Procalcitonin (PCT)-guided antibiotic discontinuation appears to decrease antibiotic use in critically ill patients, but its impact on survival remains less certain.
We searched PubMed, EMBASE, Scopus, Web of Science, and CENTRAL for RCTs of PCT-guided antibiotic discontinuation in critically ill adults reporting survival or antibiotic duration. Searches were conducted without language restrictions from inception to 07/23/2018. Two reviewers independently conducted all review stages; another adjudicated differences. Data was pooled using random-effects meta-analysis. Study quality was assessed with the Cochrane risk of bias tool and evidence was graded using GRADEpro.
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], I=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],I=0%), those without industry sponsorship (9 RCTs; RR=0.98[0.87,1.10], I=0%), high PCT-guided algorithm adherence (5 RCTs; RR=0.93 [95%CI 0.71,1.22], I=0%), and PCT-guided algorithms without CRP (8 RCTs; RR=0.96 [95%CI 0.87,1.06], I=0%). PCT-guided antibiotic discontinuation decreased antibiotic duration (mean difference 1.31 days, [95%CI -2.27, -0.35]; I=93%); low certainty).
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 CRP. Properly designed studies with mortality as the primary outcome are needed to address this question.