Abstract
Original language | English |
---|---|
Article number | e02023-16 |
Number of pages | 9 |
Journal | Antimicrobial Agents and Chemotherapy |
Volume | 61 |
Issue number | 4 |
DOIs | |
Publication status | Published - 1 Apr 2017 |
Keywords
- KPC-producing K. pneumoniae
- Meropenem
- PK/PD
- Polymyxin B
- Rifampin
Cite this
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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
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
KW - Polymyxin B
KW - Rifampin
UR - http://www.scopus.com/inward/record.url?scp=85016992159&partnerID=8YFLogxK
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 -