A 79-year-old man was presented to our hospital with 1-month cough and fever. He has visited two other local hospitals for more than three times where a series of examinations were performed. His chest computerized tomography (CT) scan revealed ground-glass nodules in the upper lobe of the right lung with multiple enlarged lymph nodes in the mediastinum which were suspected of tumors (Figure 1A). In order to clarify the nature of the lesion he further took a needle biopsy of lymph nodes under bronchoscope while pathological results showed no evidence of tumors. Presumed to be pulmonary infection, he was then given piperacillin-tazobactam, moxifloxacin, and empirical anti-tuberculosis treatment successively. His body temperature gradually returned to normal, but the cough still exists. One week later, his cough worsened without fever. Outpatient blood routine examination revealed that white cells count (WBC) 13.1 x 109/L, C-reactive protein (CRP) 183.51 mg/L. Re-examination of chest CT showed infectious lesions in both lungs, left hilar shadow increased, and mediastinal lymph nodes slightly enlarged (Figure 1B). For further treatment, he was admitted to the Department of Infectious Diseases of Ningbo First hospital. His initial diagnosis was bacterial pneumonia.
He has not taken any immunosuppressants or glucocorticoids before. He had hypertension for more than 10 years treated by amlodipine and bisoprolol, diabetes mellitus for 3 years treated by insulin with unsatisfactory glycemic control, and eczema for 10 years without therapy. He did not have chronic airway disease although he had smoked for 20 years and quitted smoking for more than 20 years. Three years ago, he had undergone Permanent Cardiac Pacemaker implantation. As a Ningbo native, he had retired from a Metal Instrument Factory where he worked as an installer of metallic parts for more than 20 years. And he hasn't been to the wild recently. He has no prior family history of malignancy, infectious diseases or psychosis. Physical examination showed large eczema-like scars on two legs and found no other positive signs.
After admission, we examined his cellular immune function for lymphocyte subsets analysis (Table 1), immunoglobulins, cytokines, and found no obvious immune deficiency. And his tuberculosis T-SPOT. TB test, human immunodeficiency virus (HIV) test, tumor biomarkers (including carcinoembryonic antigen, carbohydrate associated antigen 199, alpha-fetoprotein, and cancer antigen 125), Antinuclear antibody (ANA) and Antineutrophil autoantibodies (ANCA), serum cryptococcal antigen colloidal gold test, and serological test for syphilis were all negative.
Since he has used broad-spectrum antibiotics with poor efficacy, we performed meropenem, tigecycline consecutively (Table 2). However, the peak temperature did not drop (Figure 2), and the inflammation indexes did not improve (Table 3). During hospitalization, his galactomannan (GM) was positive in serum. Thus, we empirically add caspofungin for antifungal treatment. Meanwhile, we replaced tigecycline with linezolid. Since then, the fever seems to have gradually eased but WBC increased slowly (Figure 3). We ordered another chest CT scan which indicated the lesions of pneumonia were larger than before and pleural fluid appeared (Figure 1C). On November 5, he underwent a fiberoptic bronchoscopic examination (Figure 4) and lavage of the basal segment of the left lower lobe. Bronchoalveolar Lavage fluid (BALF) was tested for mNGS, culture, liquid-based cytology. At the same time, blood sample was sent for mNGS examination.
Four days later, we changed antibiotics to intravenous voriconazole and piperacillin-tazobactam since mNGS suggested Penicillium marneffei infection (Table 4). Moreover, we prolonged sputum culture time to one week and the fungus was further validated by culture (Figure 3). After he was prescribed targeted anti-fungal agent of voriconazole 200 mg twice daily, the clinical presentations and laboratory indicators were gradually returning to normal (Table 3). The whole process was concluded (Figure 5).
Prior to follow-up, he carried on taking voriconazole 200 mg twice daily regularly without relapse. On December 9th, his repeated chest CT scan showed that pneumonia was cured and pleural effusion were absorbed obviously (Figure 1D).