In vitro antimicrobial activity of avibactam in combination with ceftazidime, aztreonam or meropenem against carbapenem-resistant Klebsiella pneumoniae

Abstract:

Objective To study in vitro antimicrobial activity of combination of avibatam (fixed concentration of 4 μg/mL) and β-lactam antibiotics against carbapenem-resistant Klebsiella pneumoniae(CRKP). Methods Non-repetitive CRKP strains isolated from a hospital were collected, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of ceftazidime/avibatam, aztreonam/avibatam, and meropenem/avibatam against CRKP was detected with broth microdilution method, carbapenemase resistance genes were determined by polymerase chain reaction (PCR). Results Among 63 CRKP strains, 57 strains harbored bla_KPC gene, 5 strains harbored metalloenzyme gene, and 1 strain did not found common carbapenem-resistant gene. Among 57 CRKP strains with positive bla_KPC gene, MICs of ceftazidime/avibatam, aztreonam/avibatam, and meropenem/avibatam were ≤8/4, 4/4, and 0.5/4 μg/mL respectively, avibatam significantly decreased the MIC₅₀ and MIC₉₀ values of ceftazidime, aztreonam and meropenem. Among 5 CRKP strains with positive metalloenzyme gene, avibatam did not decrese MIC₉₀ of ceftazidime and meropenem, but decreased MIC₉₀ of aztreonam by 99.8%, MBC₅₀ and MIC₅₀ of three compound of avibatam against 63 strains of CRKP were identical, their MBC₉₀ and MIC₉₀ were identical. Conclusion Combination of avibatam with three common β-lactam antibiotics (ceftazidime, aztreonam and meropenem) has a good antimicrobial effect on CRKP strains expressing KPC-2 carbapenemase, combination with ceftazidime or meropenem has no inhibitory effect on metalloenzyme-harboring CRKP strains, but combination with aztreonam has a good antimicrobial effect on metalloenzyme-harboring CRKP strains.