Effectiveness of inhaled hypertonic saline application for sputum induction to improve Mycobacterium tuberculosis identification in patients with pulmonary tuberculosis.

BACKGROUND: This study assessed the effectiveness and diagnostic significance of hypertonic saline sputum induction for improving Mycobacterium tuberculosis (MTB) detection. METHODS: A prospective, randomized, open, two-arm, comparative study on MTB identification effectiveness when using inhaled sodium chloride hypertonic solution was performed in patients diagnosed with pulmonary tuberculosis (TB). Patients were randomly assigned into two groups: group 1 (inhalation group) included patients who inhaled a 7% sodium chloride solution upon admission to the hospital, and group 2 (control group) coughed up their sputum as usual. For both groups, specimens were tested by bacterioscopic, bacteriological, and molecular genetic methods. Diagnostic chest radiography was performed for all participants. RESULTS: In this study, 644 patients (mean age 42.2 years; 151 women, 23.4%) were randomly divided into two groups. Low-quality sputum samples were observed in 7.4% of patients from the inhalation group and 28.8% in the control group (p < 0.001). Acid-fast bacilli (AFB) smear was positive in 65.1% of patients from the inhalation group and 51.3% of controls (p = 0.002). A similar statistically significant situation was observed when culture methods (93.9% inhalation group and 81.9% control group, p < 0.001) and molecular genetic tests (92.2% inhalation group and 79.4% control group, p < 0.001) were used. Thus, active pulmonary TB was not verified microbiologically in 6.1% of patients from the inhalation group and in 18.1% of controls (p < 0.001). CONCLUSIONS: Hypertonic saline sputum induction improves the quality of collected samples. This method may be appropriate to increase the rate of MTB detection in sputum using microscopic, bacteriological, and molecular genetic methods for diagnosing TB on the day of specimen collection. Hypertonic saline sputum induction is suitable for middle- and low-income countries with limited resources and causes no severe adverse effects in TB patients.

Treatment effectiveness and outcome in patients with a relapse and newly diagnosed multidrug-resistant pulmonary tuberculosis.

Aim To investigate the treatment effectiveness and outcome in patients with pulmonary tuberculosis relapse and newly diagnosed multidrug resistant pulmonary tuberculosis (MDR-TB). Methods A total of 240 pulmonary MDR-TB patients, including 114 ones with tuberculosis relapse and 126 cases of newly diagnosed pulmonary tuberculosis, were examined. Effectiveness of the basic antimycobacterial therapy course was evaluated based on the time to normalization of tuberculosis clinical manifestation, sputum culture and acid-fast bacilli stain conversion, cavity closure, disappearance of infiltrative and focal changes in the pulmonary tissue. Treatment outcomes were evaluated as cured, treatment completed, treatment failed, died and lost to follow-up according to the World Health Organization guidelines. Results When assessing the treatment effectiveness in patients with MDR-TB, a worse clinical and chest radiograph dynamics was observed in tuberculosis relapse against the background of high parameters of treatment failure (18.4 %) and low cured (34.2 %) compared with newly diagnosed pulmonary tuberculosis (7.1% and 58.7 %, respectively) (p=0.008 and p<0.001, respectively). Conclusion Standard treatment effectiveness in patients with newly diagnosed MDR-TB manifested by faster improvement and stabilization of health, earlier sputum culture and smear conversion, higher frequency of cavity closure and achievement of certain clinical and radiographic improvement against the background of fewer cases of treatment failure and a higher number of cured patients compared with MDR-TB relapse.

Novel isoniazid derivative as promising antituberculosis agent.

Background: A major focus of tuberculosis drug discovery is aimed at the development of novel antibiotics with activity against drug-resistant strains of Mycobacterium tuberculosis. Results: We have synthesized ten isoniazid derivatives and investigated for antibacterial activity toward M. tuberculosis H37Rv and isoniazid-resistant strain SRI 1369. It was revealed that only one compound, isonicotinic acid (1-methyl-1H-pyrrol-2-ylmethylene)-hydrazide (1), is active toward isoniazid-resistant strain with minimum inhibitory concentration value of 0.14 µM. This compound is not cytotoxic toward human liver cells (HepG2; IC50 >100 µM), demonstrates good permeability in Caco-2 cells. Accordingly to the results of plasma protein binding assay, unbound fraction of compound 1, which potentially exhibits pharmacologic effects, is 57.9%. Conclusion: Therefore, isonicotinic acid (1-methyl-1H-pyrrol-2-ylmethylene)-hydrazide is a promising compound for further preclinical studies.

Benzaldehyde thiosemicarbazone derivatives against replicating and nonreplicating Mycobacterium tuberculosis.

In this article, we report a series of benzaldehyde thiosemicarbazone derivatives possessing high activity toward actively replicating Mycobacterium tuberculosis strain with minimum inhibitory concentration (MIC) values in the range from 0.14 to 2.2 µM. Among them, two compounds-2-(4-phenethoxybenzylidene)hydrazine-1-carbothioamide (13) and 2-(3-isopropoxybenzylidene)hydrazine-1-carbothioamide (20) also demonstrate submicromolar antimycobacterial activity against M. tuberculosis under hypoxia with MIC values of 0.68 and 0.74 µM, respectively. The activity of compounds 13 and 20 toward five investigated isoniazid-, rifampicin-, and fluoroquinolone-resistant M. tuberculosis isolates is similar to commercially available antituberculosis drugs. The compounds 13 and 20 possess good ADME properties and have low cytotoxicity toward human liver cells (HepG2). Therefore, 2-(4-phenethoxybenzylidene)hydrazine-1-carbothioamide (13) and 2-(3-isopropoxybenzylidene)hydrazine-1-carbothioamide (20) are valuable candidates for further preclinical studies.

Efficacy and safety of intravenous chemotherapy during intensive treatment phase in patients with newly diagnosed pulmonary tuberculosis.

The purpose of our study was to examine the efficacy and safety of intravenous chemotherapy during intensive treatment phase for patients with newly diagnosed pulmonary tuberculosis (pulmonary TB). MATERIALS AND METHODS: The study involved 92 patients with newly diagnosed pulmonary TB aged between 20 years and 68 years. All patient with newly diagnosed pulmonary TB and chemosensitive tuberculosis were enrolled in this study. The patients were allocated to two groups. The first (control) group of 46 patients received standard chemotherapy orally. The second (main) group consisted of 46 patients who were prescribed isoniazid, rifampin, ethambutol by i / v transfusion, and pyrazinamide orally as a part of the standard treatment. RESULTS: Symptoms of intoxication in pulmonary TB patients from the second group were eliminated faster (1.42±0.35) of a month than the same symptoms of the group 1-(2.96±0.24) of the months,p < 0.05; disappearance of respiratory symptoms of the group 2-(1.34±0.29) of a month, group 1-(2.65±0.43) of the months,p < 0.05. In the group 2, the bacterioexcretion time was reducing faster and up to 2 months it reached 37(80.43±5.85%) while the time for the control group reached 25(54.35±7.34%),p < 0.05. Destruction healing and healing frequency of destruction cavities up to 4 months amounted to 38(82.61±5.59%) (in control group - 28(60.87±7.20%),p < 0.05) and residual changes were reducing (small changes or absence of even minimal radiological changes were found in 29(63.04 ±7.12%) patients versus 18(39.13±7.20%) of the group 1, and large residual changes accordingly in 17(36.96±7.12%) and 28(60.87±7.20%),p < 0.05. CONCLUSIONS: Thanks to i/v chemotherapy clinical manifestations of the in patients with pulmonary TB were eliminated faster, severe side effects to anti-TB drugs were not noticed, time of bacterial excretion and healing destruction reduced, healing frequency of destruction cavities increased and the residual changes decreased.