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

doi:10.1128/AAC.02023-16

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

Drug Delivery Disposition & Dynamics

Research output: Contribution to journal › Article › Research › peer-review

16 Citations (Scopus)

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

Original language	English
Article number	e02023-16
Number of pages	9
Journal	Antimicrobial Agents and Chemotherapy
Volume	61
Issue number	4
DOIs	https://doi.org/10.1128/AAC.02023-16
Publication status	Published - 1 Apr 2017

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Bulman, Z. P., Satlin, M. J., Chen, L., Kreiswirth, B. N., Shin, B. S., Walsh, T. J., Holden, P. N., Forrest, A., Nation, R. L., Li, J., & Tsuji, B. (2017). New polymyxin B dosing strategies to fortify old allies in the war against KPC-2-producing Klebsiella pneumoniae. Antimicrobial Agents and Chemotherapy, 61(4), Article e02023-16. https://doi.org/10.1128/AAC.02023-16

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AU - Kreiswirth, Barry N

AU - Shin, Beom Soo

AU - Walsh, Thomas J.

AU - Holden, Patricia N

AU - Forrest, Alan

AU - Nation, Roger L

AU - Li, Jian

AU - Tsuji, Brian

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AB - 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).

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

Abstract

Keywords

UN SDGs

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