Rheumatoid arthritis and risk of osteoarticular infection and death following Staphylococcus aureus bacteraemia: A nationwide cohort study.

OBJECTIVES: Osteoarticular infection (OAI) is a feared complication of Staphylococcus aureus bacteraemia (SAB) and is associated with poor outcomes. We aimed to explore risk of OAI and death following SAB in patients with and without rheumatoid arthritis (RA) and to identify risk factors for OAI in patients with RA. METHODS: Danish nationwide cohort study of all patients with microbiologically verified first-time SAB between 2006-2018. We identified RA, SAB, comorbidities, and RA-related characteristics (e.g. orthopaedic implants, antirheumatic treatment) in national registries including the rheumatology registry DANBIO. We estimated cumulative incidence of OAI and death and adjusted hazard ratios (HRs, multivariate Cox regression). RESULTS: We identified 18 274 patients with SAB (n = 367 with RA). The 90-day cumulative incidence of OAI was 23.1%(95%CI 18.8; 27.6) for patients with RA and 12.5%(12.1; 13.0) for patients without RA (non-RA) (HR 1.93(1.54; 2.41)). For RA patients with orthopaedic implants cumulative incidence was 29.4%(22.9; 36.2) (HR 1.75(1.08; 2.85), and for current users of tumor necrosis factor inhibitors (TNFi) it was 41.9%(27.0; 56.1) (HR 2.27(1.29; 3.98) compared with non-users). All-cause 90-day mortality following SAB was similar in RA (35.4%(30.6; 40.3)) and non-RA (33.9%(33.2; 34.5), HR 1.04(0.87; 1.24)). CONCLUSION: Following SAB, almost one in four patients with RA contracted OAI corresponding to a doubled risk compared with non-RA. In RA, orthopaedic implants and current TNFi use were associated with approximately doubled OAI risk. One in three died within 90 days in both RA and non-RA. These findings encourage vigilance in RA patients with SAB to avoid treatment delay of OAI.

The impact of hemodialysis on mortality risk and cause of death in Staphylococcus aureus endocarditis.

BACKGROUND: The risk of infective endocarditis (IE) is markedly increased in patients receiving chronic hemodialysis compared with the general population, but outcome data are sparse. The present study investigated causes and risk factors of mortality in a hemodialysis-treated end-stage kidney disease- (ESKD) and a non-ESKD population with staphylococcus (S.) aureus endocarditis. METHODS: Hemodialysis-treated ESKD patients with S. aureus endocarditis were identified from Danish National Registries and Non-ESKD patients from The East Danish Database on Endocarditis. For establishing the cause of death The Danish Registry of Cause of Death was used. Independent risk factors of outcome were identified in multivariable Cox regression models. RESULTS: One hundred twenty-one hemodialysis patients and 190 non-ESKD patients with S. aureus endocarditis were included during 1996-2012 and 2002-2012, respectively. The all-cause in-hospital mortality was 22.3% in hemodialysis- and 24.7% in non-ESKD patients. One-year mortality, excluding in-hospital mortality, was 26.4% in hemodialysis patients and 15.2% in non-ESKD patients. The hazard ratio of all-cause mortality in hemodialysis was 2.64 (95% CI 1.70-4.10) at > 70 days after admission compared with non-ESKD. Age (HR 1.03 (95% CI 1.02-1.04)) and diabetes mellitus (HR 2.17 (95% CI 1.54-3.10)) were independent risk factors of all-cause mortality. The hazard ratio of cardiovascular death in hemodialysis was 3.20 (95% CI 1.78-5.77) at > 81 days after admission compared with non-ESKD. Age and diabetes mellitus were independently related to cardiovascular death. CONCLUSION: All-cause in-hospital mortality rates were similar in hemodialysis and non-ESKD patients with S. aureus endocarditis whereas one-year mortality rates were significantly increased in the hemodialysis population.

Familial Clustering of Staphylococcus aureus Bacteremia in First-Degree Relatives: A Danish Nationwide Cohort Study.

BACKGROUND: A genetic predisposition to Staphylococcus aureus bacteremia has been demonstrated in animals, suggesting that genetic differences might influence susceptibility to S aureus in humans. OBJECTIVE: To determine whether a history of S aureus bacteremia in first-degree relatives increases the rate of the disease, and whether this rate is affected by the type of family relationship (that is, parent or sibling) or by how the relative acquired the infection. DESIGN: Register-based nationwide cohort study (1992 to 2011). SETTING: Denmark. PARTICIPANTS: First-degree relatives (children or siblings) of patients previously hospitalized with S aureus bacteremia. MEASUREMENTS: Poisson regression models were used to calculate standardized incidence ratios (SIRs) of S aureus bacteremia, with the incidence rate in the population as a reference. RESULTS: 34 774 individuals (the exposed cohort) with a first-degree relative (index case patient) previously hospitalized with S aureus bacteremia were followed up for a median of 7.8 years (interquartile range, 3.6 to 13.0). A higher rate of S aureus bacteremia was observed among these first-degree relatives (SIR, 2.49 [95% CI, 1.95 to 3.19]) than in the background population. The estimate was significantly higher if the index case patient was a sibling (SIR, 5.01 [CI, 3.30 to 7.62]) than a parent (SIR, 1.96 [CI, 1.45 to 2.67]; interaction P < 0.0001). No interaction was observed regarding the sex of the first-degree relative (interaction P for parents = 0.85; interaction P for siblings = 0.92). Stratifying by disease acquisition revealed the highest rates in individuals exposed to index case patients with non-hospital-acquired infection. Few were infected with genetically identical bacteremia isolates. LIMITATION: The rarity of the outcome limited the number of variables in the multiple regression analysis, and whether nonsignificant interactions were true or caused by insufficient statistical power remains uncertain. CONCLUSION: A significant familial clustering of S aureus bacteremia was found, with the greatest relative rate of disease observed in individuals exposed to siblings with a history of the disease. PRIMARY FUNDING SOURCE: The Danish Heart Foundation and the Christian Larsen and Judge Ellen Larsen Foundation.