Efficacies of cefepime, ceftazidime, and imipenem alone or in combination with amikacin in rats with experimental pneumonia due to ceftazidime-susceptible or -resistant Enterobacter cloacae strains.
The antibacterial activities of human regimens of cefepime, ceftazidime, and imipenem alone or in combination with amikacin against an isogenic pair of Enterobacter cloacae strains (wild type and its corresponding derepressed cephalosporinase mutant) were compared by using our nonlethal model of pneumonia with 180 immunocompetent rats. Compared with untreated animals, all beta-lactam-treated rats, except those inoculated with the mutant isolate and receiving ceftazidime, had significantly lower bacterial counts in their lungs 60 h after the onset of therapy. Although the combination of a beta-lactam and amikacin was more bactericidal than each corresponding antimicrobial agent alone, true synergy was noted only with cefepime and imipenem against the constitutive derepressed strain.
Mimoz
O
O
Service d'Anesthésie-Réanimation, Hôpital Paul Brousse, Assistance Publique-Hôpitaux de Paris, 94804 Villejuif Cedex, France. oliver.mimoz@pbr.ap-hop-paris.fr
Jacolot
A
A
Leotard
S
S
Hidri
N
N
Samii
K
K
Nordmann
P
P
Petitjean
O
O
D000583:Amikacin / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077723:Cefepime; D002442:Ceftazidime / Q000493:pharmacokinetics / Q000494:pharmacology; D002511:Cephalosporins / Q000493:pharmacokinetics / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination / Q000493:pharmacokinetics / Q000494:pharmacology*; D016972:Enterobacter cloacae / Q000187:drug effects; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology; D015378:Imipenem / Q000493:pharmacokinetics / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D008826:Microbial Sensitivity Tests; D011014:Pneumonia / Q000188:drug therapy* / Q000382:microbiology; D051381:Rats; D017208:Rats, Wistar; D013845:Thienamycins / Q000493:pharmacokinetics / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D013845:Thienamycins; D015378:Imipenem; D000077723:Cefepime; D000583:Amikacin; D002442:Ceftazidime