Antimicrobial efficacy testing of moxifloxacin during the peritonitis and abscess formation stages of intra-abdominal sepsis: A controlled trial in the rat model

Abstract

Background: Moxifloxacin is a fluoroquinolone with a broad range of antimicrobial activity against gram-negative and gram-positive, facultative, and obligately anaerobic bacteria, including certain quinolone-resistant organisms. Objective: Efficacy of moxifloxacin was compared with that of a combination of clindamycin + gentamicin in a rat model of intra-abdominal sepsis, with end points including mortality during the first 2 to 4 days after initiation of sepsis and the incidence of intra-abdominal abscess noted at necropsy. The bacterial challenge was prepared from cecal contents or an enhanced cecal content preparation. Methods: Groups of 20 animals were employed in the first part of the study, which used a cecal content challenge: group 1 served as saline-treated controls; group 2 received moxifloxacin 15 mg once daily; and group 3 received a combination of clindamycin 15 mg TID + gentamicin 2 mg TID. Dosing was determined for all antimicrobial agents based on peak and trough serum levels by prior testing (ie, experiments initiated before this study to determine the appropriate dosage in animals that approximates the levels obtained in humans with the antimicrobial agent under investigation), adjusting doses according to a body surface area/body weight ratio, and comparing these doses and levels with studies in humans. In the second part of the study, moxifloxacin was compared with levofloxacin (both 15 mg once daily) in an enhanced abscess model. Results: The mortality rate was 57.9% in the control group versus 0% in the moxifloxacin group and 5% in the clindamycin + gentamicin group ( P < 0.001 for both treatment groups vs control). The incidence of abscess among survivors was 100% in the control group versus 0% in the moxifloxacin group and 5.3% in the clindamycin + gentamicin group ( P < 0.001 for both vs control). In the Bacteroides fragilis—enhanced abscess model, the incidence of abscess was significantly lower in the moxifloxacin group compared with both the saline-treated controls ( 4 19 [21.1%] vs 5 5 [100%] , respectively; P = 0.003) and the levofloxacin group ( 4 19 [21.1%] vs 11 20 [55%] , respectively; P = 0.042). Conclusions: This study shows that moxifloxacin is as effective as other established therapeutic regimens in reducing the incidence of both mortality and intra-abdominal abscesses in this animal model. In addition, moxifloxacin is extremely effective in preventing abscesses caused by obligate anaerobes, even in an enhanced model for abscess development, and its efficacy is superior to that of levofloxacin.