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Experimental Therapeutics

Assessment of Minocycline and Polymyxin B Combination against Acinetobacter baumannii

Dana R. Bowers, Henry Cao, Jian Zhou, Kimberly R. Ledesma, Dongxu Sun, Olga Lomovskaya, Vincent H. Tam
Dana R. Bowers
aDepartment of Clinical Sciences and Administration, University of Houston College of Pharmacy, Houston, Texas, USA
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Henry Cao
aDepartment of Clinical Sciences and Administration, University of Houston College of Pharmacy, Houston, Texas, USA
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Jian Zhou
aDepartment of Clinical Sciences and Administration, University of Houston College of Pharmacy, Houston, Texas, USA
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Kimberly R. Ledesma
aDepartment of Clinical Sciences and Administration, University of Houston College of Pharmacy, Houston, Texas, USA
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Dongxu Sun
bRempex Pharmaceuticals, San Diego, California, USA
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Olga Lomovskaya
bRempex Pharmaceuticals, San Diego, California, USA
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Vincent H. Tam
aDepartment of Clinical Sciences and Administration, University of Houston College of Pharmacy, Houston, Texas, USA
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DOI: 10.1128/AAC.04110-14
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    FIG 1

    Twenty-four-hour time-kill studies.

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    FIG 2

    Increased intracellular minocycline concentration with polymyxin B. The value for the minocycline-only group was fixed at 1 (reference) (shaded bars).

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    FIG 3

    Tissue burdens at 24 h for various clinical strains *, P < 0.05 for the combination group compared to either monotherapy group.

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    FIG 4

    Survival rates of animals infected with AB 1261 (P < 0.001 for treatment groups compared to placebo group).

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  • TABLE 1

    Characteristics of the bacterial isolates used

    IsolateSourceMIC (μg/ml)Resistance mechanism(s)
    MinocylineMinocyline + PAβNaPolymyxin B
    AB BAA 747Laboratory0.250.1251Reference adeB expression
    AB 7283Clinical0.50.1251Moderate overexpressionb of adeB
    AB 1261Clinical10.1252Moderate overexpression of adeB
    AB 7416Clinical1621tetB, moderate overexpression of adeB
    • ↵a PAβN, Phe-Arg b-naphtylamide (100 μg/ml).

    • ↵b Moderate overexpression, >10× the transcription level by qRT-PCR, compared to that in a wild-type isolate susceptible to minocycline.

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Assessment of Minocycline and Polymyxin B Combination against Acinetobacter baumannii
Dana R. Bowers, Henry Cao, Jian Zhou, Kimberly R. Ledesma, Dongxu Sun, Olga Lomovskaya, Vincent H. Tam
Antimicrobial Agents and Chemotherapy Apr 2015, 59 (5) 2720-2725; DOI: 10.1128/AAC.04110-14

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Assessment of Minocycline and Polymyxin B Combination against Acinetobacter baumannii
Dana R. Bowers, Henry Cao, Jian Zhou, Kimberly R. Ledesma, Dongxu Sun, Olga Lomovskaya, Vincent H. Tam
Antimicrobial Agents and Chemotherapy Apr 2015, 59 (5) 2720-2725; DOI: 10.1128/AAC.04110-14
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