In vitro activity of antibiotic combinations against multidrug-resistant strains of Acinetobacter baumannii and the effects of their antibiotic resistance determinants

Authors

  • Yoko Miyasaki,

    Corresponding author
    • Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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  • Margie A. Morgan,

    1. Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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  • Raymond C. Chan,

    1. Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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  • W. Stephen Nichols,

    1. Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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  • Kristine M. Hujer,

    1. Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, USA
    2. Department of Medicine, Case Western Reserve School of Medicine, Cleveland, OH, USA
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  • Robert A. Bonomo,

    1. Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, USA
    2. Department of Medicine, Case Western Reserve School of Medicine, Cleveland, OH, USA
    3. Department of Pharmacology, Case Western Reserve School of Medicine, Cleveland, OH, USA
    4. Department of Molecular Biology and Microbiology, Case Western Reserve School of Medicine, Cleveland, OH, USA
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  • A. Rekha Murthy

    1. Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
    2. Department of Hospital Epidemiology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Correspondence: Yoko Miyasaki, Department of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd. B-220, Los Angeles, CA 90048, USA. Tel.: +1 310 423 3896; fax: +1 310 423 4599; e-mail: yoko.miyasaki@cshs.org

Abstract

Various combinations of antibiotics are reported to show synergy in treating nosocomial infections with multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii). Here, we studied hospital-acquired outbreak strains of MDR A. baumannii to evaluate optimal combinations of antibiotics. One hundred and twenty-one strains were grouped into one major and one minor clonal group based on repetitive PCR amplification. Twenty representative strains were tested for antibiotic synergy using Etest®. Five strains were further analyzed by analytical isoelectric focusing and PCR to identify β-lactamase genes or other antibiotic resistance determinants. Our investigation showed that the outbreak strains of MDR A. baumannii belonged to two dominant clones. A combination of colistin and doxycycline showed the best result, being additive or synergistic against 70% of tested strains. Antibiotic additivity was observed more frequently than synergy. Strains possessing the same clonality did not necessarily demonstrate the same response to antibiotic combinations in vitro. We conclude that the effect of antibiotic combinations on our outbreak strains of MDR A. baumannii seemed strain-specific. The bacterial response to antibiotic combinations is probably a result of complex interactions between multiple concomitant antibiotic resistance determinants in each strain.

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