Abstract

Background: Brucella endocarditis, which is a rare condition, is the most common cause of death in human brucellosis, leading to severe cardiac complications.

Methods: Ten patients were referred to our clinic with the diagnosis of Brucella endocarditis. The patients were given a medical treatment with triple antibiotherapy including doxycycline, rifampin and ceftriaxone. In the preoperative period, one of the patients had a sign of splenic infarction due to septic embolization. Echocardiographic evaluation revealed the development stages of the mitral valve injury due to Brucella endocarditis in another patient. All patients underwent open heart surgery immediately after reducing fever and relieving other symptoms.

Results: Six patients underwent aortic valve replacement (AVR), whereas three of them underwent both aortic and mitral valve replacement. In addition, AVR in combination with mitral ring annuloplasty were performed on one of the patients. Perforation of the aortic cusps was found in four patients. Perforation located in the commissure between the right and left coronary cusps was detected in one patient. Morbidity and mortality didn't developed in our patients. All patients were discharged with double antibiotherapy for a mean follow-up of four months (range, 2 to 6 months). None of the patients required re-hospitalization or re-surgery during the long-term follow-up period.

Conclusion: Our results show that surgical therapy must be combined with adequate preoperative antibiotherapy in cases with severe valve injury. Maintenance therapy with antibiotherapy should be optimized postoperatively on the basis of scheduled visits for successful definitive therapy and long-term quality of life.

Brucellosis shows various clinical signs and can affect different organs. Although rare, endocarditis can be fatal. Endocarditis due to the Brucella species can be seen more in the regions where rheumatic heart disease is widespread.[1] Brucellosis continues to be reported from Mediterranean and Middle Eastern countries.[1,2] Ten to 15% of patients have complicated brucellosis.[2] Although endocarditis is seen in less than 2% of the cases, it is responsible for half of the deaths due to brucellosis.[3] Brucella endocarditis was first reported in 1906, but a surgical approach as a treatment modality was only introduced in 1964.[2] Immediate surgery after medical treatment is very important because a delay may lead to complications that are difficult to repair.[1] In this study, we present 10 patients with Brucella endocarditis who were treated sequentially with a combination of medical and surgical therapy between September 2001 and September 2007.

Methods

Ten patients (9 males, 1 female; mean age 41.2 years; range 29 to 60 years) were hospitalized at different times with symptoms of fever, weakness, dyspnea, fatigue, weight loss, and back pain. All of the patients had a history of intermittent fever reaching 40 ºC. Our patients inhabited rural areas and were working as farmers and livestock producers. All patients had been given different types of antibiotic therapies in various primary heathcare units. However, they were referred to our institution as their general status worsened. All of the patients were carefully examined, and routine laboratory studies were done on admission. Consecutive blood cultures were taken from the patients. Brucella standard tube agglutination tests were performed on the patients, and the results were 1/320 or higher. The data of our patients who were diagnosed with Brucella endocarditis after echocardiographic and laboratory examination is given in Table 1.

Table 1: Data of our patients

An echocardiographic evaluation of the second patient revealed mobile mass lesions compatible with vegetations on the left and noncoronary leaflets of the aortic valve and severe aortic and mitral regurgitations. Abdominal computed tomography (CT) also revealed a hypodense area as splenic infarction due to septic embolism (Figure 1).

Figure 1: Septic embolic splenic infarction as viewed in the abdominal computed tomography of our second patient.

Our ninth patient with severe rheumatic aortic valve stenosis, moderate aortic insufficiency, and mild mitral insufficiency was admitted to an institute in August 2005 but did not accept the recommended aortic valve replacement (AVR) operation (Figure 2). His job was animal husbandry, and he had been hospitalized for 15 days due to Brucellosis diagnosed in November 2005. Transthoracic echocardiography (TTE) performed in January 2006 showed that his mild mitral insufficiency had progressed and a 19.4x21.5 mm vegetation had developed in the anterior mitral leaflet. Also, the peak pressure gradient through the mitral valve secondary to mitral insufficiency had increased to 18.4 mmHg from 11.8 mmHg (Figure 3). Transesophageal echocardiography (TEE) showed a vegetation in the anterior mitral leaflet and increased mitral insufficiency (Figure 4).

Figure 2: Image of mild mitral insufficiency in our ninth patient in August 2005.

Figure 3: Doppler image when the peak gradient through the mitral valve increased to 18 mmHg confirming the increase in mitral insufficiency in January 2006.

Figure 4: Image of mitral valve vegetation on transesophageal echocardiography.

Our 10^th patient’s job was also animal husbandry. The TTE performed on admission to our institution showed that his severe aortic insufficiency had progressed, and a 23x17 mm giant vegetation had developed on the right and left coronary leaflets. An image corresponding to right coronary leaflet perforation was suspected (Figure 5).

Figure 5: I mage of transthoracic echocardiography of our 10th patient at first admittance to our institute.

The Departments of Infectious Diseases, Cardiology and Cardiovascular Surgery observed all patients. All patients had a triple-antibiotic therapy regimen (doxycycline 200 mg/d, rifampicin 600 mg/d, and ceftriaxone 2 g/d). Patients were taken for cardiac surgery without delay as the fever and other symptoms disappeared. The Department of Cardiology and Cardiovascular Surgery routinely observed the patients during their hospitalization in the Infectious Diseases Clinic for their medical treatment. Their echocardiographies were repeated weekly, and they underwent surgery after the antibiotic therapy.

Surgical technique
The patients were operated on under general anesthesia. All patients were approached via median sternotomy, and all surgeries were performed on cardiopulmonary bypass using ascending aortic and bicaval cannulation with caval snuggers and minimal manipulation. For myocardial protection, cardiac arrest was achieved with moderate hypothermia of 28 ºC and incompressive retrograde isothermic blood cardioplegia. After crossclamping the aorta, tissue loss was detected in most of the affected leaflets. Vegetations were seen in all of the patients, and perforation of the aortic cusps was seen in four (Figure 6).

Figure 6: Leaflet perforation complication of our second patient.

In our ninth patient, there was a high degree of calcification at the mitral valve, including all the anterolateral commissure which infiltrated the endocardium and myocardium. The subvalvular apparatus was normal. There were widespread, calcific, and vegetative images beginning from the anterolateral commissure and extending medially to both leaflets (Figure 7).

Figure 7: Calcific vegetation extensively invaded the anterolateral commissure at the mitral valve in our ninth patient.

Following aortotomy in our 10th patient, exploration revealed that the left coronary leaflet had a highly fragile vegetative mass of 3x3 cm in diameter on its side facing the ventricle. The right coronary leaflet also contained a vegetative mass of 2x2 cm in diameter on its ventricular face. The common commissure of these two leaflets was perforated, and the noncoronary leaflet remained intact (Figure 8).

Figure 8: The complication of perforation located at the commissure between the right and left coronary leaflets.

The affected tissues beside the valves and the native valves were carefully excised before bileaflet mechanical valve replacement. Pledgetted sutures were used. The sewing rings of the valves were washed with rifampicin. All the surgical data is contained in Table 1.

Results

There were no deaths or morbidity. The mean time to discharge was 13 days (range 10-19 days). The patients were discharged with doxycycline 200 mg/d and rifampin 600 mg/d. They were observed weekly in the first month and monthly in the following six-month period by the outpatient clinics of the Departments of Infectious Diseases and Cardiovascular Surgery. In every monthly visit, Brucella agglutination tests were examined. Double-antibiotic therapy was discontinued when it was decided that the infection had already been eradicated based on the decrease in agglutination titers and clinical evaluation of patients. Postoperative control echocardiography revealed no abnormalities. Our patients continued the postoperative double-antibiotic therapy for a mean of four months (range 2-6 months). The mean follow-up was 19.2 months (range 4-38 months). There were no related complications or need for hospitalization during follow-up.

Discussion

Brucellosis is caused by Brucella organisms and acquired by direct contact with infected animals or indirectly by ingesting unpasteurized milk or milk products.[1,2] Our patients were infected directly because they were livestock producers.

Definitive diagnosis is based on recovery of the organism from the blood.[1] Wright’s seroagglutination test is a very important serological test method for clinical diagnosis. Many cases have titers of 1:320 or higher.[4] Our cases were diagnosed by history, occupation, and positive serology along with echocardiography and showed big vegetations on the aortic and/or mitral valves.

Generally, aortic valve invasion is seen. Brucella endocarditis appears with a long-lasting subfebrile body temperature and a delayed (3 to 11 months afterwards) severe dysfunction occurring in the aortic valve.[5] Organisms such as Staphylococcus aureus, Serratia species, Pseudomonas species, Candida species, and Brucella species also injure the tissues.[2,6] Infective endocarditis injures the valve and causes insufficient flow.[7] Situations like leaflet perforation (ranging from small perforations to flail leaflets), rupture of paravalvular abscess, cardiac fistula, and leaflet prolapse due to rupture of commissure are responsible for acute valve insufficieny.[7,8]

Echocardiography is vital in determining the treatment protocol along with the morbidity and mortality rates in all infective endocarditis cases, including brucellosis.[1,6] It is a cheap, easy-to-use, noninvasive, and reproducible method. The most important point in echocardiographic evaluation is the combination of TTE and TEE. Most frequently, vegetations are examined in echocardiography and are usually found to cause insufficiency due to valve damage. If they’re big enough and unstable, they can be easily determined by TTE. On native valves, the imaging rate is 25% for vegetations smaller than 5 mm and 70% for those larger than 6 mm.[9] The sensitivity and specificity for TEE are higher for small vegetations (<2 mm) and for the determination of the perivalvular extension of the infection.[10] Native valve endocarditis studies showed a sensitivity of 46% and specificity of 95% for TTE. These rates were 93% and 96% for TEE.[9,11] If there is important valve insufficiency, new flow records of severe aortic or mitral valve insufficiency are accepted as major endocardial symptoms, as in our ninth patient. Although definitive diagnoses of four of our patients as aortic valve pathology due to Brucella endocarditis were made by the cardiology clinic via TTE and/or TEE. Perforation of cusps could only be identified during operative exploration.

Embolization risk due to vegetation is in close relation with mortality and morbidity. Post-mortem studies have shown that splenic embolization rates can be as high as 44% and brain embolization rates as high as 40%.[12] Clinical symptom rates range from 10-50% for vegetations.[10] Native mitral valve infective endocarditis has a five times higher embolization risk than that for the aortic valve, so anterior mitral valve vegetations, particularly if larger than 15 mm, or recurrent embolisms are indications for surgery.[12] We determined a splenic infarction due to septic embolization in our second patient.

Medical treatment alone is unsuccessful for Brucella endocarditis, and surgery is necessary.[2,5] This microorganism, which adapts to the intracellular course, shows resistance to medication and shows recurrence that is actually not low.[1,13] Al Kasab et al.[14] reported recurrences in their study group that had only been treated medically. The most effective option is a combination of antibiotics and surgery. Our patients underwent triple-antibiotic therapy, and the infection was controlled in 4-6 weeks, at which time surgery was performed.

The two main goals of the surgery are controlling the infection by debriding the infected and necrotic tissue and reconstructing the cardiac morphology by repairing or replacing the damaged valves. Although homografts are ideal due to low infection risk, it is hard to produce them,[15] and they are not readily available in our center. The number of of centers in Turkey that perform valvular replacement with homografts is limited. The combination of antibiotic therapy and mechanical valve replacement has a satisfactory result. Early and late reinfection incidence of mechanical valve replacement can be compared with the results and survival expectations of homografts and tissue valves.[16] Mechanical valve replacement was used for Brucella endocarditis in a study with six cases, and there was no mortality or late recurrence during the 47 weeks of follow-up.[5] We used surgical debridement along with mechanical valve replacement and added doxycicline + rifampin for the postoperative period.

The bacteria in Brucella endocarditis survive because they are in the intracellular compartment.[1] For this reason, during the postoperative period, the use of antibiotics for at least a four-week period has a positive effect on survival. We used surgical debridement in conjunction with mechanical valve replacement and added double-antibiotic therapy for two to six months. We did not see any recurrence in our patients, and this approach should prove to be helpful in the guidance of postoperative treatment.[1]

In conclusion, Brucella endocarditis is a rare form of infective endocarditis, and its diagnostic rate and surgical therapy practices have increased due to the availability of echocardiography. Brucella endocarditis does not show remission and has a high mortality if not treated. Control of the infection with preoperative antibiotic therapy and immediate surgery after improvement of the clinical status of the patient have gratifying outcomes.[1] Our study indicates that surgery increases the quality of life for a longer period of time in this type of endocarditis.[9]

Declaration of conflicting interests
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Funding
The authors received no financial support for the research and/or authorship of this article.

References

1) Ozsöyler I, Yilik L, Bozok S, El S, Emrecan B, Biçeroğlu S, et al. Brucella endocarditis: the importance of surgical timing after medical treatment (five cases). Prog Cardiovasc Dis 2005;47:226-9.

2) Cihan HB, Gülcan Ö, Türköz R. Brusella endokarditinin cerrahi tedavisi.. Turkish Thorac Cardiovasc Surg 1999;7:417-8.

3) Young EJ. Brucella species. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. Philedelphia: Churchill Livingstone; 2000. p. 2386-93.

4) al-Kasab S, al-Fagih MR, al-Yousef S, Ali Khan MA, Ribeiro PA, Nazzal S, et al. Brucella infective endocarditis. Successful combined medical and surgical therapy. J Thorac Cardiovasc Surg 1988;95:862-7.

5) Keleş C, Bozbuğa N, Sişmanoğlu M, Güler M, Erdoğan HB, Akinci E, et al. Surgical treatment of Brucella endocarditis. Ann Thorac Surg 2001;71:1160-3.

6) David TE, Bos J, Christakis GT, Brofman PR, Wong D, Feindel CM. Heart valve operations in patients with active infective endocarditis. Ann Thorac Surg 1990;49:701-5.

7) De Castro S, d’Amati G, Cartoni D, Venditti M, Magni G, Gallo P, et al. Valvular perforation in left-sided infective endocarditis: a prospective echocardiographic evaluation and clinical outcome. Am Heart J 1997;134:656-64.

8) Oakley CM, Hall RJ. Endocarditis: problems-patients being treated for endocarditis and not doing well. Heart 2001;85:470-4.

9) Shapiro SM, Young E, De Guzman S, Ward J, Chiu CY, Ginzton LE, et al. Transesophageal echocardiography in diagnosis of infective endocarditis. Chest 1994;105:377-82.

10) Roe MT, Abramson MA, Li J, Heinle SK, Kisslo J, Corey GR, et al. Clinical information determines the impact of transesophageal echocardiography on the diagnosis of infective endocarditis by the duke criteria. Am Heart J 2000;139:945-51.

11) Shively BK, Gurule FT, Roldan CA, Leggett JH, Schiller NB. Diagnostic value of transesophageal compared with transthoracic echocardiography in infective endocarditis. J Am Coll Cardiol 1991;18:391-7.

12) Di Salvo G, Habib G, Pergola V, Avierinos JF, Philip E, Casalta JP, et al. Echocardiography predicts embolic events in infective endocarditis. J Am Coll Cardiol 2001;37:1069-76.

13) Leandro J, Roberto H, Antunes M. Brucella endocarditis of the aortic valve. Eur J Cardiothorac Surg 1998;13:95-7.

14) al Kasab S, al Fagih M, al Rasheed A, Khan B, Bitar I, Shahed M, et al. Management of Brucella endocarditis with aortic root abscess. Chest 1990;98:1532-4.

15) Hadjinikolaou L, Triposkiadis F, Zairis M, Chlapoutakis E, Spyrou P. Successful management of Brucella mellitensis endocarditis with combined medical and surgical approach. Eur J Cardiothorac Surg 2001;19:806-10.

16) Guerra JM, Tornos MP, Permanyer-Miralda G, Almirante B, Murtra M, Soler-Soler J. Long term results of mechanical prostheses for treatment of active infective endocarditis. Heart 2001;86:63-8.