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Bactericidal activity of daptomycin, vancomycin, teicoplanin and linezolid against Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium using human peak free serum drug concentrations.

The bactericidal activities of daptomycin, vancomycin, teicoplanin and linezolid at human peak free serum concentrations (C(max,free)) were determined against Staphylococcus aureus (one methicillin-susceptible and two methicillin-resistant strains), Enterococcus faecalis and Enterococcus faecium (one vancomycin-susceptible and one vancomycin-resistant strain of each). Daptomycin was rapidly bactericidal against 7/7 strains at C(max,free) of 22.0 mg/L (corresponding to 63% protein binding) and against 3/7 strains at 4.8 mg/L (corresponding to 92% protein binding). Vancomycin (18.0 mg/L) was bactericidal against only two strains. Both teicoplanin (4.5 mg/L) and linezolid (10.4 mg/L) were consistently bacteriostatic. Daptomycin is a useful option for the treatment of Gram-positive infections owing to its strong bactericidal activity.

Acetamides↗

Molecular epidemiology of vancomycin-resistant Enterococcus faecium in Argentina.

OBJECTIVE: To characterize the mechanism of glycopeptide resistance and to determine the genetic relatedness among strains by pulsed-field gel electrophoresis (PFGE) in vancomycin-resistant Enterococcus faecium from Argentina. MATERIALS AND METHODS: A total of 189 vancomycin-resistant single-patient isolates of Enterococcus faecium recovered between January 1997 and December 2000 from 30 hospitals in Argentina were studied. Minimum inhibitory concentrations were determined by the agar dilution method and van genes were detected by PCR. PFGE was used for molecular typing. RESULTS: All isolates except three (vanB) were of genotype vanA. For 189 vancomycin-resistant Enterococcus faecium, SmaI-PFGE indicated 35 clonal types. Most of the isolates (56%) belonged to the same clonal type 1, which was present in 19 hospitals and dominant in 17. CONCLUSIONS: The emergence of vancomycin-resistant Enterococcus faecium in Argentina seems to be related to the intra- and inter-hospital dissemination of an epidemic clone carrying the vanA element.

Argentina↗

Regional delivery of vancomycin using pluronic F-127 to inhibit methicillin resistant Staphylococcus aureus (MRSA) growth in chronic otitis media in vitro and in vivo.

For the effective treatment of chronic otitis media caused by methicillin resistant Staphylococcus aureus (MRSA), the local delivery of vancomycin was attempted based on a formulation with pluronic F-127. The phase transition property of pluronic F-127, which is liquid at room temperature and becomes solid at body temperature, enabled convenient injection and reduced the side effects of the potent antibiotic. The temperature responsive polymer-vancomycin matrix system was also shown to effectively deliver vancomycin locally to the infected inner ear, plus the MRSA growth was inhibited by the formulation. The otitis media was completely cured by the sustained local delivery of vancomycin from the matrix in vivo. Accordingly, this system has potential clinical application for treating chronic otitis media with improved patient compliance and better therapeutic efficacy.

Animals↗

Capillary electrophoretic analysis of the antibiotic vancomycin in innovative microparticles and in commercial formulations.

A new fast capillary electrophoretic method has been developed for the analysis of the glycopeptide antibiotic vancomycin in formulations. An electrophoretic run is completed within 3.0 min; fused silica capillaries (100 microm i.d., 8.5 cm effective length and 48.5 cm total length) and a background electrolyte consisting of 12.5 mM, pH 2.5 phosphate buffer are used. The applied voltage is -20.0 kV; samples are injected by pressure (30 mbar x 3 s) at the anodic end of the capillary. The method was successfully applied to innovative controlled release microparticles consisting of a coated albumin core containing vancomycin. A simple procedure has been developed to obtain complete vancomycin extraction from microparticles using a 5% (w/v) sodium dodecyl sulphate aqueous solution. The method has been validated in terms of linearity, precision and accuracy. Good linearity was found in the 0.25-5.00 microg/mL range. Satisfactory precision was obtained, with relative standard deviation values always lower than 3.9%; accuracy was satisfactory, with recovery values between 97.8 and 102.2%. The method is also suitable for vancomycin determination in commercial capsules.

Anti-Bacterial Agents↗

Vancomycin levels in the vitreous cavity after intravenous administration.

PURPOSE: We studied the effects of inflammation, repeated antibiotic doses, and the surgical status of the eye on penetration of vancomycin hydrochloride into the rabbit vitreous cavity after intravenous administration. METHODS: We studied three anatomic states (phakic, aphakic, and aphakic, vitrectomy-treated eyes) subdividing each into inflamed and noninflamed groups. Intravenous vancomycin hydrochloride (15 mg/kg of body weight) was administered every 12 hours for 48 hours. Eyes were harvested for the assay of vitreous cavity antibiotic levels at various intervals from one to 49 hours. We determined concentrations and calculated mean values and S.E.M. RESULTS: Therapeutic levels were not established in the vitreous cavity at any time period in the two phakic groups. At 25 hours, the inflamed aphakic eyes had concentrations of 5.05 +/- 1.9 micrograms/ml and the control noninflamed aphakic eyes 4.5 +/- 1.23 micrograms/ml; slight increases were found by 49 hours. Concentrations tested in the aphakic, vitrectomy-treated eyes at two, 13, 25, and 49 hours demonstrated progressive increases both in the inflamed eyes (5.4 +/- 2.4 micrograms/ml, 9.64 +/- 4.25 micrograms/ml, 9.2 +/- 3.96 micrograms/ml, 10.34 +/- 4.49 micrograms/ml) and noninflamed eyes (3.52 +/- 2.1 micrograms/ml, 5.4 +/- 1.96 micrograms/ml, 6.8 +/- 2.53 micrograms/ml, 8.7 +/- 5.44 micrograms/ml). CONCLUSIONS: Vitreous vancomycin concentrations in aphakic and aphakic, vitrectomy-treated eyes after intravenous administration exceed the minimal inhibitory concentrations for the usual gram-positive pathogens that create endophthalmitis, suggesting a role for intravenous vancomycin in the treatment of bacterial endophthalmitis.

Animals↗

Vancomycin-resistant Enterococcus in liver transplant patients.

BACKGROUND: Vancomycin-resistant Enterococcus (VRE) infection is emerging in the transplant population, and there is no effective antibiotic therapy available. The aims of this retrospective review were to (1) investigate the outcome of and (2) identify common characteristics associated with VRE infection and colonization in orthotopic liver transplant (OLTx) candidates. METHODS: From October 1994 through September 1998, 126 isolates of VRE were identified in 42 of 234 OLTx recipients and 5 OLTx candidates who did not proceed to transplantation. Data were collected by patient chart review or from a computerized hospital database. RESULTS: The 1-year mortality rate with VRE infection was 82%, and with VRE colonization, 7%. This mortality rate contrasts with a 14% 1-year mortality for non-VRE transplant patients (P <0.01, infected patients and colonized patients). Characteristics of VRE colonized and infected patients included recent prior vancomycin (87%), coinfection by other microbial pathogens (74%), recent prior susceptible enterococcal infection (72%), concurrent fungal infection (62%), additional post-OLTx laparotomies (47%), and renal failure (Cr >2.5 mg/dL or need for dialysis; 43%). Biliary complications were seen in 52% of post-OLTx VRE-infected or VRE-colonized patients (versus 22% in non-VRE transplant patients, P <0.05). CONCLUSION: VRE infection is associated with a very high mortality rate after liver transplantation. The incidence of biliary complications prior to VRE isolation is very high in VRE-infected and VRE-colonized patients. The most common characteristics of VRE patients were recent prior vancomycin use, recent prior susceptible enterococcal infection, coinfection with other microbial pathogens, and concurrent fungal infection. With no proven effective antimicrobial therapy for VRE, stringent infection control measures, including strict and limited use of vancomycin, must be practiced.

Adult↗

Determination of vancomycin related substances by gradient high-performance liquid chromatography.

A gradient high-performance liquid chromatographic method for the determination of vancomycin related substances is described. This method was developed to profile vancomycin, co-fermentation products, and degradation products. The resultant chromatograms confirm the multifactored nature of vancomycin, separating a number of peaks from the main component. The development of acceptable chromatographic performance is described, with the final method intended for use as a control assay. Quantitation of total related substances is made by comparing the relative area of the main peak to total peak area in a pair of chromatograms from a stock solution and a twenty-five fold dilution. A rapid-scan UV detector was used to demonstrate the similar spectral characteristics of the vancomycin related substances, confirming the validity of the relative area approach. Statistical method validation data are included, evaluating the use of this method for quantitative applications. Example applications demonstrate the effectiveness of this method.

Chromatography, High Pressure Liquid↗

Chromatographic methods for the analysis of vancomycin.

Four thin-layer chromatographic systems were developed for the separation of vancomycin, related antibiotics and degradation products. Bioautography was suitable for detecting trace amounts of biologically active components. High-performance liquid chromatography was used to examine the composition of vancomycin and other glycopeptide antibiotics and to monitor the stability of vancomycin. Degradation of vancomycin lead to changes in the composition which were not matched by a similar loss of potency.

Chromatography, High Pressure Liquid↗

Antimicrobial efficacy and corneal endothelial toxicity of DexSol corneal storage medium supplemented with vancomycin.

Despite the presence of gentamicin in corneal storage medium, postoperative endophthalmitis may result from the transmission of bacteria via contaminated corneal tissue. The authors evaluated the antimicrobial activity and endothelial toxicity of vancomycin (10 micrograms/ml) in combination with gentamicin (100 micrograms/ml) in DexSol corneal storage medium. When tested against a panel of common ocular pathogens, vancomycin combined with gentamicin proved more effective than gentamicin alone for inhibiting the growth of Streptococcus pneumoniae at 4 degrees C after 1- and 5-day incubation periods. Ultrastructural and morphometric analyses of paired human corneas stored for 5 days in either DexSol supplemented with vancomycin combined with gentamicin or DexSol with gentamicin alone did not show a significant difference in endothelial toxicity between the two groups. These results suggest that vancomycin combined with gentamicin has superior antimicrobial effect and similar corneal toxicity when compared with media supplemented with gentamicin alone.

Bacteria, Aerobic↗

Vancomycin down-regulates lipopolysaccharide-induced tumour necrosis factor alpha (TNF alpha) production and TNF alpha-mRNA accumulation in human blood monocytes.

The cytokines play an important role in the cascade of the pathological events leading to septic shock. The TNF alpha produced by monocytes/macrophages upon stimulation with bacterial fragments may contribute to induction of this cytokine cascade. Moreover, the antibiotics used for antimicrobial therapy may cause the increase of TNF alpha production due to massive bacterial killing and exposure of monocytes/macrophages to bacterial cell constituents. To investigate the effect of Vancomycin on TNF alpha production, an in vitro model of LPS-stimulated monocytes was used. The level of TNF alpha protein or TNF biological activity were tested in the culture supernatants of monocytes with LPS. Vancomycin down-regulated, in dose-dependent manner, the TNF alpha production. Vancomycin also inhibited TNF alpha-mRNA accumulation in LPS-stimulated monocytes, as assessed by fluorescence in situ hybridization (FISH) in cell suspension. The down-regulation of TNF alpha production in LPS-stimulated monocytes may indicate that inhibition of this cytokine release is one of the important therapeutic effects of Vancomycin in sepsis.

Animals↗

Drug-induced linear IgA bullous dermatosis after vancomycin discontinuance in a patient with renal insufficiency.

Linear IgA bullous dermatosis (LABD) is an autoimmune, subepidermal, vesiculobullous disease that has been commonly associated with the use of vancomycin hydrochloride. Lesions typically appear during vancomycin therapy, 24 hours to 15 days after the first dose. A 65-year-old white man with renal insufficiency developed pruritic, tense bullae on the right chest, right medial arm, right flank, abdomen, and right upper thigh 14 days after his last dose of vancomycin. Histopathologic examination and immunofluorescence studies were diagnostic of LABD. Vancomycin-related LABD may appear as long as 2 weeks after the drug is discontinued.

Aged↗

Vancomycin-resistant gram-positive cocci: risk factors for faecal carriage.

This case-control study was undertaken to identify the risk factors for the gastrointestinal carriage of vancomycin-resistant, Gram-positive cocci (VRGPC) including vancomycin-resistant enterococci (VRE). Use of oral vancomycin (P = 0.003) or cephalosporins (P = 0.03) and prolonged duration of stay in the hospital (P = 0.02) were found to be the significant risk factors. Other previously suggested risk factors such as location of the patients and presence of central venous or arterial lines were not significantly associated with carriage of VRGPC. Judicious usage of glycopeptides (particularly oral vancomycin) and cephalosporins is likely to be the most effective way to prevent and control the spread of VRGPC and VRE.

Aged↗

Is single-dose antibiotic prophylaxis sufficient for coronary artery bypass surgery? An analysis of peri- and postoperative serum cefuroxime and vancomycin levels.

Preliminary findings have suggested that a single intravenous dose of antibiotic is effective for infection prophylaxis in cardiac surgery. However there are still insufficient data on this proposed regimen. We measured serum cefuroxime and vancomycin levels after three different dosage regimens, in patients undergoing coronary artery bypass grafting (CABG). Sixty patients were randomized into three cefuroxime and three vancomycin groups with 10 patients in each: a group given a one-day course, or an additional dose during cardiopulmonary bypass or a single dose. Serum levels of the antibiotics were measured at various times throughout the operative procedure and until 48 h after the start of prophylaxis. Each of the six dosage regimens maintained serum levels adequate for infection prophylaxis throughout the operative procedure. Serum levels remained above 2 mg/L for more than 8 h postoperatively, even in the single-dose cefuroxime group and above 4 mg/L for more than 24 h with all the vancomycin dosage regimens. Thus a single dose of cefuroxime (3 g or 1.5 g) or vancomycin (1.5 g) seems to achieve and maintain serum levels sufficient for infection prophylaxis several hours after CABG procedures.

Aged↗

Epidemiology and control of vancomycin-resistant enterococci (VRE) in a renal unit.

This study reports an outbreak of infection and colonization caused by vancomycin-resistant enterococci (VRE) in the renal service of a large teaching hospital. The polymerase chain reaction and pulsed-field gel electrophoresis were used to study the epidemiology of 26/34 strains of vancomycin-resistant Enterococcus faecalis and Enterococcus faecium from the outbreak in comparison with five strains from other hospitals in Edinburgh and the Borders, and three from other wards in the Royal Infirmary. The study revealed a heterogeneous population of vancomycin-resistant E. faecalis. Over 60% of E. faecium isolates had matching pulsed-field gel electrophoresis patterns and all of these were of VanA phenotype. These results suggest that clonal spread of VanA phenotype E. faecium within and possibly between hospitals is the major vancomycin-resistant enterococcal problem in Edinburgh. Screening of patients and isolation of colonized and infected patients appear to have been successful in controlling the spread of VRE.

Anti-Bacterial Agents↗

Isolation and epidemiological study of vancomycin-resistant Enterococcus faecium from patients of a haematological unit in Poland.

Enterococcus faecium has recently emerged as a serious nosocomial pathogen. Vancomycin resistant enterococci (VRE) have been isolated in Europe and the USA since 1988. This is the first report on isolation of vancomycin resistant E. faecium (VREM) strains in Poland, from Haematological Unit patients in the Clinical Hospital in Gdańsk. In total, 6412 samples were examined between December 1996 and October 1997. Five hundred and five isolates of Enterococcus spp. were collected. One hundred and one were classified as Enterococcus faecium of which 49 were resistant to vancomycin (MIC > 256 mg/L) and teicoplanin (MIC > 256 mg/L), characteristic of the VanA phenotype. Twenty-nine patients were infected or colonized. A PCR-based specific diagnostic assay confirmed the phenotype. The multiplex PCR-restriction fragment length polymorphism patterns were consistent with VanA-type of vancomycin-resistant E. faecium for all isolates examined. These isolates were epidemiologically-related as shown by PCR-fingerprinting.

Adult↗

Chemical peritonitis secondary to intraperitoneal vancomycin.

Although previously reported in the literature, the existence of chemical peritonitis due to vancomycin in patients on peritoneal dialysis remains controversial. We report four similar episodes of sterile peritonitis in three patients receiving intraperitoneal (IP) vancomycin. The prior report implicated a change in the brand of vancomycin preparation, from Vancocin to Vancoled, as a contributing factor. We noted the occurrence of such episodes following a switch from Vancocin to a generic preparation from Abbott Laboratories. High-performance liquid chromatographic (HPLC) profiles of the three preparations show Vancocin to have a lower level of impurities than the other two; the presence of certain contaminants in the other brands may be contributing to the clinical difference observed. We conclude that chemical peritonitis due to IP vancomycin administration does occur, and that increased awareness of this entity could allow other cases to be identified.

Adult↗

Vancomycin prevents polytetrafluoroethylene graft infections in pediatric patients receiving chronic hemodialysis.

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

Adolescent↗

Tubulointerstitial nephritis due to vancomycin.

Vancomycin was used to treat a patient with Staphylococcus aureus endocarditis. After 3 weeks of therapy, the patient developed a diffuse maculopapular rash, which resolved upon stopping the drug. Rechallenge with vancomycin several days later resulted in reappearance of the rash and rapid onset of acute anuric renal failure. Renal biopsy revealed acute granulomatous interstitial nephritis. This is the first report of biopsy-proven vancomycin-induced acute interstitial nephritis. Renal function should be monitored closely in patients receiving vancomycin therapy.

Aged↗