To investigate the in vivo antibacterial activity of fosfomycin combined with imipenem by using the infection model of Galleria mellonella with Klebsiella pneumonia.

Four strains of carbapenem resistant Klebsiella pneumonia (CRKP) and four strains of carbapenem sensitive Klebsiella pneumonia (CSKP) isolated from patients with bloodstream infection were collected from Wuxi Second People's Hospital Affiliated Nanjing Medical University on January to December 2020. The serotypes of Klebsiella pneumoniae capsule were typed by wzi gene sequencing. The virulence model of wax moth was used to calculate the 80% lethal dose of different strains in 96 h, then the antimicrobial susceptibility test of wax borer was carried out to analyze the antibacterial activity of fosfomycin combined with imipenem in vivo. Finally, the bacterial load was detected by the hemolymph test of wax borer.

Wzi gene sequencing showed that the serotypes of all the four CRKP strains were k64. The serotypes of four CSKP strains were K1, K2, K50 and k26, respectively. The in vivo antibacterial activity result of combined drugs showed that when the MIC value of imipenem was ≤8 mg·L^-1 and fosfomycin ≤32 mg·L^-1 in CRKP group, the antibacterial effect of the combination on two strains was significantly better than that of single drug, and the load clearance rate of hemolymph bacteria was higher. The antibacterial effect of the combination on K1-KP531 and K2-KP532 from high virulence in CSKP group was better than imipenem or fosfomycin alone, with the load clearance rate of hemolymph bacteria lower than that of low virulence strains in CSKP group.

When imipenem MIC≤8 mg·L^-1 and fosfomycin was sensitive, fosfomycin and imipenem showed synergistic effect in the Klebsiella pneumoniae infection model of Galleria mellonella.