• Kenji Kubo, Masaaki Sakuraya, Hiroshi Sugimoto, Nozomi Takahashi, Ken-Ichi Kano, Jumpei Yoshimura, Moritoki Egi, and Yutaka Kondo.
• Department of Emergency Medicine and Department of Infectious Diseases, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan.
• Crit. Care Med. 2024 Oct 1; 52 (10): e522e534e522-e534.

ObjectivesIn sepsis treatment, antibiotics are crucial, but overuse risks development of antibiotic resistance. Recent guidelines recommended the use of procalcitonin to guide antibiotic cessation, but solid evidence is insufficient. Recently, concerns were raised that this strategy would increase recurrence. Additionally, optimal protocol or difference from the commonly used C-reactive protein (CRP) are uncertain. We aimed to compare the effectiveness and safety of procalcitonin- or CRP-guided antibiotic cessation strategies with standard of care in sepsis.Data SourcesA systematic search of PubMed, Embase, CENTRAL, Igaku Chuo Zasshi, ClinicalTrials.gov , and World Health Organization International Clinical Trials Platform.Study SelectionRandomized controlled trials involving adults with sepsis in intensive care.Data ExtractionA systematic review with network meta-analyses was performed. The Grading of Recommendations, Assessments, Developments, and Evaluation method was used to assess certainty.Data SynthesisEighteen studies involving 5023 participants were included. Procalcitonin-guided and CRP-guided strategies shortened antibiotic treatment (-1.89 days [95% CI, -2.30 to -1.47], -2.56 days [95% CI, -4.21 to -0.91]) with low- to moderate-certainty evidence. In procalcitonin-guided strategies, this benefit was consistent even in subsets with shorter baseline antimicrobial duration (7-10 d) or in Sepsis-3, and more pronounced in procalcitonin cutoff of "0.5 μg/L and 80% reduction." No benefit was observed when monitoring frequency was less than half of the initial 10 days. Procalcitonin-guided strategies lowered mortality (-27 per 1000 participants [95% CI, -45 to -7]) and this was pronounced in Sepsis-3, but CRP-guided strategies led to no difference in mortality. Recurrence did not increase significantly with either strategy (very low to low certainty).ConclusionsIn sepsis, procalcitonin- or CRP-guided antibiotic discontinuation strategies may be beneficial and safe. In particular, the usefulness of procalcitonin guidance for current Sepsis-3, where antimicrobials are used for more than 7 days, was supported. Well-designed studies are needed focusing on monitoring protocol and recurrence.Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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