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J Microbiol Immunol Infect. 2014 Oct;47(5):406-11. doi: 10.1016/j.jmii.2013.05.007. Epub 2013 Jul 6.

Synergy of imipenem/colistin methanesulfonate combinations against imipenem-nonsusceptible multidrug-resistant Acinetobacter baumannii.

Author information

1
Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Chang Gung University College of Medicine, Taoyuan, Taiwan. Electronic address: hsleu@adm.cgmh.org.tw.
2
Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Chang Gung University College of Medicine, Taoyuan, Taiwan.
3
Chang Gung University College of Medicine, Taoyuan, Taiwan; Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.

Abstract

BACKGROUND:

The optimal combination ratio of imipenem to colistin methanesulfonate (CMS) against imipenem-nonsusceptible multidrug-resistant Acinetobacter baumannii (INS-MDRAB) has not been determined in previous studies. To provide an alternative therapeutic option for clinical INS-MDRAB isolates, we investigated whether clinically achievable serum concentrations of CMS in combination with imipenem enhance the in vitro activity of imipenem against the INS-MDRAB isolates.

MATERIALS AND METHODS:

Fifty-nine INS-MDRAB isolates with imipenem minimal inhibitory concentration (MIC) values of ≥8 mg/L were selected randomly from the Clinical Microbiology Laboratory at a university-affiliated medical center between July 1998 and May 2005. The in vitro activity of imipenem among these 59 clinical isolates was explored via serial two-fold dilutions containing a range of imipenem concentration from 0.125 mg/L to 256 mg/L, in combination with two fixed CMS concentrations at 0.5 mg/L and 1 mg/L. Genotype classification was performed using the pulsed-field gel electrophoresis method and infrequent-restriction-site polymerase chain reaction.

RESULTS:

A significant reversal of imipenem resistance (i.e., MICs ≤ 4 mg/L) was observed in 34 (57.6%) isolates and 44 (74.6%) isolates with the tests of CMS concentrations at 0.5 mg/L and 1 mg/L, respectively (p = 0.041). Genotype 1 was predominant (43 isolates, 72.9%) with imipenem resistance reversal rates of 51.2% and 79.1% (p = 0.004) in the tests of CMS at 0.5 mg/L and 1 mg/L, respectively.

CONCLUSION:

The synergy of imipenem/CMS against INS-MDRAB was significantly better for the CMS concentration at 1 mg/L than that at 0.5 mg/L, especially in our predominant clone. Our results provided insightful information for treating INS-MDRAB infections in clinical practice.

KEYWORDS:

Colistin; Imipenem; Multidrug-resistant Acinetobacter baumannii

PMID:
23834782
DOI:
10.1016/j.jmii.2013.05.007
[Indexed for MEDLINE]
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