ppi-0903 and Neonatal-Sepsis

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.. 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.. 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.. 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.

Topics: Administration, Intravenous; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Double-Blind Method; Female; Humans; Infant; Infant, Newborn; Internationality; Male; Neonatal Sepsis

Treatment of late-onset neonatal staphylococcal sepsis is sometimes challenging with feared side effects of vancomycin, increasing minimal inhibitory concentrations and questions about catheter management. In case of failure, ceftaroline was administered as a compassionate treatment in 16 infants (gestational age of less than 32 weeks and less than 28 postnatal days), whose first-line treatment failed. We report 11 successes and no severe adverse drug reactions. Larger data are required to confirm these encouraging results.

Topics: Anti-Bacterial Agents; Bacteremia; Ceftaroline; Humans; Infant; Infant, Newborn; Neonatal Sepsis; Sepsis; Staphylococcal Infections; Vancomycin