Asian Cardiovasc Thorac Ann 1999;7:272-275
© 1999 Asia Publishing EXchange Pte Ltd
Brucella Endocarditis: Seven Cases Treated Surgically
Attilio Renzulli, MD,
Rosario Gregorio, MD,
GianPaolo Romano, MD,
Antonio Carozza, MD,
Joseph Marmo, MD,
Riccardo Utili, MD,1,
Marisa De Feo, MD,
Maurizio Cotrufo, MD
Institute of Cardiac Surgery, V Monaldi Hospital, 2nd University of Naples, Naples, Italy
1 Institute of Medical Therapy, Gesù and Maria Hospital, Naples, Italy
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For reprint information contact: Attilio Renzulli, MD Tel: 39 081 553 9035 Fax: 39 081 553 6350 email: renzulliattilio{at}usa.net or arenzul@tin.it viaorarenzul{at}tin.it via Aquila 144, Naples 80143, Italy.
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Abstract
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Brucella endocarditis is a lifethreatening, often under-diagnosed complication of brucellosis. Seven cases of brucella endocarditis treated surgically in the last 25 years are described. The infection was localized on the aortic valve in 5 cases and on a prosthetic mitral valve in 2. All patients had a positive history of risk factors for brucella infection and all were in cardiac failure (5 in New York Heart Association functional class III and 2 in class IV). All underwent valve replacement followed by antibiotic therapy. Follow-up ranged from 1 and 206 months. One patient died following prosthetic valve replacement to treat a periprosthetic leak unrelated to the brucella infection. Brucella antibody tests and careful clinical history are mandatory in all patients with negative blood cultures in order to identify brucella earlier during the course of the infection before embolization or annular involvement occur.
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Introduction
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Brucellosis is a very common disease; according to the World Health Organization, 500,000 new cases are reported annually.1 Nevertheless, many authors support the concept that the disease is either underdiagnosed or underreported.2–4 They estimate that for each case diagnosed, another 30 are not recognized or reported.1,4 The geographic distribution is the Mediterranean area and the Middle East.25–8 Human brucellosis is caused by various species: Brucella melitensis; Brucella abortus; Brucella suis; and less frequently by Brucella canis.1 The infection is found primarily in animals and is spread to man by direct contact with infected tissue or by ingestion of infected meat, milk, or milk products. Cardiovascular complications of brucellosis include endocarditis and to a lesser extent, myocarditis and pericarditis.1
Endocarditis is a rare but lifethreatening complication of systemic brucellosis with an incidence of less than 2% among all cases of brucella infection. Brucella is an uncommon cause of endocarditis, accounting for 1% of cases. However, because of the slow development of this infection and the requirement of special culture conditions, it is likely that this figure is underestimated. Considering the incidence of this disease in the Mediterranean area, cardiac complications of systemic brucellosis might be more frequent.6,7,9 Indeed, a higher incidence (10%) has been reported in the Middle East.5–9 We reviewed our experience of surgically-treated cases of infective endocarditis in the Mediterranean area over 25 years and report the incidence, clinical course, and long-term follow-up.
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Patients and Methods
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The medical records of all cases of infective endocarditis surgically treated in our institution from 1974 were retrospectively reviewed. Diagnosis of infective endo-carditis was made in all patients according to current criteria and always confirmed at surgery. In all cases, an attempt to isolate the etiologic agent was made by collecting samples for blood culture from patients on admission. Blood samples were cultured in Castaneda biphasic bottles. Surgical specimens were cultured in thioglycolate broth and inoculated onto routine culture medium. Cultures containing pale-staining Gram-negative coccobacillary rods that were both oxidase-positive and urease-positive were classified as brucella. Brucella endocarditis was diagnosed when a patient had clinical and echocardiographic signs of endocarditis and at least one of the following signs: positive blood culture for brucella; positive culture for brucella in a heart valve explanted at surgery; a high titer of brucella antibodies (
1:320).
Between January 1974 and September 1998, 209 patients were surgically treated at our institution for infective endocarditis; 151 (72%) on a native valve and 58 (28%) on a prosthetic valve. Brucella endocarditis was diagnosed in 7 patients (3.3%), 3 males and 4 females, aged 36 to 60 years (median, 57 years). The clinical profile is shown in Table 1
. On admission, all 7 patients had a long history of fever (38° to 39°C), malaise, and night sweats. Mild anemia was observed in 4 patients and leukopenia in 3. One suffered a cerebral embolism shortly after hospi-talization. M-mode crosssectional Doppler echocardio-graphy was performed preoperatively in 6 patients and left and right heart catheterization carried out in 1. Surgical findings were recorded. All patients underwent serology tests every 4 months for 1 year during the follow-up and routine clinical, echocardiographic, and micro-biological investigations every 6 months.
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Results
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There was a history of exposure to animal carcasses prior to the onset of infection in 2 patients. The most likely source of infection in the other 5, who lived in rural areas, was the ingestion of contaminated milk products. In 4 patients, the diagnosis was made by positive blood cultures and confirmed in 1 by culture of the excised valve. In another patient, brucella was isolated only from the resected valve. In 2 patients who had negative blood cultures, the etiology was determined by an agglutination titer of 1:320 or higher (Table 2).
Rheumatic aortic regurgitation was found in 3 patients; 1 patient had a bicuspid aortic valve, 2 had a mitral valve prosthesis, and a floppy aortic valve was diagnosed in the other. Echocardiography showed a 1.5-cm area of aortic valve vegetation in 1 patient and only severe aortic valve regurgitation in 4. In the 2 patients with a prosthetic mitral valve, echocardiography showed a cuspal tear and periprosthetic leak of a porcine valve in one and vegetations on a Starr-Edwards valve in the other. In all cases, echo findings were confirmed by surgical inspection.
On the basis of microbiological or serological data, all patients received oral doxycycline of 200 mg per day and intramuscular streptomycin at a dose of 500 mg twice daily. Impending congestive heart failure or embolic risk were indications for early surgery before eradication of infection in 6 patients. In 1 patient, elective surgery was performed after 4 weeks of antibiotic treatment. Surgical findings and type of operation are summarized in Table 2
. No operative mortality was observed. All patients continued antibiotic treatment for at least 2 months postoperatively.
The mean follow-up was 96 months ranging from 1 to 206 months. Six patients are still alive with a good recovery; 2 are in New York Heart Association functional class II and 4 are in class I. One patient with aortic valve endocarditis had a perivalvular leak requiring prosthetic replacement 12 months after the first operation. A porcine bioprosthesis was implanted and the patient was doing well for 8 years. He then required another prosthetic valve replacement for calcific degeneration. A tilting-disc valve was implanted but unfortunately he was readmitted one year later to treat prosthetic dehiscence. Another tilting-disc valve was implanted but the patient died intraoperatively due to low output syndrome. Antibody titers, blood cultures, and cultures from the explanted prostheses did not show any recurrence of brucella infection.
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Discussion
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The incidence of brucella endocarditis was 3.3% in this series but because of the retrospective nature of the study and the fact that the patients had severe endocarditis requiring early surgical intervention, we believe that the true incidence may have been higher, particularly in view of the high rate of culture-negative endocarditis (20%). The prevalence of brucella endocarditis may be underestimated because of the difficulty in isolating the organism from blood. Indeed, the rates of isolation vary from 15% to 70% and the subsequent identification may be hindered by the lack of biochemical profiles for the brucella organism in some commercial computerized databases.10,11 Furthermore, the reliability of serological tests for diagnosing brucellosis is affected by the possibility of false-negative reactions due to a prozone phenomenon.12 Accordingly, brucella is still considered one of the agents of "culture-negative endocarditis." In our series, serology was determinant in diagnosing 2 cases of culture-negative endocarditis, yet it was negative in 2 other patients with positive blood cultures.
Brucella endocarditis has a subacute course that usually affects the aortic valve and major complications may occur. In reported series, approximately 85% of patients had severe heart failure.13 Thus, there is a general belief that it has a poor prognosis if surgery is not associated with medical treatment.13 In our patients, the interval between the onset of disease and the diagnosis ranged between 3 and 12 months. All cases of native-valve brucella involved the aortic valve; prosthetic mitral valves were involved in the other 2 cases. Brucella melitensis was the predominant strain in our series, it appeared more virulent than Brucella abortus and it was associated with valve destruction, whereas Brucella abortus caused vegetations. Brucella suis is rare and in this study, it was associated with destructive valve lesions. These results agree with other reports of a difference in virulence among the 3 different species of Brucella in human disease.14 The severity of the disease is underscored by the fact that our patients were in New York Heart Association functional class III or IV and surgery had to be performed during the active phase of infection in 6 of the 7 patients. Yet, with the appropriate combined antimicrobial treat-ment, no recurrence of the disease developed.
Many authors suggest that surgical treatment is the only therapeutic option for brucella endocarditis.1–35815–17 Good results in terms of hospital mortality and long-term follow-up have been reported. The infection can be eradicated with surgical debridement and antibiotic therapy. In our experience, surgery followed by antibiotic treatment achieved good results. Nevertheless, a favorable outcome with conservative antibiotic treatment alone was noted in 13 patients collated from the medical literature.10,18 It was suggested that the absence of congestive heart failure or a prosthetic valve, relatively mild extravalvular cardiac involvement, or a shorter disease history are determinants of a successful outcome in patients treated conservatively. All patients in our study as well as those reported in other surgical series, had significant valvular involvement with infection on a prosthetic valve in some cases, therefore, surgery was mandatory.1–35781516 However, it is likely that medical treatment may be a valid alternative to surgery in selected cases before significant valvular involvement occurs.
Brucella endocarditis should be suspected in all patients with a negative blood culture, especially in countries where the disease is endemic, and a careful clinical history may uncover patients at risk. Recent advances in molecular biology may provide a more reliable diagnosis in cases of negative blood culture.19 We recommend that all suspected cases as well as those who are biologically and immunologically positive, should be confirmed by molecular analysis to save time and resources. It is crucial that identification of these microorganisms and appropriate antibiotic treatment be achieved early in the course of the infection before complications such as embolization or valvular involvement occur.
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References
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Abstract
Introduction
