Mikrobiyol Bul. 2026 Jan;60(1):14-27. doi: 10.5578/mb.202601103.
ABSTRACT
Carbapenem-resistant Enterobacterales (CRE) are pathogens that cause difficult-to-treat infections and are identified as a priority threat by global health authorities. Increasing resistance rates limit the efficacy of existing antibiotics and increase the risk of mortality. Cefiderocol, an innovative siderophore cephalosporin, shows broad-spectrum in vitro activity against both serine and metallo-β-lactamases and remains largely stable against classical resistance mechanisms. This study aimed to evaluate the in vitro activity of cefiderocol, the concordance of susceptibility tests performed using three methods [broth microdilution (BMD) based commercial ComASP® panel , gradient strip and disk diffusion] and its association with major carbapenemase genes and the ceftazidime/avibactam (CZA) susceptibility. The study included 100 carbapenem-resistant Enterobacterales isolates from a single center during 2023- 2024. Species identification was performed using the VITEK 2 system. Cefiderocol susceptibility was tested using the reference method (BMD) based commercial ComASP® panel, the gradient strip test and disk diffusion. Five major carbapenemase genes (blaOXA-48, blaKPC, blaNDM, blaVIM, blaIMP) were screened by real-time polymerase chain reaction for the molecular diagnosis. Quantitative and categorical agreement between susceptibility tests were assessed using Passing-Bablok and Deming regression analyses. Cohen’s kappa, McNemar’s test and error types (major and very major) were analyzed. Comparative analyses with CZA susceptibility and genetic findings were also performed. According to BMD, 99% of the isolates were susceptible to cefiderocol and 1% were resistant; the results of the gradient strip test were categorically identical to those of BMD. In the disk diffusion test, 92% of isolates were classified as susceptible and 8% as resistant. Compared with BMD, disk diffusion showed a major error rate of 7%, a very major error rate of 0%, 93% categorical agreement, poor concordance by the kappa test and statistically significant categorical discordance by McNemar’s test (p= 0.016). A moderate correlation was found between the gradient strip test and BMD, and gradient MICs were systematically lower than those obtained by BMD. For CZA, 47% of isolates were susceptible and 53% were resistant; of the 53 CZA-resistant isolates, 98% were still susceptible to cefiderocol (McNemar’s test, p< 0.001). In the molecular analysis, OXA-48 was positive in 64% of isolates, KPC in 25%, NDM in 48%, VIM in 7%, and IMP in 18%. No association was observed between cefiderocol resistance and the presence of specific genes. However, in multivariate models, the presence of OXA-48 was significantly associated with CZA resistance (p= 0.001). Cefiderocol demonstrated very high in vitro activity against CRE isolates and retained its activity against the majority of CZA-resistant strains. However, due to the risk of major errors-especially near breakpoint zones-disk diffusion results should be interpreted with caution, and confirmation with BMD is recommended in critical cases.
PMID:41609445 | DOI:10.5578/mb.202601103