ArticleThe Journal of antimicrobial chemotherapy2023
The Neonatal and Paediatric Pharmacokinetics of Antimicrobials study (NAPPA): investigating amoxicillin, benzylpenicillin, flucloxacillin and piperacillin pharmacokinetics from birth to adolescence.
Article in The Journal of antimicrobial chemotherapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Reflections on the Theoretical Prerequisites for Initial Oral Antibiotic Treatment for Paediatric Bone and Joint Infections: A Narrative Review.Antibiotics (Basel, Switzerland) · 2026Review
- Antimicrobial resistance patterns and carbapenemase gene distribution in pediatric Pseudomonas aeruginosa isolates: molecular and epidemiological insights from an Iranian referral center.BMC microbiology · 2026Article
- Population pharmacokinetics and dose optimization of piperacillin-tazobactam in premature and term neonates with severe infections.Antimicrobial agents and chemotherapy · 2026Article
- β-Lactam dosing in critically ill children: predictors for target non-attainment.The Journal of antimicrobial chemotherapy · 2026Observational
- Evaluation of amoxicillin and benzylpenicillin therapy in early-onset neonatal sepsis: a pharmacometric external validation and simulation study.The Journal of antimicrobial chemotherapy · 2025Article
- A simplified amoxicillin regimen with dose frequency based on post-natal age in neonates with confirmed or suspected infection.Antimicrobial agents and chemotherapy · 2025Observational
- A Pooled Pharmacokinetic Analysis for Piperacillin/Tazobactam Across Different Patient Populations: From Premature Infants to the Elderly.Clinical pharmacokinetics · 2025Article
- Genetic Variations and Antibiotic-Related Adverse Events.Pharmaceuticals (Basel, Switzerland) · 2024Review
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Authors and funding
10 authors.
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Abstract
backgroundPharmacokinetic (PK) data underlying paediatric penicillin dosing remain limited, especially in critical care.
objectivesThe primary objective of the Neonatal and Paediatric Pharmacokinetics of Antimicrobials study (NAPPA) was to characterize PK profiles of commonly used penicillins using data obtained during routine care, to further understanding of PK variability and inform future evidence-based dosing.
methodsNAPPA was a multicentre study of amoxicillin, co-amoxiclav, benzylpenicillin, flucloxacillin and piperacillin/tazobactam. Patients were recruited with informed consent. Antibiotic dosing followed standard of care. PK samples were obtained opportunistically or at optimal times, frozen and analysed using UPLC with tandem MS. Pharmacometric analysis was undertaken using NONMEM software (v7.3). Model-based simulations (n = 10 000) tested PTA with British National Formulary for Children (BNFC) and WHO dosing. The study had ethical approval.
resultsFor the combined IV PK model, 963 PK samples from 370 participants were analysed simultaneously incorporating amoxicillin, benzylpenicillin, flucloxacillin and piperacillin data. BNFC high-dose regimen simulations gave these PTA results (median fT>MIC at breakpoints of specified pathogens): amoxicillin 100% (Streptococcus pneumoniae); benzylpenicillin 100% (Group B Streptococcus); flucloxacillin 48% (MSSA); and piperacillin 100% (Pseudomonas aeruginosa). Oral population PK models for flucloxacillin and amoxicillin enabled estimation of first-order absorption rate constants (1.16 h-1 and 1.3 h-1) and bioavailability terms (62.7% and 58.7%, respectively).
conclusionsNAPPA represents, to our knowledge, the largest prospective combined paediatric penicillin PK study undertaken to date, and the first paediatric flucloxacillin oral PK model. The PTA results provide evidence supportive of BNFC high-dose IV regimens for amoxicillin, benzylpenicillin and piperacillin.
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