0

The full content of Annals is available to subscribers

Subscribe/Learn More  >
Original Research |

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

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; and Christian Torp-Pedersen, MD, DMSci
[+] Article, Author, and Disclosure Information

This article was published at www.annals.org on 5 July 2016.


From Aalborg University, Aalborg, and Copenhagen University Hospital Herlev-Gentofte and Statens Serum Institut, Copenhagen, Denmark.

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, l_bruun@hotmail.com). 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, l_bruun@hotmail.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.


Ann Intern Med. 2016;165(6):390-398. doi:10.7326/M15-2762
© 2016 American College of Physicians
Text Size: A A A

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.

Figures

Grahic Jump Location
Figure 1.

Flowchart illustrating the selection of the study population.

SAB = Staphylococcus aureus bacteremia.

Grahic Jump Location
Grahic Jump Location
Figure 2.

Incidence of Staphylococcus aureus bacteremia in the Danish population from 1992 to 2011.

Grahic Jump Location
Grahic Jump Location
Figure 3.

SIRs for Staphylococcus aureus bacteremia in first-degree relatives.

The SIRs of the Poisson model for exposed individuals overall and for index case siblings and parents (family status), as well as for the way in which the bacteremia was acquired in the index case, are shown. The model is adjusted for sex, age, and calendar year. NA = not applicable; SIR = standardized incidence ratio.

Grahic Jump Location
Grahic Jump Location
Figure 4.

SIRs for Staphylococcus aureus bacteremia in first-degree relatives stratified by sex, method of bacteremic acquisition, and family status of the index case patient.

The model is adjusted for sex, age, and calendar year. NA = not applicable; SIR = standardized incidence ratio.

Grahic Jump Location
Grahic Jump Location
Figure 5.

Adjusted SIRs for Staphylococcus aureus bacteremia in first-degree relatives.

The model is adjusted for age, calendar year, sex, diabetes, cancer, chronic dialysis treatment, any surgical procedure, and presence of a prosthetic device (pacemaker or prosthetic heart valve, knee, or hip) and stratified by bacteremic acquisition of the index case. NA = not applicable; SIR = standardized incidence ratio.

Grahic Jump Location
Grahic Jump Location
Figure 6.

SIRs for Staphylococcus aureus bacteremia in first-degree relatives if children and siblings of an index case patient were not considered at risk until 1 year after the index date.

The model is adjusted for sex, age, and calendar year and stratified by family status and method of bacteremic acquisition in the index case. NA = not applicable; SIR = standardized incidence ratio.

Grahic Jump Location

Tables

References

Letters

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Comments

Submit a Comment/Letter
Submit a Comment/Letter

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.

Toolkit

Buy Now for $32.00

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Advertisement
Related Articles
Journal Club
Topic Collections
PubMed Articles
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.
(Required)
(Required)