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Antimicrobial Agents and Chemotherapy, December 1998, p. 3304-3308, Vol. 42, No. 12
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

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

Olivier Mimoz,1,* Anne Jacolot,2 Sophie Leotard,3 Nadia Hidri,3 Kamran Samii,1 Patrice Nordmann,3 and Olivier Petitjean2

Service d'Anesthésie-Réanimation, Hôpital Paul Brousse, Assistance Publique-Hôpitaux de Paris, 94804 Villejuif Cedex,1 Crépit 93, Centre de Recherche en Pathologie Infectieuse et Tropicale, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, 93009 Bobigny Cedex,2 and Service de Bactériologie-Virologie, Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre Cedex,3 France

Received 8 May 1998/Returned for modification 5 August 1998/Accepted 12 September 1998

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.

* Corresponding author. Mailing address: Service d'Anesthésie-Réanimation, Hôpital Paul Brousse, Assistance Publique-Hôpitaux de Paris, 94804 Villejuif Cedex, France. Phone: 33 1 45 59 32 19. Fax: 33 1 45 59 38 34. E-mail: olivier.mimoz{at}pbr.ap-hop-paris.fr.

Antimicrobial Agents and Chemotherapy, December 1998, p. 3304-3308, Vol. 42, No. 12
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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