Phase 2 Study of the Safety, Pharmacokinetics and Efficacy of Ceftaroline Fosamil in Neonates and Very Young Infants With Late-onset Sepsis. Issue 5 (May 2020)

• Record Type: Journal Article
• Authors: Bradley, John S.; Stone, Gregory G.; Chan, Phylinda L. S.; Raber, Susan R.; Riccobene, Todd; Mas Casullo, Veronica; Yan, Jean Li; Hendrick, Victoria M.; Hammond, Jennifer; Leister-Tebbe, Heidi K.
• Is Part Of: Pediatric infectious disease journal. Volume 39:Issue 5(2020)
• Publication Date: 2020-05
• Subjects: ceftaroline -- neonates -- pediatric -- late-onset sepsis; Communicable diseases in children -- Periodicals; Infection in children -- Periodicals; 618.929
• DOI: 10.1097/INF.0000000000002607
• Languages: English
• ISSNs: 0891-3668

Abstract

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. Abstract : Supplemental Digital Content is available in the text.