Beta-lactam dosing in children is challenging because drug exposure varies widely with age, physiology, and critical illness. The authors evaluated the role of beta-lactam therapeutic drug monitoring (BL-TDM) to determine how frequently standard regimens achieve established pharmacokinetic/pharmacodynamic (PK/PD) targets in pediatric inpatients. The primary objective reported was assessment of PK/PD target attainment for commonly used beta-lactams in pediatric hospital encounters.
This was a retrospective observational cohort study spanning 2016–2023. Included were hospitalized patients aged 18 years and younger who had plasma concentrations available for one or more of the following beta-lactams: ampicillin, aztreonam, cefazolin, cefepime, ceftriaxone, imipenem, meropenem, oxacillin, or piperacillin. The results describe 142 BL-TDM events representing 122 patients across 129 hospital encounters. The cohort had a median age of 11 years (IQR 1–17). Most encounters (76.7%) included an intensive care unit admission.
The study evaluated two clinician-selected PK/PD targets: 100% fT ≥ minimum inhibitory concentration (MIC) and 100% fT ≥ 4 × MIC. These targets reflect continuous or sustained beta-lactam exposure relative to pathogen MICs and are commonly used benchmarks for time-dependent antibiotics in severe infections.
Across all 142 BL-TDM events, 69% achieved 100% fT ≥ MIC, indicating sustained free-drug concentrations at or above the MIC over the dosing interval. A smaller proportion—41.5%—attained the more stringent 100% fT ≥ 4 × MIC target. These findings indicate that while standard pediatric regimens often meet the basic target, more aggressive exposure goals are frequently not reached.
Drug-specific reporting in the abstract highlighted that cefepime and meropenem were the most commonly assayed beta-lactams. Ampicillin and meropenem were among the agents with the highest proportions of target attainment: ampicillin met 100% fT ≥ MIC in 88.9% of assays and 100% fT ≥ 4 × MIC in 77.8%; meropenem met 100% fT ≥ MIC in 71.4% and 100% fT ≥ 4 × MIC in 62.9%.
Clinicians altered dosing after TDM in 31% of beta-lactam instances. The most frequently implemented changes were switching to a continuous infusion and increasing the total daily dose. The reported frequency of dose changes emphasizes a role for BL-TDM in guiding individualized dosing, although specific algorithms or dosing rules were not described in the abstract.
An exploratory secondary analysis evaluated clinical and microbiological success relative to PK/PD target attainment. The abstract reports high rates of clinical and microbiologic success overall, and these outcomes were reportedly high regardless of whether PK/PD targets were met. The abstract does not provide definitions for success, timepoints for assessment, organism-specific outcomes, or numeric success rates; those details were not reported in the source abstract.
Multivariable analysis identified a higher estimated glomerular filtration rate (eGFR) measured within 24 hours of TDM and younger age as independent predictors of failing to achieve PK/PD targets. This likely reflects faster drug clearance in children with augmented renal function and in younger patients, which can reduce time-above-MIC for time-dependent beta-lactams.
Key implications from the reported data are:
The source abstract reports core results but omits several details that would be important for clinical interpretation: explicit definitions and numerical rates for clinical and microbiologic success, organism- and MIC-specific distributions, timing of TDM relative to dose and illness onset, exact eGFR thresholds or effect sizes, safety or toxicity data related to higher exposures, and institutional TDM protocols or concentration assay methods. Those specifics were not included in the abstract.
In this single-center retrospective cohort of pediatric inpatients who underwent BL-TDM from 2016–2023, 69% of beta-lactam monitoring events achieved 100% fT ≥ MIC, while only 41.5% achieved 100% fT ≥ 4 × MIC. Dose adjustments were made in 31% of cases, and higher eGFR and younger age were independently associated with failure to meet PK/PD targets. The authors conclude that BL-TDM can play an important role in individualizing beta-lactam dosing in pediatric patients, given that many patients do not reach more aggressive PK/PD exposure goals with standard regimens.
(Details not reported in the abstract: exact definitions and rates for clinical/microbiologic success, organism-level MIC data, timing and methods of TDM, and magnitude of association measures for predictors.)