Non-HACEK Gram-Negative Bacillus Endocarditis

Non-HACEK Gram-Negative Bacillus Endocarditis

Susan Morpeth, MBChB;
David Murdoch, MD;
Christopher H. Cabell, MD, MHS;
Adolf W. Karchmer, MD;
Paul Pappas, MS;
Donald Levine, MD;
Francisco Nacinovich, MD;
Pierre Tattevin, MD;
Núria Fernández-Hidalgo, MD;
Stuart Dickerman, MD;
Emilio Bouza, MD, PhD;
Ana del Río, MD;
Tatjana Lejko-Zupanc, MD, PhD;
Auristela de Oliveira Ramos, MD;
Diana Iarussi, MD;
John Klein, MD;
Catherine Chirouze, MD;
Roger Bedimo, MD, MS;
G. Ralph Corey, MD;
Vance G. Fowler, Jr., MD, MHS; and
the International Collaboration on Endocarditis Prospective Cohort Study (ICE-PCS) Investigators*

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.

Abstract

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.

Article and Author Information

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.