38. Time-kill Assay and Etest Evaluation for Synergy with Polymyxin B and Rifampin against Escherichia coli Carrying the mcr-1 Gene
Session: Posters in the Park: Posters in the Park
Wednesday, October 3, 2018: 5:30 PM
Room: N Hall D Opening Reception and Posters in the Park Area
Posters
  • ID week FINAL poster (got printed).pdf (324.0 kB)
  • Background: The plasmid-mediated polymyxin resistance gene mcr-1 was first identified in China from a pig Escherichia coli (Liu et al 2015). The mcr-1 gene has since been found in various parts of the USA. It is able to move from one Gram negative bacterium to another, possibly making multidrug-resistant bacteria also resistant to the polymyxins. This increases the need for new therapeutic approaches. In 2018 MacNair et al showed potentiation of rifampin plus polymyxin E (colistin) against mcr-1-positive E. coli using the checkerboard method. We evaluated the combination of polymyxin B and rifampin against 5 mcr-1-positive E. coli using time-kill assay and an Etest® method.

    Methods: Five clinically unique mcr-1-positive E. coli were obtained from the CDC Antimicrobial Resistance Bank. MICs for polymyxin B and rifampin were determined in triplicate by Etest and broth microdilution. Synergy testing was performed in triplicate by a MIC:MIC Etest method. Results were read at 24h and summation fractional inhibitory concentration (∑FIC) calculated: synergy ≤0.5. Synergy testing by time-kill assay was performed using ½MIC of polymyxin B and rifampin. Synergy was defined as ≥2 log10 decrease in CFU/ml after 24h by the combination compared to the most potent agent alone.

    Results: MICs (µg/ml) were: polymyxin B, 3-6 (Etest) and 2-4 (broth microdilution) (>2 is considered resistant by Eucast 2018); rifampin, >32 (Etest) and 6 to >48 (broth microdilution) (no rifampin breakpoints established). The MIC:MIC Etest method showed synergy with polymyxin B plus rifampin against all 5 mcr-1-positive E. coli isolates (∑FICs, 0.2-0.3). Using the ½MIC combination of polymyxin B and rifampin, time-kill assay also showed synergy against all isolates.

    Conclusion: Synergy was seen against all mcr-1-positive E. coli isolates using polymyxin B plus rifampin by both the MIC:MIC Etest method and time-kill assay at ½MIC. In vitro synergy may or may not correlate clinically.

    Anam Kamal, M.B.B.S., Ryan Brown, BS, Deborah Ashcraft, BS and George Pankey, MD, FIDSA, Infectious Disease Translational Research, Ochsner Clinic Foundation, New Orleans, LA

    Disclosures:

    A. Kamal, None

    R. Brown, None

    D. Ashcraft, None

    G. Pankey, None

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