New Polymyxin B Dosing Strategies To Fortify Old Allies in the War against KPC-2-Producing Klebsiella pneumoniae. Academic Article uri icon

Overview

abstract

  • 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 = 0.5 mg/liter) versus the same combination with traditionally dosed polymyxin B, where resistance was amplified (MIC240 h = 32 mg/liter).

publication date

  • March 24, 2017

Research

keywords

  • Anti-Bacterial Agents
  • Klebsiella pneumoniae
  • Models, Statistical
  • Polymyxin B
  • Rifampin
  • Thienamycins

Identity

PubMed Central ID

  • PMC5365650

Scopus Document Identifier

  • 85016992159

Digital Object Identifier (DOI)

  • 10.1093/cid/cit453

PubMed ID

  • 28167549

Additional Document Info

volume

  • 61

issue

  • 4