In vitro susceptibilities of isolates of potentially naturally inducible chromosomal AmpC-producing metallo-β-lactamase-negative carbapenem-resistant Enterobacterales species to ceftazidime-avibactam: Data from the Antimicrobial Testing Leadership and Surveillance Programme, 2012–2019

Objectives: A total of 74 570 potentially naturally inducible chromosomal AmpC-producing (PNIC-AmpC) Enterobacterales isolates included in the Antimicrobial Testing Leadership and Surveillance Programme were obtained worldwide during 2012–2019 (22 503 from 2012–2014 and 52 067 from 2015–2019). Of these isolates, 117 and 711 obtained during 2012–2014 and 2015–2019, respectively, were carbapenem-resistant Enterobacterales (PNIC-AmpC-CRE). The MICs of ceftazidime-avibactam for these isolates were determined using the broth microdilution method. Methods: Genes encoding different Ambler classes of β-lactamases were investigated using multiplex PCR. After 97 isolates harbouring genes encoding metallo-β-lactamases (MβL) were excluded, 731 PNIC-AmpC MβL-negative CRE isolates (101 from 2012–2014 and 630 from 2015–2019) were included in this study. Results: Enterobacter cloacae (E. cloacae) complex species, Escherichia coli (E. coli) and Citrobacter freundii (C. freundii) complex species accounted for 36.3% (n = 265), 30.4% (n = 222) and 11.8% (n = 86), respectively, followed by Providencia species (n = 72), Serratia species (n = 52) and Klebsiella aerogenes (n = 34). The resistance rates to ceftazidime-avibactam for the overall PNIC-AmpC MβL-negative CRE isolates markedly differed between the two periods (35.6% vs. 63.3%; P < 0.001). Similar trends were observed for the MβL-negative-CR-E. cloacae complex species (47.4% vs. 65.2%; P = 0.046) and MβL-negative-CR-E. coli (16.2% vs. 63.8%; P < 0.001) but not for MβL-negative-CR-C. freundii complex species (40% vs. 62%; P = 0.153). Amongst the PNIC-AmpC MβL-negative CRE isolates, resistance rates to ceftazidime-avibactam worsened. Conclusions: Caution should be taken when empirically prescribing ceftazidime-avibactam for infections caused by PNIC-AmpC-CRE before susceptibility data are available.