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 T. Tsujia

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 T. Tsujia

Pharmacy

SUNY Buffalo
Cornell University
Public Health Research Institute, New York
Catholic University of Daegu
University of North Carolina at Chapel Hill
Monash University

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

19 Scopus citations

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 (MIC_{240 h} = 0.5 mg/liter) versus the same combination with traditionally dosed polymyxin B, where resistance was amplified (MIC_{240 h} = 32 mg/liter).

Original language	English
Article number	e02023
Journal	Antimicrobial Agents and Chemotherapy
Volume	61
Issue number	4
DOIs	https://doi.org/10.1128/AAC.02023-16
State	Published - Apr 2017

Keywords

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

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10.1128/AAC.02023-16

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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., & Tsujia, B. T. (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. https://doi.org/10.1128/AAC.02023-16

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title = "New polymyxin B dosing strategies to fortify old allies in the war against KPC-2-producing klebsiella pneumoniae",

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, Meropenem, PK/PD, Polymyxin B, Rifampin",

author = "Bulman, \{Zackery P.\} and Satlin, \{Michael J.\} and Liang Chen and Kreiswirth, \{Barry N.\} and Shin, \{Beom Soo\} and Walsh, \{Thomas J.\} and Holden, \{Patricia N.\} and Alan Forrest and Nation, \{Roger L.\} and Jian Li and Tsujia, \{Brian T.\}",

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doi = "10.1128/AAC.02023-16",

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AU - Bulman, Zackery P.

AU - Satlin, Michael J.

AU - Chen, Liang

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 - Tsujia, Brian T.

PY - 2017/4

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

KW - KPC-producing K. pneumoniae

KW - Meropenem

KW - PK/PD

KW - Polymyxin B

KW - Rifampin

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SN - 0066-4804

VL - 61

JO - Antimicrobial Agents and Chemotherapy

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ER -

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

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Keywords

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