The Safety and Efficacy of Prolonged Use of Bedaquiline for the Treatment of Patients with Pulmonary Multi-Drug Resistant/Rifampin-Resistant Tuberculosis: A Prospective, Cohort Study in China.

Objective: To evaluate the safety, tolerability, and efficacy of prolonged bedaquiline (Bdq) treatment in patients with multi-drug/rifampin-resistant tuberculosis (MDR/RR-TB). Methods: This prospective cohort study was performed from August 2018 to August 2021. Patients diagnosed with MDR/RR-TB who met the inclusion criteria were prospectively included. Patients were treated with individual regimens of 18-20 months containing Bdq for six months or a prolonged course of nine or 12 months according to treatment demands, and the efficacy and safety with a different course of Bdq-containing regimens were compared and evaluated. Results: A total of 159 MDR/RR-TB patients were included in the study, including 96 cases with six months of Bdq, 50 cases with nine months of Bdq, and 13 patients with 12 months of Bdq. The treatment success rates were 89.6%, 90%, and 84.6% in Bdq at six months, nine months, and 12 months, respectively, which were not statistically different (P = 0.85). The main adverse events (AEs) were anemia, thrombocytopenia, and liver dysfunction in all patients, with no significant difference among the three groups. Patients who had fewer drugs chosen, disseminated lesions or lesions that were slowly absorbed, and severe cavities were the common reasons for prolonged use of Bdq. Conclusion: Prolonged course use of Bdq from six months to 12 months clinically proved to be safe and efficient, and patients with severe or disseminated lesions had the chance to prolong the use of Bdq for more than six months to achieve optimal treatment outcomes.

Rapid Identification of Nontuberculous Mycobacterium Species from Respiratory Specimens Using Nucleotide MALDI-TOF MS.

We performed a prospective study to evaluate the diagnostic accuracy of nucleotide matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) in identifying nontuberculous mycobacterium (NTM) from clinical respiratory samples. A total of 175 eligible patients were prospectively enrolled, including 108 patients diagnosed with NTM pulmonary disease (NTM-PD) and 67 control patients with other diseases. All specimens were subjected to acid-fast staining, liquid culture combined with MPT64 antigen detection, and a nucleotide MALDI-TOF MS assay. NTM cultures were also subjected to the MeltPro Myco assay for species identification. Altogether, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of nucleotide MALDI-TOF MS were 77.8% (95% CI: 68.6-85.0%), 92.5% (82.8-97.2%), 94.4% (86.8-97.9%), and 72.1% (61.2-81.0%), respectively; these results were not statistically different from the results of culture + MPT64 antigen testing (75.0% [65.6-82.6%], 95.5% [86.6-98.8%], 96.4% [89.2-99.1%], and 70.3% [59.7-79.2%], respectively). In the identification of NTM species, of the 84 nucleotide MALDI-TOF MS positive samples, 77 samples (91.7%) were identified at the species level. Using culture + MeltPro Myco assay as the reference standard, nucleotide MALDI-TOF MS correctly identified 77.8% (63/81) of NTM species. Our results demonstrated that the nucleotide MALDI-TOF MS assay was a rapid single-step method that provided the reliable detection of NTM and identification of NTM species. This new method had the same sensitivity and specificity as the culture + MPT64 antigen method, but was much more rapid.

Acidovorax PSJ13, a novel, efficient polyacrylamide-degrading bacterium by cleaving the main carbon chain skeleton without the production of acrylamide.

Given the environmental challenge caused by the wide use of polyacrylamide (PAM), an environmental-friendly treatment method is required. This study demonstrates the role of Acidovorax sp. strain PSJ13 isolated from dewatered sludge in efficiently degrading PAM. To be specific, the strain PSJ13 can degrade 51.67% of PAM in 96 h (2.39 mg/(L h)) at 35 °C, pH 7.5 and 5% inoculation amount. Besides, scanning electron microscope, X-ray photoelectron spectroscopy, liquid chromatography-mass spectrometry and high-performance liquid chromatography were employed to analyze samples, and the nitrogen present in the degradation products was investigated. The results showed that the degradation of PAM by PSJ13 started from the side chain and then mainly the -C-C- main chain, which produced no acrylamide monomers. As the first study to report the role of Acidovorax in efficiently degrading PAM, this work may provide a solution for industries that require PAM management.

Efficacy and safety of an innovative short-course regimen containing clofazimine for treatment of drug-susceptible tuberculosis: a clinical trial.

In preclinical studies, a new antituberculosis drug regimen markedly reduced the time required to achieve relapse-free cure. This study aimed to preliminarily evaluate the efficacy and safety of this four-month regimen, consisting of clofazimine, prothionamide, pyrazinamide and ethambutol, with a standard six-month regimen in patients with drug-susceptible tuberculosis. An open-label pilot randomized clinical trial was conducted among the patients with newly diagnosed bacteriologically-confirmed pulmonary tuberculosis. The primary efficacy end-point was sputum culture negative conversion. Totally, 93 patients were included in the modified intention-to-treat population. The rates of sputum culture conversion were 65.2% (30/46) and 87.2% (41/47) for short-course and standard regimen group, respectively. There was no difference on two-month culture conversion rates, time to culture conversion, nor early bactericidal activity (P > 0.05). However, patients on short-course regimen were observed with lower rates of radiological improvement or recovery and sustained treatment success, which was mainly attributed to higher percent of patients permanently changed assigned regimen (32.1% vs. 12.3%, P = 0.012). The main cause for it was drug-induced hepatitis (16/17). Although lowering the dose of prothionamide was approved, the alternative option of changing assigned regimen was chosen in this study. While in per-protocol population, sputum culture conversion rates were 87.0% (20/23) and 94.4% (34/36) for the respective groups. Overall, the short-course regimen appeared to have inferior efficacy and higher incidence of hepatitis but desired efficacy in per-protocol population. It provides the first proof-of-concept in humans of the capacity of the short-course approach to identify drug regimens that can shorten the treatment time for tuberculosis.

Prediction of drug resistance profile of multidrug-resistant Mycobacterium tuberculosis (MDR-MTB) isolates from newly diagnosed case by whole genome sequencing (WGS): a study from a high tuberculosis burden country.

OBJECTIVES: Our aim was to assess the ability of the Whole-genome sequencing (WGS) in predicting drug resistance profile of multidrug-resistant mycobacterium tuberculosis (MDR-MTB) from newly diagnosed cases in China. METHODS: We validated the Phenotypic drug Sensitivity Test (pDST) for 12 anti-tuberculosis drugs using the Bactec MGIT 960 system. We described the characteristics of the isolates enrolled and compared the pDST results with resistance profiles predicted by WGS. RESULTS: The pDST showed that of the 43 isolates enrolled, 25.6% were sensitive to rifabutin (RFB); 97.7%、97.7%、93.0% and 93.0% were sensitive to cycloserine (Cs), amikacin/kanamycin (Ak/Km), para-aminosalicylic acid (Pas) and ethionamide Eto), respectively; 18.6% were resistant to fluoroquinolones (FQs) or second-line injections. Genotype DST determined by WGS of Ak/Km、Eto and RFP reached high consistency to 97.7% compared with pDST, followed by moxifloxacin (Mfx) 95.3%, levofloxaci (Lfx) and Pas 93%, streptomycin (Sm) 90.3%. The genotype DST of RFB and EMB showed low consistency with the pDST of 67.2 and 79.1%. WGS also detected 27.9% isolates of pyrazinamide(PZA)-related drug-resistant mutation. No mutations associated with linezolid (Lzd), bedaquiline (Bdq) and clofazimine (Cfz) were detectd. CONCLUSIONS: WGS has the potential to infer resistance profiles without time-consuming phenotypic methods, which could be provide a basis to formulate reasonable treatment in high TB burden areas.

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.

Kitchen waste hydrolysate enhances sewage treatment efficiency with different biological process compared with glucose.

Insufficient carbon source is the primary factor that limits biological nitrogen and phosphorus removal during sewage treatment. This study investigates the feasibility and biological process of kitchen waste hydrolysate (KWH) replacing glucose to improve pollutant removal efficiency. It was found that using KWH as carbon source achieved better removal effect than glucose during sewage treatment. And more than 96% of total nitrogen (TN), total phosphorus (TP), and the chemical oxygen demand were removed after 48 h of acclimation. Nitrogen and phosphorus introduced by adding KHW had no negative effect on the effluent quality. Compared with glucose, KWH decreased the diversity of bacteria and significantly promoted the accumulation of acid-producing bacteria (Propionibacterium) and denitrifying bacteria (Rhodobacteraceae). Moreover, KWH significantly improved the relative abundance of the amo A, nap A, and nos Z genes. This result further indicated that KWH was beneficial for denitrification and was a favorable external carbon source.

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.

[Co-fermentation of kitchen waste and excess sludge for organic acid production: a review].

Resource utilization is an effective way to cope with the rapid increase of kitchen waste and excess sludge, and volatile fatty acids produced by anaerobic fermentation is an important way of recycling organic waste. However, the single substrate limits the efficient production of volatile fatty acids. In recent years, volatile fatty acids produced by anaerobic co-fermentation using different substrates has been widely studied and applied. In this paper, we analyze the characteristics of fermentation to produce acid using kitchen waste and excess sludge alone or mixture. Influences of environmental factors and microbial community structure on the type and yield of volatile fatty acids in the anaerobic fermentation system are discussed in detail. Moreover, we propose future research directions, to provide a reference for recycling kitchen waste and excess sludge.

Exogenous Fe2+ alleviated the toxicity of CuO nanoparticles on Pseudomonas tolaasii Y-11 under different nitrogen sources.

Extensive use of CuO nanoparticles (CuO-NPs ) inevitably leads to their accumulation in wastewater and toxicity to microorganisms that effectively treat nitrogen pollution. Due to the effects of different mediums, the sources of CuO-NPs-induced toxicity to microorganisms and methods to mitigating the toxicity are still unclear. In this study, CuO-NPs were found to impact the nitrate reduction of Pseudomonas tolaasii Y-11 mainly through the action of NPs themselves while inhibiting the ammonium transformation of strain Y-11 through releasing Cu2+. As the content of CuO-NPs increased from 0 to 20 mg/L, the removal efficiency of NO3 - and NH4 + decreased from 42.29% and 29.83% to 2.05% and 2.33%, respectively. Exogenous Fe2+ significantly promoted the aggregation of CuO-NPs, reduced the possibility of contact with bacteria, and slowed down the damage of CuO-NPs to strain Y-11. When 0.01 mol/L Fe2+ was added to 0, 1, 5, 10 and 20 mg/L CuO-NPs treatment, the removal efficiencies of NO3 - were 69.77%, 88.93%, 80.51%, 36.17% and 2.47%, respectively; the removal efficiencies of NH4 + were 55.95%, 96.71%, 38.11%, 20.71% and 7.43%, respectively. This study provides a method for mitigating the toxicity of CuO-NPs on functional microorganisms.

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.

Application of endobronchial ultrasonography using a guide sheath and electromagnetic navigation bronchoscopy in the diagnosis of atypical bacteriologically-negative pulmonary tuberculosis.

BACKGROUND: In the absence of a positive sputum bacteriological result, pathological and bacteriological examinations of lung lesion biopsies are important methods to confirm bacteriological-negative tuberculosis. Endobronchial ultrasonography with guide sheath (EBUS-GS) and electromagnetic navigation bronchoscopy (ENB) are two new endobronchial diagnostic techniques, the combination of which has greatly facilitated the diagnosis of peripheral pulmonary lesions and is an especially useful, minimally invasive, effective diagnostic method for bacteriologically-negative tuberculosis cases. METHODS: A total of 78 patients were included in this study with suspected pulmonary tuberculosis based on clinical manifestations, laboratory tests, and imaging studies. The patients underwent a high-resolution chest CT scan before bronchoscopy, A method was selected (EBUS-GS alone, or EBUS-GS + ENB) based on the lesion site and the level and angle of the bronchus involved. After the lesion was found, a puncture needle, biopsy forceps, and brushing forceps were used to collect a tissue sample. RESULTS: Forty-four patients were diagnosed with tuberculosis; 1, nontuberculous Mycobacteria (NTM) lung disease; 15, lung cancer; 15, pulmonary infection; 1, allergic bronchopulmonary aspergillosis (ABPA); and 2, pneumoconiosis. A total of 25 patients of TB (56.8%) were successfully diagnosed with EBUS-GS plus ENB. Among the patients with confirmed diagnosis, 9 were diagnosed with pathological examination; 4, genetic analysis; 11, positive smear; and 14, positive culture. CONCLUSIONS: The introduction of EBUS and ENB in China has provided a new direction for the diagnosis of atypical bacteriological-negative tuberculosis, as the techniques are less invasive and less expensive than thoracoscopy.

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.

A Large Cohort Study on the Clinical Value of Simultaneous Amplification and Testing for the Diagnosis of Pulmonary Tuberculosis.

The AmpSure simultaneous amplification and testing method for the detection of Mycobacterium tuberculosis (SAT-TB assay) was designed to diagnose rapidly pulmonary tuberculosis (PTB). Unfortunately, the diagnostic advantage is unclear from previous small sample studies. In the current inquiry, a large sample size was used to reevaluate the clinical accuracy of the SAT-TB assay using sputum specimens. A total of 3608 patients with suspected PTB were enrolled prospectively for diagnosis from sputum specimens using the SAT-TB assay. Of these, 2457 had a definite diagnosis of PTB confirmed by positive microbiology, or pathologic findings of TB in the lung, or clinical diagnosis of active PTB following anti-TB treatment with a favorable response. The sensitivity, specificity and accuracy of the SAT-TB assay were 75.8%, 100%, and 80.2%, respectively. The sensitivity of SAT-TB was significantly higher than that of the sputum smear (23.8%) (X(2) = 1327.437; P = 0.000), wheresa significantly lower than that of sputum culture (89.0%) (X(2) = 148.197; P = 0.000). The specificity of SAT-TB was significantly higher than that of sputum smears (96.3%) (X(2) = 20.375, P = 0.000), whereas no significant difference was found compared with sputum cultures (99.6%) (X(2) = 2.004, P = 0.500). Positive results in the SAT-TB assay using sputum specimens indicates that active PTB is present and anti-TB treatment is strongly recommended regardless of smear and culture test results. Simultaneous amplification and testing method for detection of Mycobacterium tuberculosis is an accurate, cheap, and rapid method for PTB diagnosis.

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.

Diagnosis of tuberculosis pleurisy with adenosine deaminase (ADA): a systematic review and meta-analysis.

This systematic review and meta-analysis was performed to determine accuracy and usefulness of adenosine deaminase (ADA) in diagnosis of tuberculosis pleurisy. Medline, Google scholar and Web of Science databases were searched to identify related studies until 2014. Two reviewers independently assessed quality of studies included according to standard Quality Assessment of Diagnosis Accuracy Studies (QUADAS) criteria. The sensitivity, specificity, diagnostic odds ratio and other parameters of ADA in diagnosis of tuberculosis pleurisy were analyzed with Meta-DiSC1.4 software, and pooled using the random effects model. Twelve studies including 865 tuberculosis pleurisy patients and 1379 non-tuberculosis pleurisy subjects were identified from 110 studies for this meta-analysis. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnosis odds ratio (DOR) of ADA in the diagnosis of tuberculosis pleurisy were 45.25 (95% CI 27.63-74.08), 0.86 (95% CI 0.84-0.88), 0.88 (95% CI 0.86-0.90), 6.32 (95% CI 4.83-8.26) and 0.15 (95% 0.11-0.22), respectively. The area under the summary receiver operating characteristic curve (SROC) was 0.9340. Our results demonstrate that the sensitivity and specificity of ADA are high in the diagnosis of tuberculosis pleurisy especially when ADA≥50 (U/L). Thus, ADA is a relatively sensitive and specific marker for tuberculosis pleurisy diagnosis. However, it is cautious to apply these results due to the heterogeneity in study design of these studies. Further studies are required to confirm the optimal cut-off value of ADA.

[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.

[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.