Background Infective endocarditis (IE) often requires surgical intervention. An increasingly common cause of IE is injection drug use (IDU-IE). There is conflicting evidence on whether postoperative mortality differs between people with IDU-IE and people with IE from etiologies other than injection drug use (non–IDU-IE). In this manuscript, we compare short-term postoperative mortality in IDU-IE vs non–IDU-IE through systematic review and meta-analysis. Methods The review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Publication databases were queried for key terms included in articles up to September 2017. Randomized controlled trials, prospective cohorts, or retrospective cohorts that reported on 30-day mortality or in-hospital/operative mortality following valve surgery and that compared outcomes between IDU-IE and non–IDU-IE were included. Results Thirteen studies with 1593 patients (n = 341 [21.4%] IDU-IE) were included in the meta-analysis. IDU-IE patients more frequently had tricuspid valve infection, Staphylococcus infection, and heart failure before surgery. Meta-analysis revealed no statistically significant difference in 30-day postsurgical mortality or in-hospital mortality between the 2 groups. Conclusions Despite differing preoperative clinical characteristics, early postoperative mortality does not differ between IDU-IE and non–IDU-IE patients who undergo valve surgery. Future research on long-term outcomes following valve replacement is needed to identify opportunities for improved healthcare delivery with IDU-IE.

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