In-vitro susceptibility and in-vivo efficacy of antimicrobials in the treatment of intraabdominal sepsis in mice

Abstract

Cefoxitin, cefotetan, cefmetazole, ceftizoxime, imipenem plus cilastatin, ampicillin plus sulbactam and clindamycin alone or combined with gentamicin, ciprofloxacin, ofloxacin or aztreonam were compared in the therapy of intraabdominal infection in mice caused by Escherichia coli in combination with either Bacteroides fragilis or Bacteroides thetaiotaomicron. Mortality in the control group was 45%, and no animal receiving either imipenem, gentamicin, ciprofloxacin, ofloxacin or aztreonam died. Mortality in mice receiving cefoxitin, cefotetan, cefmetazole, or ceftizoxime was below 7% (P < 0.05%) and mortality following treatment with ampicillin-sulbactam was 23-27% (P > 0.05). The abscesses were examined ten days after inoculation. No abscesses were observed in mice treated with clindamycin or imipenem. Therapy with gentamicin, ciprofloxacin, ofloxacin, aztreonam or ceftizoxime alone did not prevent abscess formation by both Bacteroides sp. A significant reduction in abscess formation and number of E. coli and B. fragilis was observed with combination therapy of clindamycin with either ciprofloxacin, ofloxacin, aztreonam, or gentamicin and single agent therapy with either imipenem, cefoxitin, cefotetan, cefmetazole and ampicillin-sulbactam alone. However, cefotetan and cefmetazole did not reduce abscess formation or the number of B. thetaiotaomicron. These in-vivo data confirm the in-vitro activity of these antimicrobials.