Simplified Dosing Regimens for Gentamicin in Neonatal Sepsis
| Autor: | O. Della Pasqua, Salvatore D'Agate, Evelyne Jacqz-Aigrain, F. Tshinanu Musuamba |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
neonatal sepsis Population gentamicin 030226 pharmacology & pharmacy Sepsis 03 medical and health sciences 0302 clinical medicine modeling and simulation Internal medicine medicine Pharmacology (medical) 030212 general & internal medicine Dosing education Original Research Pharmacology education.field_of_study Neonatal sepsis medicine.diagnostic_test business.industry dosing optimization lcsh:RM1-950 bacterial infection medicine.disease Clinical trial Regimen lcsh:Therapeutics. Pharmacology resource-limited and remote setting Therapeutic drug monitoring Gentamicin business pharmacokinetics medicine.drug |
| Zdroj: | Frontiers in Pharmacology, Vol 12 (2021) Frontiers in Pharmacology |
| ISSN: | 1663-9812 |
| DOI: | 10.3389/fphar.2021.624662/full |
| Popis: | Background: The effectiveness of antibiotics for the treatment of severe bacterial infections in newborns in resource-limited settings has been determined by empirical evidence. However, such an approach does not warrant optimal exposure to antibiotic agents, which are known to show different disposition characteristics in this population. Here we evaluate the rationale for a simplified regimen of gentamicin taking into account the effect of body size and organ maturation on pharmacokinetics. The analysis is supported by efficacy data from a series of clinical trials in this population.Methods: A previously published pharmacokinetic model was used to simulate gentamicin concentration vs. time profiles in a virtual cohort of neonates. Model predictive performance was assessed by supplementary external validation procedures using therapeutic drug monitoring data collected in neonates and young infants with or without sepsis. Subsequently, clinical trial simulations were performed to characterize the exposure to intra-muscular gentamicin after a q.d. regimen. The selection of a simplified regimen was based on peak and trough drug levels during the course of treatment.Results: In contrast to current World Health Organization guidelines, which recommend gentamicin doses between 5 and 7.5 mg/kg, our analysis shows that gentamicin can be used as a fixed dose regimen according to three weight-bands: 10 mg for patients with body weight 4 kg.Conclusion: The choice of the dose of an antibiotic must be supported by a strong scientific rationale, taking into account the differences in drug disposition in the target patient population. Our analysis reveals that a simplified regimen is feasible and could be used in resource-limited settings for the treatment of sepsis in neonates and young infants with sepsis aged 0–59 days. |
| Databáze: | OpenAIRE |
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