Evaluation of ceftazidime/avibactam alone and in combination with amikacin, colistin and meropenem against carbapenemase-producing Klebsiella pneumoniae

Abstract

Backgound: Carbapenemase-producing Klebsiella pneumoniae (K. pneumoniae) poses a major threat to human health worldwide. Combination therapies of antibiotics with different mechanisms have been recommended in literatures. This study evaluated the in vitro antibacterial actions and synergistic actions of ceftazidime/avibactam alone and in combinations with other antibiotics. Methods: A total of 40 K. pneumoniae isolates were isolated from different clinical specimens. The revealing of carbapenemase production was performed using the modified carbapenem inactivation method. Antimicrobial susceptibility testing was conducted to determine the minimum inhibitory concentrations (MICs) of ceftazidime/ avibactam (CZA/AVI), amikacin (AK) meropenem (MEM), and colistin. The checkerboard method was used to assess the synergistic activity of these antibiotic combinations. Results: All (100%) isolates were susceptible to colistin, while only 2.5% were susceptible to CZA/AVI. All isolates were identified as carbapenemase producers, with 25% being serine carbapenemase producers and 75% being Metallo-β-lactamase producers. The fractional inhibitory concentration index (FICI) method revealed additive effect of CZA/AVI with AK in 42% of isolates, while combination of CZA/AVI with MEM was synergistic against 2.5% and additive in 55% of the isolates. Colistin displayed a synergistic effect against 7.5% of isolates and additive effect in 30% when was combined with CZA/AVI. The mean MIC value of CZA/AVI against the 40 K. pneumoniae strains decreased significantly when combined with AK, MEM and colistin and the greatest reduction was when combined with colistin (P<0.001). Conclusion: There is an emerging resistance developed against CZA/AVI. Thus, combination therapy including ceftazidime/avibactam may benefit more than monotherapy against carbapenemase-producing K. pneumoniae.