per year of life saved generated by using linezolid. Model estimates were derived from prospective trials of linezolid for ventilator-associated pneumonia and from other studies describing the costs and outcomes for ventilator-associated pneumonia. SETTING AND PATIENTS: Hypothetical cohort of 1,000 patients diagnosed with ventilator-associated pneumonia. INTERVENTIONS: In the model, patients received either linezolid or vancomycin. MEASUREMENTS AND MAIN RESULTS: The incremental cost-effectiveness of linezolid was calculated as the additional quality-adjusted life-years resulting from therapy with linezolid divided by the sum of the incremental costs arising because of use of linezolid (e.g., higher direct costs for linezolid, costs per in-hospital care of survivors, and posthospitalization costs). Despite its higher cost, linezolid was cost-effective for treatment of ventilator-associated pneumonia. The cost per quality-adjusted life-year equals approximately 30,000 dollars. The model was moderately sensitive to the estimated efficacy of linezolid over vancomycin. Nonetheless, even with all inputs simultaneously skewed against, linezolid remains a cost-effective option (cost per quality-adjusted life-year approximately 100,000 dollars). Based on Monte Carlo simulation, the results of our analysis are robust across a range of model inputs and assumptions (95% confidence interval for cost per quality-adjusted life-year ranges from 23,637 dollars to 42,785 dollars). CONCLUSIONS: Linezolid is a cost-effective alternative to vancomycin for the treatment of ventilator-associated pneumonia.

Acetamides↗

PubMed2005

Ocular hypersensitivitiy to topical vancomycin in a case of chronic endophthalmitis.

PURPOSE: To report a case of ocular allergy to topical vancomycin eye drops. METHODS: Interventional case report. RESULTS: A 76-year-old man presented with progressive itching, soreness, and burning sensations, photophobia, and tearing in his left eye 3 days after completing 2 weeks of treatment with 5% vancomycin eye drops. He had been suffering for the previous 2 years from chronic recurrent endophthalmitis and secondary glaucoma associated with cataract surgery in his left eye. He denied any history of drug or food allergy. Examination by slit-lamp microscope showed left periorbital skin erosive rash, marked hyperemia of conjunctiva, central epithelial defect, corneal stromal edema, and Descemet membrane striae. Vancomycin skin tests were positive. The patient's symptoms resolved after discontinuing vancomycin eye drops and responded well to systemic corticosteroids, antihistamines, and topical corticosteroid treatments. Teicoplanin treated his endophthalmitis successfully. CONCLUSION: A case of hypersensitivity to topical vancamycin was reported. Patients who receive topical vancomycin should be informed of this possible adverse effect and instructed to contact their ophthalmologists if allergic reactions occur.

Administration, Topical↗

PubMedDate not supplied

Prolonged stability of stored vancomycin, gentamicin, and heparin for use in the antibiotic-lock technique.

The antibiotic-lock technique has been effective in salvaging tunneled catheters in hemodialysis patients with bacteremia. However, a practical concern exists with respect to the stability of the antibiotics and heparin in normal saline, when stored for a prolonged period. Vancomycin, gentamicin, and heparin were diluted in normal saline to a final concentration of 100 microg/ml of each antibiotic and 5000 units/ml heparin. Fresh samples, and samples refrigerated at 4 degrees C for 48 hours, 1 week, 2 weeks, 3 weeks, and 4 weeks, were assayed (in triplicate) for gentamicin and vancomycin concentration and bactericidal activity (Schlichter test) using methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. An anti-Xa activity assay was used for monitoring heparin anticoagulant activity of the fresh samples and samples refrigerated for 2 and 4 weeks. Mean (+/- SD) anti-Xa activity for heparin/vancomycin solution was 7900 +/- 173 u/ml, and for heparin/gentamicin solution was 7467 +/- 751u/ml; both were stable over a 4-week storage period. Mean bactericidal titer for vancomycin was 1:121 +/- 11, and for gentamicin was 1:242 +/- 22; both were stable over a 4-week storage period. Mean vancomycin concentration was 97 +/- 4 microg/ml, and gentamicin concentration was 86 +/- 3 microg/ml; both were stable over a 4-week storage period. Vancomycin and gentamicin in a heparin/saline solution can be stored at 4 degrees C for up to 4 weeks without adversely affecting antibiotic concentration, bactericidal activity, or heparin anticoagulant activity.

Anti-Bacterial Agents↗

PubMed2004

Vancomycin-induced linear IgA disease manifesting as bullous erythema multiforme.

BACKGROUND: Vancomycin-induced linear immunoglobulin A (IgA) disease, an autoimmune, blistering disease in response to vancomycin administration, is characterized by a subepidermal, vesiculobullous eruption and linear IgA deposition along the basement membrane zone on direct immunofluorescence. CASE REPORT: We report the case of an 81-year-old man treated with vancomycin who developed diffuse erythema multiforme and tense bullae involving the palmoplantar surfaces. Discontinuation of vancomycin therapy resulted in complete resolution of this patient's cutaneous eruption. RESULTS: Biopsy of a representative skin lesion demonstrated lichenoid interface dermatitis with focal subepidermal clefting, dyskeratosis, and prominent eosinophils. Direct immunofluorescence showed linear basement membrane staining with immunoreactants to IgA; indirect immunofluorescence demonstrated the presence of circulating IgG antibodies binding in an intercellular pattern. Immunoprecipitation studies using the patient's serum revealed 210, 130, and 83 kDa target antigens. CONCLUSIONS: Presenting with an initial clinical picture suggestive of bullous erythema multiforme, this patient's subsequent clinical course and direct immunofluorescence confirm the diagnosis of linear IgA bullous disease (LABD). His indirect immunofluorescence findings and immunoprecipitation results suggest that circulating non-IgA antibodies may represent a newly recognized immunopathologic feature of vancomycin-induced linear IgA disease, underscoring the variable and unpredictable manifestations of this drug-induced cutaneous disease.

Aged↗

PubMed1995

Teicoplanin or vancomycin in the treatment of gram-positive infections?

The glycopeptide antibiotics vancomycin and teicoplanin have similar mechanisms of action on bacterial cell wall synthesis. Their spectra of activity are limited to Gram-positive bacteria, with the degree of bactericidal activity depending on the species of micro-organism. Staphylococcus aureus, Staphylococcus epidermis, enterococci and Clostridium difficile are generally sensitive, including methicillin-resistant strains of S. aureus and S. epidermidis. Glycopeptide resistance has recently emerged in staphylococci and enterococci. Vancomycin has a shorter half-life than teicoplanin and requires multiple dosing to maintain adequate serum levels. It can only be given by prolonged intravenous infusion over 1 h. In contrast, the pharmacokinetics of teicoplanin allow for once-daily dosing, either by rapid intravenous infusion or by the intramuscular route. The latter offers reliable absorption for patients with limited venous access and is also of benefit for out-patient therapy. Teicoplanin is a safer drug than vancomycin. It is associated with a lower incidence of nephrotoxicity or ototoxicity. Compared to vancomycin, the availability of the intramuscular route and the absence of a requirement for routine serum monitoring, together with the reduced need to treat drug-related side-effects make teicoplanin more cost-effective. It is as effective as vancomycin for most indications, is safe, easy to administer and an important agent for treating Gram-positive infections. Its role in hospitals is likely to increase if the price of drug acquisition is kept low.

Cell Wall↗

PubMed1992

Chrononephrotoxicity in rat of a vancomycin and gentamicin combination.

The effect of time of administration on excretion of two brush border enzymes--alanine aminopeptidase (AAP) and gamma-glutamyl transferase (gamma GT), and a lysosomal enzyme, N-acetyl-beta-D-glucosaminidase (NAG) with a single high dose of vancomycin, gentamicin or a combination of vancomycin and gentamicin was studied in male Wistar rats and compared with elimination of a control group. The rats received vancomycin intraperitoneally (200 mg.kg-1), gentamicin intramuscularly (100 mg.kg-1) or the combination of the drugs by the same route. A control group received isotonic NaCl solution. The four groups of animals received a single injection at 8 a.m., 2 p.m., 8 p.m., and 2 a.m. and urine excretion values for AAP, gamma GT and NAG were determined 24 hr later. The results show that the nephrotoxicity of gentamicin + vancomycin is greater than that observed with gentamicin, which again is greater than that observed with vancomycin. Furthermore, circadian variations in renal toxicity were observed, the least occurring at 8 a.m.

Acetylglucosaminidase↗

PubMed1996

Influence of biochemical parameters of liver function on vancomycin pharmacokinetics.

The influence of biochemical parameters of hepatic function on vancomycin pharmacokinetics was retrospectively evaluated in 76 adult patients (age 18 to 81 years), from biochemistry data gathered during routine therapeutic drug monitoring. All subjects had normal serum creatinine levels. Vancomycin concentrations were determined by fluorescence polarization immunoassay in 101 paired serum samples. All data for vancomycin concentration versus time were fitted to a one-compartment model using the bayesian approach. Bilirubin, transaminases (n = 101), gamma-glutamyl transferase (n = 97), alkaline phosphatase (n = 95), albumin (n = 92) and lactate dehydrogenase (n = 42) were determined. No strong correlation was seen between any of the pharmacokinetic and biochemistry parameters studied. In patients with hyperbilirubinaemia, the mean Vss and t1/2 were increased (Vss: 0.75 +/- 0.31 versus 0.92 +/- 0.42 1.kg-1, p = 0.020; t1/2 5.93 +/- 3.30 versus 7.48 +/- 4.44 hr, p = 0.049). When liver function was evaluated according to hepatic profile (normal, mildly altered and severely altered), no significant differences were observed in vancomycin pharmacokinetics among the groups. In conclusion, vancomycin pharmacokinetics are only weakly influenced by the biochemistry parameters of liver function.

Adolescent↗

PubMed1994

Impact of the agar medium and disc type on disc diffusion susceptibility testing against teicoplanin and vancomycin.

Susceptibility to teicoplanin and vancomycin was assessed by three disc types: two commercially available discs (NeoSensitabs and PDM disc (30 micrograms)) and one locally prepared 30 micrograms disc (SS disc) on four different medium types: Mueller-Hinton agar (MH medium), MH medium and PDM agar II supplemented with 5% horse blood (HMB medium and PDM medium, respectively), and Danish blood agar (DBA medium). Two previously studied groups of Gram-positive bacteria were tested: group B (N = 75) comprised miscellaneous cocci, and group C (N = 59) mostly rods. With NeoSensitabs, mean zone diameters were larger than with PDM and SS discs on all medium types, and mean zone diameters were larger on DBA medium than on MHB and PDM medium with all disc types. The impact of the medium type on the zone diameter was evaluated for 121 strains growing on MHB medium, PDM medium, and DBA medium. Bacterial groups B and C each divided into three MIC groups were analysed separately. We compared mean zone diameters for each specific group with the average zone diameter, i.e. the mean value for all zone diameters obtained. The smallest deviations from the average zone diameters were observed on PDM medium for both teicoplanin and vancomycin. Thirty-seven percent of strains failed to grow on MH medium, but supplementation of MH medium with horse blood significantly reduced the zone diameter for group B strains both for teicoplanin and vancomycin. Poor predictability of MIC from the zone diameter was found especially for strains with MICs < or = 1 microgram/ml. The medium type hardly affected the results of regression analysis. In contrast, the medium type markedly affected the results of error-rate bounded analysis. No errors were recorded with the SS disc on MHB medium for either teicoplanin or vancomycin, but no strains with MICs of vancomycin within the intermediate group could be correctly classified on DBA medium.

Agar↗