1148. Impact of Procalcitonin (PCT)-Guided Antibiotic Therapy on Mortality in Critically Ill Patients: A Systematic Review and Meta-Analysis of 18 Randomized Controlled Trials
Session: Poster Abstract Session: Diagnostics: Biomarkers
Friday, October 6, 2017
Room: Poster Hall CD

Background: Procalcitonin (PCT)-guided antibiotic therapy has been shown to reduce antibiotic use in critically ill patients with suspected or proven infection, but its impact on mortality remains uncertain. Our meta-analysis examines the effect of PCT-guided antibiotic therapy on survival in critically ill patients.

Methods: We searched PubMed, the Cochrane Library, Scopus, Web of Science, EMBASE and clinicaltrials.gov electronic databases up to October 2016. The meta-analysis was restricted to randomized controlled trials (RCTs) of critically ill patients receiving PCT-guided antibiotic treatment and reporting survival or antibiotic duration. Study quality was assessed using the Cochrane risk of bias tool. Two reviewers conducted all review stages independently, and a third reviewer adjudicated any differences. Data was pooled using random-effects meta-analysis.

Results: Of the 18 RCTs selected (n=5,183 patients; Table), 17 assessed mortality and 11 assessed antibiotic duration; 8 scored ≥3 and 10 scored ≤2 out of 6 on the risk of bias assessment. Compared with controls, PCT-guided antibiotic treatment was associated with a significant reduction in mortality (20.7% vs. 23.0%; risk ratio [RR] 0.90[95%CI, 0.81-0.99], I2=0%; Fig. 1). Survival benefit was retained in the RCT subset with a lower risk of bias (score ≥ 3; RR 0.87 [95%CI, 0.77,0.98], I2=0%; Fig. 2) but not with higher risk (score ≤ 2; RR 0.98 [95%CI, 0.80-1.20], I2=0%). Our analysis of the effect of PCT-guided antibiotic therapy on antibiotic duration displayed significant heterogeneity (I2=61.2%, p=0.004), which precluded reporting on aggregate effect. Important limitations were: single center RCT (n=9), lack of double blinding (all studies) and variable protocol non-adherence and timeframes examined for mortality.

Conclusion: In a meta-analysis of RCTs of critically ill patients with suspected or proven infection, PCT-guided antibiotic treatment was associated with a significant reduction in mortality. The observed survival benefit was weighted towards RCTs of relatively higher quality. However, the plausibility of this finding, as well as the impact of protocol non-adherence on outcome needs further study.

Funded by Intramural NIH and NCI Contract# HHSN261200800001E

Dominique Pepper, MD MBChB1, Junfeng Sun, PhD1, Chanu Rhee, MD, MPH2, Judith Welsh, BSN3, John H. Powers III, MD4, Robert L. Danner, MD5 and Sameer Kadri, MD1, (1)Critical Care Medicine Department, National Institutes of Health, Bethesda, MD, (2)Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, (3)National Institutes of Health Library, National Institutes of Health, Bethesda, MD, (4)Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., NCI Campus at Frederick, Frederick, MD, (5)Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, MD

Disclosures:

D. Pepper, None

J. Sun, None

C. Rhee, None

J. Welsh, None

J. H. Powers III, None

R. L. Danner, None

S. Kadri, None

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