A 16-year-old male student from Jieyang City, Guangdong Province was admitted to Foshan Fourth People's Hospital on 11 November 2020. The patient had an intermittent cough without obvious inducement 6 months ago, mainly dry cough, no fever, chest pain, or other adverse symptoms. He was previously healthy, with no history of bird feces or soil contact. On 19 October 2020, the chest CT examination was conducted at the local hospital, which revealed chest shadow and suspected tuberculosis. Then, he came to our hospital for treatment. There were no obvious abnormalities on physical examination after admission. The blood assay showed a white cell count of 7.20 x 109/L, neutrophils of 51.9% (3.73 x 109/L), and C-reactive protein of 9 mg/L. T-lymphocyte spot test (T-SPOT) and pure protein derivative (PPD) skin test (13 x 14 mm) were positive. In terms of bacteriology, sputum acid-fast staining was negative on 13, 14, and 15 November 2020. On 13 November 2020, a chest plain scan and enhanced CT showed left lower lobe and right pulmonary cavities lesions (Figure 1a), which suggested possible pyogenic inflammation, fungal infection, or secondary tuberculosis. The patient was given the diagnostic anti-infective treatment of cefotaxime sodium sulbactam 2.25 g twice a day. After 10 days of regular treatment, the chest CT scan showed little change compared with pre-treatment (Figure 1b). There were no significant abnormalities in the basic immunosuppressive status assessment (immunoglobulin level, T lymphocyte subsets, HIV detection, etc.). On 17 November 2020, a bronchoscopic examination showed that the bronchial mucosa of each lobe and subsegment on both sides was congestive and edematous (Figure 2). Microscopic examination of bronchial lavage fluid (BALF) showed a medium amount of squamous epithelium, bronchial columnar epithelial cells, and a small number of neutrophils, but no cancer cells. Microscopic examination of tracheoscopic brush film revealed a medium amount of columnar epithelial cells and no cancer cells. These results excluded etiologies other than infection.
The etiological examination using BALF revealed that GeneXpert (-): MTB-DNA: negative, rpoB: negative. G test revealed <37.50 pg/ml. No acid-fast bacilli, bacteria, spores, or hyphae were found. Examination and diagnosis: bronchitis changes.
The second tracheoscopy on 20 November 2020, indicated bilateral bronchitis. BALF GeneXpert was negative. The BALF was then sent for PACEseq mNGS (Hugobiotech, Beijing, China) on a Nextseq 550 platform (Illumina). On 21 November 2020, the mNGS result came back and showed one specific read of C. neoformans (Figure 3a). On 23 November 2020, CrAg-LFA (titer 1:80) and fungal culture (creamy mucoid colonies with relatively smooth edges on Sabouraud Dextrose Agar medium, initially colorless and which appeared lavender with time after staining using CHRMagaar color plate) revealed as positive, confirming the mNGS detection (Figure 3b). The patient was diagnosed with PC. The drug susceptibility results on 26 November 2020, suggested that this strain was sensitive to voriconazole (MIC <= 0.13), itraconazole (MIC < 0.25), fluconazole (MIC <= 4), and amphotericin B (MIC < 0.5), among which voriconazole had the lowest MIC (Table 1). Therefore, the patient was given oral voriconazole of 400 mg QD on 28 November 2020 for seven months. On 29 June 2021, a chest CT was performed and showed a progressive decrease in lesions of the patient (Figure 1c). The whole treatment process was shown in Figure 4.