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

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

3 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 languageEnglish
Article numbere02023-16
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume61
Issue number4
DOIs
Publication statusPublished - 1 Apr 2017

Keywords

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

Cite this

Bulman, Z. P., Satlin, M. J., Chen, L., Kreiswirth, B. N., Shin, B. S., Walsh, T. 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), [e02023-16]. https://doi.org/10.1128/AAC.02023-16
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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Bulman, ZP, Satlin, MJ, Chen, L, Kreiswirth, BN, Shin, BS, Walsh, TJ, Holden, PN, Forrest, A, Nation, RL, 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, vol. 61, no. 4, e02023-16. https://doi.org/10.1128/AAC.02023-16

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

TY - JOUR

T1 - New polymyxin B dosing strategies to fortify old allies in the war against KPC-2-producing Klebsiella pneumoniae

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 - Tsuji, Brian

PY - 2017/4/1

Y1 - 2017/4/1

N2 - 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).

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).

KW - KPC-producing K. pneumoniae

KW - Meropenem

KW - PK/PD

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KW - Rifampin

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U2 - 10.1128/AAC.02023-16

DO - 10.1128/AAC.02023-16

M3 - Article

VL - 61

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 1098-6596

IS - 4

M1 - e02023-16

ER -

Bulman ZP, Satlin MJ, Chen L, Kreiswirth BN, Shin BS, Walsh TJ et al. New polymyxin B dosing strategies to fortify old allies in the war against KPC-2-producing Klebsiella pneumoniae. Antimicrobial Agents and Chemotherapy. 2017 Apr 1;61(4). e02023-16. https://doi.org/10.1128/AAC.02023-16

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