A chronic hemodialysis patient with isolated pulmonary valve infective endocarditis caused by non-albicans Candida: a rare case and literature review

Background Isolated pulmonary valve infective endocarditis caused by Candida is rare in chronic hemodialysis patients. The 2009 Infectious Diseases Society of America guidelines suggest the combined use of surgery and antibiotics to treat candidiasis; however, successful nonsurgical treatment of Candida endocarditis has been reported. Case presentation A 63-year-old woman with end-stage kidney disease was admitted to our hospital after experiencing disorientation for 5 days. The patient was permanently bedridden because of depression, and denied active intravenous drug use. She received maintenance hemodialysis through a tunneled-cuffed catheter. An initial blood culture grew Candida guilliermondii without other bacteria. Subsequent blood cultures and tip culture of tunneled-cuffed catheter also grew C. guilliermondii, even after caspofungin replaced fluconazole. A 1.2-cm mobile mass was observed on the pulmonary valve. Surgical intervention was suggested, but the family of the patient declined because of her multiple comorbidities. The patient was discharged with a prescription of fluconazole, but she died soon after. Conclusion Our patient is the first case with isolated pulmonary valve endocarditis caused by C. guilliermondii in patients with uremia. Hematologic disorders, in addition to long-term central venous catheter use, prolonged antibiotic intravenous injection, and congenital cardiac anomaly, predispose to the condition. The diagnosis “isolated” pulmonary IE is difficult, and combing surgery with antifungal antibiotics is the appropriate therapeutic management for Candida related pulmonary IE.


Background
Right-sided infective endocarditis (IE) is uncommon compared with left-sided IE, representing only 5-10% of all IE cases. Isolated pulmonary valve endocarditis without involvement of another valve constitutes <2% of IE cases, whereas fungal endocarditis comprises less than 10% [1,2]. Isolated pulmonary valve IE caused by Candida is rare, and nonsurgical treatment-though not recommended by the 2009 Infectious Diseases Society of America candidiasis guidelines for Candida endocarditis (which suggest combining surgery with antibiotics) [3]-has been reported to be successful [4]. We present the case of a chronic HD patient who presented with isolated pulmonary valve IE caused by non-albicans Candida, and we review the literature on isolated pulmonary valve IE caused by Candida spp.

Case presentation
A 63-year-old woman with a history of ESRD was admitted to our hospital on June 3, 2015 after experiencing disorientation for 5 days. The patient had been receiving HD since December 2014 because of acute on chronic kidney disease due to pneumonia. She was also diagnosed with hepatitis B-related liver cirrhosis (Child-Pugh B with hepatic encephalopathy), Mycobacterium tuberculosis-related pleuritis, and IgGλ monoclonal gammopathy. Monoclonal gammapathy hadn't been treated because she was permanently bedridden. She received maintenance HD through a tunneled-cuffed catheter inserted into the right subclavian vein since December 8th, 2014. She denied active intravenous drug use. We observed drowsy consciousness and splenomegaly during physical examination. No crackles were found in either lung field, and no track marks were present on her skin. Her white blood cell, absolute neutrophil, and platelet counts were 2.86 × 10 3 /uL, 2116/mm 3 , and 14,000/uL, respectively. Her total bilirubin was 3.54 mg/dL. In addition, C-reactive protein was 2.31 mg/ dL, and her serum glucose was 992 mg/dL, without metabolic acidosis. Because of the hyperglycemic hyperosmotic status of the patient, blood culture was drawn and empiric vancomycin and cefuroxime were prescribed. The initial blood culture grew Candida guilliermondii without other bacteria. Fluconazole 200 mg once per day was administered intravenously. The tunneled-cuffed catheter was removed on June 30 because of persistent fungemia. The culture of tunneled-cuffed catheter grew Candida guilliermondii.. Blood cultures on July 14 and August 10 and 28 still grew C. guilliermondii, even after replacement of caspofungin by fluconazole on July 28. No positive culture result was found in sputum or urine during the 8 weeks after admission. Transthoracic echocardiography on July 20 and August 21 revealed no vegetation or congenital abnormality. On August 25, repeated transthoracic echocardiograms showed a 1.2-cm mobile mass on the pulmonary valve extending from the right ventricular inflow tract across the pulmonary valve (Figs. 1 and 2).
No other vegetation was found. Surgical intervention was suggested, but the family of the patient declined because of her multiple comorbidities. Therefore, amphotericin B 40 mg was administered once daily from August 30 but was discontinued on September 1 because of allergic reactions (rash and fever). After 8 weeks of caspofungin, the C. guilliermondii septicemia was still present and the vegetation on the pulmonary valve had increased in size (3.73 × 2.70 cm). Computed tomography (CT) of the chest and abdomen revealed splenic infarction and right upper lung pneumonia with septic embolism (Figs. 3 and 4). The patient and family requested hospice care, and we

Discussion
This is the first reported case of non-albican Candida related isolated pulmonary valve endocarditis in a chronic HD patient. Candida spp.-associated bloodstream infection has become more prevalent in recent decades because of the increasing incidence of immunodeficiency (e.g., HIV infection, chemotherapy, and immunosuppressant use) and diverse invasive procedures (e.g., central venous catheters and intracardiac devices) [2]. In intensive care unit patients with ESRD, central venous catheterization was the only risk factor significantly associated with candida-related blood stream infection [5]. Among Candida-caused invasive infections, C. guilliermondii is rare (0.4-1.4%), and in vitro susceptibility to fluconazole and voriconazole is 75.7 and 91.7%, respectively [6]. The percentage of C. guilliermondii in total Candida species is 1.1% in the Asian-Pacific region, and fluconazole susceptibility is 77.4% [6]. The specimen type that most commonly yields C. guilliermondii is blood, followed by skin and soft tissue [5,7]. C. guilliermondii-caused infections are rare in patients with hematologic malignancies, solid tumors, or neutropenia and concomitant bacterial infection [7]. The mechanism of immunity to non-albicans Candida species is not well understood; however, it has been observed that the antigenicity of C. guilliermondii differs from that of Candida albicans, and that the pattern recognition receptor for C. albicans-such as galectin-3-does not affect C.
guilliermondii. C. guilliermondii also secretes serine proteinase, which hydrolyzes extracellular protein and destroys a broad spectrum of relevant host proteins [8].
Isolated pulmonary valve endocarditis is rare, and the most common pathogen for the condition is Staphylococcus aureus. A lower pressure gradient leading to the pulmonic valve receiving less shear stress compared with the other valves has been proposed as a possible mechanism for the condition, whereas underlying congenital or acquired valvular abnormality involving pulmonary valves has been suggested as a less common mechanism [8]. Congenital heart disease is commonly mentioned in the literature on isolated pulmonary valve endocarditis [9]. The use of a central venous catheter, which is becoming more common, is a risk factor for health careassociated IE. Right-sided IE occurs in 5-10% of all IE patients, and isolated pulmonary valve involvement is present in 2.5% of IE cases. In our patient, the vegetation developed slowly (more than 2 months after admission); diagnosis for isolated pulmonary valve endocarditis is difficult [10]. Table 1 presents a summary of literature found using MEDLINE and PubMed on isolated pulmonary endocarditis caused by Candida or another fungus. There have been only 3 similar published cases. The data indicate that the condition is predominantly found in males and caused by Candida. In addition to congenital cardiac anomaly and prolonged intravenous drug infusion, hematologic disorders, such as transient neutropenia [8] and bone marrow infection caused by protozoa [11], are possible risk factors. Our patient had multiple risk factors such as monoclonal gammopathy and long-term catheter use. Dyspnea and respiratory failure caused by pulmonary embolism [4] is common in patients with isolated pulmonary IE. However, in the current case, splenic infarction was observed during admission, and the patient didn't need additional oxygen supply. The most widely recommended management method of isolated pulmonary valve Candida-associated endocarditis is pulmonary valve resection with prolonged antifungal antibiotics use. The American College of Cardiology and the American Heart Association guidelines list a Class 1 recommendation that fungal endocarditis be considered an indication for surgery; however, Candida-associated IE commonly occurs in patients who are poor surgical candidates because they have multiple comorbidities [12]. Although Devathi et al. treated a patient with antifungal antibiotics successfully without surgery, this approach was unsuccessful in our patient. Therefore, in patients with isolated pulmonary valve IE caused by Candida, antibiotics alone may be insufficient for treating patients with isolated pulmonary IE, and surgical resection should be mandated as the curative treatment.

Conclusion
Isolated pulmonary valve endocarditis caused by C. guilliermondii is rare. Hematologic disorders, in addition to long-term catheter use, prolonged intravenous injection, and congenital cardiac anomaly, predispose patients to the condition. The diagnosis for isolated pulmonary IE is difficult, and combing surgery with antifungal antibiotics is the appropriate therapeutic management for Candida related pulmonary IE.

Acknowledgements
We are grateful to the patient and her family for permission to publish this case report.

Funding
Cardinal-Tien Hospital, New Taipei City, Taiwan funded the microbiological analyses and therapeutic intervention. No other, especially no commercial funding was received for the case report.

Availability of data and materials
The data regarding the case belongs to clinical and laboratory charts stored in the hospital repository and cannot be shared.
Authors' contributions YH did the literature review and drafted the initial manuscript and revisions. YH and MH managed the patient. KL contributed to the analysis and identification of pulmonary infective endocarditis. DY developed the concept for the manuscript and significantly contributed to the revision of the manuscript. CC provided expertise in evaluating the image finding of the patient. All the authors have read and approved the final manuscript.
Ethics approval and consent to participate Not applicable.

Consent for publication
The patient's daughter provided informed consent for publication to our hospital in written form.