Optimization of β-Lactam Dosing Regimens in Neonatal Infections: Continuous and Extended Administration versus Intermittent Administration.
Journal
Clinical pharmacokinetics
ISSN: 1179-1926
Titre abrégé: Clin Pharmacokinet
Pays: Switzerland
ID NLM: 7606849
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
accepted:
21
02
2023
medline:
15
5
2023
pubmed:
28
3
2023
entrez:
27
3
2023
Statut:
ppublish
Résumé
In neonates, β-Lactam antibiotics are almost exclusively administered by intermittent infusion. However, continuous or prolonged infusion may be more beneficial because of the time-dependent antibacterial activity. In this pharmacokinetic/pharmacodynamic simulation study, we aimed to compare treatment with continuous, extended and intermittent infusion of β-lactam antibiotics for neonates with infectious diseases. We selected population pharmacokinetic models of penicillin G, amoxicillin, flucloxacillin, cefotaxime, ceftazidime and meropenem, and performed a Monte Carlo simulation with 30,000 neonates. Four different dosing regimens were simulated: intermittent infusion in 30 min, prolonged infusion in 4 h, continuous infusion, and continuous infusion with a loading dose. The primary endpoint was 90% probability of target attainment (PTA) for 100% ƒT>MIC during the first 48 h of treatment. For all antibiotics except cefotaxime, continuous infusion with a loading dose resulted in a higher PTA compared with other dosing regimens. Sufficient exposure (PTA >90%) using continuous infusion with a loading dose was reached for amoxicillin (90.3%), penicillin G (PTA 98.4%), flucloxacillin (PTA 94.3%), cefotaxime (PTA 100%), and ceftazidime (PTA 100%). Independent of dosing regimen, higher meropenem (PTA for continuous infusion with a loading dose of 85.5%) doses might be needed to treat severe infections in neonates. Ceftazidime and cefotaxime dose might be unnecessarily high, as even with dose reductions, a PTA > 90% was retained. Continuous infusion after a loading dose leads to a higher PTA compared with continuous, intermittent or prolonged infusion, and therefore has the potential to improve treatment with β-lactam antibiotics in neonates.
Sections du résumé
BACKGROUND AND OBJECTIVE
In neonates, β-Lactam antibiotics are almost exclusively administered by intermittent infusion. However, continuous or prolonged infusion may be more beneficial because of the time-dependent antibacterial activity. In this pharmacokinetic/pharmacodynamic simulation study, we aimed to compare treatment with continuous, extended and intermittent infusion of β-lactam antibiotics for neonates with infectious diseases.
METHODS
We selected population pharmacokinetic models of penicillin G, amoxicillin, flucloxacillin, cefotaxime, ceftazidime and meropenem, and performed a Monte Carlo simulation with 30,000 neonates. Four different dosing regimens were simulated: intermittent infusion in 30 min, prolonged infusion in 4 h, continuous infusion, and continuous infusion with a loading dose. The primary endpoint was 90% probability of target attainment (PTA) for 100% ƒT>MIC during the first 48 h of treatment.
RESULTS
For all antibiotics except cefotaxime, continuous infusion with a loading dose resulted in a higher PTA compared with other dosing regimens. Sufficient exposure (PTA >90%) using continuous infusion with a loading dose was reached for amoxicillin (90.3%), penicillin G (PTA 98.4%), flucloxacillin (PTA 94.3%), cefotaxime (PTA 100%), and ceftazidime (PTA 100%). Independent of dosing regimen, higher meropenem (PTA for continuous infusion with a loading dose of 85.5%) doses might be needed to treat severe infections in neonates. Ceftazidime and cefotaxime dose might be unnecessarily high, as even with dose reductions, a PTA > 90% was retained.
CONCLUSIONS
Continuous infusion after a loading dose leads to a higher PTA compared with continuous, intermittent or prolonged infusion, and therefore has the potential to improve treatment with β-lactam antibiotics in neonates.
Identifiants
pubmed: 36972008
doi: 10.1007/s40262-023-01230-w
pii: 10.1007/s40262-023-01230-w
doi:
Substances chimiques
Floxacillin
43B2M34G2V
Meropenem
FV9J3JU8B1
Ceftazidime
9M416Z9QNR
Anti-Bacterial Agents
0
Cefotaxime
N2GI8B1GK7
Monobactams
0
Amoxicillin
804826J2HU
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
715-724Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
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