Objective: Cefotaxime is the first-line treatment for meningitis in neonates and young infants. However, limited data on cefotaxime cerebrospinal fluid (CSF) concentrations in neonates and young infants were available. The aim of the present study is to evaluate the penetration of cefotaxime into CSF in neonates and young infants.
Methods: Blood and CSF samples were collected from neonates and young infants treated with cefotaxime using an opportunistic pharmacokinetic sampling strategy and concentrations were quantified by HPLC-MS/MS. The analysis was performed using NONMEM and R software.
Results: Thirty neonates and young infants (PMA range: 25.4-47.4 weeks) were included. A total of 67 plasma and 30 CSF samples were available for analysis. Cefotaxime plasma and CSF concentrations ranged from 2.30 to 175.42 mg/liter, and from 0.39 to 25.38 mg/liter, respectively. The median ratio of CSF to plasma concentrations was 0.28 (range 0.06-0.76). Monte Carlo simulation demonstrated that 88.4% and 63.9% of hypothetical neonates treated with 50 mg/kg TID would reach the pharmacodynamic target (70% fT>MIC) using the standard EUCAST MIC susceptibility breakpoint of 2 mg/liter and 4 mg/liter, respectively.
Conclusion: The penatration of cefotaxime into CSF was evaluted in neonates and young infants using an opportunistic sampling appoarch. A dosage regimen of 50 mg/kg TID could cover the most causative pathogens with MIC<2 mg/liter. The individual dosage adaptation was required for more resistant bacterial strains such as Staphylococcus aureus.
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