Beta-Lactam Dose Optimization Using Therapeutic Drug Monitoring in Pediatric Patients

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OBJECTIVE: Beta-lactam therapeutic drug monitoring (BL-TDM) is underused in pediatric patients where drug exposure is highly variable. This study evaluated the pharmacokinetic/pharmacodynamic (PK/PD) target attainment of BLs in pediatrics. PATIENTS AND METHODS: A retrospective observational cohort study of BL-TDM was conducted from 2016 to 2023 in hospitalized patients aged 18 years and younger receiving ampicillin, aztreonam, cefazolin, cefepime, ceftriaxone, imipenem, meropenem, oxacillin, or piperacillin with available plasma concentrations. Two PK/PD targets were assessed: 100%fT ≥ minimum inhibitory concentration (MIC) and 100% fT ≥ 4 × MIC. Clinical and microbiological success were evaluated as exploratory endpoints in relation to target attainment. RESULTS: Among 142 BL-TDM events (122 patients, 129 hospital encounters), 69% achieved 100% fT ≥ MIC, whereas 41.5% attained 100% fT ≥ 4 × MIC. Median age was 11 years (IQR, 1-17). Ninety-nine hospital encounters (76.7%) included an intensive care unit admission. Cefepime and meropenem were the most common BLs with available concentrations. Ampicillin and meropenem were among the BLs achieving the highest PK/PD target attainment at 88.9% and 71.4% for 100%fT ≥ MIC and 77.8% and 62.9% for 100%fT ≥ 4 × MIC. Dose adjustments were made in 31% of BLs, with either a switch to continuous infusion or an increase in the daily dose being the most frequently implemented. In the exploratory secondary analysis, clinical and microbiological success rates were high regardless of target attainment. A higher estimated glomerular filtration rate within 24 hours of TDM and younger age were independently associated with target non-attainment. CONCLUSIONS: Over half of all patients failed to achieve 100%fT ≥ 4 × MIC with standard BL regimens. Furthermore, dosing adjustments made in nearly one-third of cases further emphasizes BL-TDM's role in individualizing pediatric dosing.

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