A 79-year-old man was admitted to the cardiology department of our hospital, complaining of a 7-day history of fever, with a temperature up to 39.5 ℃. He denied cough, phlegm, nasal obstruction, pharyngalgia, chest pain, dizziness, or headache. Five days before admission, he was diagnosed with pulmonary infection by chest X-ray and given antibiotic therapy at a local hospital, but his symptoms did not relieve. The patient was diagnosed with diabetes mellitus two months ago and drank 2000–3000 ml of water per day. About 20 days ago, he began to present chest tightness and shortness of breath after physical activity. In addition, the patient had a history of high blood pressure for more than 20 years. On admission (day 0), physical examination showed conscious state, temperature of 36.5 ℃, heart rate of 78/min, respiratory rate of 20/min, blood pressure of 120/62 mmHg, and crackles on pulmonary auscultation. The patient reported a weight loss of 10 kg in the last six months. Laboratory investigations showed white blood cell of 7.77 × 109/L (with 90.1% neutrophil, 2.5% monocytes, and 7.2% lymphocytes), procalcitonin of 3.24 ng/ml, erythrocyte sedimentation rate of 52 mm/h, hemoglobin A1c of 9.5%, and fasting blood sugar of 8.26 mmol/L. A chest computed tomography (CT) scan showed multiple nodules and patchy infiltration in both lungs, which did not exclude the possibility of tuberculosis. The preliminary diagnosis was pulmonary infection, and empiric antibiotic treatment with intravenous piperacillin/tazobactam (4.5 g, q12h) and moxifloxacin (2 g, q12h) was given. Intravenous insulin (4 U, qd) and oral miglitol (50 mg, q12h) were used to control blood glucose level. After admission, the patient developed continuous fever and daily temperature peak exceeded 38.5 ℃. On day 1, he developed respiratory failure and received oxygen treatment. Arterial blood gas analysis showed PH 7.50, PaO2 of 57.7 mmHg, PaCO2 of 31.9 mmHg, and SaO2 of 90.2%. Serological tests for influenza A IgM, influenza B IgM, parainfluenza virus IgM, adenovirus IgM, respiratory syncytial virus IgM, Mycoplasma pneumoniae IgM, and Chlamydia pneumoniae IgM proved negative. Tuberculosis immune spot test was positive. On day 2, the patient presented polyuria and polydipsia, and his symptom of tachypnea was not relieved during oxygen treatment. Then he was transferred to the intensive care unit (ICU) and given mechanical ventilation. On day 3, the patient had a PASS score of − 1, and received analgesia and sedation with propofol and alfentanil. Bronchoscopy found bronchial mucosal inflammation and production of purulent sputum, and bronchoalveolar lavage fluid (BALF) was obtained for further detection. On day 5, the patient underwent a decreased oxygenation index (155) compared with before. No abnormalities were found in his blood culture. Serum galactomannan (1.74 ng/ml) and 1,3-β-d-glucan (424.50 ng/L) were positive. Acid-fast staining and culture of BALF were negative. M. tuberculosis DNA detection from BALF was positive. The BALF sample was also sent for metagenomic next-generation sequencing (Genskey, Beijing, China). A total of 86,398,947 raw reads were generated and 60,161,047 high quality reads were obtained after removing low quality reads. Among the high quality reads, 47,232,566 were aligned with the human reference genome (HG38) and 12,928,481 were used for downstream analysis. The mNGS of BALF reported M. tuberculosis complex (7,453,374 reads), A. lentulus (37,868 reads), and several oral colonizing microorganisms. Metagenome data is now available at NCBI under the Sequence Read Archive (SRA) database with accession no. PRJNA917778. Based on these findings, the patient was diagnosed as coinfection of M. tuberculosis and A. lentulus. Initial antibiotic treatment was changed to oral isoniazid (0.3 g, qd), rifapentine (0.45 g, qd) for anti-tuberculosis, and intravenous caspofungin (50 mg, qd) for anti-fungal. On day 6, the patient's condition aggravated again. He developed multiple organ dysfunction and fell into a light coma state. His family decided to abandon treatment because of financial problems and grave prognosis. Artificial respiration was stopped subsequently and the patient expired 1.5 h later.