Comparative Efficacy of High- and Low-Dose Ceftriaxone Regimens: A Systematic Review and Meta-Analysis

Objective: To compare the efficacy and safety of ceftriaxone (CRO) 1 g intravenously (IV) daily to higher doses for treating non-central nervous system (CNS) infections in adults. Data Sources: PubMed, Embase, Scopus, and Web of Science were used. A search was run from database inception to August 8, 2023 and rerun May 12, 2025. Search terms were CRO, Rocephin, pneumonia, intra-abdominal infections, appendicitis, typhlitis, pyelonephritis, bacteremia, and sepsis. Study Selection and Data Extraction: Articles included had to compare CRO 1 g IV daily to higher dosing for the outcomes of interest: clinical cure (CC), hospital length of stay (LOS), mortality, and toxicity. Randomized controlled trials (RCTs) or observational studies were included. Studies including pediatric, pregnant, and outpatient administration were excluded. Clinical cure was evaluated using a Mantel-Haenszel random-effects model with Peto odds ratios (pORs), and 95% confidence intervals (CIs) were calculated. Heterogeneity was identified using Cochrane I 2 statistic. Data Synthesis: Eight studies (5145 patients) were included. No statistically significant difference was found for CC (pOR 0.958; 95% CI [0.525-1.749]; I 2 = 60.23; P = .888); LOS (Std difference in means, 0.052; 95% CI [−0.418, 0.523]; I 2 = 96.047; P = .828); or mortality (pOR 0.932; 95% CI [0.789-1.100]; I 2 = 0.000; P = .405). Relevance to Patient Care and Clinical Practice: Ceftriaxone dosing ranges from 1 to 2 g IV daily for treating non-CNS infections. Optimal dosing remains controversial, as RCTs have used different doses. This meta-analysis showed no difference between high and low CRO dosing for efficacy and safety. Because infection type and pharmacokinetic factors were not accounted for, findings may not be applicable to certain high-risk infections or situations where CRO pharmacokinetics are altered, such as hypoalbuminemia. Prospective studies can compare regimens and confirm findings. Conclusions: Ceftriaxone doses greater than 1 g IV daily did not improve CC, LOS, or mortality.