Benefits and Harms of Procalcitonin- or C-Reactive Protein-Guided Antimicrobial Discontinuation in Critically Ill Adults With Sepsis: A Systematic Review and Network Meta-Analysis

Author:

Kubo Kenji1ORCID,Sakuraya Masaaki2,Sugimoto Hiroshi3,Takahashi Nozomi4,Kano Ken-ichi5,Yoshimura Jumpei6,Egi Moritoki7,Kondo Yutaka8

Affiliation:

1. Department of Emergency Medicine and Department of Infectious Diseases, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan.

2. Department of Emergency and Intensive Care Medicine, JA Hiroshima General Hospital, Hatsukaichi, Japan.

3. Department of Internal Medicine, National Hospital Organization Kinki-chuo Chest Medical Center, Osaka, Japan.

4. Centre for Heart Lung Innovation, St. Paul’s Hospital, The University of British Columbia, Vancouver, BC, Canada.

5. Department of Emergency Medicine, Fukui Prefectural Hospital, Fukui, Japan.

6. Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.

7. Department of Anesthesia, Kyoto University Hospital, Kyoto, Japan.

8. Department of Emergency and Critical Care Medicine, Juntendo University Urayasu Hospital, Urayasu, Japan.

Abstract

Objectives: In 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 Sources: A systematic search of PubMed, Embase, CENTRAL, Igaku Chuo Zasshi, ClinicalTrials.gov, and World Health Organization International Clinical Trials Platform. Study Selection: Randomized controlled trials involving adults with sepsis in intensive care. Data Extraction: A systematic review with network meta-analyses was performed. The Grading of Recommendations, Assessments, Developments, and Evaluation method was used to assess certainty. Data Synthesis: Eighteen 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). Conclusions: In 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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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