Procalcitonin-Guided Antibiotic Discontinuation and Mortality in Critically Ill Adults: A Systematic Review and Meta-analysis.

BACKGROUND:Procalcitonin (PCT)-guided antibiotic discontinuation appears to decrease antibiotic use in critically ill patients, but its impact on survival remains less certain. METHODS:We searched PubMed, Embase, Scopus, Web of Science, and CENTRAL for randomized controlled trials (RCTs) of PCT-guided antibiotic discontinuation in critically ill adults reporting survival or antibiotic duration. Searches were conducted without language restrictions from inception to July 23, 2018. Two reviewers independently conducted all review stages; another adjudicated differences. Data were pooled using random-effects meta-analysis. Study quality was assessed with the Cochrane risk of bias tool, and evidence was graded using GRADEpro. RESULTS:Among critically ill adults (5,158 randomized; 5,000 analyzed), PCT-guided antibiotic discontinuation was associated with decreased mortality (16 RCTs; risk ratio [RR], 0.89; 95% CI, 0.83-0.97; I2 = 0%; low certainty). Death was the primary outcome in only one study and a survival benefit was not observed in the subset specified as sepsis (10 RCTs; RR, 0.94; 95% CI, 0.85-1.03; I2 = 0%), those without industry sponsorship (nine RCTs; RR, 0.98; 95% CI, 0.87-1.10; I2 = 0%), high PCT-guided algorithm adherence (five RCTs; RR, 0.93; 95% CI, 0.71-1.22; I2 = 0%), and PCT-guided algorithms without C-reactive protein (eight RCTs; RR, 0.96; 95% CI, 0.87-1.06; I2 = 0%). PCT-guided antibiotic discontinuation decreased antibiotic duration (mean difference, 1.31 days; 95% CI, -2.27 to -0.35; I2 = 93%) (low certainty). CONCLUSIONS:Our findings of increased survival and decreased antibiotic utilization associated with PCT-guided antibiotic discontinuation represent low-certainty evidence with a high risk of bias. This relationship was primarily observed in studies without high protocol adherence and in studies with algorithms combining PCT and C-reactive protein. Properly designed studies with mortality as the primary outcome are needed to address this question. TRIAL REGISTRY:International Prospective Register of Systematic Reviews (PROSPERO); No.: CRD42016049715; URL: http://www.crd.york.ac.uk/PROSPERO_REBRANDING/display_record.asp?ID=CRD42016049715.