| Summary: | Cefiderocol (CFDC) is a novel, broad-spectrum siderophore cephalosporin with potential activity against multi-drug (MDR) and extensively drug-resistant (XDR) Enterobacterales, including carbapenem-resistant strains. We assessed the in vitro susceptibility to CFDC of MDR, and XDR <i>E. coli</i> isolates derived from clinical samples of hospitalized patients. Disk diffusion (DD) and MIC (minimum inhibitory concentration) test strip (MTS) methods were used. The results were interpreted based on EUCAST (version 12.0 2022) recommendations. Among all <i>E. coli</i> isolates, 98 (94.2%) and 99 (95.2%) were susceptible to CFDC when the DD and MTS methods were used, respectively (MIC range: <0.016–4 µg/mL, MIC<sub>50</sub>: 0.19 µg/mL, MIC<sub>90</sub>: 0.75 µg/mL). With the DD and MTS methods, all (MIC range: 0.016–2 µg/mL, MIC<sub>50</sub>: 0.19 µg/mL, MIC<sub>90</sub>: 0.75 µg/mL) but three (96.6%) ESBL-positive isolates were susceptible to CFDC. Out of all the metallo-beta-lactamase-positive <i>E. coli</i> isolates (MIC range: 0.016–4 µg/mL, MIC<sub>50</sub>: 0.5 µg/mL, MIC<sub>90</sub>: 1.5 µg/mL), 16.7% were resistant to CFDC with the DD method, while 11.1% were resistant to CFDC when the MTS method was used. CFDC is a novel therapeutic option against MDR and XDR <i>E. coli</i> isolates and is promising in the treatment of carbapenem-resistant <i>E. coli</i> strains, also for those carrying Verona integron-encoded metallo-beta-lactamases, when new beta-lactam-beta-lactamase inhibitors cannot be used.
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