666. Efficacy and Safety of Cefiderocol According to Renal Impairment in Patients With Complicated Urinary Tract Infection (cUTI) in a Phase 2 Study

Abstract

Background. Cefiderocol, a novel siderophore cephalosporin with broad activity against Gram‐negative bacteria, requires dose adjustment in patients with renal impairment or augmented renal clearance, similarly to other β‐lactams. The efficacy and safety of cefiderocol were assessed according to degree of renal impairment as part of a pivotal study vs. imipenem‐cilastatin (IPM/CS) in patients with cUTI (NCT02321800). Methods. A total of 448 randomized adults with cUTI received cefiderocol (2 g) or IPM/CS (1 g / 1 g), IV, q8h, for 7‐14 days (safety population), with 371 patients in the microbiological intent‐to‐treat (Micro‐ITT) population. Dose adjustments were made based on body weight (to enable IPM/CS blinding) and creatinine clearance (CrCL). The composite (clinical and microbiological) outcome at a test of cure (TOC; 7 days after treatment cessation) was analyzed by CrCL subgroup. Adverse events (AEs) according to renal subgroup were monitored throughout the study. Results. A treatment difference in the composite outcome at TOC in favor of cefiderocol vs. IPM/CS was observed across renal subgroups (table), with greater differences in moderate and severe groups, consistent with that observed in the overall population (n = 371; 18.0%, 95% confidence interval: 7.5; 28.5). The incidence of AEs in the cefiderocol group was comparable across all renal subgroups. Conversely, AE incidence increased with the degree of impairment in the IPM/CS group (table). Conclusion. In contrast to IPM/CS, the efficacy of cefiderocol was maintained across all renal function subgroups with no increase in the rate of AEs. These findings underscore the efficacy and safety of cefiderocol in patients with renal impairment and support the adequacy of the dose adjustment. (Table Presented).