Background: β-lactams are among the most frequently prescribed antibiotics for the treatment of neonatal
sepsis. Survival of extremely preterm neonates necessitates an improved understanding of how β-lactams
should be used in this vulnerable population. Appropriate dosing regimens for neonates remain unclear. We reviewed
available data on the pharmacokinetics (PK) of β -lactam drugs in neonates. Pharmacokinetic/
pharmacodynamic (PK/PD) efficacy index surrogates and minimum inhibitory concentrations (MICs) used
to support dosing regimens recommendation in the studies were also investigated.
Methods: A comprehensive literature search was undertaken to identify studies that have investigated the PK/PD
of β-lactam drugs in neonates.
Results: Data available for the PK/PD of β-lactams in neonates are limited but confirm the importance of weight,
gestational age and postnatal age as markers of growth and renal maturation. The contribution of tubular secretion
in addition to glomerular filtration is highlighted. The development of methods to assay β-lactam protein binding
in vivo has added greater understanding. Modelling and simulation techniques have aided dosing optimisation.
However, there remains a gap in the understanding of PD parameters and the appropriate PK/PD index to target
for improved clinical outcome which partly explains the various dosing recommendations. Improved data on the
efficacy of β -lactams are needed in a context of increasing global antimicrobial resistance and variable geographic
Conclusion: Prospective in vivo studies are required to validate PK/PD indexes associated with clinical efficacy.
Current antimicrobial stewardship efforts should integrate PK/PD principles and dosing optimization, taking into
account susceptibility of isolated microorganisms.
Keywords: Paediatrics, pharmacokinetics, pharmacodynamics, dosing optimization, PK/PD index, penicillins, cephalosporins, carbapenems.
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