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

6 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

Access to Document

10.1128/AAC.02023-16

Link to publication in Scopus

Cite this

Bulman, Zackery P. ; Satlin, Michael J ; Chen, Liang ; Kreiswirth, Barry N ; Shin, Beom Soo ; Walsh, Thomas J. ; Holden, Patricia N ; Forrest, Alan ; Nation, Roger L ; Li, Jian ; Tsuji, Brian. / New polymyxin B dosing strategies to fortify old allies in the war against KPC-2-producing Klebsiella pneumoniae. In: Antimicrobial Agents and Chemotherapy. 2017 ; Vol. 61, No. 4.

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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).",

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New polymyxin B dosing strategies to fortify old allies in the war against KPC-2-producing Klebsiella pneumoniae. / Bulman, Zackery P.; Satlin, Michael J; Chen, Liang; Kreiswirth, Barry N; Shin, Beom Soo; Walsh, Thomas J.; Holden, Patricia N; Forrest, Alan; Nation, Roger L ; Li, Jian; Tsuji, Brian.

In: Antimicrobial Agents and Chemotherapy, Vol. 61, No. 4, e02023-16, 01.04.2017.

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

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