Cephalexin Model-Informed Dosing Recommendations for Severe Infections: A Pooled Pharmacokinetic Analysis From Infancy to Adulthood.

Background: Cephalexin is increasingly used as initial and oral transition therapy for severe infections, but optimal dosing in this setting remains uncertain. Methods: Four cephalexin pharmacokinetic (PK) datasets spanning preterm neonates through young adults were pooled to develop a unified population PK model. Simulations estimated probability of target attainment (PTA) and cumulative fractional response (CFR, target attainment weighted across the pathogen MIC distribution) across Results: Seventy-one subjects (age 9 days-29 years) contributed 360 plasma samples, best described by a 1-compartment model with first-order absorption and lag time. Apparent volume and clearance scaled with fat-free mass, and clearance increased with postmenstrual age. Absorption was slower in neonates. Cephalexin 25 mg/kg/dose, maximum 1000 mg, every 8 hours, achieved 1-log kill targets for MSSA (PTA ≥ 98% for 35% Conclusions: Cephalexin PK varies with age but is well-captured by a unified size- and maturation-scaled model. These data support dosing within the FDA-approved range for systemic MSSA infections. Higher-dose regimens are necessary for adequate target attainment against Enterobacterales. Appropriately dosed cephalexin represents a viable option for selected severe infections, including oral transition therapy.