Urinary Biomarkers and Attainment of Cefepime Therapeutic Targets in Critically Ill Children
Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Critically ill children are at risk for subtherapeutic antibiotic concentrations. The frequency of target attainment and risk factors for subtherapeutic concentrations of cefepime in children have not been extensively studied. METHODS: We performed an observational study in critically ill children receiving a new prescription of standard dosing of cefepime for suspected sepsis (≥2 systemic inflammatory response syndrome criteria within 48 hours of cefepime start). Three plasma cefepime concentrations were measured at steady state and, a urine sample was collected prior to pharmacokinetics (PK) sampling for measurement of urinary biomarkers. Bayesian analysis determined cefepime PK for each individual, and simulations were used to estimate time above minimum inhibitory concentration ( f T > MIC) for 8 µg/mL (breakpoint for Pseudomonas ). Clinical factors and urinary biomarkers were compared between patients who did and did not achieve 100% f T > MIC. Correlations between covariates and cefepime PK parameters, as well as optimal cut points to identify <100% f T > MIC, were evaluated. RESULTS: Twenty-one subjects were enrolled and PK sampling occurred after a median of 5 doses (range, 3-9); 43% of children achieved 100% f T > MIC for an MIC of 8 µg/mL. Younger age and lower urinary biomarkers (neutrophil gelatinase-associated lipocalin and kidney injury molecule-1) were significantly associated with failure to attain 100% f T > 8 µg/mL. Urinary neutrophil gelatinase-associated lipocalin (<122.1-ng/mg creatinine) best identified individuals who failed to attain this putative target (positive predictive value, 91.7%). CONCLUSIONS: A large proportion of critically ill children failed to attain target concentrations for empiric treatment of Pseudomonas aeruginosa with cefepime. Urinary biomarkers may be a noninvasive means to identify those at higher risk for increased cefepime clearance and subtherapeutic concentrations.
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: University of Pennsylvania, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Pediatric septic acute kidney injury: personalizing antibiotic dosing through understanding acute kidney injury risk factors and biomarker profiles, Clinical Pharmacology Training Program, Institutional Clinical and Translational Science Award, The Roles of Pulmonary Hypertension and Right Ventricular Dysfunction in Pediatric Acute Respiratory Distress Syndrome, Optimizing Vancomycin Therapy in Children
OpenAlex ID: W4408347144