Introduction: Cefiderocol is typically reversed for treatment of multi-drug resistance gram negative pathogens. Package insert dosing of cefiderocol in patients with impaired renal function often wastes part of a vial. Investigating alternative dosing strategies is crucial to optimize the use of cefiderocol, potentially reducing excess costs while maintaining therapeutic efficacy. CREDIBLE-CR trial showed comparable microbiological outcomes but higher mortality in the cefiderocol group compared to the best available therapy group. The infectious diseases pharmacists at Indiana University Health (IUH) developed an alternative dosing based on pharmacodynamic modeling studies. Methods: This was a retrospective cohort study of adult patients admitted from January 1, 2019, to July 31, 2024, with carbapenem-resistant gram-negative infections using an alternative dosing scheme of cefiderocol. The alternative dosing was derived from Monte Carlo simulations and resulted in 1 gram every 6-12 hours per patient’s renal function. The two study groups were patients that would have been ineligible for CREDIBLE-CR (Group A) and those who would have been eligible (Group B). The primary endpoint was a composite of 28-day all-cause mortality or treatment failure. Our objective aimed to describe patient outcomes in adults who received alternative cefiderocol dosing in carbapenem-resistant organisms. Results: Composite of 28-day morality or treatment failure occurred in 10/30 (33.3%) patients in group A and 12/28 (42.9%) patients in group B, (p=0.445). Treatment failure occurred in 7 patients (23.3%) and 6 patients (21.4%) in groups A and B, respectively (p=0862). The primary indication for cefiderocol use in both groups was pneumonia (38%) and blood stream infections (34%) caused by Pseudomonas aeruginosa(52%) followed by Acinetobacter baumannii (14%). Conclusions: This was the first study of an alternative dosing of cefiderocol in a real-world setting. Our proposed dosing may offer potential cost savings for health systems by optimizing the vial utilization compared to package insert dosing.
Huang et al. (Sun,) studied this question.