Gastine, S;
Hsia, Y;
Clements, M;
Barker, CI;
Bielicki, J;
Hartmann, C;
Sharland, M;
(2021)
Variation in target attainment of β-lactam antibiotic dosing between international pediatric formularies.
Clinical Pharmacology & Therapeutics
, 109
(4)
pp. 958-970.
10.1002/cpt.2180.
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Abstract
As antimicrobial susceptibility of common bacterial pathogens decreases, ensuring optimal dosing may preserve the use of older antibiotics in order to limit the spread of resistance to newer agents. β-lactams represent the most widely prescribed antibiotic class, yet most were licensed prior to legislation changes mandating their study in children. As a result, significant heterogeneity persists in the pediatric doses used globally, along with quality of evidence used to inform dosing. This review summarizes dose recommendations from the major paediatric reference sources and tries to answer the question: does β-lactam dose heterogeneity matter? Does it impact on pharmacodynamic (PD) target attainment? For three important severe clinical infections - pneumonia, sepsis and meningitis - pharmacokinetic (PK) models were identified for common β-lactam antibiotics. Real-world demographics were derived from three multi-center point prevalence surveys. Simulation results were compared with minimum inhibitory concentration (MIC) distributions, to inform appropriateness of recommended doses in targeted and empiric treatment. Whilst cephalosporin dose regimens are largely adequate for target attainment, they also pose most risk of neurotoxicity. Our review highlights aminopenicillin, piperacillin and meropenem doses as potentially requiring review/optimisation in order to preserve the use of these agents in future.
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