Procalcitonin-Guided Antibiotic Therapy in ICU Patients with Sepsis: A Systematic Review and Meta-Analysis with GRADE and Trial Sequential Analysis

Abstract

Objective: To evaluate the efficacy and safety of PCT-guided antibiotic therapy compared with standard care in adult intensive care unit (ICU) patients with sepsis or septic shock.

Methods: PubMed, Scopus, the Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science were searched from database inception to January 2026 to identify randomized controlled trials (RCTs) comparing PCT-guided antibiotic strategies with standard care in adult ICU patients with suspected or confirmed bacterial infections. The primary clinical outcome was all-cause mortality at the longest available follow-up, whereas the key antimicrobial stewardship outcome was duration of antibiotic therapy. Secondary outcomes included infection relapse, new infection or superinfection, antimicrobial-free days, clinical cure, and length of ICU or hospital stay. Random-effects meta-analyses were performed using intention-to-treat data. Trial sequential analysis (TSA) and the GRADE framework were applied to assess the conclusiveness and certainty of the evidence.

Results: Sixteen RCTs involving 7,966 patients were included. PCT-guided therapy did not reduce all-cause mortality compared with standard care (RR = 0.99, 95% CI 0.92 to 1.06; p = 0.72), with trial sequential analysis indicating insufficient evidence to draw a definitive conclusion. In contrast, PCT-guided strategies significantly reduced antibiotic duration (MD = −1.51 days, 95% CI −2.24 to −0.78), with trial sequential analysis confirming a conclusive benefit. Procalcitonin guidance was associated with an increase in antimicrobial-free days without higher rates of new infection, superinfection, or clinical failure. Additionally, no significant differences were observed in ICU or hospital length of stay.

Conclusions: In adult ICU patients with sepsis or septic shock, RCT-guided antibiotic strategies were associated with reduced antibiotic exposure and increased antibiotic-free days, without a detectable improvement in survival. These findings support the use of procalcitonin as an adjunctive antimicrobial stewardship tool, provided that it integrated with clinical assessment, microbiological data, and sound clinical judgment.