Nationwide practise patterns and regional differences in antibiotic treatment of streptococcal infective endocarditis in Denmark

Introduction Streptococcal endocarditis accounts for one third of all endocarditis cases and is associated with considerable morbidity and mortality. Variation in treatment and low adherence to antibiotic guidelines has been reported in small cohorts but the extent of this issue remains uncertain. Purpose To describe antibiotic practice patterns for streptococcal endocarditis across the five geographical regions of Denmark from a nationwide, unselected cohort. Methods We conducted a retrospective nationwide cohort study with the National Danish Endocarditis Studies (NIDUS) registry, including all patients hospitalized with possible or definite IE in Denmark from 2016 to 2021. Patients with left-sided streptococcal endocarditis were included and stratified by the five Danish regions. Patient characteristics and presentation at admission were assessed as well as antibiotic treatment, mono or combination therapy within the first 10 days following diagnosis. Multivariable logistic regression and Cox proportional hazard models were used to evaluate in-hospital and 6-months mortality. Results A total of 959 patients were included, 67.5% were male and the median age was 74.4 years (IQR 65.9-81.4). Across regions, fever, dyspnoea, and myalgia were the most common symptoms at presentation whereas diabetes, prior cancer, heart failure and COPD were the most common comorbidities. Regional differences were seen for prosthetic valve endocarditis, sepsis during hospitalization, and patients undergoing heart valve surgery. Antibiotic regimens differed significantly between regions, with monotherapy administered in 45.7%-72.2% of patients between regions (p<0.001). Most patients initially received combination therapy, followed by a transition to monotherapy in the subsequent days. Penicillin was the most used agent in the monotherapy group, while penicillin/gentamicin was the most frequent regimen among patients receiving combination therapy. Adjusted analysis showed no regional differences in in-hospital or 6-month mortality. The overall in-hospital mortality was 11.3%, and the 6-month cumulative incidence of mortality was 19.2%, neither outcome differed significantly between regions (p=0.057 and p=0.537, respectively). Conclusions We found significant differences in antibiotic practice patterns for streptococcal endocarditis across geographical regions in Denmark. No statistically significant difference in mortality was detected between the two treatment groups or across regions. These findings highlight the need for high-quality evidence to guide antibiotic treatment in clinical practice and support further guideline development.