Non-HACEK Gram-Negative Bacillus Endocarditis

18 December 2007 | Volume 147 Issue 12 | Pages 829-835

Background: Infective endocarditis caused by non-HACEK (species other than Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, or Kingella species) gram-negative bacilli is rare, is poorly characterized, and is commonly considered to be primarily a disease of injection drug users.

Objective: To describe the clinical characteristics and outcomes of patients with non-HACEK gram-negative bacillus endocarditis in a large, international, contemporary cohort of patients.

Design: Observations from the International Collaboration on Infective Endocarditis Prospective Cohort Study (ICE-PCS) database.

Setting: 61 hospitals in 28 countries.

Patients: Hospitalized patients with definite endocarditis.

Measurements: Characteristics of non-HACEK gram-negative bacillus endocarditis cases were described and compared with those due to other pathogens.

Results: Among the 2761 case-patients with definite endocarditis enrolled in ICE-PCS, 49 (1.8%) had endocarditis (20 native valve, 29 prosthetic valve or device) due to non-HACEK, gram-negative bacilli. Escherichia coli (14 patients [29%]) and Pseudomonas aeruginosa (11 patients [22%]) were the most common pathogens. Most patients (57%) with non-HACEK gram-negative bacillus endocarditis had health care–associated infection, whereas injection drug use was rare (4%). Implanted endovascular devices were frequently associated with non-HACEK gram-negative bacillus endocarditis compared with other causes of endocarditis (29% vs. 11%; P < 0.001). The in-hospital mortality rate of patients with endocarditis due to non-HACEK gram-negative bacilli was high (24%) despite high rates of cardiac surgery (51%).

Limitations: Because of the small number of patients with non-HACEK gram-negative bacillus endocarditis in each treatment group and the lack of long-term follow-up, strong treatment recommendations are difficult to make.

Conclusion: In this large, prospective, multinational cohort, more than one half of all cases of non-HACEK gram-negative bacillus endocarditis were associated with health care contact. Non-HACEK gram-negative bacillus endocarditis is not primarily a disease of injection drug users.

Editors' Notes Context Infective endocarditis due to non-HACEK organisms has been considered to be associated with injection drug use. Contribution Analysis of 2761 cases of patients with infective endocarditis from an international collaborative of 61 hospitals found that non-HACEK organisms account for fewer than 2% of the cases, and that most patients with non-HACEK endocarditis had infections associated with health care. Of patients with non-HACEK infections, 59% had implanted endovascular devices or prosthetic valves, but only 4% had injection drug use. More than one half of patients with non-HACEK infections required cardiac surgery and 24% died. Implication Infective endocarditis due to non-HACEK organisms is a rare but frequently fatal condition. It is much more frequently associated with implanted endovascular devices than with injection drug use. —The Editors

 

Author and Article Information

From Duke University Medical Center and Duke Clinical Research Institute, Durham, North Carolina; University of Otago, Christchurch, New Zealand; Beth Israel Deaconess Medical Center, Boston, Massachusetts; Wayne State University Health Center, Detroit, Michigan; Instituto Cardiovascular de Buenos Aires, Buenos Aires, Argentina; Pontchaillou University Hospital, Rennes, France; Hospital Universitari Vall d'Hebron, Barcelona, Spain; New York University School of Medicine, New York University Medical Center, New York, New York; Hospital General Universitario Gregorio Marañón, Madrid, Spain; Hospital Clínic i Provincial Clinic—Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain; Medical Center Ljublijana, Ljublijana, Slovenia; Instituto Dante Pazzanese de Cardiología, São Paulo, Brazil; II Università di Napoli, Naples, Italy; St. Thomas' Hospital, London, United Kingdom; University Medical Center of Besançon, Besançon, France; and Veterans Health Affairs North Texas, University of Texas Southwestern Medical Center, Dallas, Texas.

Grant Support: From the National Institutes of Health (Dr. Fowler) (grant no. R01-AI068804) and the Hubert-Yeargan Center for Global Health (Dr. Morpeth).

Potential Financial Conflicts of Interest: Consultancies: G.R. Corey (Theravance, Cubist Pharmaceuticals, Cerexa, Astellas Pharma, Pfizer, Johnson & Johnson), V.G. Fowler (Biosynexus, Astellas Pharma, Inhibitex, Nabi, Merck & Co., Theravance, Cubist Pharmaceuticals, Johnson & Johnson). Honoraria: G.R. Corey (Cubist Pharmaceuticals, Pfizer, Astellas Pharma), V.G. Fowler (Cubist Pharmaceuticals). Grants received: V.G. Fowler (Cubist Pharmaceuticals, Merck & Co., Nabi, National Institutes of Health, Theravance). Grants pending: V.G. Fowler (Cerexa, National Institutes of Health).

Requests for Single Reprints: Vance G. Fowler Jr., MD, MHS, Box 3281, Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC 27710; e-mail, vance.fowler{at}duke.edu.

Current Author Addresses: Drs. Morpeth and Fowler: Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, NC 27710.

Dr. Murdoch: Department of Pathology, University of Otago, Christchurch, PO Box 4345, Christchurch, New Zealand.

Drs. Cabell and Corey: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27710.

Dr. Karchmer: Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215.

Mr. Pappas: Outcomes Research and Assessment Group, Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27710.

Dr. Levine: University Health Center, Wayne State University, 3663 Woodward Avenue, #200, Detroit, MI 48201.

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

Dr. Tattevin: Maladies Infectieuses et Réanimation Médicale, Pontchaillou University Hospital, Rennes 35033, France.

Dr. Fernández-Hidalgo: Hospital Universitari Vall d'Hebron, Servei de Malalties Infeccioses, AVDP, Vall d'Hebron, 119-129 Barcelona 08035, Spain.

Dr. Dickerman: School of Medicine, New York University Medical Center, 550 First Avenue, New York, NY 10016.

Dr. Bouza: Sevicio de Microbiología Clínica y Enfermedades Infecciosas, Hospital General Universitario Gregorio Marañón, Dr. Esquerdo 46, Madrid 28007, Spain.

Dr. del Río: Infectious Diseases Service, Hosp. Clinic—IDIBAPS, University of Barcelona, Villarroel, 170 Barcelona 08036, Spain.

Dr. Lejko-Zupanc: Department of Infectious Diseases, Medical Center Ljublijana, Japljeva 2, Ljublijana 1000, Slovenia.

Dr. de Oliveira Ramos: Instituto Dante Pazzanese de Cardiología, Av. Jurema 534/101, São Paulo 04079-001, Brazil.

Dr. Iarussi: II Università di Napoli, Naples 80135, Italy.

Dr. Klein: Department of Infection, 5th Floor North Wing, St. Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, United Kingdom.

Dr. Chirouze: University Medical Center of Besançon, Service de Maladies Infectieuses et Tropicales, Besançon F-25030, France.

Dr. Bedimo: University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390.

Author Contributions: Conception and design: S. Morpeth, D. Murdoch, C.H. Cabell, A.W. Karchmer, P. Pappas, P. Tattevin, E. Bouza, G.R. Corey, V.G. Fowler.

Analysis and interpretation of the data: S. Morpeth, D. Murdoch, C.H. Cabell, A.W. Karchmer, P. Pappas, D. Levine, P. Tattevin, S. Dickerman, J. Klein, G.R. Corey, V.G. Fowler.

Drafting of the article: S. Morpeth, C.H. Cabell, P. Tattevin, S. Dickerman, G.R. Corey, V.G. Fowler.

Critical revision of the article for important intellectual content: S. Morpeth, D. Murdoch, C.H. Cabell, A.W. Karchmer, P. Pappas, D. Levine, F. Nacinovich, P. Tattevin, N. Fernández-Hidalgo, S. Dickerman, E. Bouza, A. del Río, T. Lejko-Zupanc, A.de Oliveira Ramos, J. Klein, R. Bedimo, G.R. Corey, V.G. Fowler.

Final approval of the article: S. Morpeth, D. Murdoch, C.H. Cabell, A.W. Karchmer, P. Pappas, F. Nacinovich, P. Tattevin, N. Fernández-Hidalgo, S. Dickerman, E. Bouza, T. Lejko-Zupanc, J. Klein, C. Chirouze, V.G. Fowler.

Provision of study materials or patients: D. Murdoch, D. Levine, F. Nacinovich, P. Tattevin, N. Fernández-Hidalgo, E. Bouza, A. del Río, T. Lejko-Zupanc, A.de Oliveira Ramos, D. Iarussi, J. Klein, V.G. Fowler.

Statistical expertise: P. Pappas.

Obtaining of funding: C.H. Cabell, V.G. Fowler.

Administrative, technical, or logistic support: V.G. Fowler.

Collection and assembly of data: S. Morpeth, D. Murdoch, E. Bouza, T. Lejko-Zupanc, R. Bedimo, V.G. Fowler.

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