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Bacteroides fragilis-induced intra-abdominal abscess in an experimental model treated with telithromycin (HMR 3647)
H Thadepalli1, S K Chuah, S Qazi
1Charles R Drew, University of Medicine and Sciencs, Los Angeles, CA 90059, USA. geriatrics@pol.net
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 BaSO(4) 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.
Insights
Telithromycin demonstrated efficacy against Bacteroides fragilis in an animal model, showing comparable results to clindamycin. This ketolide antibiotic warrants further investigation for treating human infections.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Telithromycin (HMR 3647) is a novel ketolide antibiotic.
- In vitro studies indicate telithromycin's activity against Bacteroides fragilis.
Purpose of the Study:
- To evaluate the efficacy of telithromycin in an animal model of intra-abdominal abscess caused by B. fragilis.
- To compare telithromycin with established antibiotics like clindamycin, cefotetan, and metronidazole.
Main Methods:
- An animal model of intra-abdominal abscess was induced using B. fragilis.
- Telithromycin was administered at two doses (1.25 and 2.0 mg/dose twice daily) and compared to clindamycin, cefotetan, and metronidazole (2.0 mg/dose twice daily) for 10 days.
- Cure was defined as the absence of bacteria at the infection site.
Main Results:
- Telithromycin achieved a cure rate of 74%, comparable to clindamycin (82%) and superior to metronidazole (61%) and cefotetan (59%).
- High tissue concentrations of telithromycin were observed, correlating with its efficacy.
- Delayed treatment initiation resulted in a significantly lower cure rate (32%).
- Both tested doses of telithromycin were equally effective.
Conclusions:
- Telithromycin is as effective as clindamycin and more effective than metronidazole and cefotetan in this experimental B. fragilis infection model.
- These findings suggest telithromycin's potential for treating human B. fragilis infections.