To assess the in vitro antibacterial activity of polymyxin B in combination with meropenem, amikacin, and fosfomycin against carbapenem-resistant Enterobacteriaceae (CRE) strains carrying various resistance genes.

A total of 76 CRE strains isolated from the clinical laboratory of our hospital between 2019 and 2021 were collected for identification and confirmation of carbapenemase genotype. The minimum inhibitory concentrations (MIC) of polymyxin B, meropenem, amikacin, and fosfomycin against CRE were determined using the broth microdilution method.The in vitro combined sensitivity tests of polymyxin B with meropenem, amikacin, and fosfomycin were performed using the microdilution checkerboard method to calculate the fractional inhibitory concentration index (FICI) for determining their interactions.

Among the 76 strains of CRE, 24 strains were identified to carry the bla_KPC, while 28 strains carried the bla_NDM and another 24 strains carried the bla_OXA-48-like. The drug-resistance rates of CRE strains to polymyxin B, meropenem, amikacin, and fosfomycin were determined as 3%, 92%, 39%, and 45%, respectively. The highest synergistic + partial synergistic rate was observed in combination of polymyxin B with meropenem (54%), followed by fosfomycin (43%) and amikacin (18%). For CRE carrying bla_KPC, bla_OXA-48-like, or bla_NDM, the synergistic + partial synergistic rates of polymyxin B combined with fosfomycin were 37%, 42%, and 50%, respectively, while combined with meropenem were 75%, 21%, and 64%, respectively, and combined with amikacin were 8%, 25%, and 21%, respectively. No antagonistic effect was observed between polymyxin B and these three antibiotics.

The combination of polymyxin B and meropenem exhibits the best synergistic antibacterial effect against CRE, and the combined effect is related to the drug-resistance genotype of bacteria, so active detection of drug-resistance genes can help to promote the rational use of antibiotics in clinical practice.