Cunninghamella bertholletiae Infection Mimicking Myocardial Infarction

Clinical infection with Cunninghamella bertholletiae is extremely rare, and in immunocompromised hosts it is almost always devastating and usually fatal. Here we report the first example of a patient with acute leukemia who developed heart failure as a consequence of massive cardiac involvement with this fungus. Our case illustrates the difficulties of diagnosing C. bertholletiae and intervening with appropriate therapy. A 35-year-old man was admitted to our hospital with a history of night sweats, weakness, petechial bleeding, and fever. After the diagnosis of acute myelogenous leukemia (French-American-British classification M2) was established, chemotherapy with a double-induction protocol was initiated. Neutropenic fever was treated with empirical antibiotics with initial success, but during persisting neutropenia (33 days after chemotherapy), the patient developed signs and symptoms (ra-dio-graphic and CT) compatible with aspergillosis of the right lung. Amphotericin B therapy was added to the regimen (total dose, 225 mg) and replaced after 5 days by voriconazole (total dose, 25,000 mg; duration, 9 weeks), but on bronchoscopy, the etiology could not be ascertained. Two weeks later, the fever retreated and there were signs of improvement of the pulmonary lesions on CT scans. When the patient developed fever again (neutropenia lasting >70 days), CTs documented further improvement of the previous lesions. Ten days later, signs of peri-carditis led to the observation of a minor pericardial effusion on echocardiography and ST-segment alterations in the electrocardiogram. Culture of sputum yielded mucormycosis once, and the fungus was identified as Cunninghamella bertholletiae. The identification was confirmed by Dr. D. W. Warnock (Public Health Laboratory Service, Mycology Reference Laboratory, Bristol, UK). Results of bronchoscopy (with biopsy) and bronchoalveolar lavage remained inconclusive. During the next days, symptoms evolved to severe substernal pain with a peri-cardial friction rub and elevated ST segments in the precordial (V3 through V6) and limb leads (I, II, aVL) of the electro-cardiogram. A bone-marrow aspirate was hypocellular and without evidence of leukemia. Because of the severe infection, it was decided that an allogeneic stem cell transplantation with a fast restoration of normal neutrophil counts was the only potentially curative treatment. Immunosuppressive conditioning with fludarabine and antithymocyte globulin was initiated. CTs now showed a new infiltration in the lingula adjacent to the pericardium; enzyme studies and an electrocardiogram were consistent with anterolateral myocardial infarction. A subsequent echocardiogram showed a large left-ventricular echodense mass inferoapical and lateroapical with akinesia of the corresponding myocardial segments. MRI showed a tumor-like mass originating from the lung with continuous myocardial penetration (figure 1). The patient had progressive cardiac failure and died 106 days after initiation of chemotherapy and 5 days after stem cell transfusion without evidence of engraftment. MRI scan, coronal TSE (turbo spin echo) T1-weighted images of patient infected with Cunninghamella bertholletiae (patient holding breath) after gadolinium injection, showing large tumor mass with continuous myocardial penetration originating from lung. Note strong enhancement in peripheral zone of tumor mass (arrowhead) and complete necrosis in central parts of myocardium. On autopsy, a disseminated fungal infection was documented. Mycotic hemorrhagic pneumonia of the left upper lobe had penetrated per continuitatem from the lingula to the peri-cardium and the left ventricle, with concretio pericardii measuring 5 cm on the level of the left ventricular apicolateral wall. A massive mycotic myocarditis with acute necrosis was predominant in the apex of the heart. Fungal infection appeared as mycotic mural endocarditis with the formation of a 3-cm massive ventricular parietal thrombus. There was no evidence of persistent leukemia. Fluorescence microscopy of wet mounts from sections of lung, heart, spleen, and kidney, made with 20% potassium hydroxide containing 0.4% blankophore under UV light, yielded ribbon-like, rarely septated hyphae. Cultures yielded C. bertholletiae only from lung specimens. This fungus, which is one of the confirmed facultative pathogenic genera of the Mucorales [1], has been increasingly identified as a cause of opportunistic infection in patients with underlying chronic disease, with AIDS, or who are receiving immunosuppressive or cytotoxic therapy [2]. Patients with a Cunninghamella infection, which is rarely diagnosed before death, have a very high mortality rate. In leukemia, these infections have been uniformly fatal [3]. To our knowledge, only a few patients with localized infections have survived after therapy [4].