Objective:To explore the application value of metagenomic next-generation sequencing (mNGS) in the diagnosis of pulmonary tuberculosis (PTB) combined with non-tuberculous mycobacterial pulmonary disease (NTM-PD), compare it with conventional pathogen detection methods, and analyze its clinical characteristics.Methods:A retrospective analysis was conducted on the clinical data of 72 patients with PTB complicated by NTM-PD who were admitted to Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine (Nanjing Second Hospital) from November 2021 to November 2023. All patients were diagnosed using bronchoalveolar lavage fluid (BALF) mNGS and compared with traditional culture methods. Data on patient demographics, clinical manifestations, imaging features, and treatment outcomes were collected to analyze the advantages and clinical significance of mNGS in diagnosis.Results:The positive detection rate of Mycobacterium tuberculosis by mNGS was 100% (72/72), significantly higher than that of traditional culture 27.8%(20/72). The diagnostic time of mNGS was significantly shorter (2 d vs. 45 - 60 d, P<0.001). The majority of patients were elderly (mean age: 55.92 years) and often had underlying structural lung diseases (e.g., bronchiectasis, COPD) or immunocompromised conditions (e.g., diabetes). The main clinical manifestations were cough (68.06%) and sputum production (52.78%). Imaging features included bronchiectasis (63.89%), nodular shadows (47.22%), and tree-in-bud signs (25.00%). After 6 months of follow-up, 73.8% of patients showed significant improvement in lung lesions, while 26.2% had no significant change or disease progression. Conclusions:mNGS demonstrates rapid and accurate diagnostic advantages for PTB combined with NTM-PD, significantly outperforming traditional culture methods, and provides critical support for precise clinical treatment.

Objective:To explore the application value of metagenomic next-generation sequencing (mNGS) in the diagnosis of pulmonary tuberculosis (PTB) combined with non-tuberculous mycobacterial pulmonary disease (NTM-PD), compare it with conventional pathogen detection methods, and analyze its clinical characteristics.Methods:A retrospective analysis was conducted on the clinical data of 72 patients with PTB complicated by NTM-PD who were admitted to Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine (Nanjing Second Hospital) from November 2021 to November 2023. All patients were diagnosed using bronchoalveolar lavage fluid (BALF) mNGS and compared with traditional culture methods. Data on patient demographics, clinical manifestations, imaging features, and treatment outcomes were collected to analyze the advantages and clinical significance of mNGS in diagnosis.Results:The positive detection rate of Mycobacterium tuberculosis by mNGS was 100% (72/72), significantly higher than that of traditional culture 27.8%(20/72). The diagnostic time of mNGS was significantly shorter (2 d vs. 45 - 60 d, P<0.001). The majority of patients were elderly (mean age: 55.92 years) and often had underlying structural lung diseases (e.g., bronchiectasis, COPD) or immunocompromised conditions (e.g., diabetes). The main clinical manifestations were cough (68.06%) and sputum production (52.78%). Imaging features included bronchiectasis (63.89%), nodular shadows (47.22%), and tree-in-bud signs (25.00%). After 6 months of follow-up, 73.8% of patients showed significant improvement in lung lesions, while 26.2% had no significant change or disease progression. Conclusions:mNGS demonstrates rapid and accurate diagnostic advantages for PTB combined with NTM-PD, significantly outperforming traditional culture methods, and provides critical support for precise clinical treatment.

A 72-year-old male patient with secondary pulmonary tuberculosis developed skin erythema and pruritus of both lower limbs after 10 months of antituberculosis treatment with isoniazid, rifampin, ethambutol, and pyrazinamide, followed by blisters and bullae, and the skin lesions gradually spread to his whole body. The skin biopsy showed bullous pemphigoid, and the antibodies to bullous pemphigoid 180 detected by enzyme-linked immunosorbent assay was 156.8 U/ml. Considering that the patient′s bullous pemphigoid might be induced by rifampin, rifampin was discontinued and antitu-berculosis therapy was changed to isoniazid, ethambutol, pyrazinamide, and moxifloxacin. Prednisone acetate and symptomatic and supportive treatments were given at the same time. Two weeks later, the lesions were markedly improved, and the original erosive surface got scabs and basically healed. At 6 months of follow-up, the lesions recovered, and no new lesions or blisters occurred.

A 72-year-old male patient with secondary pulmonary tuberculosis developed skin erythema and pruritus of both lower limbs after 10 months of antituberculosis treatment with isoniazid, rifampin, ethambutol, and pyrazinamide, followed by blisters and bullae, and the skin lesions gradually spread to his whole body. The skin biopsy showed bullous pemphigoid, and the antibodies to bullous pemphigoid 180 detected by enzyme-linked immunosorbent assay was 156.8 U/ml. Considering that the patient′s bullous pemphigoid might be induced by rifampin, rifampin was discontinued and antitu-berculosis therapy was changed to isoniazid, ethambutol, pyrazinamide, and moxifloxacin. Prednisone acetate and symptomatic and supportive treatments were given at the same time. Two weeks later, the lesions were markedly improved, and the original erosive surface got scabs and basically healed. At 6 months of follow-up, the lesions recovered, and no new lesions or blisters occurred.

Objective To analyze the relationship between pyrazinamide plasma concentration and liver injury in patients with tuberculosis and explore the early prediction method of drug-induced liver injury (DILI) in initial treatment in patients with tuberculosis.Methods Data of tuberculosis patients (all the patients were initially treated, no other complications, and underlying disease) receiving 2HREZ/4HR treatment regimen [isoniazid, rifampicin, ethambutol, and pyrazinamide were given at the first 2 months of treatment, isoniazid and rifampicin were given at the later 4 months of treatment] in Nanjing Chest Hospital, Medical School of Southeast University from January to December 2016 were collected.According to the pyrazinamide concentration in serum on the 6th day of treatment, patients were divided into 3 groups, the <20 mg/L group, 20-40 mg/L group, and >40 mg/L group.The incidences of DILI in the 3 groups were compared.Results A total of 45 patients in accordance with the criteria were collected, including 33 males and 17 females with age from 18 to 50 years and an average age of (34±10) years.Among them, 36 patients had pulmonary tuberculous, 9 patients had tuberculous pleurisy, and 5 patients had tuberculosis meningitis.The pyrazinamide concentrations in serum were 16-51 mg/L and the average concentration was (35±9) mg/L.There were 4 patients in the <20 mg/L group, 28 patients in the 20-40 mg/L group, and 13 patients in the >40 mg/L group.Of the 45 patients, 11 patients developed DILI and the incidence was 24.4%.The pyrazinamide plasma concentrations in the 11 patients with DILI were 26 mg/L to 51 mg/L, 4 patients′ concentrations were 40 mg/L and 7 patients′ concentrations were >40 mg/L.The incidences of DILI in the <20 mg/L, 20-40 mg/L, and >40 mg/L groups were 0/4, 14.2 %(4/28), and 53.85% (7/13), respectively.The difference between the 20-40 mg/L and the >40 mg/L groups was statistically significant (X2=7.708, P=0.008).Conclusions The DILI incidence in initial treatment of tuberculosis patients increased with increase of pyrazinamide plasma concentration.Early therapeutic drug monitoring for pyrazinamide could predict the occurrence of DILI and was beneficial for reducing or avoiding the effect of DILL for tuberculosis treatment.

Objective To analyze the relationship between pyrazinamide plasma concentration and liver injury in patients with tuberculosis and explore the early prediction method of drug-induced liver injury (DILI) in initial treatment in patients with tuberculosis.Methods Data of tuberculosis patients (all the patients were initially treated, no other complications, and underlying disease) receiving 2HREZ/4HR treatment regimen [isoniazid, rifampicin, ethambutol, and pyrazinamide were given at the first 2 months of treatment, isoniazid and rifampicin were given at the later 4 months of treatment] in Nanjing Chest Hospital, Medical School of Southeast University from January to December 2016 were collected.According to the pyrazinamide concentration in serum on the 6th day of treatment, patients were divided into 3 groups, the <20 mg/L group, 20-40 mg/L group, and >40 mg/L group.The incidences of DILI in the 3 groups were compared.Results A total of 45 patients in accordance with the criteria were collected, including 33 males and 17 females with age from 18 to 50 years and an average age of (34±10) years.Among them, 36 patients had pulmonary tuberculous, 9 patients had tuberculous pleurisy, and 5 patients had tuberculosis meningitis.The pyrazinamide concentrations in serum were 16-51 mg/L and the average concentration was (35±9) mg/L.There were 4 patients in the <20 mg/L group, 28 patients in the 20-40 mg/L group, and 13 patients in the >40 mg/L group.Of the 45 patients, 11 patients developed DILI and the incidence was 24.4%.The pyrazinamide plasma concentrations in the 11 patients with DILI were 26 mg/L to 51 mg/L, 4 patients′ concentrations were 40 mg/L and 7 patients′ concentrations were >40 mg/L.The incidences of DILI in the <20 mg/L, 20-40 mg/L, and >40 mg/L groups were 0/4, 14.2 %(4/28), and 53.85% (7/13), respectively.The difference between the 20-40 mg/L and the >40 mg/L groups was statistically significant (X2=7.708, P=0.008).Conclusions The DILI incidence in initial treatment of tuberculosis patients increased with increase of pyrazinamide plasma concentration.Early therapeutic drug monitoring for pyrazinamide could predict the occurrence of DILI and was beneficial for reducing or avoiding the effect of DILL for tuberculosis treatment.