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Antimicrob Agents Chemother. 2017 Mar 24;61(4). pii: e02023-16. doi: 10.1128/AAC.02023-16. Print 2017 Apr.

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

Author information

1
Laboratory for Antimicrobial Dynamics, NYS Center of Excellence in Bioinformatics & Life Sciences, Buffalo, New York, USA.
2
School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, USA.
3
Weill Cornell Medical College, Cornell University, New York, New York, USA.
4
Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
5
Catholic University of Daegu, Hayang, South Korea.
6
Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.
7
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia.
8
Laboratory for Antimicrobial Dynamics, NYS Center of Excellence in Bioinformatics & Life Sciences, Buffalo, New York, USA btsuji@buffalo.edu.

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).

KEYWORDS:

KPC-producing K. pneumoniae; PK/PD; meropenem; polymyxin B; rifampin

PMID:
28167549
PMCID:
PMC5365650
DOI:
10.1128/AAC.02023-16
[Indexed for MEDLINE]
Free PMC Article

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