Investigation of in vitro efficacy of meropenem/ polymyxin B and meropenem/fosfomycin combinations against carbapenem resistant Klebsiella pneumoniae strains

Adaleti, Riza and Nakipoglu, Yasar and Calik, Seyma and Arici, Neslihan and Kansak, Nilgun and Senbayrak, Seniha and Aksaray, Sebahat (2023) Investigation of in vitro efficacy of meropenem/ polymyxin B and meropenem/fosfomycin combinations against carbapenem resistant Klebsiella pneumoniae strains. ACTA MICROBIOLOGICA ET IMMUNOLOGICA HUNGARICA, 70 (2). pp. 155-160. ISSN 1217-8950

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Abstract

The incidence of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) is increasing worldwide, and very limited number of effective antibiotics are available for therapy. In our study, the in vitro efficacy of meropenem/polymyxin B and meropenem/fosfomycin combinations against CRKP strains was investigated. The efficiency of meropenem/polymyxin B and meropenem/fosfomycin combinations was tested by checkerboard microdilution and checkerboard agar dilution methods, respectively, against 21 CRKP strains containing major carbapenem resistant genes (7 blaKPC, 7 blaOXA-48 gene, and 7 blaOXA-48 thorn blaNDM), and seven additional CRKP strains without carbapenemase genes. Among the 28 CRKP strains, the meropenem/polymyxin B combination was synergistic in ten (35.7%), partially synergistic in 12 (42.8%), and indifferent in six (21.4%) isolates. The meropenem/ fosfomycin combination was found to be synergistic in three isolates (10.7%), partially synergistic in 20 (71.4%), and indifferent in five (17.8%). In 21 strains containing carbapenem resistance genes, meropenem/polymyxin B and meropenem/fosfomycin combinations exhibited synergistic/partial synergistic effects in 15 (71.4%) and 16 (76.2%) strains, respectively, compared to 100% synergistic/partial synergistic efficiency in both combinations in seven strains free of carbapenemase genes. No antagonistic effect was detected in either combination.Regardless of presence or absence of carbapenem resistance genes, meropenem/polymyxin B and meropenem/fosfomycin combinations both demonstrated high synergistic and partial synergistic activity against 78.4% and 82.1% of CRKP strains, respectively. Also, they have no antagonistic effects and can be used successfully to prevent therapeutic failure with monotherapy, according to our in vitro studies.

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