Factors Associated with Treatment Outcome in Patients with Nontuberculous Mycobacterial Pulmonary Disease: A Large Population-Based Retrospective Cohort Study in Shanghai.

Infectious diseases caused by nontuberculous mycobacteria (NTM) are increasingly common. This retrospective cohort study examined factors associated with outcomes in patients from Shanghai who had NTM pulmonary disease (NTMPD) from January 2014 to December 2018. The causative bacterial species, drug susceptibility test results, treatment outcomes, sputum culture conversion rate, and risk factors associated with treatment failure were determined. The most common species were Mycobacterium avium complex (MAC) (50%), M. abscessus (28%), and M. kansasii (15%). Over five years, the proportions of M. kansasii and M. abscessus increased, and that of MAC decreased. The treatment success rate was significantly greater for patients infected with M. kansasii (89.9%) than MAC (65.0%, p < 0.001) and M. abscessus (36.1%, p < 0.001). Multivariate analysis indicated the risk factors for treatment failure were pathogenic NTM species (M. abscessus: aOR = 9.355, p < 0.001; MAC: aOR = 2.970, p < 0.001), elevated ESR (>60 mm/h: aOR = 2.658, p < 0.001), receipt of retreatment (aOR = 2.074, p < 0.001), and being middle-aged or elderly (>60 years-old: aOR = 1.739, p = 0.021; 45-60 years-old: aOR = 1.661, p = 0.034). The main bacterial species responsible for NTMPD were MAC, M. abscessus, and M. kansasii. Patients who were infected by M. abscessus or MAC, with elevated ESR, received retreatment, and were middle-aged or elderly had an increased risk of treatment failure.

[In vitro activities of clofazimine against different drug-resistant types of Mycobacterium tuberculosis].

OBJECTIVE: To study the in vitro antituberculous activities of clofazimine (CLF) to different drug-resistant types of Mycobacterium tuberculosis. METHODS: The minimal inhibitory concentration (MIC) of CLF and isoniazid (INH), rifampicin (RFP), ofloxacin (OFLX), amikacin (AK), and capreomycin (CPM) against sensitive, single-drug resistant (SDR), poly-drug resistant (PDR), multi-drug resistant (MDR), and extensive-drug resistant (XDR) Mycobacterium tuberculosis strains isolated clinically were determined by microplate assays. RESULTS: The MICs of CLF for sensitive, SDR, PDR, MDR and XDR strains of clinically isolated Mycobacterium tuberculosis were 0.06 - 4.00 mg/L, 0.03 - 4.00 mg/L, 0.06 - 8.00 mg/L, 0.06 - 8.00 mg/L, 0.03 - 8.00 mg/L. For the sensitive group, the MIC of CLF (0.06 - 4.00 mg/L) was higher than that of INH (0.06 - 0.25 mg/L) and RFP (0.06 - 0.25 mg/L), while there was no significant difference among OFLX (0.06 - 2.00 mg/L), AK (0.06 - 4.00 mg/L), and CPM (0.50 - 4.00 mg/L). For the single-drug resistant group, there was no significant difference among CLF (0.03 - 4.00 mg/L), INH (0.06 - 0.25 mg/L), and RFP (0.06 - 0.25 mg/L), but the MIC of CLF was lower than that of OFLX (0.25 - 8.00 mg/L), AK (0.06 - 4.00 mg/L), and CPM (0.50 - 8.00 mg/L). For the MDR group, there was no significant difference between CLF (0.06 - 8.00 mg/L) and AK (0.25 - 8.00 mg/L), but the MIC of CLF was lower than that of OFLX (0.125 - 8.00 mg/L) and CPM (0.50 - 8.00 mg/L). For the XDR group, the MIC of CLF (0.03 - 8.00 mg/L) was lower than that of others. CONCLUSION: CLF showed good in vitro activity against Mycobacterium tuberculosis, especially MDR and XDR strains.

Clinical value of endobronchial ultrasound-guided aspiration and local isoniazid injection in the treatment of mediastinal tuberculous lymphadenitis.

BACKGROUND: This study aimed to investigate the value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) guided purulence aspiration and local isoniazid injection after lymph node puncture in the treatment of refractory mediastinal tuberculous lymphadenitis (MTLA) as compared to systemic anti-tuberculosis treatment. METHODS: This was a retrospective study. A total of 92 patients with MTLA and suppurative lymphadenitis who were treated in the Shanghai Pulmonary Hospital between January 2015 and December 2018 were included into present study and divided into systemic chemotherapy (CT) group and interventional therapy (IT) group. In the CT group, patients received systemic chemotherapy alone; in the IT group, patients received EBUS-TBNA guided lymph node aspiration and local isoniazid injection besides systemic chemotherapy. The recovery of lymphadenitis and adverse effects were observed. RESULTS: Seventy patients were included for final analysis, 35 patients in each group. In the IT group, aspiration and local injection were done 137 times; 4R (53.1%) and 7 groups of lymph nodes (30.6%) were the most common site of aspiration; the median number of local treatment was 3 times, and the median duration of local injection was 29 days. The recovery rate of lymphadenitis was 88.6% (31/35) in the IT group and 57.1% (20/35) in the CT group, showing marked difference (χ2=8.741, P<0.05). The most common symptoms of patients with MTLA were cough, fever, dyspnea and anorexia, and the time to recovery of these symptoms in the IT group was 0.83±0.32, 0.89±0.29, 1.00±0.18 and 1.07±0.15 months, respectively, which were markedly shorter than in the CT group 2.60±0.74, 2.46±0.73, 2.70±0.40 and 2.67±0.43 months (t=7.608, P<0.05; t=6.442, P<0.05; t=6.755, P<0.05; t=5.237, P<0.05). All the patients received EBUS-TBNA under local anesthesia, and evident adverse effects were not observed. They were followed up for 2 years, and recurrence was not noted. CONCLUSIONS: As compared to systemic chemotherapy, EBUS-TBNA guided lymph node aspiration and local isoniazid injection combined with systemic chemotherapy may significantly improve the therapeutic efficacy, which provides a new, safe and reliable management for the refractory MTLA.

[Associated factors for the infection of Beijing genotype Mycobacterium tuberculosis].

OBJECTIVE: to analyze the risk factors for the infection of Beijing genotype Mycobacterium tuberculosis (MTB) and the relationship to drug resistance and clinical symptoms. METHODS: sputum samples were collected from patients with pulmonary tuberculosis who were admitted to the hospital during July, 2007 to March, 2008. The sputum was cultured with L-J method, and then the bacterial DNA was isolated and genotyped with VNTR-7 (variable-number tandem repeats, VNTR) and RD105 deletion method respectively. The association between different genotypes and risk factors was analyzed. RESULTS: a hundred and sixteen clinical sputum isolates were obtained from 172 positive sputum cases. There were 112 isolates of MTB, and isolates of non-tuberculosis mycobacterium (NTM). Among the 97 isolates from Shanghai, Zhejiang and Jiangsu areas, Beijing genotype accounted for 86.6% (84/97), and non-Beijing genotype for 13.4% (13/97). The rates of MDR (multi-drug resistance), PDR (poly-drug resistance) and single drug resistance in Beijing genotype were not significantly higher than those in non-Beijing genotype. Among the risk factors, female gender, and CD(4)/CD(8)< 1 in patients with newly-treated tuberculosis, were associated with higher rate of Beijing genotype, chi(2) = 4.436, 4.494 and all P < 0.05, respectively. The Beijing genotype isolates were subdivided into 31 VNTR-7 types, and the distribution of quantity and resistance among different VNTR-7 genotypes was not even. A large number of MTB isolates (47.6%, 40/84) and drug resistant isolates (43.6%, 17/39) were among four VNTR-7 genotypes. CONCLUSION: Beijing genotype is the most prevalent MTB in Shanghai, Zhejian and Jiangsu areas. Female gender and low CD(4)/CD(8) ratio in patients with newly-treated TB are risk factors for infecting Beijing genotype MTB, which may have no relationship with drug resistance and clinical symptoms.

Diagnostic Value of Virtual Bronchoscopic Navigation in the Bronchial Tuberculosis Induced Central Airway Stenosis.

INTRODUCTION: Electronic bronchoscopy is invasive and may cause pain. This study aimed to explore the clinical value of virtual bronchoscopic navigation (VBN) in the diagnosis of benign central airway stenosis (CAS) secondary to tracheobronchial tuberculosis (TBT). METHODS: Sixty-eight patients with benign CAS caused by TBT were recruited between July 2015 and December 2017. The location, length and diameter of stenoses were independently determined by VBN and electronic bronchoscopy (EOB), and the sensitivity and specificity of VBN in identifying stenosis were assessed with EOB as the gold standard. RESULTS: In 68 patients with TBT, the overall coincidence between EOB and VBN in the identification of stenosis was 100%. A total of 188 sites were selected from the central airway, and the stenosis was graded into 0%, ≤ 25%, 26-50%, 51-75%, 76-90% and > 90%. The sensitivity of VBN in determining the degree of stenosis was 98.45%, 100.00%, 100.00%, 100.00%, 84.62% and 0.00%, respectively; the specificity was 91.53%, 96.07%, 97.09%, 97.08%, 97.14% and 97.30%, respectively; the accuracy rate was 96.28%, 96.28%, 97.34%, 97.34%, 96.28% and 95.7%, respectively. The length of airway stenosis on EOB was divided into < 10 mm, 10-30 mm, 30-50 mm and > 50 mm. There was no significant difference in the length of airway stenosis between VBN and EOB (t = 0.083, P = 0.936; t = 1.340, P = 0.199; t = 1.297, P = 0.216; t = 2.186, P = 0.081). In three patients who received stent placement, VBN was able to accurately assess the postoperative expansion. CONCLUSION: VBN is helpful for the diagnosis of TBT-induced CBS and may provide important information on the location, length, diameter and cross-sectional area of stenosis for further EOB examination and interventional therapy. VBN is recommended for patients with TBT and those with contradictions to bronchoscopy, as well as for regular follow-up of stable TBT, because it reduces the incidence of injury, avoids repeat operations and shortens treatment time.

Identification of HLA-A2-Restricted Mycobacterial Lipoprotein Z Peptides Recognized by T CellsFrom Patients With ActiveTuberculosis Infection.

Identification of HLA-restricted peptides derived from mycobacterial antigens that are endowed with high affinity and strong antigenicity is not only of interest in tuberculosis (TB) diagnostics and treatment efficacy evaluation, but might also provide potential candidates for the development of therapeutic vaccines against drug-resistant TB. Our previous work demonstrated that lipoprotein Z (LppZ) displayed high immunogenicity and antigenicity in active TB patients. In the present study, ten HLA-A2-restricted LppZ peptides (LppZp1-10) were predicted by bioinformatics, among which LppZp7 and LppZp10 were verified to possess high affinity to HLA-A2 molecules using T2 cell-based affinity binding assay. Moreover, results from ELISpot assay showed that both LppZp7 and LppZp10 peptides were able to induce more IFN-γ producing cells upon ex vivo stimulation of PBMC from HLA-A2+ active TB (ATB) patients as compared to those from healthy controls (HCs). Also, the numbers of LppZp7 and LppZp10-specific IFN-γ producing cells exhibited positive correlations with those of ESAT-6 peptide (E6p) or CFP-10 peptide (C10p) in ATB. Interestingly, stimulation with LppZp7/p10 mixture was able to induce higher intracellular expression of IFN-γ and IL-2 cytokines in CD8+ and CD4+ T cells from ATB as compared to HC, associated with lower expression of TNF-α in both CD8+ and CD4+ T cells. Taken together, HLA-A2-restricted LppZp7 and LppZp10 peptides display high immunoreactivity in HLA-matched ATB patients demonstrated by high responsiveness in both CD8+ and CD4+ T cells. With the ability to induce strong antigen-specific cellular responses, LppZp7 and LppZp10 are of potential value for the future applications in the prevention and control of TB.

Drug-induced lymphocyte stimulation test in the prediction of drug-induced hypersensitivity to antituberculosis drugs.

Antituberculosis (TB) chemotherapeutic drugs may cause a variety of adverse drug reactions (ADRs). To assess the potential of drug-induced lymphocyte stimulation test (DLST) in screening ADRs in patients treated with anti-TB drugs, we performed DLST in 272 TB patients (176 cases with ADRs and 96 controls without ADRs) treated with anti-TB drugs isoniazid (INH), rifampicin (RFP), ethambutol (EMB), and pyrazinamide (PZA). The ADRs were diagnosed by drug provocation test based on clinical and laboratory examinations. The sensitivities of DLST in the diagnosis of INH-, RFP-, EMB-, or PZA-induced ADRs were 57.8%, 37.1%, 42.4%, and 23.1%, respectively, with the corresponding specificities being 93.4%, 94.0%, 97.5%, and 98.8%. DLST has high specificity and limited sensitivity in the diagnosis of anti-TB drug-induced ADRs. In combination with clinical observation and drug use history, DLST could have a predictive validity of ADRs, especially when a positive result is obtained.