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Antimicrobial Agents and Chemotherapy, June 1999, p. 1406-1411, Vol. 43, No. 6
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

In Vivo Efficacies of Combinations of beta -Lactams, beta -Lactamase Inhibitors, and Rifampin against Acinetobacter baumannii in a Mouse Pneumonia Model

Michel Wolff,1 Marie-Laure Joly-Guillou,2,* Robert Farinotti,3 and Claude Carbon4

Clinique de Réanimation des Maladies Infectieuses,1 Service de Pharmacie,3 and Institut National de la Santé et de la Recherche Médicale U13,4 Hôpital Bichat-Claude Bernard, 75018 Paris, and Service de Microbiologie, Hôpital Louis Mourier, 92701 Colombes,2 France

Received 28 September 1998/Returned for modification 3 February 1999/Accepted 7 April 1999

The effects of various regimens containing combinations of beta -lactams, beta -lactam inhibitor(s), and rifampin were assessed in a recently described mouse model of Acinetobacter baumannii pneumonia (M. L. Joly-Guillou, M. Wolff, J. J. Pocidalo, F. Walker, and C. Carbon, Antimicrob. Agents Chemother. 41:345-351, 1997). Two aspects of the therapeutic response were studied: the kinetics of the bactericidal effect (treatment was initiated 3 h after intratracheal inoculation, and bacterial counts were determined over a 24-h period) and survival (treatment was initiated 8 h after inoculation, and the cumulative mortality rate was assessed on day 5). Two clinical strains were used: a cephalosporinase-producing strain (SAN-94040) and a multiresistant strain (RCH-69). For SAN-94040 and RCH-69, MICs and MBCs (milligrams per liter) were as follows: ticarcillin, 32, 64, 256, and >256, respectively; ticarcillin-clavulanate, 32, 64, and 512, and >512, respectively; imipenem, 0.5, 0.5, 8, and 32, respectively; sulbactam, 0.5, 0.5, 8, and 8, respectively; and rifampin, 8, 8, 4, and 4, respectively. Against SAN-94040, four regimens, i.e., imipenem, sulbactam, imipenem-rifampin, and ticarcillin-clavulanate (at a 25/1 ratio)-sulbactam produced a true bactericidal effect (>= 3-log10 reduction of CFU/g of lung). The best survival rate (i.e., 93%) was obtained with the combination of ticarcillin-clavulanate-sulbactam, and regimens containing rifampin provided a survival rate of >= 65%. Against RCH-69, only regimens containing rifampin and the combination of imipenem-sulbactam had a true bactericidal effect. The best survival rates (>= 80%) were obtained with regimens containing rifampin and sulbactam. These results suggest that nonclassical combinations of beta -lactams, beta -lactamase inhibitors, and rifampin should be considered for the treatment of nosocomial pneumonia due to A. baumannii.

* Corresponding author. Mailing address: Service de Microbiologie, Hôpital Louis Mourier, 178 rue des Renouillers, 92701 Colombes, France. Phone: 33 1 47 60 60 13. Fax: 33 1 47 60 60 48. E-mail: marie-laure.joly-guillou{at}lmr.ap-hop-paris.fr.

Antimicrobial Agents and Chemotherapy, June 1999, p. 1406-1411, Vol. 43, No. 6
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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