The Effects of Colistin on Imipenem MICs in OXA-48 Producing Klebsiella pneumoniae Isolates: An In Vitro Study

Abstract

Introduction: A new approach to carbapenem resistance-K. pneumoniae infections is to use combination drug therapies. However, little data are available about the effectiveness of the in vitro carbapenem plus colistin combination against oxacillinase-48 (OXA-48) producing K. pneumoniae. Therefore, the aim of this study is to assess the potential synergistic activity of imipenem plus colistin in OXA-48-producing K. pneumoniae strains and investigate the changes in the imipenem minimal inhibitory concentrations (MICs) to varying MICs of colistin. Materials and Methods: Carbapenem and colistin resistance (ColR) genes were investigated by polymerase chain reaction. In the first stage, synergistic properties were determined by the checkerboard combination method. In the second step, at varying colistin concentrations, changes in the imipenem MICs were investigated. Results: Colistin MIC50 2 µg/ml, MIC90 16 µg/ml, and imipenem MIC50 32 µg/ml, MIC90 128 µg/ml were found, respectively. According to the fractional inhibitor concentration (FIC) formula, 62.2% of the isolates were synergistic, and 37.8% were indifference. When the colistin was fixed at 0.125 µg/ml, 0.25 µg/ml, 0.5 µg/ml, 1 µg/ml, and 2 µg/ml, respectively. Significant decreases were observed in the imipenem MICs, especially of colistin-sensitive isolates. However, imipenem MICs of ColR isolates did not decrease to susceptible levels. Conclusion: This information will facilitate the design of antibiotic regimens that are more suitable for treating infections due to such pathogens producing OXA-48 and prolong these antibiotics’ efficacy. Further in vitro research is required to determine which treatment combination is best and its optimal use as combination therapy to treat these infections.

Keywords

• colistin
• imipenem
• combination
• klebsiella pneumoniae
• oxa-48