2041. Minocycline (MINO) Activity is Enhanced by Polymyxin B (PmB) in TetB Containing Isolates of Acinetobacter baumannii (ACB), Including Those Resistant to PmB
Session: Poster Abstract Session: Antimicrobial Resistant Infections: Treatment
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • 2041 IDWeek MINO enhanced with PmB.pdf (295.4 kB)
  • Background: MINO has recently emerged as one of the few treatment options for infections caused by multidrug resistant strains of ACB. Acquired MINO resistance (R) in ACB is associated with the presence of the TetB efflux pump. The objective of this study was to assess activity of MINO in combination with PmB against the TetB containing strains of ACB, including PmB-R strains.

    Methods: The in vitro activity of MINO in combination with PmB was evaluated by checkerboard assays against the panel of 167 TetB-containing clinical isolates of Acinetobacter baumannii, including six PmB-resistant isolates. The presence of the tetB gene was confirmed by PCR. pmrCABoperon was sequenced in PmB-R strains. 93% and 100% of strains were also R to meropenem and levofloxacin, respectively.

    Results:

    MINO and PmB MIC50/MIC90 (range) were 16/32 (0.5-32) µg/ml and 1/2 (0.5-8) µg/ml, respectively. Only 12% of TetB-containing isolates were susceptible (S) to ≤ 4 µg/ml MINO (FDA & CLSI susc. breakpoint). PmB at 0.25 or 0.5 µg/ml increased MINO potency 2 -256-fold bringing MIC50/MIC90 to 0.5/4 µg/ml. 100% of TetB strains were S to MINO with PmB at 0.5 µg/ml (Table). Six PmB-R strains (PmB MIC ≥ 4 µg/ml), had mutations in pmrA or pmrB. In these strains, the MINO MIC alone or in combination with PmB at 0.5 µg/ml ranged from 8 to 32 µg/ml and from 2 to 4 µg/ml, respectively.

    Cumulative % of Strains Inhibited at each MIC

    ≤0.06

    0.125

    0.25

    0.5

    1

    2

    4

    8

    16

    32

    MINO

    0.0%

    0.0%

    0.0%

    1.2%

    1.8%

    3.6%

    12.0%

    34.1%

    86.2%

    100.0%

    w/PmB at 0.25 µg/ml

    0.0%

    0.0%

    0.0%

    1.8%

    3.0%

    6.6%

    58.1%

    95.2%

    100.0%

    100.0%

    w/PmB at 0.5 µg/ml

    41.3%

    47.3%

    49.7%

    57.5%

    65.3%

    79.6%

    100.0%

    100.0%

    100.0%

    100.0%

    PmB

    0.0%

    0.0%

    0.0%

    35.3%

    88.6%

    96.4%

    98.8%

    100.0%

    100.0%

    100.0%

     

    Conclusion:

    PmB enhanced the potency of MINO against TetB-containing ACB isolates, including those resistant to PmB. This combination warrants further evaluation in the management of patients with infections due to ACB.

    Olga Lomovskaya, PhD, Kirk Nelson, BS, Debora Rubio-Aparicio, BS, Dongxu Sun, PhD, David Griffith, BS and Michael N. Dudley, Pharm.D., The Medicines Company, San Diego, CA

    Disclosures:

    O. Lomovskaya, The Medicines Company: Employee , Salary

    K. Nelson, The Medicines Company: Employee , Salary

    D. Rubio-Aparicio, The Medicines Company: Employee , Salary

    D. Sun, The Medicines Company: Employee , Salary

    D. Griffith, The Medicines Company: Employee , Salary

    M. N. Dudley, The Medicines Company: Employee , Salary and stock options

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.