All patients admitted for the first episode of IE between 1 January 2010 and 31 December 2020 were identified using the following ICD-8/10 diagnosis codes for infective endocarditis: 421 (ICD-8), DI33.0, DI38.0, and DI39.8. To increase the accuracy of the IE diagnosis, only patients who were hospitalized for >14 days or died within the first 14 days of admission were included, as descried previously, with a positive predictive value of 90% in the Danish National Patient Registry [22 (link),23 (link)]. The study population was stratified according to treatment choice: (i) patients who underwent surgery during the initial admission (procedure codes are available in Supplementary Table S1) and (ii) patients who received medical therapy only. The microbiological etiology was identified as a positive blood culture collected within 30 days of the index date and until the discharge date of IE. We ranked the possible microbiological etiologies to identify the most likely primary microorganisms causing IE: (1) S. aureus, Streptococcus spp., HACEK (Haemophilus (not including Haemophilus influenzae), Aggregatibacter, Cardiobacterium, Eikenella, and Kingella), and Enterococcus spp.; (2) coagulase-negative Staphylococci (CoNS); (3) “other microbiological etiologies”; and (4) negative blood cultures. Subsequently, patients were categorized according to the following groups of microorganisms: (1) S. aureus, (2) Streptococcus spp., (3) Enterococcus spp., (4) CoNS, (5) “other microbiological etiologies” (including HACEK and fungi) referred to as “other IE”, and (6) blood-culture-negative IE, referred to as “Negative IE”. The specific bacteria assessed in the parent groups of microbiological etiologies are shown in Supplementary Table S2a–c. Patients without available blood cultures within 30 days of the index date were excluded (Figure 1).
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