In vitro activity of ceftazidime/avibactam against carbapenem-resistant Klebsiella pneumoniae clinical isolates and comparison of susceptibility methods

Abstract

Background: Due to the limited availability of therapeutic options, carbapenem-resistant Klebsiella pneumoniae is a clinical challenge. Carbapenem resistance can occur with or without carbapenemase production; in both cases, ceftazidime/avibactam is a promising treatment alternative. Methods: The in vitro activity of ceftazidime/avibactam was evaluated in 186 clinical isolates of carbapenem-resistant K. pneumoniae from 11 hospitals in Chile; 59 were bla_KPC-producing and 127 were non-carbapenemase-producing. The minimum inhibitory concentration (MIC) was determined by broth microdilution and compared with epsilometry and disk diffusion. Results: 100% of carbapenem-resistant K. pneumoniae isolates were susceptible to ceftazidime/avibactam with MICs between 0.25 and 8 µg/mL. Fifteen isolates (12 non-carbapenemase-producing) showed an MIC of 8 µg/mL. High concordance (>96%) was noted when broth microdilution was compared with epsilometry and disk diffusion. Discussion: Ceftazidime/avibactam was active in Chilean clinical isolates of carbapenem-resistant K. pneumoniae. Given that isolates with MICs close to the cut-off point were observed, it is recommended that their activity be monitored. The findings of epsilometry and disk diffusion showed satisfactory agreement with broth microdilution; therefore, they are suggested as alternatives in clinical practice.  

Keywords: ceftazidime/avibactam, Klebsiella pneumoniae, carbapenem resistance.