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Pediatr Crit Care Me · Jul 2022
Clinical TrialSuboptimal Beta-Lactam Therapy in Critically Ill Children: Risk Factors and Outcome.
- Tatjana Van Der Heggen, Evelyn Dhont, Jef Willems, Ingrid Herck, Joris R Delanghe, Veronique Stove, Alain G Verstraete, Sophie Vanhaesebrouck, Peter De Paepe, and De CockPieter A J GPAJGDepartment of Basic and Applied Medical Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.Department of Pediatric Intensive Care, Ghent University Hospital, Gent, Belgium.Department of Pharmacy, Ghe.
- Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent, Belgium.
- Pediatr Crit Care Me. 2022 Jul 1; 23 (7): e309-e318.
ObjectivesIn critically ill children, severely altered pharmacokinetics may result in subtherapeutic β-lactam antibiotic concentrations when standard pediatric dosing regimens are applied. However, it remains unclear how to recognize patients most at risk for suboptimal exposure and their outcome. This study aimed to: 1) describe target attainment for β-lactam antibiotics in critically ill children, 2) identify risk factors for suboptimal exposure, and 3) study the association between target nonattainment and clinical outcome.DesignPost hoc analysis of the "Antibiotic Dosing in Pediatric Intensive Care" study (NCT02456974, 2012-2019). Steady-state trough plasma concentrations were classified as therapeutic if greater than or equal to the minimum inhibitory concentration of the (suspected) pathogen. Factors associated with subtherapeutic concentrations and clinical outcome were identified by logistic regression analysis.SettingThe pediatric and cardiac surgery ICU of a Belgian tertiary-care hospital.PatientsOne hundred fifty-seven patients (aged 1 mo to 15 yr) treated intravenously with amoxicillin-clavulanic acid, piperacillin-tazobactam, or meropenem.InterventionsNone.Measurements And Main ResultsThree hundred eighty-two trough concentrations were obtained from 157 patients (median age, 1.25 yr; interquartile range, 0.4-4.2 yr). Subtherapeutic concentrations were measured in 39 of 60 (65%), 43 of 48 (90%), and 35 of 49 (71%) of patients treated with amoxicillin-clavulanic acid, piperacillin-tazobactam, and meropenem, respectively. Estimates of glomerular filtration rate (eGFR; 54% increase in odds for each sd increase in value, 95% CI, 0.287-0.736; p = 0.001) and the absence of vasopressor treatment (2.8-fold greater odds, 95% CI, 1.079-7.253; p = 0.034) were independently associated with target nonattainment. We failed to identify an association between antibiotic concentrations and clinical failure.ConclusionsSubtherapeutic β-lactam concentrations are common in critically ill children and correlate with renal function. eGFR equations may be helpful in identifying patients who may require higher dosing. Future studies should focus on the impact of subtherapeutic concentrations on clinical outcome.Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.
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