Optimizing Cefiderocol Dosing Through Population Pharmacokinetic/Pharmacodynamic Simulation: An Assessment of Drug Cost Reductions.

ABSTRACT

BACKGROUND: Cefiderocol is a siderophore cephalosporin antibiotic with bactericidal activity against carbapenem-resistant Enterobacterales. However, an efficient dosing strategy is yet to be developed. This study aimed to evaluate efficient lower-dose regimens and estimate potential drug cost reductions. METHODS: This simulation study used a virtual population of 10,000 resampled individuals based on a reported population pharmacokinetic model. The target index for maximal bactericidal activity was the time for the unbound cefiderocol concentration to be above the minimum inhibitory concentration (TAM_unbound) of 100%, which was determined using a minimum inhibitory concentration distribution or specific value. RESULTS: The probability of achieving 100% TAM_unbound with the standard, low- (reduced by 1 g or one dose), and extended low- (reduced by 2 g or 2 doses) dose regimens was nearly 100%. The lowest probability of achieving 100% TAM_unbound with the extended low-dose regimen at a creatinine clearance range of 90-120 mL/min was 86.4%. The probability of achieving TAM_unbound of 100% was more than 90% for MIC of ≤0.5 mcg/mL with the extended low-dosing regimen. Furthermore, using an efficient dosing regimen reduced the medical costs over a 10-day treatment period for 10 patients, from $122,826.50 to $62,665.69 $ and ¥12,598,187 $ to ¥5,451,173 in the United States and Japan, respectively. CONCLUSIONSS A lower dosing regimen for cefiderocol could result in substantial reductions in drug costs while still achieving 100% TAM_unbound.