Impact of Procalcitonin (PCT)-Guided Antibiotic Therapy on Mortality in Critically Ill Patients: A Systematic Review and Meta-Analysis of 18 Randomized Controlled Trials

Abstract

Abstract 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%; Figure 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%; Figure 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 Disclosures All authors: No reported disclosures.