Clinical effectiveness of procalcitonin- or C-reactive protein-guided antibiotic discontinuation protocols for adult patients who are critically ill with sepsis: a rapid systematic review and meta-analysis

Abstract

Introduction: Antibiotics are a first-line treatment for sepsis, with guidelines recommending a 7- to 10-day course. Prolonged antibiotic use carries significant risks, prompting growing interest in using inflammatory biomarkers, such as procalcitonin or C-reactive protein, to guide clinical decision-making on the duration of antibiotic therapy in patients who are critically ill. This rapid systematic review aims to assess the effectiveness and safety of using procalcitonin- or C-reactive protein-guided protocols for antibiotic discontinuation in patients who are critically ill with sepsis. Methods: We conducted systematic searches for articles published after January 2005 in relevant databases. Eligible studies included randomised controlled trials comparing procalcitonin- or C-reactive protein-guided protocols for antibiotic discontinuation with standard care, or with each other. Primary outcomes were duration of antibiotic therapy and mortality. Secondary outcomes included infection recurrences; secondary infections or superinfections; and the duration of intensive care and hospital stays. Results: We identified 21 eligible studies. Moderate certainty evidence from 19 trials, involving 6382 patients, indicated that procalcitonin-guided protocols probably reduced antibiotic therapy by, on average, 2.0 days (95%CI -2.6 to -1.4) compared with standard care. Moderate certainty evidence from 18 trials, involving 6228 patients, suggested an average 5% reduction in mortality risk when using procalcitonin-guided protocols compared with standard care (risk ratio 0.95, 95%CI 0.83–1.07). The evidence regarding C-reactive protein-guided protocols versus standard care approaches remained unclear, with very low to low certainty evidence available. Discussion: Combining relevant trials suggests that procalcitonin-guided discontinuation protocols may be both safe and effective for patients who are critically ill with sepsis, with no increased risk in mortality. In contrast, the evidence supporting C-reactive protein-guided protocols is limited. These findings underscore the potential importance of utilising procalcitonin to inform antimicrobial stewardship practices, particularly in critical care settings.