Late Prosthetic Valve Endocarditis Caused By Bulkholderia Cepacia And Candida Dubliniensis-The First Reported Case In The Medical Literature
V Saaraswat, Y Barzani, B Saaraswat, S Mishra, M Adler, P Chandra
bulkholderia cepacia, candida dubliniensis, endocarditits, prosthetic valve, transthoracic echocardiography
V Saaraswat, Y Barzani, B Saaraswat, S Mishra, M Adler, P Chandra. Late Prosthetic Valve Endocarditis Caused By Bulkholderia Cepacia And Candida Dubliniensis-The First Reported Case In The Medical Literature. The Internet Journal of Cardiology. 2009 Volume 9 Number 2.
Valvular heart disease is very complex with potentially fatal consequences (1). It can be managed either medically or surgically. Cardiac valve replacement with mechanical valves or bioprosthetic valves has been an effective therapeutic modality in the management of valvular heart disease. Cardiac valve replacement is not without complications. Some of the complications associated with mechanical valves are thromboembolic requiring long-term anticoagulation; however, mechanical valves are structurally strong with low incidence of configuration failure. While complications of prosthetic valve include: structural deteriation, valve obstruction due to pannus formation, & paravalvular leak. The occurrence of these complications depends on the type of valve used, the position of the valve, structural or underlying heart disease, age and sex of the patient (7-9), and other co-morbid factors. The incidence of complications in patients undergoing cardiac valve surgery is about 3% annually (2-6). Infection is often a major feared complication post cardiac valve surgery. It can arise early or later after surgery.
Prosthetic valve endocarditis (PVE) is classified as either early PVE or late PVE. Early PVE is acquired perioperatively and late being unrelated to the valve operation. There is decreased incidence of early PVE due to antibiotic prophylaxis. Late PVE is more severe, causing death in 15% of the patients. The epidemiology, pathogenesis, microbiology and clinical manifestations of both early and late PVE are different. Studies have shown that the risk of acquiring PVE is highest during the first three months after cardiac surgery and then it gradually falls to a rate of 0.4% annually. (10-14).The predictably of pathogens causing PVE becomes apparent when categorizing PVE by time after implantation. (1, 15). The usual pathogens causing early PVE (within two months of implantation) in decreasing order of frequency include: S. aureus, coagulase negative staphylococci, culture negative and very rarely B. cepacia and C. dubliniensis; Similarly, late PVE (after two months of implantation) is usually caused by coagulase negative staphylococci, staphylococci, culture negative, enteroccoci, and viridans streptococci. Although, reports of early PVE caused by B.cepacia and C.dubinesis have been reported previously, however, to the best of our knowledge, there have not been any reports of B.cepacia and C.dubinesis causing late PVE. Graphs (11)
B.Cepacia (formerly Pseudomonas cepacia), an aerobic, catalase positive, glucose non fermenting gram negative rod was first described in 1949 by Walter Burkholder as the agent responsible for onion skin rot and as a opportunistic pathogen in the mid 1950s (16) it is known for its resilient nature and can survive inhospitable environments with minimal nutrients. (17) studies show that it can well survive a 10% iodine solution for over a year and to be the culprit causing pneumonia in patients with underlying lung disease such as cyctic fibrosis, leading to complications and increasing the morbidity and mortality rate in such pateitns (18-19) .
C.dubienss, a fungal opportunistic pathogen was first isolated in 1995 from patients with human immunodeficiency virus (HIV) (20) studies have shown that it can cause both mucocutaneous as well as invasive disease leading to fungemia, especially in patients with a weak immune system such as patients receiving bone marrow, solid organs or those infected with HIV. It has often been a diagnostic challenge to laboratory personnel to distinguish C. dub from C. albicans with routine lab methods; therefore, molecular techniques such as real-time multiplex PCR are recommended in the identification of C.dub. (21-24) The management of PVE depends on the type of bacteria or fungi isolated from the blood cultures and their sensitivities to the antibiotics and antifungals.
In this article, we present the first reported case of late PVE caused by Bulkholderia cepacia and Candida dubliniensis.
A 47-year-old white male presented to the emergency room (ER) complaining of progressive and severe shortness of breath, increasing bilateral lower extremity edema and a twenty six pound weight gain over a two month period. He also complained of paroxysmal nocturnal dyspnea, orthopenia, occasional nausea and vomiting, productive cough in the morning, and discomfort from his tense edema in the lower extremities bilaterally. The patient denied fever, chills, diarrhea, constipation, and chest pain.
His past medical history was significant for IV drug abuse with heroin, hepatitis C, recurrent endocarditis status post aortic and mitral valve replacements, coronary artery disease status post myocardial infarction, congestive heart failure, right heart failure, atrial fibrillation, seizure disorder, antisocial personality disorder, polysubstance abuse, and chronic stasis dermatitis. The patient was hospitalized and treated for bacterial and fungal endocarditis with caspofungin and cefepime two months ago/prior to this event. His past surgical history included surgery for an incarcerated umbilical hernia, a cervical spine fracture, open reduction internal fixation of right tibia-fibula fracture, and two vessel coronary artery bypass graft (CABG). Additionally, the patient had tissue aortic valve and mitral valve replacement with subsequent mechanical mitral valve replacement a year later about ten years prior to his admission to our ED.
On physical examination, the patient was found to be in severe distress and afebrile. Upon cardiac examination, a loud click was heard and the heart rate was irregularly irregular.
Laboratory tests revealed: serum sodium 133 (reference range [RR] 140-150); aspartate aminotransferase 56 (RR <38); alkaline phosphatase 204 (RR 40-129). Urinalysis was unremarkable but urine toxicology screen was positive for opiates.
Blood cultures grew B. cepacia sensitive to cefepime and C. dubliniensis sensitive to caspofungin. The patient was successfully treated with IV caspofungin and IV cefepime for 6 weeks.
Figures A and B showing vegetations on the aortic valve
A common complication following replacement of a diseased heart valve with a prosthetic valve is endocarditic. The presenting signs and symptoms are similar to those occurring in native endocarditis and include: fever, heart murmur, and septic emboli. The diagnostic modalities include: Transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE). Although, TTE has a low sensitivity but its specificity approaches 100% (25) Contrary, TEE has a much higher sensitivity rate than TTE and is much more sensitive than TTE in detecting vegetations and abscess, and in the diagnosis of PVE.
LPVE is a diverse disorder with many different prognostic scales. It is important to distinguish the most severe prognosis from the least severe as early as possible. The two treatment modalities include medical and surgical approaches. Surgical treatment carries better prognosis in LPVE with specific features. Karchmer et al. (26) provided criteria for choosing one therapy over the other. They suggest an early surgical intervention for patients with LPVE who have at least two of the following: nonstretococccal etiology, undue persistence of fever despite antibiotic therapy, a new regurgitant murmur, and congestive heart failure associated with prosthesis dysfunction.
LPVE is a severe condition carrying a high mortality and morbidity rate. Thus, it is important to prevent any incidence of LPVE development using prophylactic antibiotics. The American Heart Association currently recommends antibiotic prophylaxis during dental procedures in patients with prosthetic cardiac valve, history of previous endocarditis, and cardiac transplant recipients with valvular disease. It recommended prophylaxis in congenital heart disease in the following cases: Unrepaired cyanotic heart disease, repaired congenital heart disease with prostethtic material, and repaired congenital disease with residual defect at the site of prosthetic device. In our patient, TEE revealed decreased left ventricle function with regional wall motion abnormalities, mild aortic insufficiency, bi-atrial enlargement, severe tricuspid regurgitation, and vegetations on the aortic valve. Upon suspecting endocarditis, blood cultures were obtained prior to broad spectrum antibiotic therapy. Two sets of aerobic and anaerobic broth media were used for blood sample inoculation. Bacteria or fungi isolated from the positive blood cultures were then tested for antibiotic susceptibility in the microbiology laboratory by using the standard disc diffusion method. The treatment plan was determined based on the antibiotic susceptibility test results. Our patient was successfully treated with IV caspofungin and cefepime for 6 weeks
Tables 1 and 2 illustrate susceptibility results for both B.cepacia and C.dubliensis isolated from the patients blood culture.
Prosthetic valve endocarditis is a major post-operation complication. It may arise early or late after the surgery. Early infection is usually caused by direct contamination during surgery or through hematogenous spread during the early phase (27). In the early phase, the, endothelialization has not occurred yet, thus the structure is still coated with host proteins, making it prone to organism adherence (27). However, in the late phase, endothelialization alters the site of adherence making the pathogenesis of late prosthetic valve similar to the native valve endocarditis (27). The best test for diagnosis is TTE which shows early vegetations that cannot be visualized by TEE (28).
Endocarditis prophylaxis is extremely important in patients with prosthetic heart valves undergoing invasive procedures. In a study by Horstkotte, in 533 patients with prosthetic heart valves, antibiotics were given to 304 patients before going for invasive procedures, while 229 similar patients did not receive any prophylaxis antibiotics (29). As a result, none of the patients on prophylaxis developed endocarditis, while 6 patients on no antibiotic therapy developed endocarditis.
Bacteremia and/or fungemia, occurring early or late after cardiac valve surgery, has been associated with fatal consequences if not appropriately managed. Therefore, prompt management of both early and late PVE medically by appropriate antibiotics and antifungals and surgically by valve replacement treatment can significantly reduce the morbidity and mortality caused by these pathogens.
Although, there have been reports of PVE caused by B. cepacia and C. dubliniensis early after surgery, but to the best of our knowledge this report represents the first published case of PVE by these pathogens late after surgery.