In Vitro Efficacy of Ceftazidime-avibactam Against blaOXA-48-producing Klebsiella pneumoniae Isolates

Abstract

Introduction: The healthcare burden of carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae) infections is growing. The newly developed beta-lactam/beta-lactamase inhibitor combination, ceftazidime-avibactam, shows promise in the treatment of such infections. We aimed to explore the in vitro efficacy of ceftazidime-avibactam against carbapenem-resistant K. pneumoniae isolates carrying the blaOXA-48 gene. Materials and Methods: The isolates were identified using MALDI-TOF MS (Brucker, USA). The isolates that were non-susceptible to imipenem, meropenem, or ertapenem by the disk diffusion method using the European Committee of Antimicrobial Susceptibility Testing (EUCAST) breakpoints were screenes. Minimum inhibitory concentration (MIC) values were determined via broth microdilution according to the EUCAST criteria. A time-kill study was performed according to Clinical and Laboratory Standards Institute guidelines. Beta-lactamase genes were screened for using polymerase chain reaction with previously published primers. Results: A total of 129 K. pneumoniae isolated between April 2011 and February 2021 were studied. Of these, 98, 23, and eight isolates carried the blaOXA-48, blaNDM, and blaOXA-48 with blaNDM genes, respectively. All isolates carrying the blaNDM gene were resistant to ceftazidime-avibactam. Approximately 79.6% of the blaOXA-48-positive isolates were susceptible to ceftazidime-avibactam. The time-kill study for ceftazidime-avibactam was performed with one blaOXA-48-positive isolate (MIC, 4 mg/l). Ceftazidime-avibactam time-kill kinetics were evaluated in multiples of MIC. There was a decrease of ≥3-log10 in CFU/ml count at a concentration of 8, 16, and 32 MIC at 6 hours. The minimum bactericidal concentration was 8 mg/l. Conclusion: Ceftazidime-avibactam is an important treatment alternative alternative for blaOXA-48 positive carbapenem-resistant K. pneumoniae infections. The most rational approach to the treatment of carbapenem-resistant K. pneumoniae infections appears to be the initiatiion of targeted therapy according to culture antibiogram results or revision of the empirically initiated combination or monotherapy as early as possible according to culture antibiogram results.

Keywords

• blaoxa-48
• blandm
• ceftazidime-avibactam
• antimicrobial susceptibility
• klebsiella pneumoniae