In vivo efficacies of combinations of beta-lactams, beta-lactamase inhibitors, and rifampin against Acinetobacter baumannii in a mouse pneumonia model

The effects of various regimens containing combinations of beta-lactams, be ta-lactam inhibitor(s), and rifampin were assessed in a recently described mouse model of Acinetobacter baumannii pneumonia (M. L. Joly-Guillou, M. Wo lff, 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 ere determined over a 24-h period) and survival (treatment was initiated 8 h after inoculation, and th e cumulative mortality rate was assessed on day 5). Two clinical strains we re used: a cephalosporinase-producing strain (SAN-94040) and a multiresista nt 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, respecti vely; and rifampin, 8, 8, 4, and 4, respectively. Against SAN-94040, four r egimens, i.e., imipenem, sulbactam, imipenem-rifampin, and ticarcillin-clav ulanate (at a 25/1 ratio)-sulbactam produced a true bactericidal effect (gr eater than or equal to 3-log(10) reduction of CFU/g of lung). The best surv ival rate (i.e., 93%) was obtained with the combination of ticarcillin-clav ulanate-sulbactam, and regimens containing rifampin provided a survival rat e of greater than or equal to 65%. Against RCH-69, only regimens containing rifampin and the combination of imipenem-sulbactam had a true bactericidal effect. The best survival rates (greater than or equal to 80%) were obtain ed with regimens containing rifampin and sulbactam, These results suggest t hat nonclassical combinations of beta-lactams, beta-lactamase inhibitors, a nd rifampin should be considered for the treatment of nosocomial pneumonia due to A. baumannii.