Cefiderocol is a novel cephalosporin–siderophore conjugate antibiotic with significant potential in combating infections caused by multidrug-resistant (MDR) Gram-negative bacilli. Its antibacterial activity remains largely unaffected by most β-lactamases, including metallo-β-lactamases, and—due to its siderophore-mediated uptake—it demonstrates reduced susceptibility to resistance mechanisms such as porin loss or active efflux, compared to other β-lactam agents. This study aimed to evaluate the in vitro susceptibility of carbapenemase-producing Gram-negative bacilli isolated from hospitalized patients to cefiderocol. A total of 102 clinical isolates of carbapenemase-producing Enterobacterales and non-fermenting Gram-negative bacteria were collected from hospitals in Łódź, Poland. Antimicrobial susceptibility to cefiderocol was determined using minimum inhibitory concentration (MIC) test strips and disc diffusion methods. The findings were inconclusive, as the presence of a technical uncertainty zone made the interpretation of results challenging. The high cost of cefiderocol therapy and the difficulties associated with interpreting susceptibility results currently limit its clinical application. Further research is needed to establish standardized, reliable, and widely accessible methods for determining cefiderocol susceptibility.
