Cefiderocol: early clinical experience for multi-drug resistant gram-negative infections

Multi-drug resistant gram-negative bacteria present a significant global health threat. Cefiderocol (CFDC), a siderophore cephalosporin, has shown potential in combating this threat, but with the currently available data, its role in therapy remains poorly defined. This multi-center, retrospective cohort study evaluated the real-world application of CFDC across six U.S. medical centers from January 2018 to May 2023. Patients aged ≥18 years and who had received ≥72 hours of CFDC were included. The primary outcome was a composite of clinical success: survival at 30 days, absence of symptomatic microbiologic recurrence at 30 days following CFDC treatment initiation, and resolution of signs and symptoms. Secondary outcomes included time to CFDC therapy and on-treatment non-susceptibility to CFDC. A total of 112 patients were included, with median (interquartile range [IQR]) APACHE II scores of 15 (19-18). Clinical success was observed in 68.8% of patients, with a mortality rate of 16.1% and comparable success rates across patients infected with carbapenem-resistant gram-negative infections. The most common isolated organisms were Pseudomonas aeruginosa (61/112, 54.5%, of which 55/61 were carbapenem-resistant) and carbapenem-resistant Acinetobacter baumannii (32/112, 28.6%). Median (IQR) time to CFDC therapy was 77 (14-141) hours. Two patients experienced a non-anaphylactic rash as an adverse drug reaction. On-treatment non-susceptibility to CFDC was found in six patients, notably due to P. aeruginosa and A. baumannii.IMPORTANCECFDC was safe and clinically effective as a monotherapy or in combination in treating a variety of carbapenem-resistant gram-negative infections. Further prospective studies are warranted to confirm these findings.