Efficacy and Safety of Bufei Jiedu Granules in Treating Multidrug-Resistant Pulmonary Tuberculosis: A Multi-center, Double-Blinded and Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy and safety of Bufei Jiedu (BFJD) ranules as adjuvant therapy for patients with multidrug-resistant pulmonary tuberculosis (MDR-PTB). METHODS: A large-scale, multi-center, double-blinded, and randomized controlled trial was conducted in 18 sentinel hospitals in China from December 2012 to December 2016. A total of 312 MDR-PTB patients were randomly assigned to BFJD Granules or placebo groups (1:1) using a stratified randomization method, which both received the long-course chemotherapy regimen for 18 months (6 Am-Lfx-P-Z-Pto, 12 Lfx-P-Z-Pto). Meanwhile, patients in both groups also received BFJD Granules or placebo twice a day for a total of 18 months, respectively. The primary outcome was cure rate. The secondary outcomes included time to sputum-culture conversion, changes in lung cavities and quality of life (QoL) of patients. Adverse reactions were monitored during and after the trial. RESULTS: A total of 216 cases completed the trial, 111 in the BFJD Granules group and 105 in the placebo group. BFJD Granules, as an adjuvant treatment, increased the cure rate by 13.6% at the end of treatment, compared with the placebo (58.4% vs. 44.8%, P=0.02), and accelerated the median time to sputum-culture conversion (5 months vs. 11 months). The cavity closure rate of the BFJD Granules group (50.6%, 43/85) was higher than that of the placebo group (32.1%, 26/81; P=0.02) in patients who completed the treatment. At the end of the intensive treatment, according to the 36-item Short Form, the BFJD Granules significantly improved physical functioning, general health, and vitality of patients relative to the placebo group (all P<0.01). Overall, the death rates in the two groups were not significantly different; 5.1% (8/156) in the BFJD Granules group and 2.6% (4/156) in the placebo group. CONCLUSIONS: Supplementing BFJD Granules with the long-course chemotherapy regimen significantly increased the cure rate and cavity closure rates, and rapidly improved QoL of patients with MDR-PTB (Registration No. ChiCTR-TRC-12002850).

Efficacy of Moxifloxacin against Mycobacterium abscessus in Zebrafish Model in vivo.

OBJECTIVE: Moxifloxacin (MFX) shows good in vitro activity against Mycobacterium abscessus and can be a possible antibiotic therapy to treat M. abscessus infection; however, other studies have shown a lower or no activity. We aimed to evaluate MFX activity against M. abscessus using zebrafish (ZF) model in vivo. METHODS: A formulation of M. abscessus labeled with CM-Dil was micro-injected into ZF. Survival curves were determined by recording dead ZF every day. ZF were lysed, and colony-forming units (CFUs) were enumerated. Bacteria dissemination and fluorescence intensity in ZF were analyzed. Inhibition rates of MFX and azithromycin (AZM, positive control) were determined and compared. RESULTS: Significantly increased survival rate was observed with different AZM concentrations. However, increasing MFX concentration did not result in a significant decrease in ZF survival curve. No significant differences in bacterial burdens by CFU loads were observed between AZM and MFX groups at various concentrations. Bacterial fluorescence intensity in ZF was significantly correlated with AZM concentration. However, with increasing MFX concentration, fluorescence intensity decreased slightly when observed under fluorescence microscope. Transferring rates at various concentrations were comparable between the MFX and AZM groups, with no significant difference. CONCLUSION: MFX showed limited efficacy against M . abscessus in vivo using ZF model. Its activity in vivo needs to be confirmed.

Improvement cues of lesion absorption using the adjuvant therapy of traditional Chinese medicine Qinbudan tablet for retreatment pulmonary tuberculosis with standard anti-tuberculosis regimen.

BACKGROUND: China is the second highest pulmonary tuberculosis (PTB) burden country worldwide. However, retreatment of PTB has often developed resistance to at least one of the four first-line anti-TB drugs. The cure rate (approximately 50.0-73.3%) and management of retreatment of PTB in China needs to be improved. Qinbudan decoction has been widely used to treat PTB in China since the 1960s. Previously clinical studies have shown that the Qinbudan tablet (QBDT) promoted sputum-culture negative conversion and lesion absorption. However, powerful evidence from a randomized controlled clinical trial is lacking. Therefore, the aim of this study was to compare the efficacy and safety of QBDT as an adjunct therapy for retreatment of PTB. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial in China. People diagnosed with PTB were enrolled who received previous anti-TB treatment from April 2011 to March 2013. The treatment group received an anti-TB regimen and QBDT, and the control group was administered an anti-TB regimen plus placebo. Anti-TB treatment options included isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin for 2 months (2HRZES), followed by isoniazid, rifampicin, ethambutol for 6 months (6HRE), daily for 8 months. Primary outcome was sputum-culture conversion using the MGIT 960 liquid medium method. Secondary outcomes included lung lesion absorption and cavity closure. Adverse events and reactions were observed after treatment. A structured questionnaire was used to record demographic information and clinical symptoms of all subjects. Data analysis was performed by SPSS 25.0 software in the full analysis set (FAS) population. RESULTS: One hundred eighty-one cases of retreatment PTB were randomly divided into two groups: the placebo group (88 cases) and the QBDT group (93 cases). A total of 166 patients completed the trial and 15 patients lost to follow-up. The culture conversion rate of the QBDT group and placebo group did not show a noticeable improvement by using the covariate sites to correct the rate differences (79.6% vs 69.3%; rate difference = 0.10, 95% confidence interval (CI): - 0.02-0.23; F = 2.48, P = 0.12) after treatment. A significant 16.6% increase in lesion absorption was observed in the QBDT group when compared with the placebo group (67.7% vs 51.1%; rate difference = 0.17, 95% CI: 0.02-0.31; χ2 = 5.56, P = 0.02). The intervention and placebo group did not differ in terms of cavity closure (25.5% vs 21.1%; rate difference = 0.04, 95% CI: - 0.21-0.12; χ2 = 0.27, P = 0.60). Two patients who received chemotherapy and combined QBDT reported pruritus/nausea and vomiting. CONCLUSIONS: No significant improvement in culture conversion was observed for retreatment PTB with traditional Chinese medicine plus standard anti-TB regimen. However, QBDT as an adjunct therapy significantly promoted lesion absorption, thereby reducing lung injury due to Mycobacterium tuberculosis infection. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov, NCT02313610.

[Mycobacterium abscessus group lung disease: case reports and review of the literature].

OBJECTIVE: To analyze the clinical manifestations and efficacy of a combination antibiotic therapy including cefoxitin for Mycobacterium abscessus (M.abscessus) group lung disease. METHODS: We retrospectively analyzed the clinical manifestations of 16 patients with M.abscessus group lung disease, and the responses of 5 cases treated with whole-course clarithromycin and moxifloxacin, initially intensified with intravenous amikacin and cefoxitin therapy for the first 12 weeks. RESULTS: Radiological study showed that 14 patients with M.abscessus group pulmonary disease were classified as nodular bronchiectasis form, and 1 patient as upper lobe cavity form and 1 patient was unclassifiable. The radiological characteristics of M.abscessus group pulmonary disease included multiple micronodules (14/16), bronchiectasis (14/16), tree in bud sign (13/16), cavity (5/16), consolidation (5/16), nodules (5/16), and collapse of lung (3/16). Five cases were treated with a combination antibiotic therapy including cefoxitin. After 3 months treatment for the initial phase, 2 of them got improvement in symptoms, CT manifestations and sputum conversion. Two of them improved in symptoms and CT manifestations, but not in sputum conversion. One case showed no improvement in the initial phase, and continuation therapy also failed to improve symptoms, CT abnormalities or sputum conversion. CONCLUSIONS: Nodular bronchiectasis is the main manifestation of M.abscessus group lung disease. The main imaging characteristics included multiple micronodules, bronchiectasis and tree in bud sign. A therapeutic regimen including cefoxitin may be moderately effective in treating M.abscessus group lung disease.

[Clinical analysis of protionamide and para-aminosalicylic acid induced hepatotoxicity in 129 cases].

OBJECTIVE: To investigate drug-induced liver injury (DILI) in tuberculosis (TB) patients treated with protionamide (Pto) and (or) para-aminosalicylic acid (PAS), and therefore to provide data for using second-line anti-tuberculosis drugs and risk prediction of liver damage. METHODS: A retrospective analysis was performed for TB patients treated with regimens containing Pto and (or) PAS in Beijing Chest Hospital during Jan. 2008 to Jan. 2013. Cases with DILI were identified, and associated factors including patients' age and gender, time of onset, severity, clinical manifestations and prognosis of DILI were analyzed. The 2 groups were compared with χ(2) test. P < 0.05 was considered to be significant. RESULTS: A total of 1714 cases were admitted, among whom 226 experienced liver damage during treatment, of which 97 cases were excluded because of underlying alcoholic liver disease, viral hepatitis B and C. Finally, 129 cases were diagnosed as having DILI, resulting in an overall incidence of 7.5% (129/1714), being 9.2% (59/641) in females, and 6.5% (70/1073) in males (χ(2) = 4.143, P < 0.05). DILI in most patients occurred between 1 week to 2 months, with 30.2% (39/129) within 2-4 weeks. 47.3% (61/129) of the patients showed no obvious clinical symptoms of hepatotoxicity. Among different regimens, combination of Pto, PAS and PZA resulted in the highest rate of DILI (20.7%, 19/92), while the rate was 9.8% (8/82) for the combination of Pto and PZA, P < 0.05. CONCLUSIONS: DILI caused by Pto and PAS should be taken into account, especially in female patients and for multi-drug combination therapy. Liver function should be monitored even in patients without related clinical manifestations for early identification and treatment, and therefore avoiding severe liver damage.

[Comparison of clinical manifestations between Mycobacterium avium-intracellulare complex and Mycobacterium abscessus pulmonary diseases].

OBJECTIVE: To compare the clinical manifestations of nontuberculous mycobacterial (NTM) pulmonary diseases caused by Mycobacterium avium-intracellulare complex (MAC) and Mycobacterium abscessus. METHODS: The clinical manifestations of 18 patients with MAC and 9 patients with Mycobacterium abscessus pulmonary diseases diagnosed from 2010 to 2011 were reviewed. RESULTS: There were no significant differences in the gender, age, body mass index, predisposed diseases, symptoms and positive sputum acid-fast bacillus between MAC and Mycobacterium abscessus groups. Upper lobe cavities were more frequently observed in the MAC group (13/18), whereas nodular bronchiectatic changes were more frequent in the Mycobacterium abscessus group (3/9). Compared with MAC pulmonary diseases, several imaging characteristics were more common in the Mycobacterium abscessus group, including bilateral micro nodules (Mycobacterium abscessus group 8/9 vs MAC group 7/18), tree-in-bud sign (Mycobacterium abscessus group 7/9 vs MAC group 6/18) and multiple bronchiectasis (Mycobacterium abscessus group 8/9 vs MAC group 5/18). CONCLUSIONS: There was considerable overlap in clinical characteristics of MAC and Mycobacterium abscessus pulmonary diseases. However, bilateral micro nodules, tree-in-bud sign and multiple bronchiectasis were more frequently seen in Mycobacterium abscessus than in MAC pulmonary diseases, while upper lobe cavities were more frequently seen in MAC than in Mycobacterium abscessus pulmonary diseases.

[Analysis of the antimycobacterial activities of rifabutin and the relationship between drug-resistance and rpoB mutations of Mycobacterium tuberculosis].

OBJECTIVE: To compare the antimycobacterial activities of rifampicin (RFP) and rifabutin (RBT), and to evaluate the correlation between RBT resistance and genetic alterations in the rpoB gene. METHODS: The microplate-based alamar blue assay (MABA) method was performed to detect the antimycobacterial activities of RFP and RBT in 168 strains of Mycobacterium tuberculosis (M. tuberculosis). Meanwhile, we also analyzed the 81 bp core region of rpoB gene by DNA sequencing. The rate of gene mutations was analyzed by chi-square test. RESULTS: RBT was sensitive for all of the 66 RFP-sensitive strains with no mutations in 81 bp core region of rpoB gene. But of the 102 RFP-resistant strains, 76 strains were also resistant to RBT. Cross resistance between RFP and RBT was 74.5% (76/102). Alterations at codons 516, 526, 531 in the rpoB gene correlated with resistance to both RFP and RBT. While point mutations at codons 511 and 533 possibly influenced the susceptibility to RFP but not to RBT. The mutation rate (92.1%, 70/76) of rpoB gene of RBT-resistant strains was significantly higher than that (23.9%, 22/92) of RBT-sensitive strains (χ(2) = 78.12, P < 0.05). CONCLUSIONS: RBT was more active against M. tuberculosis as compared to RFP. The RFP-resistant strains with MIC ≤ 4 mg/L were still susceptible to RBT. Our results suggest that analysis of genetic alterations in the rpoB gene is useful for predicting RFP-resistance, and may have implications for evaluating RBT-resistance.

[Study on the efficacy and safety of short-term treatment including fluoroquinolones anti-tuberculosis drugs for rifampicin resistant pulmonary tuberculosis].

OBJECTIVE: To evaluate the efficacy and safety of short-term treatment including fluoroquinolones anti-tuberculosis drugs for rifampicin resistant pulmonary tuberculosis (TB) in those areas carrying out the 'TB control project'. METHODS: TB cases involved in this study were from TB drug resistance surveillance in Heilongjiang province, Zhejiang province and Shenzhen city from 2004 to 2006. TB cases with rifampicin resistant were randomly divided into the treatment group (including fluoroquinolones anti-tuberculosis drugs group) and the control group (re-treatment regimen group). The treatment group was treated with 3RFT AM Ofx Pto PAS-INH/5RFT Ofx Pto PAS-INH while the control group was treated with 3 H3R3Z3E3S3/5 H3R3E3. Efficacy of short-term treatment was analyzed by per-protocol analysis (PP analysis) and intention-to-treat analysis (ITT analysis) while drug adverse reactions was also observed. RESULTS: (1) 154 patients with rifampicin resistant pulmonary tuberculosis were recruited among them, 25 (16.2%) were only resistant to rifampicin, 114 (74.0%) to MDR-TB and 15 (9.8%) to others (resistant R+S, resistant R+E and resistant R+E+S). 114 TB cases completed the full course of treatment,with 71 in the treatment group and 43 in the control group. (2) Sputum negative conversion rate of the treatment group and the control group were 78.9% and 65.1% (chi2CMH = 4.558, P = 0.011) respectively, by per-protocol analysis. Sputum negative conversion rate of the treatment group and the control group were 65.9% and 40.6% (chi2CMH = 0.272, P = 0.001) respectively, by intention-to-treat analysis. The sputum negative conversion rate of the treatment group was higher than in the control group when treating rifampicin resistant pulmonary tuberculosis and MDR-TB patients. (3) Three patients withdrew in each of the two groups because of adverse effects to the drugs. Rates of adverse reaction to drugs appeared to be 23.9% (17/71) and 18.6% (8/43) in the treatment and in the control groups, with no statistically significant difference between the two groups. CONCLUSION: The efficacy of treatment including fluoroquinolones anti-tuberculosis drugs group seemed better than the re-treatment regimen group in treating patients with rifampicin resistant pulmonary tuberculosis and those MDR-TB patients.

[Tissue distribution and deposition of clofazimine in mice following oral administration of isoniazid].

OBJECTIVE: Tissue distribution and deposition of clofazimine in mice were investigated following administration of clofazimine with or without isoniazid. METHODS: Kunming mice were given clofazimine suspension orally at a daily dose of 13 mg/kg body weight either alone or with isoniazid (25 mg/kg body weight) for a single dose or for 1 or 2 months. Tissues (liver, lung, spleen, small intestine, kidneys, fat) and pooled plasma were analyzed for clofazimine in all the treated groups by high-performance liquid chromatography. RESULTS: The levels of clofazimine in fat tissues, kidneys, spleens, livers, lungs and small intestine were the highest in mice receiving the drug continuously for 2 months, and were also higher in mice receiving the drug for 1 month as compared to mice receiving a single dose administration. After continuous administration for 1 or 2 months, the clofazimine level was the highest in fat tissues as compared to other tissue samples. The clofazimine level in the lungs was higher in mice receiving concomitant administration of isoniazid [1 month (57 +/- 11) microg/g, 2 months (73 +/- 49) microg/g]than in those receiving clofazimine alone [1 month (32 +/- 8) microg/g, 2 months (47 +/- 12) microg/g], but the clofazimine level in the fat tissue was significantly lower in mice receiving concomitant isoniazid [1 month (289 +/- 30) microg/g, 2 months (275 +/- 119) microg/g], than in those receiving clofazimine alone [1 month (433 +/- 53) microg/g, 2 months (527 +/- 158) microg/g]. CONCLUSION: Concomitant administration of isoniazid reduced clofazimine levels significantly in fat tissues while resulted in an increase of its level in lung tissues.

[Activities of clofazimine against Mycobacterium tuberculosis in vitro and in vivo].

OBJECTIVE: To evaluate the in vitro and in vivo antituberculous activities of clofazimine. METHODS: The MIC of clofazimine against H(37)Rv and 30 MDR-TB clinical strains were determined by microplate Alamar blue assays. Female BALB/c mice were infected with M. tuberculosis H(37)Rv (10(5) CFU/mouse). The infected mice were divided into the following groups: a control group, treated with saline 5 times per week; isoniazid treatment group, 25 mg/kg, 5 times per week; clofazimine 20 mg/kg group, 5 times per week; clofazimine 10 mg/kg group, 5 times per week, and another clofazimine 20 mg/kg group, but the drug was given twice weekly. The drugs and saline were administered by gavage, and the treatment lasted for 30 days after infection. Five mice from each group were assessed for bacterial CFU count and organ weights of the lung and spleen on day 30. RESULTS: The MIC of clofazimine against M. tuberculosis H(37)Rv was 0.12 - 0.24 microg/ml, and the MIC against 30 MDR-TB clinical strains ranged from 0.12 to 1.92 microg/ml. In the murine model, clofazimine treatments decreased the CFU by 1.39 - 2.92 lg as compared to that of the control group on day 30. CONCLUSIONS: Clofazimine has in vitro and in vivo activities against M. tuberculosis.

[The effect of interventional therapy in multimodality treatment on multi-drug resistant pulmonary tuberculosis].

OBJECTIVE: To evaluate the effect of interventional therapy with antituberculous drug instillation to the lesions in the treatment of multi-drug resistant pulmonary tuberculosis (MDR-PTB) on conventional therapy. METHODS: Sixty-one cases of MDR TB were included from January 2001 to October 2002 in five hospitals. Pasiniazide, rifapentine levofloxacin, ethambutol, ethionamide, amikacin and clarithromycin were used as the basic chemotherapy regimen. In addition, M. vaccac and interventional therapy were used, and chemotherapy was continued for a total of 18 months. RESULTS: The sputum negative conversion rate (including sputum smear and culture) was 50.8% (31/61) after 3 months of interventional therapy. The rate increased to 83.6% (51/61) after 18 months of therapy. Chest X-ray showed that, the foci were markedly absorbed in 50.8% (31/61), and the effective rate was 93.4% (57/61) after 3 months of therapy. The foci were markedly absorbed in 78.7% (48/61) after 18 months of treatment. The effective rate was 96.7%. The rate of cavity closure was 21.3% (13/61) after 3 months of interventional therapy and it increased to 49.2% (30/61) after 18 months of treatment. The rate of symptom disappearance was 73.2%-94.4%, including fever, hemoptysis and dyspnea. CONCLUSION: For the treatment of MDR-TB, interventional therapy is effective in improving sputum negative conversion, lesion absorption and cavity closure.

[Effects of two treatment regimens for drug-resistant tuberculosis in tuberculosis control project areas: a comparative study].

OBJECTIVES: To search for an ideal therapeutic regimen for multidrug resistant tuberculosis conforming to the situation of China. METHODS: One hundred and fifty-four patients with rifampin-resistant tuberculosis, 114 multi-drug resistant (MDR-TB) and 40 resistant to other drugs, in Heilongjiang, Zhejiang, and Shenzhen, 107 males and 47 females, aged 39 (19-77), were randomly divided into 2 groups: 85 patients in the group of drug-resistant regimen, 3RFT AM Ofx Pto PAS-INH/5RFT Ofx Pto PAS-INH regimen, including rifapentine (RFT), amikacin (Am), ofloxacin (Ofx), protionamide (Pto), para-aminosalicylic acid-isoniazid (PAS-INH) for 3 months and then RFT, Ofx, Pto, and PAS-INH for 5 months, and 69 in the retreatment regimen group undergoing 3 H3R3Z3E3S3/5 H3R3E3, including isoniazid (H), rifampin (R), pyrazinamide (Z), ethambutol (E), and streptomycin (S) for 3 months and then H, R, and E for 5 months. Sputum smear was checked and the sputum smear conversion rate was calculated as an effective treatment indicator 3, 6, and 8 months later. RESULTS: One hundred and fourteen of the 154 patients were treated for a good 8 months. The sputum smear conversion rate 8 months after treatment of the drug-resistant regimen group was 65.9% (56/85), significantly higher than that of the retreatment regimen group [40.6% (28/69), chi2 = 9.834, P = 0.002]. Eighty-five of the 114 MDR-TB patients had been treated for a good 8 months with a sputum smear conversion rate of 61.8% (42/68), significantly higher than that of the retreatment regimen group [39.1% (18/46), chi2 = 5.638, P = 0.018]. Sputum smear conversion at the end of the 8th month was related to age, course of disease, therapeutic regimen, and the type of drug-resistance (all P < 0.05). The side-effect rate of the drug-resistant regimen group was 23.9% (17/71), higher than that of the retreatment regimen group [18.6% (8/43)], but not significantly (chi2 = 0.446, P = 0.504). CONCLUSION: The drug-resistant regimen recommended above is more effective than the retreatment regimen and should be considered in the areas where the WHO guideline fails to be followed or drug sensitivity test (DST) cannot be conducted and adjusted according to the results of DST and treatment.

[The clinical significance of serum tuberculosis specific antigen antibody in the diagnosis of tuberculosis].

OBJECTIVE: To evaluate the significance of serum tuberculosis specific antigen (TB-SA) antibody detection in the diagnosis of tuberculosis. METHODS: TB-SA antibody in the serum samples from 829 cases of tuberculosis, 278 patients with non-tuberculosis lung diseases and 125 healthy volunteers were detected using enzyme-linked immunosorbent assay (ELISA). Tuberculosis was confirmed by clinical, bacteriology, X-ray examination and pathology studies. RESULTS: The sensitivity of TB-SA antibody in diagnosis of bacteriologically positive and negative pulmonary tuberculosis and extrapulmonary tuberculosis was 75.1% (272/362), 68.9% (226/328) and 71.2% (99/139), respectively; the combined sensitivity was 72.0% (597/829), and the specificity 82.1% (331/403). The relationship between the OD(405) of TB-SA antibody and PPD positivity showed no linear relationship, suggesting that BCG vaccination did not affect the value of serum TB-SA antibody. CONCLUSION: The results suggest that measurement of serum TB-SA is a relatively sensitive and specific method for the diagnosis and differential diagnosis of tuberculosis.

[A controlled clinical trial of long course chemotherapy regimens containing rifabutin in the treatment of multi-drug resistant pulmonary tuberculosis].

OBJECTIVE: To evaluate the curative effect and safety of a long course regimen containing Chinese-made rifabutin as compared to the regimen containing rifapentine in the treatment of multi-drug resistant pulmonary tuberculosis. METHOD: During 18 month treatment, 130 patients with multi-drug resistant pulmonary tuberculosis were divided into a treatment group (rifabutin, pasiniazide, levofloxacin, ethambutol, ethionamide, amikacin for 3 months, rifabutin, pasiniazide, levofloxacin, ethambutol, ethionamide for 6 months, rifabutin, pasiniazide, levofloxacin, ethambutol for 9 months), and a control group (rifapentine, pasiniazide, levofloxacin, ethambutol, ethionamide, amikacin for 3 months, rifabutin, pasiniazide, levofloxacin, ethambutol, ethionamide for 6 months, rifabutin, pasiniazide, levofloxacin, ethambutol for 9 months) with proportion 1:1 random, and parallel compared method. RESULTS: After intensive phase, the sputum negative conversion rates (smear negative, culture negative) of the treatment group and the control group were 41.54% (27/65) and 35.94% (23/65), chi(2) = 2.42, P > 0.05, respectively. The remarkable effective rates in chest X-ray of the two groups were all 10.77% (7/65), chi(2) = 0.01, P > 0.05, and the effective rates were 67.69% (44/65) and 56.92% (37/65), chi(2) = 1.44, P > 0.05, respectively. At the end of the treatment, the sputum negative conversion rate (smear negative, culture negative) of the treatment group was 75.0% (48/65), and of the control group was 65.08% (41/65), chi(2) = 1.88, P > 0.05. The remarkable effective rates in chest X-ray of the two groups were 46.15% (30/65) and 44.62% (29/65), chi(2) = 0.02, P > 0.05, and the effective rates were 76.92% (50/65) and 73.85% (48/65), chi(2) = 0.19, P > 0.05, respectively. The cavity closure rates were 23.64% (13/55) and 33.33% (17/51), chi(2) = 0.00, P > 0.05, respectively. CONCLUSION: Regimens containing rifabutin or rifapentine. are very effective in sputum negative conversion rate, lesion absorption and cavity closing for the treatment of multi-drug resistant pulmonary tuberculosis, with good safety and tolerance.

[Susceptibility test to rifampin by using quantitative analysis of Mycobacterium tuberculosis mRNA].

OBJECTIVE: To evaluate the significance of quantitative analysis of Mycobacterium tuberculosis mRNA in the test of susceptibility of Mycobacterium tuberculosis strains to rifampin. METHODS: The susceptibility to rifampin of fifty-three clinical isolated strains was test by the percentage of Mycobacterium tuberculosis 85B mRNA copies before and after the use of rifampin, and 1% and 10% were used as the standards for drug resistance, which was compared with the absolute concentration method. Among them, 29 were rifampin resistant strains and 24 rifampin sensitive strains. RESULTS: When the concentration of rifampin was 1 micro g/ml, and 1% and 10% were used as the standards, the accuracy of quantitative analysis of Mycobacterium tuberculosis mRNA with the absolute concentration method was 70% and 81% respectively, and the sensitivity of quantitative analysis of Mycobacterium tuberculosis mRNA was 100% and 100% respectively, while the specificity of quantitative analysis of Mycobacterium tuberculosis mRNA was 33% and 58%. When the concentration of rifampin was 2 micro g/ml, the accuracy of quantitative analysis of mRNA with the absolute concentration method was 85% and 93% respectively, and the sensitivity was 100% and 97% respectively, while the specificity was 67% and 88% respectively. When the concentration of rifampin was 4 micro g/ml, the accuracy was 93% and 93%, and the sensitivity was 93% and 93%, while the specificity was 92% and 92%. CONCLUSIONS: Quantitative analysis of Mycobacterium tuberculosis mRNA was a rapid, sensitive method in rifampin resistance screening. We suggest that the critical concentration of rifampin be 2 micro g/ml, and the critical proportion of mRNA copy be 10%.

[A controlled clinical study on the efficacy of recombinant human interleukin-2 in the treatment of pulmonary tuberculosis].

OBJECTIVE: To study and evaluate the efficacy and safety of recombinant human interleukin-2 (IL-2) in the treatment of pulmonary tuberculosis. METHODS: Two hundred and nine cases with re-treated Mycobacterium tuberculosis-positive pulmonary tuberculosis were randomly divided into a trial group (106 cases, treated with 3PaZ (TH)L(2)VE(AK) + IL-2/4PaL(2)V) and a control group (103 cases, treated with 3PaZ(TH)L(2)VE(AK)/4PaL(2)V). The efficacy of 203 cases was available for evaluation when the course was completed (trial group 103 cases, control group 100 cases). RESULTS: The sputum smear-negative conversion rates at the 1st and the 2nd month of therapy were 33.3% and 69.4% in the trial group, and 7.2% and 44.9% in the control group (P < 0.01). At the completion of the therapy, the X-ray resolution rates were 64.1% and 36.0% respectively for the trial and the control groups, the difference being significant (P < 0.001). There were significant differences in CD(4) T cells, the ratio of CD(4)/CD(8) and NK cells between the two groups (P < 0.01). The level of soluble interleukin-2 receptor (sIL-2R) was significantly different between the two groups after treatment for 3 months (P < 0.05). IL-2 associated side effects were rare and mild. CONCLUSION: As an effective and relatively safe biological agent, IL-2 can be added to the standard chemotherapy for pulmonary tuberculosis.