Therapeutic drug monitoring (TDM) of antimicrobial agents in a paediatric setting succeeds in recognizing out-of-range serum drug concentrations (SDC), specifically for vancomycin and aminoglycosides, according to a single-centre study.
Moreover, potentially toxic concentrations have been noted in nearly one in five hospital stays, often at the first TDM assessment. Such cases are common in patients with cardiovascular comorbidities, renal failure, and greater illness severity.
“In this context, TDM may represent a useful tool for individualized antimicrobial dosing in complex paediatric patients,” the investigators said.
A total of 427 SDC tests from 90 hospital stays were conducted in 83 patients (median age 0.2 years, 41.1 percent female). About one in five tests (22.0 percent) exceeded toxicity thresholds, with vancomycin as the most frequently monitored antimicrobial agent. [Br J Clin Pharmacol 2026;92:2723-2740]
Based on binary classification, the toxic group had a substantially shorter time-to-first SDC and higher rates of cardiovascular and renal comorbidities than the nontoxic group. In expert-based classification, 50 percent were out-of-range, 26.7 percent in-range, and 23.3 percent indeterminate.
In-range patients had higher rates of renal failure, continuous renal replacement therapy (CRRT) use, and mortality than those in the out-of-range group (20.8 percent vs 4.4 percent; p=0.045). However, these did not reach statistically significance in sensitivity analyses. Furthermore, no survival difference was observed in Kaplan‒Meier curves.
“Although no significant differences in short-term all-cause mortality were observed between patients with in-range and out-of-range drug concentrations across different classification, TDM may still provide clinically relevant information by identifying early and frequent alterations in antimicrobial exposure in vulnerable paediatric populations,” the investigators said.
“Further studies are required to confirm these findings and to better elucidate the associations between antimicrobial exposure, adverse drug reactions, and additional clinically meaningful outcomes beyond mortality,” they added.
Toxicity profile
TDM for antifungal agents in paediatric patients was rarely performed in this study. However, the nonoccurrence of recorded toxicity does not justify the absence of TDM for this drug class, given the observed toxicity profile of antifungals, according to the investigators.
For instance, an earlier study by Brüggemann ang colleagues found that the first measured voriconazole concentration was below the therapeutic target in 44 percent of patients. [Pediatr Infect Dis J 2011;30:533-534]
“Thus, the implementation of antifungal TDM may enable rapid dose optimization to achieve clinical efficacy, further supporting the need for routine antifungal TDM in complex paediatric [patients], while the low number of antifungal measurements in our cohort likely reflects underutilization rather than a low clinical demand,” the investigators said.
Although a significant association between TDM implementation and improved clinical outcomes in paediatric settings has not been conclusively shown yet for antimicrobial therapy, such a correlation has been observed in other clinical fields, is supported by a pharmacological rationale, and is recommended by some publications reporting promising results. [ J Crohns Colitis. 2025;19:jjaf164; EJC Paediatr Oncol 2025;5:100225; Front Pharmacol 2021;12:750080; Antimicrob Agents Chemother 2022;66:e0013822]
Furthermore, a systematic review and meta-analysis of 10 randomized controlled trials found improvements in patients who received personalized antimicrobial dosing, particularly in target attainment, treatment failure prevention, and nephrotoxicity reduction. A trend towards reduction in all-cause mortality, clinical cure, and microbiological outcomes was also noted, albeit not statistically significant. [Clin Microbiol Infect 2023;29:845-857]
“These findings suggest that microbiological cure may not be the main determinant to reduce mortality, especially in critical patients, where concomitant conditions severely affect the risk of mortality,” the investigators said. “Nevertheless, in this scenario, not achieving infection resolution would be further detrimental for the clinical outcome, and TDM may be a useful tool to improve antimicrobial therapy.”
The current study included paediatric patients who underwent SDC testing for antimicrobials between 2021 and 2022. TDM utilization was the primary objective, while secondary objectives included clinical outcomes and factors linked to out-of-range SDC levels. The investigators used two TDM classifications, namely binary based on toxicity thresholds and expert-based.