ACTIVITY OF FLEROXACIN ALONE AND IN COMBINATION WITH CLINDAMYCIN OR METRONIDAZOLE IN EXPERIMENTAL INTRAABDOMINAL ABSCESSES

To assess the potential efficacy of fleroxacin in combination with cli ndamycin or metronidazole in mixed aerobic and anaerobic infections, w e used a rat model of intra-abdominal abscesses in which the inoculum consisted of pooled rat feces mixed with BaSO4. Two hours after bacter ial challenge, antimicrobial therapy was begun intravenously with regi mens designed to simulate human pharmacokinetics. A combination of cli ndamycin and gentamicin was included as an established treatment regim en. After 8.5 days of therapy, final bacterial counts in abscesses sho wed that fleroxacin alone or combined with metronidazole or clindamyci n effectively eradicated Escherichia coli, with bacterial densities of less than or equal to 2.84 +/- 0.1, less than or equal to 2.9 +/- 0.1 , and less than or equal to 2.95 +/- 0.1 (mean +/- standard error of t he mean) log(10) CFU/g, respectively. The addition of either clindamyc in or metronidazole to fleroxacin substantially enhanced the effective ness of the regimens against Bacteroides fragilis, with bacterial coun ts of less than or equal to 3.0 +/- 0.1 or less than or equal to 2.9 /- 0.1 log(10) CFU/g, respectively, versus 9.2 +/- 0.2 log(10) CFU/g f or fleroxacin alone. The combination of metronidazole and fleroxacin a lso resulted in a significantly greater reduction of peptostreptococci and Bacteroides thetaiotaomicron than fleroxacin alone (less than or equal to 2.9 +/- 0.1 versus 6.1 +/- 0.9 log(10) CFU/g and 3.3 +/- 0.4 versus 8.3 +/- 0.1 log(10) CFU/g, respectively). Except for those of B . fragilis, counts of other anaerobes were reduced to a greater extent by metronidazole plus fleroxacin than by clindamycin plus fleroxacin, although differences were not always significant. Metronidazole plus fleroxacin was at least as active as clindamycin plus gentamicin again st all species and was significantly more active against Clostridium s pp. No regimen effectively eradicated enterococci from the abscesses. These results suggest that the addition of either metronidazole or cli ndamycin would effectively enhance the spectrum of fleroxacin for trea tment of mixed aerobic and anaerobic infections.