Evidence map›Paper›PMID 39699827›Full record

SynthesisClinical drug investigation2025

Optimizing Individualized Antimicrobial Dosing in Pediatric Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Nadir Yalçın, Yağmur Dirik, İzgi Bayraktar, Mutlu Umaroğlu, Karel Allegaert

Abstract readSystematic ReviewMeta-Analysis
PubMed Publisher
In one paragraph

Synthesis in Clinical drug investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Nadir YalçınDepartment of Clinical Pharmacy, Faculty of Pharmacy, Hacettepe University, 06100, Ankara, Turkey. nadir.yalcin@hotmail.com.ORCID http://orcid.org/0000-0002-2280-8727
Yağmur DirikFaculty of Pharmacy, Hacettepe University, Ankara, Turkey.ORCID http://orcid.org/0009-0004-1391-2313
İzgi BayraktarDepartment of Clinical Pharmacy, Faculty of Pharmacy, Hacettepe University, 06100, Ankara, Turkey.ORCID http://orcid.org/0000-0002-2694-4072
Mutlu UmaroğluInstitutional Big Data Management Coordination Office, Middle East Technical University, Ankara, Turkey.ORCID http://orcid.org/0000-0002-4122-6431
Karel AllegaertDepartment of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium.ORCID http://orcid.org/0000-0001-9921-5105

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTherapeutic drug monitoring (TDM) and target concentration intervention (TCI) represent significant advancements in individualized medicine, aiming to tailor dosages based on patient-specific characteristics. These approaches account for intra- and inter-individual physiological and clinical variability, with the goal of improving target attainment and clinical remission while reducing treatment failure and adverse effects.

objectivesThe objective is to assess and enhance the current body of randomized controlled trials (RCTs) that have investigated alternative personalized dosing strategies, such as TDM and TCI, in terms of their efficacy and safety for individualized antimicrobial dosing in pediatric populations. Only studies that compared different dosing regimens and reported plasma concentrations were included in the analysis.

methodsDatabases such as MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched until January 3rd, 2024. Only published, peer-reviewed RCTs were considered for inclusion. The study focused on human subjects aged < 18 years who were receiving an antimicrobial drug. The interventions compared experimental dosing versus standard dosing with TDM or TCI. The risk of bias was assessed using version 2 of the Cochrane risk-of-bias tool for randomized trials. The primary outcome was the attainment of target concentrations, while secondary outcomes included adverse effects, clinical remission, and treatment failure. Data synthesis was performed using the restricted maximum likelihood method, and the risk ratio (RR) was used as the measure of effect size.

resultsOnly 11 TDM-based RCTs were included in the study [experimental vs standard doses: 592 (51.3%) patients vs 563 (48.7%) patients]. Experimental dose was significantly associated with improvement in target attainment (RR 1.2587, OR 1.0717-1.4786; p = 0.0051). However, experimental antimicrobial dose optimization was non-significantly associated with a numerical decrease in treatment failure (RR 0.8966, OR 0.7749-1.0374; p = 0.1424). In addition, it was not significant associated with higher adverse effects [RR 1.3408, odds ratio (OR) 0.1783-10.0825; p = 0.7757] and clinical remission rates (RR 4.0589, OR 0.2494-66.0558; p = 0.3250).

conclusionsThis meta-analysis showed that only target attainment using TDM was significantly improved in pediatric patients treated with experimental doses of antimicrobials compared to standard doses. Larger TCI-focused RCTs are needed to significantly improve treatment failure, adverse effects, and clinical remission.

Indexed as

Anti-Bacterial AgentsAnti-Infective AgentsPrecision MedicineAdolescentChildDose-Response Relationship, DrugDrug MonitoringHumansRandomized Controlled Trials as TopicAnti-Bacterial AgentsAnti-Infective Agents

Identifiers

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.