1567. Pharmacokinetic/Pharmacodynamic Target Attainment in Adult and Pediatric Patients following Administration of Ceftaroline Fosamil as a 5-Minute Infusion

Abstract Background Ceftaroline fosamil is approved in the United States for treating patients ≥2 months old with acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia, and for similar indications in Europe. The active metabolite, ceftaroline, has in vitro activity against common Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus and Streptococcus pneumoniae. Population pharmacokinetic (popPK) modeling and simulation were used to assess systemic exposure and PK/pharmacodynamic (PK/PD) target attainment for S. aureus and S pneumoniae for 5- and 60-minute infusions. Methods A simultaneous popPK model, including 2 compartments each, for ceftaroline fosamil and ceftaroline was previously developed using an extensive database of adult and pediatric data. An effect of renal function maturation as a function of postmenstrual age was included on ceftaroline clearance for children <2 years. This model was used to conduct simulations for-approved ceftaroline doses administered as 5- and 60-min infusions to adult and pediatric patients with normal renal function and mild renal impairment. For adults, 100 simulations of 300 patients each were performed for each dose regimen, and covariates were generated from a multivariate normal distribution using covariate correlations from observed data. For pediatric patients, 100 simulations were performed for each dose regimen with 600 patients in each 1-month age group. Weights for pediatric age groups were based on CDC growth charts. Results The median proportion of simulated patients with normal renal function achieving %fT>MIC targets of 35% and 44% (associated with 1-log kill of S. aureus and S pneumoniae, respectively), are shown for 5- and 60-min infusions (figure). PK/PD target attainment was similar for both infusion times and was >99% at an MIC of 1 mg/L for S. aureus and an MIC of 0.5 mg/L for S pneumoniae. Ceftaroline AUC was similar for both infusion times, and Cmax was approximately 30%–40% higher for the 5-min infusion. Conclusion Ceftaroline fosamil gave as a 5-min infusion to adult and pediatric patients ≥2 months of age achieved similar PK/PD target attainment as a 60-min infusion for S. aureus and S pneumoniae for MICs up to 1 mg/L and 0.5 mg/L, respectively. Disclosures All authors: No reported disclosures.