Difloxacin (A-56619) and A-56620, two novel fluoroquinolones, were tested in comparison with ciprofloxacin, cefoxitin, and combined clindamycin and gentamicin in the treatment of experimentally induced intraabdominal abscess associated with Bacteroides fragilis. Difloxacin was found to be as effective as clindamycin-gentamicin. A-56620, despite achieving subtherapeutic levels in serum, was found to be as effective as cefoxitin. Both difloxacin and A-56620 were effective in vivo against experimentally induced intra-abdominal abscess in rats.

The efficacy of trovafloxacin in treating Bacteroides fragilis and Escherichia coli infections was investigated and compared to the efficacy of combined clindamycin and gentamicin therapy in an experimental model of intra-abdominal abscesses in rats. Rats were treated with different doses of CP-116,517-27, a parenteral prodrug of trovafloxacin. Response to treatment was evaluated by mortality rate and elimination of infection (cure rate). Mortality in the control group was 85.4%, whereas in rats treated with trovafloxacin, it was close to 0%. The highest cure rate (89.3%) resulted from the administration of 40 mg of CP-116,517-27 per kg of body weight three times a day (TID) for 10 days (equivalent to 18.15 mg of active drug trovafloxacin per rat per day). The therapeutic response with trovafloxacin was comparable to that of a combination therapy of clindamycin (75 mg/kg) plus gentamicin (20 mg/kg) TID (cure rate, 74%; mortality rate, 5%). The measured peak levels of trovafloxacin in serum and abscess pus were 2.6 +/- 0.3 and 5.2 micrograms/ml, respectively. The tumor necrosis factor alpha levels in the untreated animals were high compared to those for rats treated with trovafloxacin or clindamycin plus gentamicin. These results demonstrate that trovafloxacin as a single agent appears to be as successful as clindamycin plus gentamicin in the treatment of experimental intra-abdominal abscesses in rats.

We investigated the in vivo effects of rufloxacin and ciprofloxacin on T-cell subsets and tumor necrosis factor production in mice infected with Bacteroidesfiagiis. These quinolones did not alter the helper/suppressor ratio but did modulate the kinetics of tumor necrosis factor production in infected animals. This result correlated with the observed therapeutic efficacies of the quinolones.Several recent reports indicate that quinolone antibiotics at clinically achievable levels modulate the in vitro growth of T cells and the production of cytokines by activated lymphoid cells (1,2,5,(7)(8)(9). The purpose of this investigation was to determine whether quinolones in vivo alter the T-cell response and cytokine production in an infection model. Intra-abdominal abscesses produced by Bacteroides fragilis are a good model to study the in vivo effects of quinolones because, first, abscess formation and elimination of abscesses require T-cell function (10, 11) and, second, the cytokines play an important role in elimination of infection (3,11).Five-to six-week-old female C3HIHeN mice were infected with an abscess-forming mixture of B. fragilis with sterile cecal contents and BaSO4 as previously described (3). Six hours after the inoculation, the mice were treated with rufloxacin (50 mg/kg of body weight) once a day or with ciprofloxacin (40 mg/kg) twice daily for 10 days. Each group contained 11 animals. The antibiotics were given intraperitoneally. Rufloxacin was given once a day because of its long half-life (6). As a control, a group of mice were treated with saline. In addition, a group of uninfected animals used as controls received either ciprofloxacin or rufloxacin so as to determine the effect of the quinolones on T-cell subsets without the associated effects of infection with B. fragilis. On day 11 posttreatment, mice were sacrificed by cervical dislocation under anesthesia, the spleens were removed, and a single cell suspension was prepared as previously described (4). Cells were stained with fluorescein isothiocyanate-labeled Thy 1.2 (total T-cell), L3T4 (helper), or LYT2 (suppressor) antibody (Becton Dickinson, San Jose, Calif.). The binding of antibodies to T lymphocytes was analyzed with a FACScan flow cytometer (Becton Dickinson). Mice treated with or without drugs were bled at 2, 24, 48, and 72 h posttreatment, sera were pooled, and tumor necrosis factor (TNF) levels in the serum were determined by enzyme-linked immunosorbent assay as suggested by the manufacturer (Genzyme, Cambridge, Mass.). Mice were killed 1 day after completion of therapy; their abdomens were opened and examined for the presence or absence of ab-* Corresponding author.scesses. If abscesses were present, then pus was cultured to confirm the presence of B. fragilis. B. fragilis was recovered from the abdominal abscess pus of all control untreated animals. The absence of B. fragilis was considered to indicate that the animals had been cured. The results were analyzed for statistical significance by chi-square analysis, and P values of ...

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