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.
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.
Joly-Guillou
M L
ML
Department of microbiology, Bichat-Claude Bernard University, Paris, France.
Decré
D
D
Herrman
J L
JL
Bourdelier
E
E
Bergogne-Bérézin
E
E
D000150:Acinetobacter / Q000187:drug effects* / Q000201:enzymology; D000151:Acinetobacter Infections / Q000382:microbiology*; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004347:Drug Interactions; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000032:analysis / Q000302:isolation & purification; D047090:beta-Lactams
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D001618:beta-Lactamases