A 61-year-old female who had never smoked was referred to Osaka University Hospital with a productive cough, shortness of breath, and wheezing for 5 years. She had a high eosinophil range of 6–20% (normal, 2–4%) and transient recurrent infiltrates on serial chest X-rays. Eosinophilic pneumonia with bronchial asthma had been diagnosed and treatment with oral prednisolone resulted in the remission of symptoms for 2–3 weeks at a time.\nThe patient complained of up to 10 mL of sputum per day which was purulent, malodorous and sometimes formed mucoid plugs. She was prescribed with inhaled corticosteroids and long-acting beta-agonists. She was found to have bilateral coarse crepitations with biphasic polyphonic rhonchi on pulmonary examination. Blood cell analysis revealed a total leukocyte count of 7240 cells/μL; with 44.7% polymorphs, 36.8% lymphocytes, 5.5% monocytes, 11.9% eosinophils, and 1.1% basophils. The absolute eosinophil count was elevated at 861/μL. Serum biochemistry findings were unremarkable, and Aspergillus spp. IgG antibody was negative. Total IgE was within the normal range (70.36 IU/mL), but specific IgE for Aspergillus spp. was found to be positive.\nA chest X-ray showed infiltrates in the right lower lung (A), and computed tomography revealed bilateral dilation of the central bronchi in the right upper lobe (B). The involved bronchi contained hyperattenuating mucus. Bilateral central bronchiectasis was diagnosed. The patient was further investigated because saccular bronchiectasis is a feature of allergic bronchopulmonary aspergillosis (ABPA). Direct analysis of sputum samples using random sequencing (shotgun sequence) using a next-generation sequencer revealed fungal DNA. Aspergillus fumigatus was dominant and four other fungal sequences including Schizophyllum commune were found ().\nMicroscopic assessment of sputum was negative for acid-fast bacilli (AFB) and other bacteria. However, Charcot–Leyden crystals that are generated through the breakdown of eosinophils and hyphae were identified (C and D). Direct microscopy of KOH wet mounts of three consecutive sputum specimens and expectorated sputum/mucoid plugs revealed two types of septate and branching hyphae (A and B). Homogenized sputum and mucoid plugs inoculated onto Sabouraud's glucose agar (SGA) developed green and white colonies with a wooly texture after 4 days at 2 °C (C and D).\nOne of the fungi was morphologically identified as A. fumigatus (A and C), but the other (B and D) remained obscure. Therefore, DNA was extracted and the internal transcribed spacer region (ITS) and the D1/D2 region of large subunit rRNA gene were amplified by PCR. Direct sequencing of the PCR products showed that the sequences of the ITS and D1/D2 regions were 100% similar to those of various S. commune strains, such as IFM 46097. The diagnosis of allergic bronchopulmonary mycosis (ABPM) due to co-infection with A. fumigatus and S. commune was made.\nThe susceptibility of the isolated A. fumigatus and S. commune strains to antifungal drugs (minimum inhibitory concentration; MIC) was as follows: amphotericin B (1 and 0.5 μg/mL), 5-fluorocytosine (64 and 0.25 μg/mL), fluconazole (>64 and 4 μg/mL), itraconazole (0.12 and 0.25 μg/mL), voriconazole (0.5 and 0.12 μg/mL), and micofungin (0.03 and >16 μg/mL), respectively.\nThe administration of oral itraconazole and prednisolone, improved the symptoms in this patient.
A 38-year-old male presented with a cough for 3 days, hemoptysis, fevers, and chills for 1 day (). He denied cough, fevers, night sweats, or weight loss prior to 3 days before admission. He had emigrated to the U.S.A. from Mexico seven years previously and had no foreign travel subsequently. In his previous life, he had worked as an automobile mechanic, in construction, and gardening. His past medical history indicated treatment for a lung infection, with an inability to work, 9 years previously, but he did not recall the diagnosis. During that time, he was treated concurrently with 3 different types of medications for 7 months but was never told that he had tuberculosis. He had no history of risk factors for an anaerobic lung abscess, such as aspiration, alcohol use, smoking or seizures.\nOn admission, his temperature was 39.4°C, leukocyte count was 6500/mm3, and HIV test was negative. Therapy with piperacillin-tazobactam and vancomycin was initiated and the patient remained hospitalized for 2 weeks. Computed tomography of the lung on hospital day 2 demonstrated an 8.2 × 5.5 cm cystic structure in the left upper lobe with an internal air-fluid level, fluid debris levels and a thick, irregular wall, consistent with a pulmonary abscess. There were surrounding areas of “ground-glass” opacities and consolidation in the left upper and lower lobes. Sputum cultures grew methicillin-susceptible Staphylococcus aureus and Klebsiella oxytoca, prompting discontinuation of vancomycin on hospital day 8. On hospital day 9, transthoracic left upper lobe pulmonary abscess drainage was performed, with an aspiration of 140 cc of dark green–black fluid. Cytologic examination of the aspirated fluid did not show malignant cells, but had abundant neutrophils, numerous erythrocytes, and necrotic debris. Smear and culture for mycobacteria, and anaerobic culture, were negative. Fungal culture yielded two colonies of a filamentous non-sporulating fungus. The therapy was then switched to oral amoxicillin-clavulanate. At discharge, his cough had improved and he denied dyspnea.\nAfter discharge, he reported two weeks of mild intermittent dyspnea, but otherwise remained asymptomatic. The amoxicillin-clavulanate therapy was discontinued. However, serial chest radiographs demonstrated a persistent air-fluid level within a thin-walled cystic structure in the posterior left upper lobe. These radiographs were unchanged for four months. He reported two weeks of mild, intermittent dyspnea in the 4th-month post-discharge.\nA chest tomogram performed 5 months post-discharge, to better characterize the disease, revealed a thin-walled cystic cavity in the left upper lobe apical posterior segment, measuring 5.0 × 4.6 cm. The fluid within the lesion was hyperdense, and there was a calcified component posteriorly. Cephalad to the lesion, there was an architectural distortion and bronchiectasis with adjacent scarring and likely adjacent cicatricial emphysema. The oblique fissure was displaced anteriorly, posterior to this region, secondary to the associated volume loss and/or scar. There was less consolidation in this area compared to prior tomograms.\nA sputum bacterial culture was unremarkable, sputum smear for parasites was negative, as were antibody tests for Histoplasma, Coccidioides (IgG and IgM), and Echinococcus, and 2 blood cultures. A test for HIV was again negative. Sputum fungal culture grew Candida albicans and a filamentous fungus, morphologically similar to the previously isolated fungus. With a diagnosis of a persistent abscess, he proceeded to left upper lobectomy and extensive lysis of pleural adhesions. He was hospitalized 8 days, during which time he had intermittent fevers. Initially, there was a mild leukocytosis, which subsided. The intra-operative findings revealed an abscess that was located deep within the posterior aspect of the left upper lobe. The posterior fissure was completely fused and required extensive dissection. Intra-operative cultures were positive for a fungus, identified by sequencing as Gloeostereum sp. This was morphologically similar to the filamentous fungus that had been cultured on the previous occasions. Susceptibility testing of the fungus by macrobroth dilution indicated low MIC to amphotericin B (0.5 µg/ml), but high to voriconazole (MIC of >8 µg/ml) and fluconazole (MIC 16 µg/ml). Candida albicans was not cultured in the specimen, nor seen in the histopathology. No antifungal chemotherapy was given.\nHistopathology of the resected specimen was interpreted as chronic inflammation in a bronchogenic cyst with a lining of ciliated pseudostratified columnar epithelium, some muscle and fibrous tissue, subepithelial chronic inflammation and pulmonary congestion (). The cyst contents showed fungal hyphae (). The fungus was sent to the Westerdijk Fungal Biodiversity Institute for definitive speciation and deposited there under number CBS 145006. The patient was seen in clinic 2 weeks post-discharge, at which time he denied fevers, chills. He remained well in subsequent visits.