{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:11:37Z","timestamp":1788948697780,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>The treatment of infective endocarditis (IE) in patients who inject drugs (PWID) is complex and challenging. These patients face stigma in the healthcare system, as well as higher mortality, longer length of hospital stay, higher rates of recurrent infections, and lower likelihood of antibiotic completion. Standard treatment for IE involves several weeks of antibiotics. For PWID, these prolonged courses often mean intravenous antibiotics administered in the inpatient setting for at least 4 to 6 weeks, which increases both healthcare costs and the risk of patient-directed discharge against medical advice. Effective treatment of IE in PWID involves a combination of addiction management and appropriate antibiotic therapy. To promote rational use of healthcare resources and optimize antibiotic stewardship, novel approaches to antibiotic therapy must be utilized. This review discusses evidence supporting treatment strategies outside of the inpatient hospital setting, including outpatient parenteral antibiotic therapy (OPAT), long-acting lipoglycopeptides, and oral antibiotic therapy for the treatment of endocarditis. Optimal treatment of IE in PWID involves support from a multidisciplinary healthcare team, management of substance use disorder, and effective antibiotic therapy.<\/jats:p>","DOI":"10.3390\/antibiotics15090881","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T09:24:02Z","timestamp":1788945842000},"page":"881","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optimizing Treatment of Infective Endocarditis in Patients Who Inject Drugs"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5205-693X","authenticated-orcid":false,"given":"Jarett","family":"Worden","sequence":"first","affiliation":[{"name":"College of Pharmacy & Health Sciences, Belmont University, Nashville, TN 37212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Baumeister","sequence":"additional","affiliation":[{"name":"Pharmacy, Williamson Medical Center, Franklin, TN 37067, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Eaton","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1161\/CIR.0000000000000296","article-title":"Infective endocarditis in adults: Diagnosis, antimicrobial therapy, and management of complications: A scientific statement for healthcare professionals from the American Heart Association","volume":"132","author":"Baddour","year":"2015","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1016\/j.mayocp.2019.08.023","article-title":"Clinical and economic burden of hospitalizations for infective endocarditis in the United States","volume":"95","author":"Alkhouli","year":"2020","journal-title":"Mayo Clin. 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