John S Bradley1, Gregory G Stone2, Phylinda L S Chan3, Susan R Raber4, Todd Riccobene5, Veronica Mas Casullo5, Jean Li Yan6, Victoria M Hendrick3, Jennifer Hammond7, Heidi K Leister-Tebbe7. 1. From the Department of Pediatrics, Rady Children's Hospital/University of California San Diego School of Medicine, San Diego, California. 2. Microbiology, Internal Medicine, Pfizer, Groton, Connecticut. 3. Clinical Pharmacology, Pfizer, Sandwich, Kent, United Kingdom. 4. Clinical Pharmacology, Pfizer, La Jolla, California. 5. Clinical Pharmacology, Allergan plc, Madison, New Jersey. 6. Biostatistics, Pfizer, New York, New York. 7. Global Medical Affairs, Pfizer, Collegeville, Pennsylvania.
Abstract
BACKGROUND: With increasing antimicrobial resistance, antibiotic treatment options for neonatal late-onset sepsis (LOS) are becoming limited. Primary objective of this study was assessment of the safety of ceftaroline fosamil in LOS. METHODS: Eligible neonates and very young infants 7 to <60 days of age with LOS were enrolled in this phase 2, open-label, multicenter study (NCT02424734) and received ceftaroline fosamil 4 or 6 mg/kg every 8 hours by 1-hour intravenous infusion plus intravenous ampicillin and optional aminoglycoside for 48 hours-14 days. Safety was assessed through the final study visit (21-35 days after the last study therapy dose). Efficacy, assessed as clinical and microbiologic response, was evaluated at end-of-treatment and test-of-cure. Pharmacokinetic samples were collected via sparse-sampling protocol. RESULTS: Eleven patients [54.5% male, median (range) age 24 (12-53) days] were enrolled and received ceftaroline fosamil for a median (range) duration of 8 (3-15) days. Ten adverse events (AEs) occurred in 5 (45.5%) patients (safety population); most frequent AE was diarrhea (n = 2). All except 1 AE (diarrhea) were nontreatment-related. Predominant baseline pathogen was Escherichia coli. No patients were clinical failures at end-of-treatment/test-of-cure. Observed sparse steady-state pharmacokinetics data (19 samples) were comparable to previous pediatric data and generally within 90% model prediction intervals; neonatal probability of target attainment was >95% based on established pharmacokinetic/pharmacodynamic targets. CONCLUSIONS: Safety in neonates and very young infants was consistent with the known ceftaroline fosamil safety profile. These results support the use of ceftaroline fosamil (6 mg/kg every 8 hours) as a potential treatment option for LOS.
BACKGROUND: With increasing antimicrobial resistance, antibiotic treatment options for neonatal late-onset sepsis (LOS) are becoming limited. Primary objective of this study was assessment of the safety of ceftaroline fosamil in LOS. METHODS: Eligible neonates and very young infants 7 to <60 days of age with LOS were enrolled in this phase 2, open-label, multicenter study (NCT02424734) and received ceftaroline fosamil 4 or 6 mg/kg every 8 hours by 1-hour intravenous infusion plus intravenous ampicillin and optional aminoglycoside for 48 hours-14 days. Safety was assessed through the final study visit (21-35 days after the last study therapy dose). Efficacy, assessed as clinical and microbiologic response, was evaluated at end-of-treatment and test-of-cure. Pharmacokinetic samples were collected via sparse-sampling protocol. RESULTS: Eleven patients [54.5% male, median (range) age 24 (12-53) days] were enrolled and received ceftaroline fosamil for a median (range) duration of 8 (3-15) days. Ten adverse events (AEs) occurred in 5 (45.5%) patients (safety population); most frequent AE was diarrhea (n = 2). All except 1 AE (diarrhea) were nontreatment-related. Predominant baseline pathogen was Escherichia coli. No patients were clinical failures at end-of-treatment/test-of-cure. Observed sparse steady-state pharmacokinetics data (19 samples) were comparable to previous pediatric data and generally within 90% model prediction intervals; neonatal probability of target attainment was >95% based on established pharmacokinetic/pharmacodynamic targets. CONCLUSIONS: Safety in neonates and very young infants was consistent with the known ceftaroline fosamil safety profile. These results support the use of ceftaroline fosamil (6 mg/kg every 8 hours) as a potential treatment option for LOS.