Activity of ceftazidime-avibactam combinations against carbapenem-resistant Klebsiella pneumoniae assessed by checkerboard method

The aim of this study is to detect the carbapenemase type and to determine the in vitro effects of ceftazidime/avibactam-colistin, ceftazidime/avibactam-meropenem and ceftazidime/avibactam-tigecycline combinations against Carbapenem-Resistant Klebsiella pneumoniae (CRKP) isolates. A total of 35 CRKP isolates were included to the study. The minimum inhibitory concentrations of ceftazidime/avibactam, meropenem, colistin and tigecycline were determined by broth dilution method. Synergistic effects of ceftazidime/avibactam-colistin, ceftazidime/avibactam-meropenem and ceftazidime/avibactam-tigecycline were investigated by microdilution checkerboard method. Carbapenemase genes (blaOXA-48, blaNDM, blaKPC, blaIMP, blaVIM) were detected by multiplex PCR. All of the isolates were resistant to meropenem, whereas 77.1% of the isolates were resistant to ceftazidime/avibactam and 14.3% of the isolates were resistant to colistin.The carbapenemase genes of the CRKP isolates were determined as 17 OXA-48+NDM, 9 KPC, 6 OXA-48, 1 NDM, 1 KPC+NDM and 1 KPC+OXA-48. Ceftazidime/avibactam-colistin, ceftazidime/avibactam-meropenem and ceftazidime/avibactam-tigecycline combinations were synergistic against 5.7% (2/35), 17.1% (6/35), and 5.7% (2/35) of the isolates, respectively. Ceftazidime/avibactam-meropenem was the most effective synergistic combination in our study, showing synergism in 17.1% of isolates, however, the synergistic effect varied depending on the CRKP isolate tested.