Cefiderocol non-susceptibility among carbapenem-resistant Enterobacterales: Data from the 2024 Antimicrobial Testing...

To evaluate cefiderocol (FDC) activity against carbapenem-resistant Enterobacterales (CRE) globally, characterize the β-lactamase gene profiles of non-susceptible isolates by metallo-β-lactamase status, and assess alternative agents.

Cefiderocol minimum inhibitory concentrations for 1657 CRE isolates from the 2024 Antimicrobial Testing Leadership and Surveillance programme were determined by broth microdilution. Isolates underwent molecular screening for carbapenemase, extended-spectrum β-lactamase, and AmpC genes. Between-group differences were assessed using odds ratios (ORs) with Fisher's exact tests.

Overall FDC susceptibility rate was 93.1% by Clinical and Laboratory Standards Institute and 80.7% by EUCAST criteria, respectively. Non-susceptibility varied substantially by genus: Escherichia spp. 25.3%, Providencia spp. 14.0%, Enterobacter spp. 12.5%, and Klebsiella spp. 3.5%. FDC non-susceptibility rates revealed further heterogeneity within genera; notably, Enterobacter cloacae (23.1%) and Enterobacter kobei (50.0%) had substantially higher non-susceptibility than Enterobacter hormaechei (7.2%), and Providencia rettgeri (22.2%) exceeded Providencia stuartii (8.0%). Asia had the highest unadjusted non-susceptibility rate (10.5%; OR 4.73, P = 0.002); however, in a multivariable logistic regression adjusting for genus, age, and specimen source, genus was the dominant independent predictor (Escherichia spp. adjusted OR 8.21, 95% confidence interval 4.75-14.17), and the Asia effect was attenuated to a non-significant trend (adjusted OR 3.99, 0.93-17.14, P = 0.063). Among 115 non-susceptible isolates, 51 (44.3%) were metallo-β-lactamase-positive, predominantly bla_NDM (94.1%), with high extended-spectrum β-lactamase co-carriage (bla_CTX-M 74.5%), while 50 (43.5%) harboured no identifiable carbapenemase gene.

FDC remains active against most CRE globally, although non-susceptibility varies by genus, species and region. Notably, nearly half of non-susceptible isolates lacked detectable carbapenemase genes.