Louise B. Oestergaard, MD; Mia N. Christiansen, MD; Michelle D. Schmiegelow, MD, PhD; Robert L. Skov, MD; Paal S. Andersen, PhD; Andreas Petersen, PhD; Kristian Aasbjerg, MD; Thomas A. Gerds, PhD; Per K. Andersen, PhD, DMSci; Christian Torp-Pedersen, MD, DMSci
Grant Support: By grant R99-A6001 from the Danish Heart Foundation and a scholarship from the Christian Larsen and Judge Ellen Larsen Foundation, a minor fund supporting research in the fields of infectious diseases and cancer.
Disclosures: Dr. Torp-Pedersen reports grants and personal fees from Bayer and grants from Biotronic, outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?ms Num=M15-2762.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol: See the Supplement. Statistical code: Available from Dr. Oestergaard (e-mail, firstname.lastname@example.org). Data set: Not available.
Requests for Single Reprints: Louise B. Oestergaard, MD, Department of Cardiology, Copenhagen University Hospital Herlev-Gentofte, Kildegaardsvej 28, Post-635, 2900 Hellerup, Denmark; e-mail, email@example.com.
Current Author Addresses: Drs. Oestergaard and Schmiegelow: Department of Cardiology, Copenhagen University Hospital Herlev-Gentofte, Kildegaardsvej 28, Post-635, 2900 Hellerup, Denmark.
Dr. Christiansen: Rigshospitalet afd. 944, Blegdamsvej 9, 2100 Copenhagen OE, Denmark.
Dr. Skov: Microbiology and Infection Control, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
Dr. P.S. Andersen: Microbiology and Infection Control, Statens Serum Institut, 5 Artillerivej, 47/217, DK-2300 Copenhagen S, Denmark.
Dr. Petersen: Microbiology & Infection Control, Statens Serum Institut, 5 Artillerivej, 46/104, DK-2300 Copenhagen S, Denmark.
Dr. Aasbjerg: Department of Ophthalmology, Aalborg University Hospital, Hobrovej 18-22, PO Box 365, DK-9000 Aalborg, Denmark.
Drs. Gerds and P.K. Andersen: Section of Biostatistics, Øster Farimagsgade 5 opg. B, PO Box 2099, DK-1014 Copenhagen K, Denmark.
Dr. Torp-Pedersen: Department of Health Science and Technology, Niels Jernes Vej 12, Room A5-208, 9220 Aalborg Ø, Denmark.
Author Contributions: Conception and design: L.B. Oestergaard, M.N. Christiansen, M.D. Schmiegelow, C. Torp-Pedersen.
Analysis and interpretation of the data: L.B. Oestergaard, M.N. Christiansen, M.D. Schmiegelow, P.S. Andersen, K. Aasbjerg, T.A. Gerds, P.K. Andersen, C. Torp-Pedersen.
Drafting of the article: L.B. Oestergaard.
Critical revision for important intellectual content: L.B. Oestergaard, M.N. Christiansen, M.D. Schmiegelow, R.L. Skov, P.S. Andersen, P.K. Andersen, C. Torp-Pedersen.
Final approval of the article: L.B. Oestergaard, M.N. Christiansen, M.D. Schmiegelow, R.L. Skov, P.S. Andersen, A. Petersen, K. Aasbjerg, T.A. Gerds, P.K. Andersen, C. Torp-Pedersen.
Provision of study materials or patients: R.L. Skov, P.S. Andersen.
Statistical expertise: L.B. Oestergaard, K. Aasbjerg, T.A. Gerds, P.K. Andersen, C. Torp-Pedersen.
Obtaining of funding: L.B. Oestergaard, C. Torp-Pedersen.
Administrative, technical, or logistic support: M.D. Schmiegelow, C. Torp-Pedersen.
Collection and assembly of data: P.S. Andersen, C. Torp-Pedersen.
A genetic predisposition to Staphylococcus aureus bacteremia has been demonstrated in animals, suggesting that genetic differences might influence susceptibility to S aureus in humans.
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.
Register-based nationwide cohort study (1992 to 2011).
First-degree relatives (children or siblings) of patients previously hospitalized with S aureus bacteremia.
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.
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.
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.
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.
The Danish Heart Foundation and the Christian Larsen and Judge Ellen Larsen Foundation.
Oestergaard LB, Christiansen MN, Schmiegelow MD, Skov RL, Andersen PS, Petersen A, et al. Familial Clustering of Staphylococcus aureus Bacteremia in First-Degree Relatives: A Danish Nationwide Cohort Study. Ann Intern Med. [Epub ahead of print 5 July 2016]165:390–398. doi: 10.7326/M15-2762
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Published: Ann Intern Med. 2016;165(6):390-398.
Published at www.annals.org on 5 July 2016
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