Inappropriate Use of Third-Generation Cephalosporins and Antimicrobial Resistance in Hospital Settings: A Systematic Review and Meta-Analysis

Abstract

Background: Patient safety is seriously threatened by the worldwide rise in antimicrobial resistance (AMR), particularly in hospital environments. Despite being one of the most commonly given antibiotics in inpatient treatment, third-generation cephalosporins are also regularly linked to improper use, which greatly contributes to the creation of resistance organisms.

Aim: To systematically review and conduct a meta-analysis on the inappropriate use of third-generation cephalosporins in hospital settings and its association with antimicrobial resistance.

Methods: A comprehensive literature search across PubMed, Scopus, Embase, and Web of Science identified 1,238 relevant articles up to January 1, 2018 to July 5, 2025.  After screening, 15 studies met inclusion criteria, encompassing a total sample of 4,850 hospitalized patients. Meta-analysis was conducted using a random-effects model in R (version 4.3.1) with the meta and metafor packages to estimate pooled odds ratios (ORs) and prevalence rates. Subgroup and publication bias analyses, including Egger’s test and funnel plots, were also performed.

Results: The pooled odds ratio for developing resistant infections following inappropriate cephalosporin use was 2.56 (95% CI: 1.84–3.55, p < 0.001). Inappropriate use was most commonly due to incorrect indications (52%), prolonged duration (33%), and incorrect dosing (15%). Resistance was highest in Escherichia coli (51.7%). Subgroup analysis revealed higher risk in surgical prophylaxis and in low- and middle-income countries. Moderate heterogeneity (I² = 48%) was observed, and no significant publication bias was detected.

Conclusion: Inappropriate use of third-generation cephalosporins is highly prevalent in hospital settings and significantly contributes to antimicrobial resistance. Targeted interventions and stricter adherence to prescribing guidelines are urgently needed to mitigate resistance trends.

Recommendations: Hospitals should implement robust antimicrobial stewardship programs, enhance prescriber training, and use diagnostic support tools to reduce inappropriate antibiotic use. Policymakers should prioritize surveillance and stewardship, particularly in resource-limited settings.

Keywords: Third-generation cephalosporins, antimicrobial resistance, inappropriate antibiotic use, hospital settings, meta-analysis