New polymyxin B dosing strategies to fortify old allies in the war against KPC-2-producing Klebsiella pneumoniae

Zackery P. Bulman, Michael J Satlin, Liang Chen, Barry N Kreiswirth, Beom Soo Shin, Thomas J. Walsh, Patricia N Holden, Alan Forrest, Roger L Nation, Jian Li, Brian Tsuji

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Pharmacodynamics of a polymyxin B, meropenem, and rifampin triple combination were examined against Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) ST258. In time-kill experiments against three KPC-Kp isolates, triple combination generated 8.14, 8.19, and 8.29 log10 CFU/ml reductions within 24 h. In the hollow-fiber infection model, the triple combination caused maximal killing of 5.16 log10 CFU/ml at 78 h and the time required for regrowth was more than doubled versus the 2-drug combinations. Remarkably, combinations with a high single-dose polymyxin B burst plus rifampin preserved KPC-Kp polymyxin susceptibility (MIC240 h 0.5mg/liter) versus the same combination with traditionally dosed polymyxin B, where resistance was amplified (MIC240 h 32 mg/liter).
Original languageEnglish
Article numbere02023-16
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Issue number4
Publication statusPublished - 1 Apr 2017


  • KPC-producing K. pneumoniae
  • Meropenem
  • PK/PD
  • Polymyxin B
  • Rifampin

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