Bacteroides fragilis-Induced Intra-Abdominal Abscess in an Experimental Model Treated with Telithromycin (HMR 3647)

Abstract

Background: Telithromycin (HMR 3647), a novel ketolide, is known to have activity against Bacteroides fragilis in vitro. Methods: We tested this ketolide in an animal model of intra-abdominal abscess produced by intraperitoneal injection of B. fragilis with sterile feces and BaSO₄ mixture. Telithromycin was tested at two doses, 1.25 and 2.0 mg/dose twice daily, and compared with clindamycin, cefotetan or metronidazole, all given at 2.0 mg/dose twice daily for 10 days. Absence of bacteria at the infected site was considered a cure and a positive culture considered a failure. Results: The cure rate was 18% (5/28) on saline therapy, 74% (20/27) on telithromycin and 82% (23/28) on clindamycin, whereas it was 61% (17/28) on metronidazole and 59% (16/27) on cefotetan therapy. A high tissue antibiotic concentration (3–5 times the MIC) of telithromycin was found and this is presumably related to its superior efficacy. Delayed therapy initiated 7 days after infection instead of immediate therapy cured only 32% of the animals treated. The lower dose of telithromycin (1.25 mg/dose twice daily) was as effective as the higher dose (2 mg/dose twice daily). Conclusions: We found that telithromycin is as effective as clindamycin and more effective than metronidazole and cefotetan in this experimental model. These results suggest that telithromycin may be tested in future for the treatment of B. fragilis infections in humans.