ArticleThe journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG2025
Dosing Recommendations for Ampicillin and Ceftriaxone in the Treatment of Pediatric Community-Acquired Pneumonia Using Monte Carlo- and Physiologic-Based Pharmacokinetic Simulations.
Article in The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveSince 2011, Ampicillin (AMP) has been recommended as the parenteral antibiotic of choice for pediatric community-acquired pneumonia (CAP), but ceftriaxone (CRO) is recommended for unvaccinated children and those with complicated CAP. Using penicillin and CRO susceptibility data for pneumococcus, we evaluated the adequacy of currently recommended doses of AMP and CRO.
methodsWith nonlinear mixed-effects modeling v7.3, Monte Carlo simulations (MCS, N = 10,000) for AMP and CRO were conducted for 6 virtual patients aged 3 months, 1, 2, 5, 10, and 15 years. PK-Sim v9.0 was used to develop physiologic-based pharmacokinetic (PBPK) models for AMP (N = 4000) and CRO (N = 3000). The probability of target attainment (PTA) was determined for both serum and lung (epithelial lining fluid [ELF]) exposure to achieve free drug concentrations above the minimum inhibitory concentration (%
resultsWe performed simulations based on susceptibility data from 21 pneumococci isolated from children with CAP and found all 21 (100%) to be susceptible to AMP and CRO using Clinical & Laboratory Standard Institute/US Food and Drug Administration breakpoints, where susceptible, intermediate, and resistant strains of
conclusionIn the pneumococcal conjugate era, standard doses of AMP and CRO appear to provide the appropriate serum and ELF exposure for clinical and microbiologic success for >98% of children with pediatric CAP. The required dose to achieve the desired outcomes may change if beta-lactam resistance in pneumococcus increases.
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