Characteristics of Infective Endocarditis in Intravenous Drug Users vs. Non-Users: A Retrospective Study Conducted in Bucharest, Romania

<i>Background and Objectives</i>: Infective endocarditis (IE) remains a severe infection with high morbidity and mortality, particularly among people who inject drugs (PWID). Data from Eastern Europe are limited, despite the increasing burden of intravenous drug use in the region. <i>Materials and Methods</i>: We conducted a retrospective, observational cohort study of 153 patients diagnosed with IE and admitted to the "Dr. Victor Babeș" Clinical Hospital for Infectious and Tropical Diseases in Bucharest, Romania, between August 2019 and July 2024. Patients were classified into PWID (<i>n</i> = 51) and non-PWID (<i>n</i> = 102). Clinical characteristics, microbiological profiles, echocardiographic findings, complications, and outcomes (in-hospital, 10-week, and 12-month mortality) were compared between groups. <i>Results</i>: PWID were significantly younger (mean 34.0 ± 6.6 years vs. 64.3 ± 13.1 years; <i>p</i> < 0.001), predominantly male (86.3% vs. 62.7%; <i>p</i> = 0.003) and had higher rates of HIV (64.7%) and HCV (98.1%). Right-sided IE and larger vegetations were more common in PWID, whereas non-PWID had more left-sided disease, pre-existing valvular pathology, and prosthetic valve involvement. <i>Staphylococcus aureus</i> predominated in PWID (68.6% vs. 27.5%; <i>p</i> < 0.001), while non-PWID had more Streptococcus spp. and Coxiella burnetii cases. Embolic complications, particularly pulmonary emboli, and valvular rupture were significantly more frequent in PWID, while non-PWID had higher rates of heart failure and surgical interventions. In-hospital mortality was similar (17.6% vs. 11.8%; <i>p</i> = 0.318), but 12-month mortality was higher in PWID (27.5% vs. 13.7%; <i>p</i> = 0.038). <i>Conclusions</i>: IE in PWID shows a distinct clinical and microbiological profile, with more aggressive complications and worse long-term survival. Tailored management, early diagnosis, harm reduction programs, and dedicated follow-up are urgently needed in this high-risk population.