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

OBJECTIVES: Infective endocarditis (IE) 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 IE at the population level remains poorly characterised. We aimed to evaluate the association between AMR and in-hospital mortality among adults hospitalised with bacterial IE in a real-world, nationwide setting. METHODS: We conducted a nationwide, population-based retrospective cohort study using the Spanish RAE-CMBD administrative hospital discharge database. We included adults (≥18 y) hospitalised with bacterial IE and a single identified causative microorganism between 1 January 2017 and 31 December 2022. AMR was defined by the presence of International Classification of Diseases, 10th Revision, Clinical Modification 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 d and alternative logistic regression model. RESULTS: Among 9540 hospitalisations with bacterial IE included in the analysis, 729 (7.64%) were coded as AMR infections. Overall, in-hospital mortality was 18.57% (1722 deaths). Mortality was higher among patients with AMR IE 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 1.68, 95% confidence interval 1.45-1.93). After multivariable adjustment, AMR remained independently associated with in-hospital mortality (adjusted hazard ratio 1.39, 95% confidence interval 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. CONCLUSIONS: In this nationwide cohort, AMR was independently associated with a substantially increased risk of in-hospital mortality among adults with bacterial IE. These findings highlight AMR as an important prognostic factor in IE and underscore the need for early identification of resistant pathogens, optimisation of antimicrobial therapy, and strengthened antimicrobial stewardship strategies.