In vitro and in vivo Effect of Antimicrobial Agent Combinations Against Carbapenem-Resistant Klebsiella pneumoniae with Different Resistance Mechanisms in China

This study aimed to evaluate the in vitro and in vivo effects of different combinations of antimicrobial agents against carbapenemase-producing and non-producing from China. A checkerboard assay of meropenem (MEM), amikacin (AK), tigecycline (TGC), colistin (COL) and their combinations was carried out against 58 clinical carbapenem-resistant (CRKp) isolates, including 11 carbapenemase-non-producing isolates and 21 isolates producing KPC-2 enzyme, 11 NDM-1, 13 IMP, one VIM-1 and one OXA-48. The checkerboard assay was analyzed by the fractional inhibitory concentration index (FICI). A time-kill assay and infection model were conducted to evaluate the in vitro and in vivo effects of the four drugs alone and in combination. In the checkerboard assay, TGC+AK and MEM+AK combinations showed the highest synergistic effect against KPC-2 and NDM-1 carbapenemase-producing isolates, with synergy+partial synergy (defined as FICI