Global susceptibility profiles and potential resistance mechanisms of ceftazidime-avibactam-resistant, non-carbapenemase-producing carbapenem-resistant Enterobacterales: 2020-23 data from the Antimicrobial Testing Leadership and Surveillance.

OBJECTIVES

A total of 2361 ceftazidime-avibactam-resistant non-carbapenemase-producing (CP) carbapenem-resistant Enterobacterales (CRE) isolates were identified, accounting for 45.8% of global non-CP-CRE (n = 5156) and 3.0% of all Enterobacterales isolates (n = 78 371) during 2020-23. The high prevalence of non-CP-CRE resistant to ceftazidime-avibactam prompted investigations into alternative antibiotics for the effective management of ceftazidime-avibactam-resistant non-CP-CRE infections.

METHODS

Using the susceptibility breakpoints for Enterobacterales recommended by CLSI 2025 (for ceftazidime-avibactam, amikacin and meropenem-vaborbactam), EUCAST 2025 (for aztreonam-avibactam, colistin) and the US FDA (for tigecycline), susceptibility data of key antibiotics against global ceftazidime-avibactam-resistant non-CP-CRE isolates were extracted from the 2020-23 Antimicrobial Testing Leadership and Surveillance database. Additionally, data on genes encoding ESBL and plasmid-mediated AmpC enzymes were also analysed.

RESULTS

In vitro susceptibility rates of global ceftazidime-avibactam-resistant non-CP-CRE isolates to aztreonam-avibactam, colistin and tigecycline all exceeded 86%. In contrast, non-susceptibility rates to amikacin and meropenem-vaborbactam were 78.7% and 94.8%, respectively. These high non-susceptibility rates for amikacin and meropenem-vaborbactam persisted regardless of region, infection source or species [Klebsiella pneumoniae (n = 1576), Escherichia coli (n = 388) and potentially chromosomal AmpC hyperproducers (n = 337)]. The prevalence of blaCTX-M-15 (the predominant ESBL) was closely correlated with amikacin non-susceptibilities across all three species groups (r = 0.901; P = 0.286).

CONCLUSION

Based on the data from this study, poor in vitro susceptibility rates for amikacin and meropenem-vaborbactam against contemporary ceftazidime-avibactam-resistant non-CP-CRE were observed. In contrast, aztreonam-avibactam, colistin and tigecycline appear to be reasonable options for the management of infections caused by ceftazidime-avibactam-resistant non-CP-CRE.