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Meta-Analysis
. 2019 Jun;155(6):1109-1118.
doi: 10.1016/j.chest.2018.12.029. Epub 2019 Feb 14.

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

Dominique J Pepper  1 , Junfeng Sun  2 , Chanu Rhee  3 , Judith Welsh  4 , John H Powers 3rd  5 , Robert L Danner  2 , Sameer S Kadri  2
Affiliations
Meta-Analysis

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

Dominique J Pepper et al. Chest. 2019 Jun.

Abstract

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.

Keywords: antibiotic; critical illness; mortality; procalcitonin; sepsis.

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Figures

Figure 1
Figure 1
Search strategy. *In one study results were inconsistent and in another study the data were not normally distributed. Therefore two of these 13 studies were omitted and a total of 11 studies were included in the meta-analysis for hospital length of stay. RCT = randomized controlled trial.
Figure 2
Figure 2
Survival in 16 randomized clinical trials assessing procalcitonin-guided antibiotic discontinuation in critically ill adults. RR = risk ratio.
Figure 3
Figure 3
Testable hypotheses for the potential mechanism of a survival benefit from procalcitonin-guided antibiotic discontinuation. C.diff = Clostridium difficile; PCT = procalcitonin.
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