Role of ceftazidime dose regimen on the selection of resistant Enterobacter cloacae in the intestinal flora of rats treated for an experimental pulmonary infection.

摘要: Objectives: The effect of ceftazidime dosing increments and frequency on the selection ceftazidime-resistant Enterobacter cloacae in intestine was studied rats, during treatment a pulmonary infection caused by Klebsiella pneumoniae. Methods: Rats with (n 5 10 per group) received therapy doses at 3.1 to 400 mg/kg day every 6,12 or 24 h for 18 days, starting after bacterial inoculation lung. Emergence resistance intestinal E. monitored culturing fresh stool specimens days 0, 8, 15, 22, 29, 36 43 agar plates (6.4 mg/L) without ceftazidime. Pharmacodynamic indices time within mutant window (MSW) were assessed infected rats each regimen. Ceftazidime-resistant mutants characterized determination β-lactamase activity under cefoxitin-induced non-induced conditions. Results: A reduction ceftazidime-susceptible observed showed significant correlation fAUC/MIC 15 22 fCmaxon 29 36. More treated 12-25 50-100 6 found colonized than animals 12 h. proportion correlated which plasma concentrations boundaries MSW. Only demonstrated between fCmaxand significantly fewer cloacae. (MIC ≥ 128 as stable derepressed mutants. Conclusions: Colonization particularly occurred when exposed moderate (12-25 day) administered