title: In vitro activities of the beta-lactamase inhibitors clavulanic acid, sulbactam, and tazobactam alone or in combination with beta-lactams against epidemiologically characterized multidrug-resistant Acinetobacter baumannii strains.
abstract: Acinetobacter baumannii is an important nosocomial pathogen usually in the context of serious underlying disease. Multidrug resistance in these organisms is frequent. The beta-lactamase inhibitors clavulanic acid, sulbactam, and tazobactam have intrinsic activity against Acinetobacter strains. To evaluate their potential therapeutic usefulness, we determined the in vitro activity of ampicillin, sulbactam, ampicillin-sulbactam, cefoperazone, cefoperazone-sulbactam, piperacillin, piperacillin-sulbactam, tazobactam, piperacillin-tazobactam, amoxicillin, clavulanic acid, amoxicillin-clavulanic acid, ticarcillin, and ticarcillin-clavulanic acid against multidrug-resistant A. baumannii. All isolates were epidemiologically characterized by RAPD [random(ly) amplified polymorphic DNA] analysis and/or pulsed-field gel electrophoresis and represented different strain types, including sporadic strains, as well as outbreak-related strains. The MICs were determined by agar dilution on Mueller-Hinton agar (using fixed concentrations, as well as fixed ratios for beta-lactamase inhibitors) and the E-test. The majority of E-test results were within two dilutions of those recorded by agar dilution, with the exception of piperacillin-tazobactam. Sulbactam was superior to clavulanic acid and tazobactam and may represent an alternative treatment option for infections due to multiresistant A. baumannii strains. beta-Lactamase inhibitors have intrinsic activity but do not enhance activity of beta-lactams against A. baumannii. Testing with the inhibitor added at a fixed concentration as recommended for piperacillin-tazobactam and ticarcillin-clavulanic acid by the National Committee for Clinical Laboratory Standards may falsely suggest high activity or gives uninterpretable results due to trailing. If combinations are used for testing, fixed ratios may give more useful results.
authors.affiliation: Institute for Medical Microbiology, Immunology, and Hygiene, University of Cologne, 50935 Cologne, Germany.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Higgins
authors.forename: Hilmar
authors.initials: H
authors.lastname: Wisplinghoff
authors.forename: Danuta
authors.initials: D
authors.lastname: Stefanik
authors.forename: Harald
authors.initials: H
authors.lastname: Seifert
mesh_terms: D000151:Acinetobacter Infections / Q000382:microbiology*; D040981:Acinetobacter baumannii / Q000187:drug effects*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D019818:Clavulanic Acid / Q000494:pharmacology*; D004247:DNA / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination; D016521:Electrophoresis, Gel, Pulsed-Field; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013407:Sulbactam / Q000494:pharmacology*; D000078142:Tazobactam; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D019818:Clavulanic Acid; D010397:Penicillanic Acid; D004247:DNA; D013407:Sulbactam; D000078142:Tazobactam