Histoplasma capsulatum Prosthetic Valve Endocarditis with Negative Fungal Blood Cultures and Negative Histoplasma Antigen Assay in an Immunocompetent Patient

Abstract

We report a case of Histoplasma capsulatum endocarditis in which Histoplasma antigen assay and fungal blood cultures were negative. The diagnosis was made by microscopic examination and culture of the excised valve. Histoplasma capsulatum should be considered in the differential diagnosis of culture-negative endocarditis in regions where it is endemic and in travelers. CASE REPORTThe patient, a 59-year-old female living in northeastern Ohio, with a history significant for coronary artery disease, hypertension, bicuspid aortic valve, and aortic stenosis, had an aortic bioprosthetic valve replacement in 2004. In April 2010, she presented to her primary care physician with fever, chills, dry cough, and shortness of breath persisting for 10 days and was prescribed amoxicillin-clavulanate for presumed bronchitis. Her symptoms continued to worsen, and she presented to the emergency room in our institution. On examination, her vital signs were significant for a temperature of 101°F, respiratory rate of 22 breaths/min, heart rate of 105 beats/min, blood pressure of 129/50 mm Hg, and oxygen saturation of 100% on 2 liters nasal cannula supplemental oxygen. The physical exam was remarkable for oral caries and an aortic systolic ejection murmur. There were no peripheral stigmata of infective endocarditis or signs of heart failure. A complete blood count showed a white blood cell count of 8,400 cells/mm 3 with 82% neutrophils, hemoglobin of 11.2 g/dl, and a platelet count of 206,000/mm 3 . Other investigations were remarkable for an erythrocyte sedimentation rate of 108 mm/h (normal, Ͻ30 mm/h), C-reactive protein level of 5.96 mg/dl (normal, Ͻ0.8 mg/dl), and creatinine level of 1.37 mg/dl. Liver function tests were normal. Chest X ray was normal, but transesophageal echocardiography (TEE) showed a 5-by 6-mm vegetation on the aortic valve with mild aortic regurgitation. Numerous blood cultures, including three fungal cultures using 10-ml Isolator tubes, were negative. The presumptive diagnosis was culture-negative endocarditis associated with recent antibiotic use. Initially, the patient was started on vancomycin, gentamicin, ceftriaxone, and rifampin. Subsequently, ceftriaxone was switched to meropenem due to the concern for drug fever. Despite antibiotic therapy, the patient continued to have persistent fevers and rigors. A magnetic resonance image (MRI) of the brain and a computed tomography (CT) of the abdomen and pelvis did not reveal embolic lesions or abscesses. Fourteen days after the initial TEE, a repeat TEE demonstrated enlargement of the vegetation on the aortic valve with no definite periannular abscess. The patient underwent an aortic valve replacement, during which vegetations were found on all three aortic leaflets. The aortic annulus, left ventricular free wall, and septum were not involved. Direct microscopic examination of the vegetations stained with calcofluor white-KOH disclosed numerous small, oval yeasts. Histopathology of the excised valve showed chronic inflammation consistent with infection of the b...

Fungal endocarditis after transfemoral aortic valve implantation

“…Secondly, the uncommon causative microorganism H. capsulatum has shown to be diagnostically challenging [7,8]. The time between the onset of symptoms and diagnosis is delayed to up to 9 months, and it has therefore been associated with a high risk of mortality in prosthetic valve endocarditis (PVE) [8].…”

Culture Negative Endocarditis: Advances in Diagnosis and Treatment

“…Commercial tests that detect fungal wall antigens such as galactomannan [2,61,62] and β-1,3-D-glucan [62] can show good sensitivity and specificity in diagnosis of fungal CNE. Jinno et al [56] reported negative urine Histoplasma antigen results in their patient with H. capsulatum CNE, with diagnosis based on valvular pathology and tissue culture.…”

“…Among cases in the recent literature, infections with Aspergillus spp. [53][54][55], Histoplasma capsulatum [56][57][58] and Trichosporin spp. [59,60] are the most widely reported.…”

CouldHistoplasma capsulatumBe Related to Healthcare-Associated Infections?

“…Epidemiological surveillance definitions of HAI include surgical site infections associated with surgical implants or medical indwelling devices, when they occur within 30–90 days after the surgical procedure [ 4 ]. Clinically, H. capsulatum infections have been identified in individuals with invasive devices or surgical implants, and some authors have described endovascular histoplasmosis in patients with vascular prosthetic or synthetic implants [ 80 , 81 , 116 – 119 ]. Usually, the diagnosis is made by isolation of the fungus in vegetation or over synthetic materials.…”

“…Usually, the diagnosis is made by isolation of the fungus in vegetation or over synthetic materials. In addition, histopathological observation has revealed fibrin, large aggregates of yeast cells, mild chronic inflammatory cell infiltrates (predominantly macrophages) [ 80 , 116 , 118 ], and H. capsulatum hyphae (M-phase) in a few cases [ 117 ]. Furthermore, H. capsulatum endocarditis has also been described in native heart valves [ 118 – 120 ].…”