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In vivo efficacy of moxifloxacin monotherapy against clinical isolates of B. fragilis with intermediate susceptibility

Abstract number: P1065

Glenschek-Sieberth M., Merfort K., Obertegger S., Kne[zcaron]evic I., Endermann R.

Objectives: Moxifloxacin (MXF) is the only marketed fluoroquinolone with FDA approval for the monotherapy of complicated intra-abdominal infections. The obligate anaerobic bacterium, Bacteroides fragilis, is implicated in intra-abdominal infections. In this study, the antibacterial efficacy of MXF against clinical isolates of B. fragilis with intermediate susceptibility (4 mg/L) was evaluated using a murine granuloma pouch model. Breakpoints (susceptible leqslant R: less-than-or-eq, slant2 mg/L, intermediate=4 mg/L, resistant geqslant R: gt-or-equal, slanted8 mg/L) for B. fragilis were defined by CLSI.

Methods: Twenty clinical isolates of B. fragilis (MIC=4 mg/L) and B. fragilis ATCC 25285 (MIC=0.5 mg/L) were used. Pouches for the murine granuloma pouch model were created by injecting 5 mL of air and 0.5 mL of 0.1% croton oil in olive oil under the skin of the back. After removing the air (day 3), a bacterial suspension was injected into the pouch (day 5). Infected mice were treated with MXF 100 mg/kg IV, b.i.d. for 2 days. This dose simulates the AUC of the human 400 mg once-daily MXF IV dosage. To compare the efficacy of MXF with piperacillin/tazobactam (PIP/TAZ), three of the strains (the ATCC 25285 strain and two intermediate isolates) were studied in the pouch model. Mice were treated with PIP/TAZ 400 mg/kg IV, b.i.d., a dose that simulates the human PK/PD driver time above MIC of 3.375 g q.i.d. PIP/TAZ IV therapy.

Efficacy was assessed by the reduction in colony forming units (CFUs) in pouch exudates 48 hours post-infection compared with the infection control.

Results: MXF, 100 mg/kg b.i.d., achieved a CFU reduction of >99.9% in 15/20 intermediate susceptible strains, >99% in 3/20 strains and >90% in 1/20 strains. A CFU reduction of <90% only occurred in 1/20 strains.

The comparison of MFX and PIP/TAZ demonstrated similar efficacy against the ATTC strain and the two clinical isolates despite the differences in the breakpoint category (intermediate [MXF] vs susceptible [PIP/TAZ]).

Conclusions: In a murine granuloma pouch model, MXF achieved a CFU reduction of >2 logs against 90% of clinical B. fragilis isolates with intermediate susceptibility (4 mg/L). Furthermore, MXF was as effective as PIP/TAZ against two strains that were intermediate for MXF but susceptible to PIP/TAZ.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Barcelona, Spain
Presentation type:
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