Beta-lactam exposure and safety in intermittent or continuous infusion in critically ill children: an observational monocenter study

• Published in: European journal of pediatrics 2023-03, Vol.182 (3), p.965-973
• Main Authors: Debray, Agathe, Callot, Delphine, Hirt, Déborah, Bille, Emmanuelle, Renolleau, Sylvain, Chouchana, Laurent, Tréluyer, Jean-Marc, Oualha, Mehdi, Béranger, Agathe
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - adverse effects; Antibiotics; Bayes Theorem; Bayesian analysis; beta-Lactams - adverse effects; beta-Lactams - pharmacokinetics; Cefotaxime; Child; Children; Critical Illness - therapy; Humans; Infusions, Intravenous; Mathematical models; Medicine; Medicine & Public Health; Meropenem; Meropenem - adverse effects; Original Article; Pediatrics; Pharmacokinetics; Piperacillin; Piperacillin - pharmacokinetics; Prospective Studies; Tazobactam; Therapeutic drug monitoring; Toxicity; β-Lactam antibiotics
• ISSN: 1432-1076; 0340-6199; 1432-1076
• DOI: 10.1007/s00431-022-04716-0

The aim of this study was to assess the pharmacokinetic (PK) exposure and clinical toxicity for three beta-lactams: cefotaxime, piperacillin/tazobactam, and meropenem, depending on two lengths of infusion: continuous and intermittent, in critically ill children. This single center observational prospective study was conducted in a pediatric intensive care unit. All hospitalized children who had one measured plasma concentration of the investigated antibiotics were included. Plasma antibiotic concentrations were interpreted by a pharmacologist, using a Bayesian approach based on previously published population pharmacokinetic models in critically ill children. Exposure was considered optimal, low, or high according to the PK target 100% f T > 4 × MIC and a trough concentration below the toxic concentration (50 mg.L −1 for cefotaxime, 150 mg.L −1 for piperacillin, and 44 mg.L −1 for meropenem). Between May 2019 and January 2020, 80 patients were included and received 106 antibiotic courses: 74 (70%) were administered in intermittent infusion (II) and 32 (30%) in continuous infusion (CI). Compared to II, CI provided more optimal PK exposure ( n  = 22/32, 69% for CI versus n  = 35/74, 47% for II, OR 1.2, 95%CI 1.01–1.5, p  = 0.04), less underexposure ( n  = 4/32, 13% for CI versus n  = 36/74, 49% for II, OR 0.7, 95%CI 0.6–0.84, p