Persistence of rRNA operon mutated copies and rapid re-emergence of linezolid resistance in Staphylococcus aureus.

Objectives: The G2576T mutation in domain V of 23S rRNA has been most often associated with the rare cases of linezolid resistance in Staphylococcus aureus. In a linezolid-susceptible S. aureus (A8761B) possessing a single mutated (G2576T) copy, originally derived from a resistant clinical isolate, we assessed the persistence of the mutation on further passage on antibiotic-free medium and the selection of resistance upon re-exposure of the susceptible strain to linezolid.

Induction of daptomycin heterogeneous susceptibility in Staphylococcus aureus by exposure to vancomycin.

We studied vancomycin and daptomycin susceptibility in methicillin-resistant Staphylococcus aureus from patients exposed to vancomycin, glycopeptide-intermediate S. aureus, and S. aureus passaged in vancomycin-containing medium.

In vivo activity of evernimicin (SCH 27899) against methicillin-resistant Staphylococcus aureus in experimental infective endocarditis.

Currently, there exist few satisfactory alternatives to vancomycin for therapy of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. We employed a rat model of aortic valve endocarditis to assess the potential efficacy of evernimicin (SCH 27899) compared with vancomycin against infection with a strain susceptible to both agents (MICs of 0.25 and 0.

In vivo activities of evernimicin (SCH 27899) against vancomycin-susceptible and vancomycin-resistant enterococci in experimental endocarditis.

To assess the potential efficacy of evernimicin (SCH 27899) against serious enterococcal infections, we used a rat model of aortic valve endocarditis established with either a vancomycin-susceptible Enterococcus faecalis or a vancomycin-resistant Enterococcus faecium strain. Animals infected with either one of the test strains were assigned to receive no treatment (controls) or 5-day therapy with one of the following regimens: evernimicin 60-mg/kg of body weight intravenous (i.v.

Activities of taurolidine in vitro and in experimental enterococcal endocarditis.

In vitro, the antimicrobial agent taurolidine inhibited virtually all of the bacteria tested, including vancomycin-resistant enterococci, oxacillin-resistant staphylococci, and Stenotrophomonas maltophilia, at concentrations between 250 and 2,000 microg/ml. Taurolidine was not effective in experimental endocarditis. While it appears unlikely that this antimicrobial would be useful for systemic therapy, its bactericidal activity and the resistance rates found (<10(-9)) are favorable indicators for its possible development for topical use.

Activities of the oxazolidinones linezolid and eperezolid in experimental intra-abdominal abscess due to Enterococcus faecalis or vancomycin-resistant Enterococcus faecium.

The in vivo effectiveness of oxazolidinones eperezolid (U-100592) and linezolid (U-100766) against one strain each of Enterococcus faecalis and vancomycin-resistant Enterococcus faecium was examined in a rat model of intra-abdominal abscess. MICs of both drugs were 2 microg/ml for each strain. At doses of 25 mg/kg of body weight twice daily intravenously or orally, linezolid produced small but statistically significant reductions in abscess bacterial density for E.

A cluster of VanD vancomycin-resistant Enterococcus faecium: molecular characterization and clinical epidemiology.

VanD-mediated glycopeptide resistance has been reported for an isolate of Enterococcus faecium, BM4339. Three clinical isolates of vancomycin-resistant E. faecium collected from 3 patients during a 6-week period in 1993 had agar dilution MICs of vancomycin and teicoplanin of 128 and 4 microg/mL, respectively.

Efficacies of piperacillin-tazobactam and cefepime in rats with experimental intra-abdominal abscesses due to an extended-spectrum beta-lactamase-producing strain of Klebsiella pneumoniae.

The in vivo activities of piperacillin-tazobactam and cefepime were compared with those of ticarcillin-clavulanate, ceftazidime, cefotaxime, and imipenem in a rat model of intra-abdominal abscess with a strain of Klebsiella pneumoniae elaborating an extended-spectrum beta-lactamase (TEM-26). With the exception of ceftazidime, all of the antimicrobial agents significantly reduced bacterial counts within abscesses at the end of therapy compared with those in untreated controls. Residual viable cell counts (mean +/- standard deviation in log10 CFU/gram) were as follows: control, 8.

Activity of fleroxacin alone and in combination with clindamycin or metronidazole in experimental intra-abdominal abscesses.

To assess the potential efficacy of fleroxacin in combination with clindamycin or metronidazole in mixed aerobic and anaerobic infections, we used a rat model of intra-abdominal abscesses in which the inoculum consisted of pooled rat feces mixed with BaSO4. Two hours after bacterial challenge, antimicrobial therapy was begun intravenously with regimens designed to stimulate human pharmacokinetics. A combination of clindamycin and gentamicin was included as an established treatment regimen.

Efficacy of ceftriaxone plus tazobactam in a rat model of intraabdominal abscess due to Bacteroides fragilis.

Using a rat model of intraperitoneal abscess due to Bacteroides fragilis, we evaluated therapy with the combination of ceftriaxone plus the beta-lactamase inhibitor tazobactam in comparison with ceftriaxone or cefotaxime alone. When treatment was begun five hours after bacterial challenge, final bacterial counts within abscesses at 3.5 days of treatment were as follows (mean +/- S.

A gene conferring resistance to vancomycin but not teicoplanin in isolates of Enterococcus faecalis and Enterococcus faecium demonstrates homology with vanB, vanA, and vanC genes of enterococci.

We report the sequence of a 630-bp fragment of a gene associated with resistance to high levels of vancomycin in a clinical isolate of Enterococcus faecalis which retained susceptibility to teicoplanin. This gene was similar to the recently sequenced vanB and partially homologous with vanA, but it showed less-marked similarity to vanC. A DNA probe, derived from this polymerase chain reaction-amplified gene fragment, hybridized specifically with genomic DNA from Enterococcus faecium and E.

Activity of ampicillin-sulbactam and oxacillin in experimental endocarditis caused by beta-lactamase-hyperproducing Staphylococcus aureus.

Using a rat model of aortic valve infective endocarditis, we previously found that oxacillin was equally effective against an oxacillin-susceptible strain of Staphylococcus aureus and a beta-lactamase-hyperproducing borderline oxacillin-susceptible strain of S. aureus; also, ampicillin-sulbactam was less effective than oxacillin against both isolates and at low doses was less effective against the borderline-susceptible strain than against the fully oxacillin-susceptible strain (C. Thauvin-Eliopoulos, L.

Contribution of animal models in the search for effective therapy for endocarditis due to enterococci with high-level resistance to gentamicin.

Earlier studies suggest that ampicillin and amoxicillin are more effective than other beta-lactam agents in killing enterococci, although beta-lactam agents are slowly and incompletely bactericidal against most strains of Enterococcus faecalis. We previously showed that continuous infusion of ampicillin is more effective than intermittent administration in decreasing the number of enterococci in valvular vegetations of rats with catheter-induced endocarditis that are treated for 5 days. In this model, we found ampicillin plus sulbactam more effective than ampicillin alone against a beta-lactamase-producing enterococcal strain with high-level resistance to gentamicin.

Failure of trimethoprim-sulfamethoxazole therapy in experimental enterococcal endocarditis.

To assess the potential efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) against serious enterococcal infections, we used a rat enterococcal endocarditis model comparing TMP-SMX therapy (500 mg of TMP plus 2,500 mg of SMX per kg of body weight per day given every 8 h by intragastric gavage) with intravenous ampicillin therapy (1,000 mg/kg per day). Despite concentrations of active drug in serum well in excess of the MIC and MBC, the mean residual vegetation bacterial titer in TMP-SMX-treated rats was similar to that in untreated controls (8.4 +/- 1.

Efficacy of oxacillin and ampicillin-sulbactam combination in experimental endocarditis caused by beta-lactamase-hyperproducing Staphylococcus aureus.

Optimal therapy of infections caused by borderline oxacillin-susceptible, beta-lactamase-hyperproducing Staphylococcus aureus has not been established. We used a rat model of aortic valve endocarditis to examine efficacies of antibiotic regimens against a borderline oxacillin-susceptible strain as compared with a fully susceptible S. aureus strain.

Efficacy of teicoplanin in two dosage regimens for experimental endocarditis caused by a beta-lactamase-producing strain of Enterococcus faecalis with high-level resistance to gentamicin.

Optimal therapy for the treatment of infections caused by strains of enterococci demonstrating high-level resistance to gentamicin and other aminoglycosides has not been established. The present study examined the efficacy of teicoplanin, a glycopeptide antibiotic active against gram-positive bacterial infections in various animal models, in the treatment of experimental endocarditis due to a beta-lactamase-producing strain of Enterococcus faecalis with high-level resistance to gentamicin. Vancomycin was used as a comparative antibiotic.

Treatment of experimental Escherichia coli pyelonephritis in rat by ciprofloxacin in comparison with tobramycin.

The ciprofloxacin efficacy was compared to that of tobramycin in an Escherichia coli pyelonephritis model in rat. Treatments started 48 h after ligation of the left ureter and inoculation of the bladder and continued for 5 days. Ciprofloxacin (2.