Evaluation of In Vitro Activity of Ceftolozane-tazobactam and Ceftazidime-avibactam Against Carbapenemase-producing Multi-drug Resistant Klebsiella pneumoniae Isolates

Abstract

Introduction: This study aims to assess the in vitro activity of ceftazidime-avibactam (CZA) and ceftolozane-tazobactam (C/T) against the multi-drug resistant (MDR) Klebsiella pneumoniae. Furthermore, we aimed to determine the types of carbapenemase enzyme responsible for carbapenem resistance and compare the activity of ceftolozane-tazobactam and CZA according to the types of carbapenemase enzymes produced. Materials and Methods: Twenty-two MDR isolates were investigated in the study. The identification and antimicrobial susceptibilities of the isolates were performed by VITEK 2 (BioMérieux, France) automated system. The activity of C/T and CZA was determined by the gradient strip test (Liofilchem MIC strip test, Italy). In all K. pneumoniae isolates, blaIMP-1, blaKPC, blaNDM-1, blaOXA-48 and blaVIM gene regions encoding the carbapenemase enzyme were investigated by using Xpert CARBA-R test kits (Cepheid, Sunnyvale, CA, USA) of the Gene-Xpert® system. Results: Ceftolozane-tazobactam resistance was detected in 21 (95%) isolates, whereas CZA resistance was detected in six (27%) isolates. Among the 22 K. pneumoniae isolates, NDM-1 gene region was detected in three, NDM-1+OXA-48 gene region was detected in two, OXA-48 was detected in eight, and KPC gene region was detected in nine isolates. VIM and IMP-1 gene regions were not detected. Ceftolozane-tazobactam resistance was detected in seven isolates, whereas CZA resistance was not detected among the eight K. pneumoniae isolates producing only OXA-48. NDM-1 and OXA-48 co-producing isolates were detected resistant to C/T and CZA with high minimum inhibitory concentration (MIC) levels (MIC ≥256 µg/ml). All NDM-1 producing isolates had high MIC levels (MIC ≥256 µg/ml) to both C/T and CZA. Ceftazidime-avibactam resistance was detected in only one isolate, whereas C/T resistance was detected in all K. pneumoniae isolates producing KPC. Ceftolozane-tazobactam was detected inefficient whereas CZA was found very efficient in MDR K. pneumoniae isolates producing KPC. Conclusion: According to the obtained data, we detected the in vitro antibacterial activity of CZA against the MDR K. pneumoniae isolates was superior to that of C/T. Ceftolozane-tazobactam was found to be weakly efficient, whereas CZA was found to be highly efficient against the MDR K. pneumoniae isolates producing OXA-48 and KPC. Because avibactam can inhibit the activity of KPC-type carbapenemase, the combination drug CZA should be considered to be effective in the treatment of KPC-type carbapenemase-producing strains but noneffective against NDM-type carbapenemase-producing strains.

Keywords

• klebsiella pneumoniae
• multi-drug resistant
• ceftazidime-avibactam
• ceftolozane-tazobactam
• carbapenemase enzymes