A Seven-Year Microbiological and Molecular Study of Bacteremias Due to Carbapenemase-Producing Klebsiella Pneumoniae: An Interrupted Time-Series Analysis of Changes in the Carbapenemase Gene's Distribution after Introduction of Ceftazidime/Avibactam

Background: Ceftazidime/avibactam (CZA) is a new option for the treatment of KPC-producing Klebsiella pneumoniae. The aim of this study was to determine resistance patterns and carbapenemase genes among K. pneumoniae (CP-Kp) bacteremic isolates before and after CZA introduction. Methods: K. pneumoniae from blood cultures of patients being treated in a Greek university hospital during 2015-21 were included. PCR for bla(KPC), bla(VIM), bla(NDM) and bla(OXA-48) genes was performed. Results: Among 912 K. pneumoniae bacteremias: 725 (79.5%) were due to carbapenemase-producing isolates; 488 (67.3%) carried bla(KPC); 108 (14.9%) bla(VIM); 100 (13.8%) bla(NDM); and 29 (4%) carried a combination of bla(KPC), bla(VIM) or bla(NDM). The incidence of CP-Kp bacteremias was 59 per 100,000 patient-days. The incidence of CP-Kp changed from a downward pre-CZA trend to an upward trend in the CZA period (p = 0.007). BSIs due to KPC-producing isolates showed a continuous downward trend in the pre-CZA and CZA periods (p = 0.067), while BSIs due to isolates carrying bla(VIM) or bla(NDM) changed from a downward trend in the pre-CZA to an upward trend in the CZA period (p < 0.001). Conclusions: An abrupt change in the epidemiology of CP-Kp was observed in 2018, due to the re-emergence of VIM-producing isolates after the suppression of KPC-producing ones via the use of CZA.