Ceftriaxone stands as a cornerstone in global antibiotic therapy owing to its potent antibacterial activity, broad spectrum coverage, and low toxicity. Nevertheless, its efficacy is impeded by widespread inappropriate prescribing and utilization practices, significantly contributing to bacterial resistance. The aim of this study is to determine the overall national pooled prevalence of inappropriate ceftriaxone utilization and its predictor factors in Ethiopia. A systematic search was conducted across multiple databases including, PubMed, Science Direct, Hinari, Global Index Medicus, Scopus, Embase, and a search engine, Google Scholar, to identify relevant literatures that meet the research question, from March 20 to 30, 2024. This meta-analysis, which was conducted in Ethiopia by incorporating 17 full-text articles, unveiled a national pooled inappropriate ceftriaxone utilization of 55.24% (95% CI, 42.17%, 68.30%) with a substantial heterogeneity index (I2 = 99.24%, p value < 0.001). The review has also identified predictive factors for the inappropriate use of ceftriaxone: empiric therapy (AOR 21.43, 95% CI; 9.26–49.59); multiple medication co-prescription (AOR: 4.12, 95% CI; 1.62–8.05). Emergency ward (AOR: 4.22, 95% CI; 1.8-12.24), surgery ward (AOR: 2.6, 95% CI; 1.44–7.82) compared to medical ward, prophylactic use (AOR: 500, 95% CI; 41.7–1000), longer hospital stay-8-14 Days; (AOR: 0.167, 95% CI; 0.09–0.29), > 14 days; (AOR: 0.18, 95% CI; 0.1–0.32). The study reveals a high national pooled prevalence of inappropriate ceftriaxone utilization, standing at 55.24%, highlighting a significant hazard in the use of this antibiotic. This could be attributed to instances of overuse, misuse or prescription practices that deviates from established guidelines. This eminent challenge can lead to the development of antibiotic resistance, increased healthcare costs, adverse drug reactions, and treatment failures, necessitating multifaceted approach such as improved antibiotic stewardship, better adherence to guidelines, and enhanced clinician education on appropriate antibiotic use.
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