Pharmacodynamics of moxifloxacin against anaerobes studied in an in vitro pharmacokinetic model

Abstract

The antibacterial effects of moxifloxacin against Bacteroides fragilis, Clostridium perfringens, and gram-positive anaerobic cocci (GPAC) were studied in an in vitro pharmacokinetic model. Initially, a dose-ranging study with area under the concentration-time curve (AUC)/MIC ratios of 6.7 to 890 was used to investigate the effect of anaerobic conditions on the AUC/MIC antibacterial effect (ABE) relationship with Escherichia coli. The AUC/MIC ratios for 50% and 90% effects, using a log CFU drop at 24 h as the antibacterial effect measure, were 34 and 59, respectively, aerobic and 54 and 96, respectively, anaerobic. These values are not significantly different. Dose ranging at AUC/MIC ratios of 9 to 216 against the anaerobes indicated a differing AUC/MIC ABE pattern, and the AUC/MICs for 50% and 90% effects were lower: for B. fragilis, they were 10.5 and 25.7, respectively; for C. perfringens, they were 8.6 and 16.2; and for GPAC, they were 7.3 and 17.4. The maximum-effect log drops were as follows: for B. fragilis, -3.2 +/- 0.2 logs; for C. perfringens, -3.7 +/- 0.1 logs; and for GPAC, -2.5 +/- 0.1 logs. Although the anaerobes were not eradicated, there was no emergence of resistance. Comparison of the ABE of moxifloxacin to that of ertapenem against B. fragilis indicated that moxifloxacin was superior at 24 h and 48 h. In contrast, ertapenem was superior to moxifloxacin against GPAC at 24 h and 48 h and against C. perfringens at 48 h. Both drugs performed equivalently against C. perfringens at 24 h. Monte Carlo simulations using human serum AUC data and an AUC/MIC anaerobe target of 7.5 suggests a >90% target achievement at MICs of <2 mg/liter. This divides the B. fragilis wild-type MIC distribution. The pharmacodynamic properties of moxifloxacin against anaerobes are different than those against aerobic species. The clinical implications of these differences need further exploration.

FIG. 1.

Relationship of AUC/MIC and AUBKC for E. coli under aerobic (solid symbols) and anaerobic (open symbols) conditions. Squares represent AUBKC_0-24, and circles represent AUBKC_0-48.

FIG. 2.

Antibacterial effects of moxifloxacin at AUC/MIC ratios in a range of 9 to 216 against B. fragilis. Ratios: 9, ▪; 18, □; 36, •; 72, ○; 216, ▴. Growth control, ✹.

FIG. 3.

Antibacterial effects of moxifloxacin at AUC/MIC ratios in a range of 9 to 216 against C. perfringens. Ratios: 9, ▪; 18, □; 36, •; 72, ○; 216, ▴. Growth control, ✹.

FIG. 4.

Antibacterial effects of moxifloxacin at AUC/MIC ratios in a range of 9 to 216 against GPAC. Ratios: 9, ▪; 18, □; 36, •; 72, ○; 216, ▴. Growth control, ✹.

FIG. 5.

The antibacterial effects of piperacillin-tazobactam against B. fragilis (▪) and C. perfringens (•).

FIG. 6.

Antibacterial effects of ertapenem against B. fragilis (▪), C. perfringens (•), and GPAC (▴).