Outcome and Treatment of Bartonella Endocarditis

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Outcome and Treatment of Bartonella Endocarditis ORIGINAL INVESTIGATION Outcome and Treatment of Bartonella Endocarditis Didier Raoult, MD, PhD; Pierre-Edouard Fournier, MD, PhD; Franc¸ois Vandenesch, MD, PhD; Jean-Luc Mainardi, MD, PhD; Susannah J. Eykyn, FRCP, FRCS, FRCPath; James Nash, MD; Edward James, MD; Catherine Benoit-Lemercier, MD; Thomas J. Marrie, MD Background: Endocarditis caused by Bartonella spe- Bartonella species from whole blood, serum, and/or val- cies is a potentially lethal infection characterized by a sub- vular biopsy specimens. A standardized questionnaire was acute evolution and severe valvular lesions. completed by investigators for each patient. Objectives: To evaluate the outcome of patients with Results: Twelve of the 101 patients died and 2 re- Bartonella endocarditis and to define the best antibiotic lapsed. Patients receiving an aminoglycoside were more regimen using the following measures: recovery, re- likely to fully recover (P=.02), and those treated with lapse, or death. aminoglycosides for at least 14 days were more likely to survive than those with shorter therapy duration (P=.02). Methods: We performed a retrospective study on 101 patients who were diagnosed in our laboratory as having Conclusion: Effective antibiotic therapy for Bartonella Bartonella endocarditis between January 1, 1995, and April endocarditis should include an aminoglycoside pre- 30, 2001. Bartonella infection was diagnosed using im- scribed for a minimum of 2 weeks. munofluorescence with a 1:800 cutoff, polymerase chain reaction amplification of DNA, and/or culture findings of Arch Intern Med. 2003;163:226-230 ARTONELLA SPECIES are small, by polymerase chain reaction (PCR). The gram-negative bacilli that purpose of this article is to examine the have recently been shown to treatment and outcome of the 101 pa- cause endocarditis.1 Cur- tients with Bartonella endocarditis and to rently, Bartonella quintana, define the most effective antibiotic regi- the agent of trench fever, and Bartonella men for this disease. From the Unite´ des Rickettsies, B Faculte´deMe´decine, Universite´ henselae, the agent of cat-scratch disease, de la Me´diterrane´e, Marseille, are the major causes of Bartonella endo- METHODS France; (Drs Raoult and carditis.2-5 Single cases of endocarditis Fournier); Laboratoire de caused by Bartonella elizabethae and Bar- Patients were considered to have definite en- Microbiologie, Hoˆpital Edouard tonella vinsonii subspecies berkhoffii have docarditis according to the Duke criteria.8 Bar- Herriot, Lyon, France; also been reported.6,7 tonella infection was diagnosed by culture find- (Dr Vandenesch); Service de The treatment of Bartonella endocar- ings or positive results on Bartonella DNA Microbiologie, Hoˆpital Georges ditis is not clearly established. Many of the amplification from valvular tissue or blood or Pompidou (Dr Mainardi), and when patients exhibited IgG titers of 1:800 or Laboratoire de Microbiologie, described patients have been cured by em- more as determined by microimmunofluores- piric therapies for blood culture–nega- 9 Hoˆpital Bichat ␤ cence. The study sites included Unite´ des Rick- (Dr Benoit-Lemercier), Paris, tive endocarditis, which include -lac- ettsies, Faculte´deMe´decine; Laboratoire de France; Department of tam and aminoglycoside antibiotics, and Microbiologie, Hoˆpital Edouard Herriot; De- Infection, St Thomas’ Hospital often the surgical resection of the in- partment of Infection, St Thomas’ Hospital; De- (Dr Eykyn), and Microbiology fected valve. At the Unite´ des Rickettsies, partment of Medicine and Microbiology, Dal- Department, St Bartholomew’s we have received samples from patients housie University, Halifax, Nova Scotia; Public Hospital (Dr James), London, with blood culture–negative endocardi- Health Laboratory Service, William Harvey Hos- England; Public Health tis. A total of 101 of these patients, all of pital, Willesborough; Microbiology Depart- Laboratory Service, William whom were classified as having definite en- ment, St Bartholomew’s Hospital; and Labora- Harvey Hospital, toire de Microbiologie, Hoˆpital Bichat. Willesborough, Ashford, docarditis according to the Duke criteria Between January 1, 1995, and April 30, England; (Dr Nash); and for the diagnosis of infective endocardi- 2001, the Unite´ des Rickettsies received se- 8 Department of Medicine, tis, were shown to have Bartonella endo- rum specimens from 52500 patients for the de- University of Alberta, carditis by serologic analysis and/or cul- tection of antibodies to Rickettsia species, Coxi- Edmonton (Dr Marrie). ture findings and genomic amplification ella burnetii, and Bartonella species. Of these, (REPRINTED) ARCH INTERN MED/ VOL 163, JAN 27, 2003 WWW.ARCHINTERNMED.COM 226 ©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 593 patients had endocarditis, including 228 patients with blood species were detected from serum using a nested PCR assay culture–negative endocarditis. The 365 patients with positive that incorporated primers derived from the riboflavin syn- blood culture findings were hospitalized in Marseille and were thase–encoding gene (Zaher Zeaiter, P.-E.F., Gilbert Greub, systematically tested serologically, whereas specimens from the MD, D.R., unpublished data, 2002). In all PCR reactions, se- 228 patients with blood culture–negative endocarditis were sent rum specimens or valve biopsy specimens from patients with- from the various study sites, mostly for the detection of anti- out Bartonella infection were processed as described herein bodies to C burnetii and Bartonella species. Blood samples and and used as negative controls for every 7 samples. The identi- material from excised heart valves, when available, were sub- fication of the amplified DNA was determined by base-se- mitted for PCR amplification and culture. In 61 patients, Bar- quence determination as previously described.1 tonella endocarditis was diagnosed by culture or PCR findings and in 40 patients on the basis of positive Bartonella serologic STATISTICAL ANALYSIS test results, which were recently demonstrated to have a posi- tive predictive value of 0.955 for the detection of Bartonella in- The Fisher exact test was used to compare proportions, and fection among patients with endocarditis.9 In the latter group the t test (2-tailed) for matched samples was used to compare of patients, no other origin of endocarditis could be found de- means using Epi Info version 6.04a statistical software.14 spite extensive investigation. A standardized questionnaire was completed for each pa- RESULTS tient. Questions included those used in the diagnostic score of the Duke Endocarditis Service,8,10 previous antibiotic therapy, the outcome within 1 year following the diagnosis of culture- From January 1, 1995, to April 30, 2001, 101 patients negative endocarditis (a relapse of Bartonella endocarditis was were diagnosed as having Bartonella endocarditis. Sixty- defined as a new episode of definite endocarditis based on the one of these had direct evidence of the infecting species Duke criteria8 after at least 3 months following therapy with- by culture or PCR findings: 49 were infected with B quin- out any clinical or echocardiographic signs of endocarditis and tana and 12 with B henselae. In the remaining 40 pa- the isolation or PCR amplification of a Bartonella from the pa- tients, elevated IgG titers to Bartonella species were the tient’s specimens), presence of vegetations or other cardio- only proof of infection. We observed no demographic, logic findings consistent with the infective endocarditis, and epidemiologic, or clinical difference between patients with presence of environmental exposure factors, such as homeless- a direct evidence of Bartonella infection and those with ness (people who did not have customary and regular access only a positive serologic test result (Table 1). There- to a conventional dwelling or residence for the past year), chronic alcoholism (Ͼ100 g/d of alcohol for more than 1 year), and im- fore, we analyzed the 101 patients together. munodeficiency, which are epidemiologic features associated The mean±SD age of the 101 patients with Barton- with other Bartonella-induced diseases. If such data were not ella endocarditis was 50±15 years (range, 16-81 years). available in the medical records, the patients were contacted Eighty-six patients (85%) were male. Epidemiologic in- by telephone. Data were analyzed at the Unite´ des Rickettsies. formation was partially missing for some of the pa- tients; 38 (38%) of 101 were homeless, 47 (48%) of 97 MICROBIOLOGICAL AND MOLECULAR METHODS were alcoholic, 17 (18%) of 93 had contact with body lice, 31 (33%) of 94 reported cat bites or scratches, and Bartonella quintana strain Oklahoma; B quintana strain Mar- 3 14 (15%) of 92 reported contact with cat fleas. Clinical seille, isolated from a French patient from this series ; B henselae information was available for all patients; endocarditis strain Houston-1 (ATCC 49882T); B henselae strain Mar- seille2; and B elizabethae (ATCC 49927T) were used as anti- occurred on native valves in 100 patients and on a bio- gens. The bacteria, between the fourth and seventh passages prosthesis in 1 patient; 58 (57%) had previously known in a human endothelial cell line (ECV 304), were harvested, valvular heart disease, 84 (83%) presented with fever (tem- pelleted, and used as crude antigen in a microimmunofluores- perature, Ͼ38°C) on admission, and 44 (43%) had em- cence assay performed as described previously.1
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