Association between antimicrobial resistance and in-hospital mortality in adults with bacterial infective endocarditis: a nationwide cohort study

• Mortality due to AMR IE is higher than in those without AMR: 29.36% vs 17.68% • AMR is associated with a 40% increased risk of hospital mortality: adjusted HR=1.40 • AMR is an important prognostic factor in IE • Early identification of resistant pathogens and optimisation of antimicrobial therapy may be relevant to the management of infective endocarditis. Infective endocarditis is a severe infection associated with high morbidity and mortality. Although antimicrobial resistance (AMR) is increasingly recognised as a major global public health threat, its impact on outcomes in infective endocarditis at the population level remains poorly characterised. We aimed to evaluate the association between AMR and in-hospital mortality among adults hospitalised with bacterial infective endocarditis in a real-world, nationwide setting. We conducted a nationwide, population-based retrospective cohort study using the Spanish RAE-CMBD administrative hospital discharge database. We included adults (≥18 years) hospitalised with bacterial infective endocarditis and a single identified causative microorganism between Jan 1, 2017, and Dec 31, 2022. AMR was defined by the presence of ICD-10-CM resistance codes (Z16.1 or Z16.2) linked to the causative pathogen. The primary outcome was in-hospital mortality. Time-to-event analyses were performed using Cox proportional hazards models, with adjustment for age, sex, comorbidity burden (Elixhauser–van Walraven index), sepsis (modelled as a time-varying covariate), cardiac surgery, and prosthetic valve endocarditis. Sensitivity analyses included censoring follow-up at 90, 30 and 18 days and alternative logistic regression model. Among 9 540 hospitalisations with bacterial infective endocarditis included in the analysis, 729 (7.64%) were coded as AMR infections. Overall in-hospital mortality was 18.57% (1 722 deaths). Mortality was higher among patients with AMR infective endocarditis than among those without resistance (29.36% vs 17.68%; p<0.0001). Staphylococcus aureus was the most frequently identified resistant pathogen. In univariable analysis, AMR was associated with increased in-hospital mortality (hazard ratio HR 1.68, 95% CI 1.45–1.93). After multivariable adjustment, AMR remained independently associated with in-hospital mortality (adjusted HR 1.39, 95% CI 1.19–1.59; p<0.0001). Increasing age and comorbidity burden were associated with higher mortality, whereas cardiac surgery was associated with improved survival. Prosthetic valve endocarditis was not independently associated with in-hospital mortality. Results were consistent across all sensitivity analyses. In this nationwide cohort, AMR was independently associated with a substantially increased risk of in-hospital mortality among adults with bacterial infective endocarditis. These findings highlight AMR as an important prognostic factor in infective endocarditis and underscore the need for early identification of resistant pathogens, optimisation of antimicrobial therapy, and strengthened antimicrobial stewardship strategies.