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.

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.