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

ABSTRACT

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 ß-lactamases were investigated using multiplex PCR. After 97 isolates harbouring genes encoding metallo-ß-lactamases (MßL) were excluded, 731 PNIC-AmpC MßL-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 MßL-negative CRE isolates markedly differed between the two periods (35.6% vs. 63.3%; P < 0.001). Similar trends were observed for the MßL-negative-CR-E. cloacae complex species (47.4% vs. 65.2%; P = 0.046) and MßL-negative-CR-E. coli (16.2% vs. 63.8%; P < 0.001) but not for MßL-negative-CR-C. freundii complex species (40% vs. 62%; P = 0.153). Amongst the PNIC-AmpC MßL-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.