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Health Care–Associated Native Valve Endocarditis: Importance of Non-nosocomial Acquisition

Natividad Benito, MD, PhD; José M. Miró, MD, PhD; Elisa de Lazzari, MSs; Christopher H. Cabell, MD, MHS; Ana del Río, MD, PhD; Javier Altclas, MD; Patrick Commerford, MD; Francois Delahaye, MD, MPH; Stefan Dragulescu, MD, PhD; Helen Giamarellou, MD, PhD; Gilbert Habib, MD; Adeeba Kamarulzaman, MBBS; A. Sampath Kumar, MD; Francisco M. Nacinovich, MD; Fredy Suter, MD; Christophe Tribouilloy, MD, PhD; Krishnan Venugopal, MD, DM; Asuncion Moreno, MD, PhD; Vance G. Fowler Jr., MD, MHS, the ICE-PCS (International Collaboration on Endocarditis Prospective Cohort Study) Investigators
[+] Article and Author Information

For a list of the ICE-PCS investigators, see the Appendix.


From Hospital de la Santa Creu i Sant Pau, University Autónoma of Barcelona, and Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain; Duke University Medical Center, Durham, North Carolina; Sanatorio Mitre and Instituto Cardiovascular, Buenos Aires, Argentina; Groote Schuur Hospital, Cape Town, South Africa; Hôpital Louis Pradel, Lyon, Faculté de Médecine de Marseille, Marseille, and South Hospital Amiens, Amiens, France; Victor Babes University of Medicine and Pharmacy, Timişoara, Romania; Attikon University General Hospital, Athens, Greece; University of Malaya Medical Center, Kuala Lumpur, Malaysia; All India Institute of Medical Sciences, New Delhi, and Medical College Calicut, Kerala, India; and Ospedali Riuniti di Bergamo, Bergamo, Italy.


Grant Support: By the National Institutes of Health (grant R01-AI068804); the American Heart Association (grant 0455802U); the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, Spanish Network for the Research in Infectious Diseases (grant REIPI RD06/0008); and the Fundación Privada Máximo Soriano Jiménez, Barcelona, Spain (grant supporting the Hospital Clínic Endocarditis database). Dr. Miró received a Research Grant from the Institut d'Investigacions Biomèdiques August Pi i Sunyer and the Conselleria de Salut de la Generalitat de Catalunya, Barcelona, Spain.

Potential Financial Conflicts of Interest:Consultancies: F. Suter (Roche, Aventis), V.A. Fowler (Biosynexus, Cubist, Inhibitex, Merck, Johnson & Johnson). Honoraria: J.M. Miró (Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Chiron, Cubist, Novartis, GlaxoSmithKline, Gilead Sciences, Oxford Immunotec, Pfizer, Roche, Theravance), V.A. Fowler (Cubist, Pfizer). Grants received: F. Suter (Bristol-Myers Squibb), V.A. Fowler (Cubist, Inhibitex, Merck, Nabi, Theravance). Grants pending: V.A. Fowler (Merck, National Institutes of Health).

Reproducible Research Statement:Study protocol, statistical code, and data set (ICE-PCS database): Available to approved individuals through written agreements with the International Collaboration on Endocarditis Steering Committee.

Requests for Single Reprints: José M. Miró, MD, PhD, Hospital Clínic Universitari, Helios-Villarroel Building, Desk No. 26, Villarroel, 170, 08036 Barcelona, Spain; e-mail, jmmiro@ub.edu.

Current Author Addresses: Dr. Benito: Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, University Autónoma of Barcelona, Sant Antoni Maria, Claret 167, 08025 Barcelona, Spain.

Drs. Miró, del Río, and Moreno: Infectious Diseases Service, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain.

Ms. de Lazzari: Biostatistic Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain.

Dr. Cabell: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27710.

Dr. Altclas: Department of Infectious Disease, Sanatorio Mitre, Bartlone Mitre 2553, 1039 Buenos Aires, Argentina.

Dr. Commerford: Cardiac Clinic, E25 Room 87, Groote Schuur Hospital, 7925 Cape Town, South Africa.

Dr. Delahaye: Department of Cardiology, Hopital Louis Pradel, 28 Avenue du Doyen Lépine, 69677 Besançon, France.

Dr. Dragulescu: Institute of Cardiovascular Diseases, 13A Gh. Adam Street, 300310 Timişoara, Romania.

Dr. Giamarellou: Fourth Department of Internal Medicine, Attikon University General Hospital, 12462 Athens, Greece.

Dr. Habib: Faculté de Médecine de Marseille, Department of Medicine, Service de Cardiologie BBD, Jean Moulin, 13005 Marseille, France.

Dr. Kamarulzaman: University of Malaya Center, 50603 Kuala Lumpur, Malaysia.

Dr. Kumar: Department of Cardiothoracic and Vascular Surgery, All India Institute of Medical Sciences, Ansari Nagar, India.

Dr. Nacinovich: Infectious Diseases and Infection Control, Instituto Cardiovascular, Bonpland 2265–PB B, 1425 Buenos Aires, Argentina.

Dr. Suter: Infectious Diseases, Department of Internal Medicine, Ospedali Riuniti di Bergamo, 24100 Bergamo, Italy.

Dr. Tribouilloy: Department of Medicine, South Hospital Amiens, Avenue René Laënnec, 80054 Amiens, France.

Dr. Venugopal: Department of Cardiology, Calicut Medical College, Medical College P.O. Calicut–673 008, Kerala, India.

Dr. Fowler: Duke University Medical Center, Department of Medicine–Infectious Diseases, Box 3281, Durham, NC 27710.

Author Contributions: Conception and design: N. Benito, J.M. Miró.

Analysis and interpretation of the data: N. Benito, J.M. Miró, E. de Lazzari, A. del Río, F. Delahaye, A. Moreno.

Drafting of the article: N. Benito, J.M. Miró, E. de Lazzari.

Critical revision of the article for important intellectual content: J.M. Miró, A. del Río, P. Commerford, F. Delahaye, H. Giamarellou, G. Habib, A. Kamarulzaman, F.M. Nacinovich, F. Suter, A. Moreno, V.G. Fowler.

Final approval of the article: N. Benito, J.M. Miró, C.H. Cabell, A. del Río, F. Delahaye, H. Giamarellou, G. Habib, A. Kamarulzaman, F.M. Nacinovich, F. Suter, C. Tribouilloy, A. Moreno, V.G. Fowler.

Provision of study materials of patients: N. Benito, A. del Río, J. Altclas, P. Commerford, S. Dragulescu, H. Giamarellou, G. Habib, A.S. Kumar, F.M. Nacinovich, F. Suter, C. Tribouilloy, K. Venugopal, V.G. Fowler.

Statistical expertise: E. de Lazzari.

Collection and assembly of data: J.M. Miró, C.H. Cabell, J. Altclas, F. Delahaye, A. Kamarulzaman, A.S. Kumar, A. Moreno, V.G. Fowler.


Ann Intern Med. 2009;150(9):586-594. doi:10.7326/0003-4819-150-9-200905050-00004
Text Size: A A A

Background: The clinical profile and outcome of nosocomial and non-nosocomial health care–associated native valve endocarditis are not well defined.

Objective: To compare the characteristics and outcomes of community-associated and nosocomial and non-nosocomial health care–associated native valve endocarditis.

Design: Prospective cohort study.

Setting: 61 hospitals in 28 countries.

Patients: Patients with definite native valve endocarditis and no history of injection drug use who were enrolled in the ICE-PCS (International Collaboration on Endocarditis Prospective Cohort Study) from June 2000 to August 2005.

Measurements: Clinical and echocardiographic findings, microbiology, complications, and mortality.

Results: Health care–associated native valve endocarditis was present in 557 (34%) of 1622 patients (303 with nosocomial infection [54%] and 254 with non-nosocomial infection [46%]). Staphylococcus aureus was the most common cause of health care–associated infection (nosocomial, 47%; non-nosocomial, 42%; P = 0.30); a high proportion of patients had methicillin-resistant S. aureus (nosocomial, 57%; non-nosocomial, 41%; P = 0.014). Fewer patients with health care–associated native valve endocarditis had cardiac surgery (41% vs. 51% of community-associated cases; P < 0.001), but more of the former patients died (25% vs. 13%; P < 0.001). Multivariable analysis confirmed greater mortality associated with health care–associated native valve endocarditis (incidence risk ratio, 1.28 [95% CI, 1.02 to 1.59]).

Limitations: Patients were treated at hospitals with cardiac surgery programs. The results may not be generalizable to patients receiving care in other types of facilities or to those with prosthetic valves or past injection drug use.

Conclusion: More than one third of cases of native valve endocarditis in non–injection drug users involve contact with health care, and non-nosocomial infection is common, especially in the United States. Clinicians should recognize that outpatients with extensive out-of-hospital health care contacts who develop endocarditis have clinical characteristics and outcomes similar to those of patients with nosocomial infection.

Primary Funding Source: None.

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