Supplementary Material for: Efficacy and Safety of Procalcitonin-guided Antibiotic Therapy versus Standard of Care for Sepsis: A Systematic Review and Meta-analysis

Objectives: This systematic review and meta-analysis assesses the efficacy and safety of procalcitonin (PCT) guided therapy compared to standard of care (SOC) in septic patients. Methods: A comprehensive literature search was performed using the Cochrane Library, ClinicalTrials.gov, Embase, and MEDLINE, covering studies from their inception to April 2025. RevMan was used to perform a random-effects meta-analysis, and forest plots were used to visualize the pooled estimates. The Mantel-Haenszel method was applied to analyze dichotomous outcomes. The inverse variance method was applied to analyze continuous outcomes. Results: Sixteen randomized controlled trials (RCTs), with a total of 6,885 patients, were included. PCT-guided therapy was associated with significantly improved antibiotic treatment duration (standardized mean difference [SMD] -0.81, 95% CI -1.17 to -0.45, I2 97%), duration of mechanical ventilation (SMD -0.47, 95%CI -0.57 to - 0.37, I2 0%) and antibiotic-free days (SMD 0.14, 95% CI 0.04-0.25, I2 0%). Both groups were comparable in terms of ICU mortality, hospital mortality, 30-day mortality, 90-day mortality, ICU stay, hospital stay, new infection and clinical recovery. PCT was associated with greater reinfection (RR 1.12, 95% CI 1.00- 1.26, I2 0%). Conclusion: PCT-guided therapy was associated with shorter antibiotic treatment duration, though substantial heterogeneity was observed, while mortality outcomes were comparable between groups. Standardized PCT-based protocols are needed to improve consistency and clinical applicability.