PMID- 32091493
OWN - NLM
STAT- MEDLINE
DCOM- 20210322
LR  - 20231213
IS  - 1532-0987 (Electronic)
IS  - 0891-3668 (Linking)
VI  - 39
IP  - 5
DP  - 2020 May
TI  - Phase 2 Study of the Safety, Pharmacokinetics and Efficacy of Ceftaroline Fosamil 
      in Neonates and Very Young Infants With Late-onset Sepsis.
PG  - 411-418
LID - 10.1097/INF.0000000000002607 [doi]
AB  - 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.
FAU - Bradley, John S
AU  - Bradley JS
AD  - From the Department of Pediatrics, Rady Children's Hospital/University of 
      California San Diego School of Medicine, San Diego, California.
FAU - Stone, Gregory G
AU  - Stone GG
AD  - Microbiology, Internal Medicine, Pfizer, Groton, Connecticut.
FAU - Chan, Phylinda L S
AU  - Chan PLS
AD  - Clinical Pharmacology, Pfizer, Sandwich, Kent, United Kingdom.
FAU - Raber, Susan R
AU  - Raber SR
AD  - Clinical Pharmacology, Pfizer, La Jolla, California.
FAU - Riccobene, Todd
AU  - Riccobene T
AD  - Clinical Pharmacology, Allergan plc, Madison, New Jersey.
FAU - Mas Casullo, Veronica
AU  - Mas Casullo V
AD  - Clinical Pharmacology, Allergan plc, Madison, New Jersey.
FAU - Yan, Jean Li
AU  - Yan JL
AD  - Biostatistics, Pfizer, New York, New York.
FAU - Hendrick, Victoria M
AU  - Hendrick VM
AD  - Clinical Pharmacology, Pfizer, Sandwich, Kent, United Kingdom.
FAU - Hammond, Jennifer
AU  - Hammond J
AD  - Global Medical Affairs, Pfizer, Collegeville, Pennsylvania.
FAU - Leister-Tebbe, Heidi K
AU  - Leister-Tebbe HK
AD  - Global Medical Affairs, Pfizer, Collegeville, Pennsylvania.
LA  - eng
SI  - ClinicalTrials.gov/NCT02424734
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pediatr Infect Dis J
JT  - The Pediatric infectious disease journal
JID - 8701858
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Cephalosporins)
SB  - IM
MH  - Administration, Intravenous
MH  - Anti-Bacterial Agents/*pharmacokinetics/*therapeutic use
MH  - Cephalosporins/*pharmacokinetics/*therapeutic use
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Internationality
MH  - Male
MH  - Neonatal Sepsis/*drug therapy
MH  - Ceftaroline
EDAT- 2020/02/25 06:00
MHDA- 2021/03/23 06:00
CRDT- 2020/02/25 06:00
PHST- 2020/02/25 06:00 [pubmed]
PHST- 2021/03/23 06:00 [medline]
PHST- 2020/02/25 06:00 [entrez]
AID - 00006454-202005000-00010 [pii]
AID - 10.1097/INF.0000000000002607 [doi]
PST - ppublish
SO  - Pediatr Infect Dis J. 2020 May;39(5):411-418. doi: 10.1097/INF.0000000000002607.