Bacteroides fragilis-induced intra-abdominal abscess in an experimental model treated with telithromycin (HMR 3647).
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.
Thadepalli
H
H
Charles R Drew, University of Medicine and Sciencs, Los Angeles, CA 90059, USA. geriatrics@pol.net
Chuah
S K
SK
Qazi
S
S
Thadepalli
F
F
Gollapudi
S V
SV
D018784:Abdominal Abscess / Q000188:drug therapy* / Q000382:microbiology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001442:Bacteroides Infections / Q000188:drug therapy* / Q000382:microbiology; D001441:Bacteroides fragilis / Q000187:drug effects; D015313:Cefotetan / Q000494:pharmacology; D002981:Clindamycin / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D048628:Ketolides; D018942:Macrolides; D008297:Male; D008795:Metronidazole / Q000494:pharmacology; D051379:Mice
D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; D008795:Metronidazole; D002981:Clindamycin; D015313:Cefotetan; C106791:telithromycin