Open AccessNew Polymyxin B Dosing Strategies To Fortify Old Allies in the War against KPC-2-Producing Klebsiella pneumoniae
Author(s) -
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 T. Tsuji
Publication year - 2017
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.02023-16
Subject(s) - klebsiella pneumoniae , microbiology and biotechnology , polymyxin b , polymyxin , meropenem , antibiotics , medicine , biology , antibiotic resistance , escherichia coli , gene , biochemistry
Pharmacodynamics of a polymyxin B, meropenem, and rifampin triple combination were examined againstKlebsiella pneumoniae carbapenemase-producingKlebsiella 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).
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom