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Pooled frequency of ceftriaxone-induced urolithiasis in pediatric patients: a systematic review and meta-analysis
Tahneem Yaseen1, Muhammad Umair Afzal1, Mustafa A Alhamaidah1
1Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia.
Insights
Ceftriaxone antibiotic use in children is linked to a 7% incidence of urinary tract lithiasis. Study design and region significantly impact these rates, necessitating further research for accurate risk assessment.
Area of Science:
- Pediatric Nephrology
- Pharmacovigilance
- Evidence Synthesis
Background:
- Ceftriaxone is a common antibiotic in pediatrics.
- Ceftriaxone-associated biliary pseudolithiasis is documented.
- The incidence of ceftriaxone-induced urolithiasis in children is not well-defined.
Purpose of the Study:
- To determine the pooled frequency of ceftriaxone-induced urolithiasis in pediatric patients.
- To provide the first meta-analysis focused specifically on pediatric urolithiasis linked to ceftriaxone.
Main Methods:
- Systematic search of major scientific databases (PubMed, Scopus, etc.) up to November 2025.
- Inclusion of studies reporting urolithiasis in pediatric patients receiving ceftriaxone.
- Pooled proportion calculation using a random-effects model with meta-analysis.
Main Results:
- Eight studies were included, yielding a pooled frequency of 7% for ceftriaxone-induced urolithiasis.
- Significant heterogeneity was observed, with higher rates in retrospective Asian studies (up to 34%) and lower rates in prospective Western studies.
- Sensitivity analysis and detection of publication bias suggest potential underreporting of lower incidence rates.
Conclusions:
- Ceftriaxone-associated urinary tract lithiasis affects approximately 7% of pediatric patients.
- Variability in incidence is influenced by study design and diagnostic methods.
- Further high-quality prospective studies are needed to establish true incidence and risk factors.
Background:
Ceftriaxone-associated biliary pseudolithiasis is well reported, but the true risk of urolithiasis remains less clearly defined. Prior reviews frequently combine biliary and urinary tract calcifications or rely mainly on descriptive findings, limiting accurate incidence estimates.
Objective:
This systematic review and meta-analysis aimed to provide the first pooled frequency estimate specifically for ceftriaxone-induced urolithiasis in children.
Data Sources:
A systematic search of PubMed, Google Scholar, Web of Science, and Scopus was conducted up to November 2025.
Study Eligibility Criteria:
Studies reporting the cases of urolithiasis in pediatric patients receiving ceftriaxone were included.
Study Appraisal And Data Synthesis:
Data extraction and synthesis were performed by two independent reviewers and analyzed by Stata 19.5. Pooled proportions were calculated using a random-effects model with REML estimation to determine overall frequency, between-study variance (τ2), and 95% prediction intervals (PI).
Results:
Eight studies met the inclusion criteria. The pooled frequency of ceftriaxone-induced urolithiasis was 7% (95% CI: 2-12%). Heterogeneity was substantial (I2 = 89.8%; τ2 = 0.0034), and the 95% PI ranged from 2.7 to 15.8%. Subgroup analyses showed that retrospective studies from Asian regions reported markedly higher rates (up to 34%), whereas prospective Western studies consistently demonstrated lower frequencies. Sensitivity analysis excluding the main outlier reduced the pooled estimate to 4% (p = 0.004). Publication bias was detected (Egger's test, p = 0.006), indicating underreporting of studies with low event rates.
Conclusions And Implications Of Key Findings:
This meta-analysis suggests that ceftriaxone-associated urinary tract lithiasis occurs in approximately 7% of pediatric patients, with substantial variability driven by study design and diagnostic approach. Well-powered, prospective studies with standardized imaging protocols are required to define the true incidence and modifiable risk factors. SYSTEMATIC REVIEW REGISTRATION NUMBER: (CRD42024598001).
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