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At least 19 recordsLinked to original sources
PubMed1997

Impact of a vancomycin restriction policy on use and cost of vancomycin and incidence of vancomycin-resistant Enterococcus.

OBJECTIVE: To review the appropriateness of vancomycin therapy, changes in vancomycin use, and the incidence of vancomycin-resistant Enterococcus (VRE) after implementation of a limited restriction policy requiring approval from the Infectious Diseases Approval service to continue vancomycin therapy beyond 72 hours. DESIGN: A prospective chart review was conducted in April 1995. Pharmacy billing data and infection control data were compared before and after policy implementation. SETTING: A 725-bed university teaching institution. PATIENTS: All patients receiving vancomycin during April 1995. MAIN OUTCOME MEASURES: Appropriateness of use was based on the Centers for Disease Control and Prevention (CDC) recommendations for prudent vancomycin use. RESULTS: A total of 333 courses of vancomycin therapy were reviewed. Vancomycin use was appropriate in 219 (66%) courses. Of the 114 courses that did not meet the CDC guidelines, 76 (67%) were for empiric use, 35 (31%) were for prophylactic use, and 3 (3%) were for therapeutic use. Overall, the total number of grams used decreased 9%, grams per 1000 patient-days decreased by 10, and the total number of patients exposed to vancomycin decreased 0.5%. Several services had large decreases in vancomycin use. Vancomycin expenditures decreased by $15788 for the 7-month time period. The incidence of VRE remained unchanged, at 30% of all enterococcal isolates 2 years after policy implementation. CONCLUSIONS: The limited restriction policy was effective in decreasing the total grams of vancomycin used. However, one-third of vancomycin therapy was inappropriate and the incidence of VRE was unchanged. A more stringent restriction policy could potentially increase appropriate use, further decrease the amount of vancomycin used, and decrease the incidence of VRE.

Anti-Bacterial Agents↗
PubMed2001

Solid- and solution-phase synthesis of vancomycin and vancomycin analogues with activity against vancomycin-resistant bacteria.

Vancomycin, the prototypical member of the glycopeptide family of antibiotics, is a clinically used antibiotic employed against a variety of drug-resistant bacterial strains including methicillin-resistant Staphylococcus aureus (MRSA). The recent emergence of vancomycin resistance, viewed as a growing threat to public health, prompted us to initiate a program aimed at restoring the potency of this important antibiotic through chemical manipulation of the vancomycin structure. Herein, we describe the development of synthetic technology based on the design of a novel selenium safety catch linker, application of this technology to a solid-phase semisynthesis of vancomycin, and the solid- and solution-phase synthesis of vancomycin libraries. Biological evaluation of these compound libraries led to the identification of a number of in vitro highly potent antibacterial agents effective against vancomycin-resistant bacteria. In addition to aiding these investigations, the solid-phase chemistry described herein is expected to enhance the power of combinatorial chemistry and facilitate chemical biology and medicinal chemistry studies.

Anti-Bacterial Agents↗
PubMed2025

In vitro and in vivo efficacy of vancomycin against Elizabethkingia species and the impact of increased vancomycin MICs.

UNLABELLED: This study aimed to evaluate the concordance of vancomycin susceptibility testing methods, its in vivo and in vitro efficacy, and the mechanisms underlying elevated MICs in Elizabethkingia spp. Vancomycin susceptibilities of 18 E. anophelis isolates were determined using multiple assays. The efficacy of vancomycin against five clinical isolates and one laboratory-induced mutant with an elevated vancomycin MIC was evaluated using time-kill assays and Galleria mellonella and murine models. Vancomycin MICs (16-32 mg/L) determined by broth microdilution were consistent with agar dilution, Etest, and MBC assay results. All isolates had zone diameters < 17 mm and were, thus, categorized as non-susceptible according to the CLSI criteria for Enterococcus spp. Time-kill assays of five clinical isolates demonstrated that vancomycin at a clinically relevant concentration (4 mg/L) exhibited poor bactericidal activity similar to that of teicoplanin. Vancomycin improved Galleria mellonella survival in a dose-dependent manner, whereas teicoplanin, dalbavancin, oritavancin, and daptomycin were ineffective. Murine models revealed that vancomycin at a human-equivalent dose (25 mg/kg twice daily) prolonged survival in most infections and modestly reduced bacterial load, while teicoplanin remained ineffective. Vancomycin efficacy was significantly reduced in G. mellonella and mice infected with a mutant strain exhibiting an elevated MIC (128 mg/L), which was attributable to spontaneous mutations in pbp4. In conclusion, E. anophelis were consistently non-susceptible to vancomycin as determined by multiple in vitro assays. However, vancomycin demonstrated unique in vivo activity among glycopeptides although this effect was abrogated by spontaneous mutations leading to elevated MICs. IMPORTANCE: Elizabethkingia anophelis is a multidrug-resistant pathogen associated with limited treatment options and high mortality. Most commonly considered agents, including fluoroquinolones, piperacillin/tazobactam, and trimethoprim/sulfamethoxazole, are increasingly compromised by resistance, toxicity, or inconsistent efficacy. Although vancomycin is not routinely used for Gram-negative infections due to limited outer membrane permeability, case reports have suggested potential benefit in Elizabethkingia infections under critical conditions. In this study, we show that E. anophelis isolates are uniformly non-susceptible to vancomycin in vitro and exhibit minimal bactericidal activity. However, vancomycin conferred a modest but statistically significant survival benefit in two independent animal models. Importantly, this effect was lost in strains with vancomycin-induced MIC elevation, and genome analysis identified pbp4 mutations as a potential underlying mechanism. These findings suggest vancomycin may offer therapeutic benefit when no preferred options are available. They support cautious use in selected cases and highlight the need for continued monitoring of susceptibility and resistance development.

Vancomycin↗
PubMed1999

Analysis of vancomycin population susceptibility profiles, killing activity, and postantibiotic effect against vancomycin-intermediate Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus strains with decreased vancomycin susceptibility have been isolated from patients in the United States and Japan. The impact of decreased vancomycin susceptibility on the drug's pharmacodynamic parameters has not been addressed. We studied the activity of vancomycin against three clinical strains of vancomycin intermediate-susceptible Staphylococcus aureus (VISA) under high- and low-inoculum conditions, with stationary- and logarithmic-growth-phase kill curves, and in postantibiotic effect (PAE) experiments. We also investigated the stability of the decreased vancomycin susceptibility by using population susceptibility profiles. The respective vancomycin microdilution MICs and MBCs for VISA strains HIP5836, 14379, and Mu50 were 8 and 8, 8 and 8, and 8 and 16 microg/ml. HIP5836 had the most homogeneous elevation of vancomycin MICs, because the MIC for nearly all bacteria in the inoculum was 8 microg/ml. The population MICs (defined as the lowest vancomycin concentration inhibiting 99. 9% of growth) for the first serial passages of HIP5836, Mu50, and 14379 were 8, 4, and 2 microg/ml, respectively. After 10 passages, they decreased to 4, 2, and 1 microg/ml, respectively. The Mu50 population MIC increased to 12 microg/ml after five serial passages on vancomycin agar. In the low- and high-inoculum kill curves, time to 99.9% killing was significantly (P < 0.05) longer for both Mu50 and HIP5836 than that for 14379 and a control strain. However, colony counts at 24 h were similar to those of the vancomycin-sensitive strain for all VISA strains. The PAE (at 4x MIC) ranged from 1.3 h for 14379 to 2.0 h for HIP5836 and was similar to or greater than the PAE against the vancomycin-sensitive strain. In conclusion, we found that the decreased vancomycin susceptibility increased during persistent exposures to the drug and decreased upon removal of the selective pressure. The decreased vancomycin susceptibility decreased the rate of vancomycin killing, but did not affect the extent of killing or the PAE.

Anti-Bacterial Agents↗
PubMed1973

Synergism of vancomycin-gentamicin and vancomycin-streptomycin against enterococci.

The in vitro activity of vancomycin and combinations of vancomycin-gentamicin and vancomycin-streptomycin against enterococci was investigated. The minimal inhibitory concentration of vancomycin for 99 of 100 enterococcal strains isolated clinically was 3.12 mug or less/ml. When cultures of eight strains were incubated with vancomycin, regardless of the inoculum size (10(6), 10(5), or 10(4)) and concentration of vancomycin (10 or 20 mug/ml), there was no significant reduction in the number of viable enterococci at 6, 24, and 48 h. Gentamicin and streptomycin in concentrations attainable clinically were not effective against enterococci. Vancomycin combined with gentamicin or streptomycin was tested against 41 enterococcal strains. With the combination of vancomycin at 10 mug/ml and gentamicin at 4 mug/ml or vancomycin at 5 mug/ml and gentamicin at 4 mug/ml, synergism was demonstrated against all 41 strains at 6 h. The combination of vancomycin at 10 mug/ml and streptomycin at 10 mug/ml was only synergistic against 25 of 41 strains at 6 h, and only 22 of 41 strains were affected synergistically at 6 h by vancomycin at 5 mug/ml with streptomycin at 10 mug/ml. With few exceptions, the enhanced killing was more pronounced at 24 and 48 h. The combination of vancomycin and gentamicin or vancomycin and streptomycin (where in vitro studies demonstrate synergism) may be a useful alternate therapy in enterococcal endocarditis.

Bacteria↗
PubMed2001

The activity of vancomycin against heterogeneous vancomycin-intermediate methicillin-resistant Staphylococcus aureus explored using an in vitro pharmacokinetic model.

Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) may account for treatment failure with vancomycin and act as a precursor of vancomycin-intermediate or -resistant S. aureus. The activity of vancomycin was assessed against vancomycinsusceptible, hVISA and VISA strains in a dilutional pharmacokinetic model. Over a 48 h period, total bacteria and cells with a vancomycin-intermediate phenotype were quantified. Total counts of hVISA were reduced by vancomycin in a similar way to a vancomycin-susceptible control. The vancomycin-intermediate sub-population was eradicated from the model within one dose interval. Exposure to low vancomycin concentrations did not result in an increase in the proportion of cells which were vancomycin intermediate. Short-term exposure of hVISA to vancomycin at gradient concentrations did not increase the proportion of cells with vancomycin-intermediate phenotype.

Anti-Bacterial Agents↗
PubMed2003

Linezolid, levofloxacin, and vancomycin against vancomycin-tolerant and fluoroquinolone-resistant Streptococcus pneumoniae in an in vitro pharmacodynamic model.

STUDY OBJECTIVE: To compare the pharmacodynamic profiles of linezolid, levofloxacin, and vancomycin against clinical strains of Streptococcus pneumoniae, including vancomycin-tolerant and fluoroquinolone-resistant isolates. DESIGN: In vitro pharmacodynamic model. SETTING: Biosafety level 2, university research laboratory. BACTERIAL STRAINS: Ciprofloxacin-susceptible (79), ciprofloxacin-resistant (R921), and vancomycin-tolerant (P9802-020) clinical strains of S. pneumoniae. INTERVENTION: An in vitro pharmacodynamic model was used to simulate standard dosing regimens of linezolid, levofloxacin, and vancomycin against the isolates 79, R921, and P9802-020. MEASUREMENTS AND MAIN RESULTS: Bacterial density was profiled over 48 hours. Minimum inhibitory concentrations (MICs) for linezolid, levofloxacin, and vancomycin, respectively were 1, 1, 0.5 microg/ml for isolate 79; 1, 4, 0.5 microg/ml for R921; and 0.5, 0.5, 0.5 microg/ml for P9802-020. Vancomycin minimum bactericidal concentration (MBC) values varied across large ranges for the tested strains. Linezolid achieved 99.9% kill against 79 and R921 by 24 and 28 hours, respectively. Levofloxacin achieved 99.9% kill against 79 and P9802-020 by 28 and 4 hours, respectively. Vancomycin achieved 99.9% kill against 79 and R921 by 8 and 24 hours, respectively. Levofloxacin did not demonstrate activity against R921 at the 48-hour end point. Minimal kill (< 2 log) at 48 hours was noted for vancomycin and linezolid against P9802-020. Conclusion. Vancomycin tolerance appeared to be more reliably characterized by persistent viability in time-kill analyses than by MBC:MIC ratios. Vancomycin exhibited bactericidal activity against the non-vancomycin-tolerant strains of S. pneumoniae. Linezolid exhibited both bactericidal and bacteriostatic activity against all three strains tested, whereas levofloxacin demonstrated bactericidal activity against the fluoroquinolone-susceptible isolates. Further investigation of treatment alternatives for infections due to vancomycin-tolerant S. pneumoniae are needed.

Acetamides↗
PubMed2000

Activities of LY333328 and vancomycin administered alone or in combination with gentamicin against three strains of vancomycin-intermediate Staphylococcus aureus in an in vitro pharmacodynamic infection model.

Staphylococcus aureus with intermediate glycopeptide susceptibility (glycopeptide-intermediate S. aureus [GISA]) has been isolated from patients with apparent therapy failures. We studied the killing activity of vancomycin over a range of simulated conventional doses (1 to 1.5 g every 12 h) against three of these GISA strains in an in vitro pharmacodynamic infection model. We also studied the activity of a new glycopeptide (LY333328) at a simulated dose of 3 mg/kg of body weight every 24 h or 5 mg/kg every 24 h, as well as the potential for vancomycin and gentamicin synergy against these GISA strains. Four doses of vancomycin with or without gentamicin or two doses of LY333328 were administered over the 48-h study period. The vancomycin and LY333328 MICs and minimal bactericidal concentrations (MBCs) for the three GISA strains (strains 14379, 992, and Mu50) were 8 and 8 microgram/ml and 1 and 2 microgram/ml, respectively, for GISA 14379, 6 and 6 microgram/ml and 1 and 1 microgram/ml, respectively, for GISA 992, and 8 and 12 microgram/ml and 2 and 8 microgram/ml, respectively, for GISA Mu50. Vancomycin and LY333328 MICs and MBCs were 0.75 and 1.0 microgram/ml and 1 and 1 microgram/ml, respectively for a vancomycin-susceptible comparator strain (methicillin-resistant S. aureus [MRSA] 494). The addition of albumin to the growth medium increased the LY333328 MICs and MBCs approximately 8- to 16-fold. Vancomycin was bacteriostatic against the three GISA strains at doses of 1, 1.125, and 1.25 g every 12 h. Vancomycin was bactericidal at the dose of 1.5 g every 12 h against all strains; bactericidal activity occurred against the GISA strains at 8- to 10-fold lower ratios of the peak concentration to the MIC and the area under the concentration-time curve from time zero to 24 h (AUC(0-24)) to the MIC compared to those for the vancomycin-sensitive control strain. Overall, vancomycin activity was significantly correlated with the AUC(0-24) (R(2) = 0.79; P < 0.001) by multiple stepwise regression analyses. The addition of gentamicin did not significantly affect killing activity against any strain. LY333328 was bactericidal against GISA strains 14379 and 992 and against MRSA 494 only with the 5-mg/kg/day dose simulations. The higher dose of LY333328 also prevented regrowth over the 48-h experiments for all strains tested. Higher doses of vancomycin (1.5 g every 12 h) and LY333328 (5 mg/kg every 24 h) may represent potential treatment options for infections caused by GISA strains.

Anti-Bacterial Agents↗
PubMed1996

Local application of vancomycin for prophylaxis of graft infection: release of vancomycin from antibiotic-bonded Dacron grafts, toxicity in endothelial cell culture, and efficacy against graft infection in an animal model.

Methicillin-resistant strains of Staphylococcus epidermidis cause an increasing number of prosthetic infections. This prompted us to test the uptake of vancomycin in various graft materials in vitro, its influence on graft healing, and its efficacy against graft infection in pigs. Incubation of six different Dacron graft materials in a vancomycin solution (20 gm/L) was performed. Grafts were then placed in plasma, and samples were taken over 72 hours to determine vancomycin levels. Release of vancomycin ranged from 775 micrograms/cm2 to 3691 micrograms/cm2 after 1 hour of incubation. Gelatin-covered grafts increased release of vancomycin fourfold when incubation time was extended to 24 hours: uncovered grafts or the collagen-covered graft did not. Graft healing was not complicated when a vancomycin-bonded, gelatin-impregnated Dacron graft was implanted to replace the common femoral artery in pigs. Four weeks after implantation, histologic examination revealed normal development of neointima and perigraft scar tissue in the vancomycin-treated (n = 4) and untreated (n = 5) grafts. To test the efficacy of local vancomycin against graft infection, grafts were implanted in the groin of pigs and contaminated with 2 x 10(7) colony-forming units of Staphylococcus aureus. Four weeks after implantation, all grafts were infected in the untreated group (n = 6), with abscess, nonincorporated graft, and detection of S. aureus from the graft. In the treatment group (n = 6) vancomycin was added to the contaminated grafts. As a carrier for the vancomycin, we used a resorbable gelatin-glycerol foam. All grafts healed without infection. The difference between the treated and untreated groups is statistically significant (p < 0.05). We conclude that it may be effective to prevent graft infection with local application of vancomycin if an in situ replacement of infected graft (infected by gram-positive bacteria) is necessary or if there is a high risk of infection by methicillin-resistant- staphylococci.

Animals↗
PubMed2003

Topical vancomycin applied on closure of the sternotomy wound does not prevent high levels of systemic vancomycin.

OBJECTIVE: Vancomycin is effective in reducing the risk of mediastinits and topical vancomycin has been hypothesised to give high local dose concentrations while avoiding high systemic levels, thus avoiding the risk of bacterial resistance to this second-line antibiotic. However, this theory has never been tested and the degree to which vancomycin is absorbed systemically is unknown. METHODS: Fourteen patients undergoing elective coronary artery bypass grafts (CABG) received 500mg of topical vancomycin prior to sternotomy closure. Serum samples were taken at 30, 60, 120, 180 and 720min post-operatively. In addition, samples were taken from the drain bottles and urine samples taken daily for 5 days. Vancomycin levels were measured by fluorescence polarisation immunoassay, using the reverse dilution method to give a detection limit of 0.8mg/l. RESULTS: Vancomycin was detected in almost all serum samples. Peak concentration was at 30min and the mean value was 2.96mg/l (range, 0.99-5.00mg/l). This mean fell to 1.32mg/l at 6h. Of the 500mg of vancomycin applied, a mean of only 8.8mg was found to have been lost into the drain bottles in the first 24h (range, 0.17-12.5mg). When 5 consecutive days of urine collection was achieved, a mean of 151mg of vancomycin was excreted (range, 40-195mg) and vancomycin was detectable in the urine till day 5. The mean concentration of vancomycin in the urine was maximal on day 1 and was 24.4mg/l (range, 4.49-44.98mg/l). CONCLUSIONS: Topical vancomycin causes significant systemic concentrations in the 6h post-surgery and can be detected in the urine for up to 5 days post-surgery.

Administration, Topical↗
PubMed1999

Vancomycin use in a university medical center: effect of a vancomycin continuation form.

OBJECTIVE: To examine the impact of a new policy to ensure appropriate use of vancomycin in a 461-bed tertiary-care hospital. DESIGN: We instituted a policy that allowed physicians to prescribe vancomycin but that required them to complete a vancomycin continuation form and document that use conformed to Hospital Infection Control Practices Advisory Committee (HICPAC) guidelines if they wished to continue the drug beyond 72 hours. Vancomycin was stopped automatically at 72 hours if use was not consistent with guidelines, if an infectious diseases consultant did not approve the drug, or if the form was not completed. A pharmacist and infectious diseases specialist monitored use of vancomycin prospectively and interacted with prescribers when indicated. Educational efforts were limited to printing the HICPAC guidelines on the form and providing information about the policy in a newsletter. Patterns of prescribing and the economic impact of the form were evaluated over a 6-month period. RESULTS: Only 29% to 48% of vancomycin orders initially met HICPAC guidelines, but 77% to 96% of use was appropriate after 72 hours when the form was used. Inappropriate surgical prophylaxis, empirical therapy of intensive-care unit and transplant patients, and therapy for inadequately documented coagulase-negative staphylococcal infections remained problems. Vancomycin use fell from a mean of 136 (+/-52) g/1,000 patient days in the 12 months before the form to 78 (+/-22) g/1,000 patient days in the 9 months after institution of the form (P<.05). Net vancomycin acquisition costs and costs of ordering vancomycin serum levels fell by $357 and $19 per 1,000 patient days, respectively (P<.05). This represented annualized saving of approximately $47,000 in drug and monitoring costs. No adverse patient outcomes were seen as a result of the program. CONCLUSIONS: A vancomycin continuation form can decrease inappropriate vancomycin use and may save money. Additional educational efforts may be required to increase compliance with HICPAC guidelines during initial prescribing.

Academic Medical Centers↗
PubMed2025

The toxin-antitoxin system SavRS contributes to vancomycin resistance in vancomycin-intermediate Staphylococcus aureus by mediating cell wall thickening.

BACKGROUND: The emergence of vancomycin-intermediate Staphylococcus aureus (VISA) has significantly challenged the treatment of S. aureus infection. Toxin-antitoxin (TA) systems have been reported to mediate bacterial stress adaptation and virulence, but their role in vancomycin resistance remains elusive. This study investigated the vancomycin resistance mechanism regulated by the TA system SavRS in VISA. METHODS: savRS mutants in Mu50 and XN108 were generated via homologous recombination. To investigate the regulatory mechanism of vancomycin resistance mediated by savRS in VISA, phenotypic analyses including MICs, growth kinetics and cell wall thickness measurements were performed. Expression of cell wall synthesis-related genes was analysed using quantitative RT-PCR (RT-qPCR) and promoter-lacZ reporter assay. Electrophoretic mobility shift assay (EMSA) was performed to assess the binding of SavRS to the promoters of the cell wall synthesis-related genes. Pull-down assay identified an upstream regulatory element of savRS associated with vancomycin resistance. Quantitative assessment of bacterial burden in murine organ systems following vancomycin administration revealed the critical regulatory role of savRS in mediating vancomycin resistance in vivo. RESULTS: Compared with the WT, the savRS mutant exhibited enhanced vancomycin sensitivity, accelerated growth and reduced cell wall thickness. Correspondingly, RT-qPCR revealed marked down-regulation of the cell wall synthesis-related genes (glyS, dltA, scdA, pbp2, ddl). EMSA and promoter-lacZ reporter assay confirmed direct binding of SavRS to a conserved promoter motif, MGHYYTCCTCA. Pull-down assay identified UspA as an upstream regulator of SavRS, demonstrating that UspA directly controls savRS transcription and modulates VISA resistance. Mouse infection experiments showed that savRS promotes VISA to vancomycin resistance in vivo. CONCLUSIONS: SavRS critically regulates vancomycin resistance in VISA.

Cell Wall↗
PubMed2002

The in vitro and in vivo antibacterial characterization of vancomycin and linezolid against vancomycin-susceptible and -resistant enterococci.

The present study was designed to compare in vitro antibacterial activities of linezolid and vancomycin against vancomycin-susceptible Enterococcus faecalis (VSEF) and vancomycin-resistant enterococci (VRE) isolated in Japan with those of quinupristin-dalfopristin, teicoplanin and minocycline, and the in vitro short time bactericidal activity and the in vivo activities of linezolid and vancomycin against vancomycin-susceptible and -resistant E. faecalis. The MIC90s of linezolid, quinupristin-dalfopristin, vancomycin, teicoplanin and minocycline for VSEF and VRE were both 2 mg/L, both 2 mg/L, 2 and >128 mg/L, 0.25 and >128 mg/L, and both 32 mg/L, respectively. The efficacy of linezolid for mice with bacteraemia caused by VSEF was similar to that of vancomycin, but the elimination ratio of viable organisms from the blood of mice treated with vancomycin was significantly higher than in linezolid-treated and untreated mice at 2 h post-administration, and those of the two groups at 4 and 6 h were significantly higher than in untreated mice. Moreover, linezolid was highly active in mice with bacteraemia caused by vancomycin-resistant E. faecalis because this drug had potent in vitro activity against the organisms. Our results indicate that linezolid is suitable for the treatment of VRE and VSEF bacteraemia, and vancomycin is suitable for VSEF bacteraemia.

Acetamides↗
PubMed1991

Influence of low-level resistance to vancomycin on efficacy of teicoplanin and vancomycin for treatment of experimental endocarditis due to Enterococcus faecium.

Emergence of vancomycin-resistant strains among enterococci raises a new clinical challenge. Rabbits with aortic endocarditis were infected with Enterococcus faecium BM4172, a clinical strain resistant to low levels of vancomycin (MIC, 16 micrograms/ml) and susceptible to teicoplanin (MIC, 1 micrograms/ml), and against its susceptible variant E. faecium BM4172S obtained in vitro by insertional mutagenesis (MICs, 2 and 0.5 micrograms/ml, respectively). Control animals retained 8 to 10.5 log10 CFU/g of vegetation. We evaluated in this model the efficacy of vancomycin (30 mg/kg of body weight; mean peak and trough serum levels, 27 and 5 micrograms/ml, respectively), teicoplanin (standard dose, 10 mg/kg; mean peak and trough levels, 23 and 9 micrograms/ml, respectively; and high dose, 20 mg/kg; mean peak and trough levels, 63 and 25 micrograms/ml, respectively), gentamicin (6 mg/kg; mean peak and trough levels, 8.6 and less than 0.1 micrograms/ml, respectively), alone or in combination, given every 12 h intramuscularly for 5 days. Teicoplanin standard dose was as active as vancomycin against both strains. Vancomycin was not effective against E. faecium BM4172 but was highly effective against E. faecium BM4172S (7.5 +/- 1.1 log10 CFU/g of vegetation versus 4.9 +/- 1.0 log10 CFU/g of vegetation for vancomycin against E. faecium BM4172 and E. faecium BM4172S, respectively; P = 0.0012). A high dose of teicoplanin was more effective than vancomycin against E. faecium BM4172 (4.4 +/- 1.8 log10 CFU/g of vegetation versus 7.5 +/- 1.1 log10 CFU/g of vegetation for teicoplanin high dose and vancomycin, respectively; P less than 0.05). Against E. faecium BM4172 glycopeptide-gentamicin combinations were the most effective regimens in vitro and in vivo (2.8 +/- 0.7 and 3.5 +/- 1.3 log10 CFU/g of vegetation for vancomycin plus gentamicin and teicoplanin standard dose plus gentamicin, respectively; P < 0.05 versus single-drug regimens). We concluded that high-dose teicoplanin or the combination of a glycopeptide antibiotic plus gentamicin was effective against experimental infection due to E. faecium with low-level resistance to vancomycin.

Animals↗
PubMed1999

Combinations of vancomycin and beta-lactams are synergistic against staphylococci with reduced susceptibilities to vancomycin.

Evidence of synergism between combinations of vancomycin and beta-lactam antibiotics against 59 isolates of methicillin-resistant staphylococci (Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus haemolyticus) for which vancomycin MICs ranged from 1 to 16 microg/ml were tested by broth microdilution checkerboard, disk diffusion, agar dilution, and time-kill antimicrobial susceptibility tests. The combination of vancomycin and oxacillin demonstrated synergy by all test methods against 30 of 59 isolates; no antagonism was seen. Synergy with vancomycin was also found by modified disk diffusion testing for ceftriaxone, ceftazidime, cefpodoxime, and amoxicillin-clavulanate but not for aztreonam. Evidence of synergy correlated directly with vancomycin MICs. The efficacy of vancomycin given alone and in combination with nafcillin was tested in the rabbit model of experimental endocarditis caused by three clinical isolates of glycopeptide-intermediate-susceptible S. aureus (GISA) (isolates HIP5827, HIP5836, and MU50). Two of the GISA isolates (isolates MU50 and HIP5836) were extremely virulent in this model, with 27 of 42 (64%) animals dying during the 3-day trial. Therapy with either vancomycin or nafcillin given as a single agent was ineffective for animals infected with HIP5827 or MU50. However, the combination of vancomycin and nafcillin resulted in a mean reduction of 4.52 log10 CFU/g of aortic valvular vegetations per g compared to the reduction for controls for animals infected with HIP5827 and a reduction of 4. 15 log10 CFU/g for animals infected with MU50. Renal abscesses caused by HIP5827 were sterilized significantly better with the combination of vancomycin and nafcillin than by either treatment alone. We conclude that the combination of vancomycin and beta-lactams with antistaphylococcal activity is an effective regimen for the treatment of infections with clinical strains of staphylococci which demonstrate reduced susceptibility to glycopeptides.

Animals↗
PubMed2003

Vancomycin treatment failure associated with heterogeneous vancomycin-intermediate Staphylococcus aureus in a patient with endocarditis and in the rabbit model of endocarditis.

Heterogeneous resistance to vancomycin is thought to precede emergence of intermediate susceptibility to vancomycin in Staphylococcus aureus, but the clinical significance of heterogeneous resistance is unknown. Paired S. aureus isolates from a patient with endocarditis who relapsed after vancomycin treatment were tested for heterogeneous resistance to vancomycin. The pretreatment and the relapse clinical isolates (strains SF1 and SF2, respectively) were genotyped by pulsed-field gel electrophoresis. Susceptibility to vancomycin was assessed by the broth dilution method, population analysis, and time-kill studies and in the rabbit model of endocarditis. Strains SF1 and SF2 had similar genotypes, and the vancomycin MICs for the strains were </=2 micro g/ml. SF2 exhibited heterogeneous resistance to vancomycin. Vancomycin eradicated SF1 in the rabbit model of endocarditis, while SF2 persisted at pretreatment levels. Vancomycin treatment failure in this patient with endocarditis was attributable to heterogeneous resistance to vancomycin.

Animals↗
PubMed1995

Vancomycin-dependent Enterococcus faecium isolated from stool following oral vancomycin therapy.

The isolation of clinical strains of enterococci requiring vancomycin for growth has only recently been reported. We describe the isolation of Enterococcus faecium requiring vancomycin for growth from the stool of a patient who had completed oral vancomycin therapy. Growth of the vancomycin-dependent E. faecium was supported by ristocetin and D-alanyl-D-alanine but not by daptomycin, teicoplanin, or D,L-alanine. Spontaneous revertants not requiring vancomycin occurred at a rate of 1 in 10(6). Both the vancomycin-dependent E. faecium and the revertant hybridized with a vanB gene probe and had identical contour-clamped homogeneous electrophoresis patterns. The majority of revertant colonies were resistant to teicoplanin, suggesting constitutive production of the vanB ligase. We believe the vancomycin-dependent E. faecium evolved from a vancomycin-resistant, vancomycin-independent E. faecium in the presence of high concentrations of vancomycin in the intestine.

Aged↗
PubMed1999

The association between antecedent vancomycin treatment and hospital-acquired vancomycin-resistant enterococci: a meta-analysis.

BACKGROUND: The association between vancomycin hydrochloride treatment and vancomycin-resistant enterococci (VRE) has been investigated in numerous studies with variable results. OBJECTIVES: To conduct a meta-analysis to estimate the magnitude of the association between vancomycin treatment and individual risk of VRE and to identify study characteristics that accounted for heterogeneity in study results. METHODS: Studies were identified using MEDLINE with index terms "Enterococcus," "Enterococcus faecalis," or "Enterococcus faecium" and "vancomycin," "drug resistance," "drug resistance, microbial," or "drug resistance, multiple or risk factors." Reports from conferences and reference lists of recent reviews were used. A total of 420 published reports and 98 conference reports were reviewed; 20 studies described in 15 published reports were included in the analysis. We recorded study period, hospital setting, case and control definitions, length of hospital stay, method of adjustment for differences in length of stay, and data on treatment with vancomycin. The odds ratio (OR) of vancomycin treatment provided the measure of association analyzed. A random-effects model was used to estimate the pooled OR. RESULTS: When results from all 20 studies were combined, the pooled OR was 4.5 (95% confidence interval, 3.0-6.9), but the test for heterogeneity was highly significant (P<.001). The 5 studies that used patients with vancomycin-susceptible enterococci as controls found a stronger association (pooled OR, 10.7; 95% confidence interval, 4.8-23.8) than the 15 studies that used controls who had no VRE isolated (pooled OR, 2.7; 95% confidence interval, 2.0-3.8). After restricting the analysis to the latter studies only, no heterogeneity was evident in the unadjusted study results. Patients with VRE had stayed in the hospital much longer than control patients. Studies that adjusted for this difference found only a small and nonsignificant association between vancomycin treatment and VRE (pooled OR, 1.4; 95% confidence interval, 0.74-2.60). We also detected publication bias, favoring report of studies that found a large measure of association. CONCLUSIONS: The reported strong association between vancomycin treatment and hospital-acquired VRE results from the selection of the reference group, confounding by duration of hospitalization, and publication bias. Studies that accounted for these factors found only a small and nonsignificant association.

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