Bactericidal in-vitro activity of beta-lactams and beta-lactamase inhibitors, alone or associated, against clinical strains of Acinetobacter baumannii: effect of combination with aminoglycosides.

Abstract

Five Acinetobacter baumannii strains of various phenotypes were selected on the basis of the results of a national survey in France in 1991. beta-Lactamases in Acinetobacter isolates were characterized by isoelectrofocusing. We carried out a 24 h time-kill study to assess the bactericidal effect of antibiotic alone or in combination against A. baumannii strains. The initial inoculum was 10(6) cfu/mL. Antibiotics were tested at MIC x 2 when an antibiotic was tested alone and at the MIC for each combination including ticarcillin, piperacillin, ceftazidime or imipenem with or without amikacin or netilmicin and/or beta-lactamase inhibitors. Concentration of inhibitors were: 2 mg/L for clavulanic acid, 4 mg/L for tazobactam and 8 mg/L for sulbactam. Sulbactam and tazobactam showed an intrinsic in-vitro activity against strains susceptible to ticarcillin. A complete killing at 24 h was observed when beta-lactams were combined with amikacin in comparison with antibiotics alone. Synergy was lost when the strain presented a low resistance level to beta-lactams or aminoglycosides except for ticarcillin. Combinations of sulbactam with ticarcillin showed the best bactericidal activity against strains multiresistant to beta-lactams.