ABSTRACT Staphylococcus aureus increasingly causes late-onset neonatal sepsis with mortality ≤25%. Oxacillin treats methicillin-susceptible Staphylococcus aureus (MSSA). No previous studies inform dosing. Time above MIC of unbound oxacillin ( f T>MIC) 100% of dosing interval is a desired pharmacodynamic (PD) target in immunocompromised/septic patients. Our objective was to characterize oxacillin pharmacokinetics (PK) and PD in young infants. We conducted a prospective PK/PD study in infants ≤90 days. We divided four cohorts per gestational (GA MIC 0.5 throughout the dosing interval for >90% of modeled patients for all age groups on 160 mg/kg/day continuous infusions. Infants with PNA ≤28 days met PD targets at MIC 1; <90% of all modeled patients on continuous infusion met PD targets at MIC 2. Modeled infants receiving 200 mg/kg/day oxacillin divided q4h/q6h failed to meet PD targets up to MIC 2. All patients survived to discharge. A few serious adverse events were noted. 160 mg/kg/day continuous oxacillin was well tolerated and achieved PD targets for MIC ≤0.5 across all age groups. Modeled intermittent dosing ≤200 mg/kg/day divided q4h/q6h, 8 times the Food and Drug Administration-labeled dose of 25 mg/kg daily, failed to achieve PD targets. The FDA-recommended oxacillin dose is inadequate and may help explain high mortality.
Lee et al. (Mon,) studied this question.