Outcomes in Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus Infective Endocarditis Compared With Staphylococcus lugdunensis Infective Endocarditis

Abstract

Importance: Infective endocarditis (IE) caused by Staphylococcus aureus remains associated with high early mortality. Staphylococcus lugdunensis is a virulent coagulase-negative species, but endocarditis-specific comparisons remain limited, and prior comparisons pooled methicillin-susceptible and methicillin-resistant S aureus. Objective: To compare 30-day mortality and major complications across methicillin-susceptible S aureus (MSSA), methicillin-resistant S aureus (MRSA), and S lugdunensis infective endocarditis. Design, Setting, and Participants: This cohort study used the Protege database frozen June 4, 2026 (4,950,000 patients). Adults with a first coded IE episode and organism evidence within 30 days formed 3 mutually exclusive groups. Patients with mixed organism evidence were excluded from the primary analysis. The analytic cohort included 4,388 adults: 290 with S lugdunensis, 2,338 with MSSA, and 1,760 with MRSA endocarditis. Exposure: Infective endocarditis organism group: MSSA, MRSA, or S lugdunensis. Main Outcomes and Measures: The primary outcome was death within 30 days after the index date. Secondary outcomes within 30 days included valve surgery, septic embolism, stroke, sepsis, heart failure, acute kidney injury, osteomyelitis, septic arthritis, and epidural abscess. Results: Patients with S lugdunensis were older (mean age, 58.3 years vs 53.3 years for MSSA and 50.7 years for MRSA). Crude 30-day mortality was 5.4% (15 of 280) with S lugdunensis, 7.2% (164 of 2,292) with MSSA, and 7.4% (128 of 1,719) with MRSA. After overlap weighting, MRSA had higher 30-day mortality than S lugdunensis (8.7% vs 5.4%, risk ratio, 1.63 [95% CI, 1.02-3.47]). MSSA mortality was also higher (7.9%, risk ratio, 1.47 [95% CI, 0.99-2.82]). Overlap-weighted HRs were 1.49 (95% CI, 0.86-2.58) and 1.67 (95% CI, 0.95-2.92). Valve surgery within 30 days was more frequent with S lugdunensis (weighted risk, 7.7% vs 5.3% for MSSA and 3.6% for MRSA). Septic embolism and osteoarticular coded outcomes were more frequent in both S aureus groups. Conclusions and Relevance: MRSA and MSSA infective endocarditis had higher 30-day mortality than S lugdunensis infective endocarditis after overlap weighting. Valve surgery was more frequent with S lugdunensis, and embolic and osteoarticular outcomes were more frequent with S aureus. Organism and methicillin susceptibility should be reported separately in endocarditis outcome studies.