Ronald L Cisneros1, Andrew B Onderdonk1. 1. Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts, USA ; Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
Abstract
BACKGROUND: In intra-abdominal infections, the activity of antimicrobial agents against Bacteroides fragilis and phenotypically related organisms, and the increasing resistance of these organisms, are of particular importance and concern to surgeons. In vitro data suggest that moxifloxacin is more active than other quinolones against obligately anaerobic organisms, including Bacteroides spp. OBJECTIVE: The aim of this study was to compare the efficacy of moxifloxacin monotherapy versus gatifloxacin monotherapy and 2 combination therapies (piperacillin-tazobactam and clindamycin plus gentamicin) in a rat model of intra-abdominal sepsis. The end point was marked by the incidence of mortality and intra-abdominal abscesses at necropsy 7 days after bacterial challenge. METHODS: Three different strains of B fragilis with different degrees of resistanceto moxifloxacin (minimum inhibitory concentrations [MICs]: 4, 8, and 16 pg/mL) were added to the challenge inoculum in 3 separate experiments. Groups of 20 animals were used in each experiment. Group 1 served as saline-treated controls; group 2 received moxifloxacin 15 mg QD; group 3 received gatifloxacin 25 mg QD; group 4 received piperacillin-tazobactam 93 mg (-83 mg of piperacillin) QD; and group 5 received a combination of clindamycin 15 mg TID plus gentamicin 2 mg TID. All treatments were given intramuscularly. For all antimicrobials, dose was based on peak and trough serum drug concentrations determined by prior testing, with animal doses adjusted based on the ratio of body surface area to body weight, and comparing these doses and levels with studies in humans. RESULTS: In all 3 experiments, the mortality rate with moxifloxacin was significantlylower or statistically similar compared with antibiotic active comparators (P ≤ 0.024). In addition, there were no significant differences in the incidence of abscess with moxifloxacin versus its comparators or between the 3 moxifloxacin groups across experiments. The best results for moxifloxacin were found in the experiment in which the B fragilis strain with MIC 16 μg/mL was added to the inoculum. CONCLUSION: The results of this study in an animal model of intra-abdominalsepsis induced by fluoroquinolone-resistant B fragilis suggest that moxifloxacin monotherapy performs as well as combination regimens such as piperacillin-tazobactam and clindamycin plus gentamicin, and is as effective as other fluoroquinolones with antianaerobic activity, such as gatifloxacin.
BACKGROUND: In intra-abdominal infections, the activity of antimicrobial agents against Bacteroides fragilis and phenotypically related organisms, and the increasing resistance of these organisms, are of particular importance and concern to surgeons. In vitro data suggest that moxifloxacin is more active than other quinolones against obligately anaerobic organisms, including Bacteroides spp. OBJECTIVE: The aim of this study was to compare the efficacy of moxifloxacin monotherapy versus gatifloxacin monotherapy and 2 combination therapies (piperacillin-tazobactam and clindamycin plus gentamicin) in a rat model of intra-abdominal sepsis. The end point was marked by the incidence of mortality and intra-abdominal abscesses at necropsy 7 days after bacterial challenge. METHODS: Three different strains of B fragilis with different degrees of resistanceto moxifloxacin (minimum inhibitory concentrations [MICs]: 4, 8, and 16 pg/mL) were added to the challenge inoculum in 3 separate experiments. Groups of 20 animals were used in each experiment. Group 1 served as saline-treated controls; group 2 received moxifloxacin 15 mg QD; group 3 received gatifloxacin 25 mg QD; group 4 received piperacillin-tazobactam 93 mg (-83 mg of piperacillin) QD; and group 5 received a combination of clindamycin 15 mg TID plus gentamicin 2 mg TID. All treatments were given intramuscularly. For all antimicrobials, dose was based on peak and trough serum drug concentrations determined by prior testing, with animal doses adjusted based on the ratio of body surface area to body weight, and comparing these doses and levels with studies in humans. RESULTS: In all 3 experiments, the mortality rate with moxifloxacin was significantlylower or statistically similar compared with antibiotic active comparators (P ≤ 0.024). In addition, there were no significant differences in the incidence of abscess with moxifloxacin versus its comparators or between the 3 moxifloxacin groups across experiments. The best results for moxifloxacin were found in the experiment in which the B fragilis strain with MIC 16 μg/mL was added to the inoculum. CONCLUSION: The results of this study in an animal model of intra-abdominalsepsis induced by fluoroquinolone-resistant B fragilis suggest that moxifloxacin monotherapy performs as well as combination regimens such as piperacillin-tazobactam and clindamycin plus gentamicin, and is as effective as other fluoroquinolones with antianaerobic activity, such as gatifloxacin.
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