Treatment outcomes and risk factors for an unsuccessful outcome among patients with highly drug-resistant tuberculosis in Ukraine.

OBJECTIVES: To describe demographics, clinical features, and treatment outcomes of patients with highly drug-resistant tuberculosis (TB) in Ukraine, and to evaluate risk factors for an unsuccessful outcome. METHODS: Data from patients with multi-, pre-extensively, or extensively drug-resistant TB were collected prospectively from TB dispensaries in 15 out of 24 Ukrainian oblasts (regions) from 2020 to 2021. Treatment outcomes were evaluated using WHO definitions. Risk factors for an unsuccessful outcome were identified using a multivariable logistic regression model. RESULTS: Among 1748 patients, the overall proportion of successful outcomes was 58% (95% confidence interval [95% CI] 56-60) (n = 1015/1748), ranging from 65% (95% CI: 62-69) (n = 531/814) for multidrug-resistant TB to 54% (95% CI: 49-58) (n = 301/563) for pre-extensively drug-resistant TB and 49% (95% CI: 44-55) (n = 183/371) for extensively drug-resistant TB. Results were similar across oblasts, with few exceptions. The strongest risk factors for an unsuccessful outcome were extensively drug-resistant TB (adjusted OR [aOR] 3.23; 95% CI: 1.88-5.53), total serum protein below 62 g/L in adults and below 57 g/L for children and adolescents (aOR 2.79; 95% CI: 1.93-4.04), psychiatric illness (aOR 2.79; 95% CI: 1.46-5.33), age at TB diagnosis >65 years (aOR 2.50; 95% CI: 1.42-4.42), and alcohol misuse (aOR 2.48; 95% CI: 1.89-3.26). DISCUSSION: The overall proportion of successful outcomes among Ukrainians treated for highly drug-resistant TB was 58%, notably better compared with previous years, but still low for extensively drug-resistant TB. Risk factors for unsuccessful outcomes highlight that addressing socioeconomic factors in TB management is crucial. Efforts in maintaining TB dispensaries during and following the ongoing war are highly warranted.

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.

Effectiveness of Intravenous Isoniazid and Ethambutol Administration in Patients with Tuberculosis Meningoencephalitis and HIV Infection.

BACKGROUND: The aim of this study was to investigate the effectiveness of intravenous isoniazid (H) and ethambutol (E) administered in patients with new sputum positive drug-susceptible pulmonary tuberculosis (TB) with tuberculous meningoencephalitis (TM) and human immunodeficiency virus (HIV) co-infection in the intensive phase of treatment. METHODS: Fifty-four patients with TB/TM and HIV co-infection were enrolled for this study. Group 1 comprised of 23 patients treated with E and H intravenously, while rifampicin and pyrazinamide were prescribed orally. Group 2 consisted of 31 patients treated with the first-line anti-TB drugs orally. The concentrations of H and E in blood serum were detected using a chromatographic method. RESULTS: A significant improvement in the clinical symptoms and X-ray signs in patients treated intravenously with H and E was observed and compared to group 2. The sputum Mycobacterium tuberculosis positivity was observed during the second month of the treatment in 25.0% of patients from group 1 and 76.1% of the patients from the control group (p=0.003). In addition, nine patients (39.1%) died up to 6 months when H and E were prescribed intravenously compared with 22 (70.9%) in group 2 (p=0.023). CONCLUSION: In TB/TM with HIV, the intravenous H and E treatment was more effective than oral H and E treatment at 2 months of intensive treatment in sputum conversion as well as in clinical improvement, accompanied by significantly higher mean serum concentrations. In addition, the mortality rate was lower in intravenous H and E treatment compared to oral treatment.

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.

Changes in nitric oxide synthase and nitrite and nitrate serum levels in patients with or without multidrug-resistant tuberculosis undergoing the intensive phase of antituberculosis therapy.

OBJECTIVE/BACKGROUND: There is a paucity of published data on the effect of tuberculosis (TB) chemotherapy on nitric oxide (NO) synthesis and metabolism in newly diagnosed and relapsed patients with or without multidrug-resistant TB (MDR-TB). METHODS: The pattern of NO response in 140 patients with pulmonary TB, including 74 with MDR-TB (1st group) and 66 without MDR-TB (2nd group) has been studied and compared with the NO status of 30 healthy donors (3rd group). Patients comprised those with newly diagnosed pulmonary TB (Subgroups 1B and 2B) and recurrent or relapsed TB (Subgroups 1A and 2A). The NO status was assessed by measuring inducible NO synthase (iNOS), nitrites, and nitrates levels. This was measured prior to treatment initiation and 2months after the prescribed chemotherapy. RESULTS: Increased levels of NO indices were found in patients with TB when compared with healthy controls-1st group: iNOS, 231.6±6.65pmol/min/mgB; nitrites, 5.626±0.15µmol/L; and nitrates, 62.89±1.42µmol/L (Subgroup 1A: iNOS, 208.40±8.26pmol/min/mgB; nitrites, 5.027±0.17µmol/L; and nitrates, 59.29±1.79µmol/L and Subgroup 1B: iNOS, 260.4±8.56pmol/min/mgB; nitrites, 6.371±0.19µmol/L; and nitrates, 67.36±2.03µmol/L); 2nd group: iNOS, 286.3±5.92pmol/min/mgB; nitrites, 6.747±0.17µmol/L; and nitrates, 72.02±1.43µmol/L (Subgroup 2A: iNOS, 260.9±14.12pmol/min/mgB; nitrites, 5.686±0.20µmol/L; and nitrates, 66.26±1.89µmol/L and Subgroup 2B: iNOS, 293.7±6.13pmol/min/mgB; nitrites, 7.059±0.19µmol/L; and nitrates, 73.72±1.71µmol/L) versus healthy controls (iNOS, 81.03±2.36pmol/min/mgB; nitrites, 3.83±0.093µmol/L; and nitrates, 37.98±1.30µmol/L). After 2months of chemotherapy, a significant decrease in NO indicators was observed in the patients with TB, particularly in those without MDR-TB-1st group: iNOS, 114.9±3.2pmol/min/mgB; nitrites, 4.21±0.13µmol/L; and nitrates, 46.65±1.04µmol/L (Subgroup 1A: iNOS, 125.3±4.5pmol/min/mgB; nitrites, 4.42±0.14µmol/L; and nitrates, 49.38±1.30µmol/L and Subgroup 1B: iNOS, 102±3.53pmol/min/mgB; nitrites, 3.93±0.13µmol/L; and nitrates, 43.26±1.50µmol/L) and 2nd group: iNOS, 91.4±2.53pmol/min/mgB; nitrites, 3.67±0.09µmol/L; and nitrates, 35.65±1.06µmol/L (Subgroup 2A: iNOS, 106.7±5.2pmol/min/mgB; nitrites, 4.04±0.19µmol/L; and nitrates-40.53±1.83µmol/L and Subgroup 2B, iNOS, 86.7±2.59pmol/min/mgB; nitrites, 3.56±0.1µmol/L; and nitrates, 34.22±1.19µmol/L). The decline in NO activity was less prominent in patients with recurrent TB and MDR-TB, which suggests lower level of immunologic and reparative processes in such patients. CONCLUSION: In patients with pulmonary TB, significantly higher levels of NO activity were observed as compared with the levels in healthy individuals. In patients with recurrent TB and MDR-TB, significantly lower levels of NO indicators were observed in comparison with patients with newly diagnosed pulmonary TB. After 2months on chemotherapy, a significant decrease in iNOS activity and NO metabolites was observed in patients with pulmonary TB, but the decrease in NO indicators was manifested mostly in the newly diagnosed pulmonary TB patients and patients without MDR-TB as opposed to patients with recurrent TB and MDR-TB, which suggests lower levels of immunologic and reparative processes in such patients. Therefore, the levels of nitrites and nitrates as well as iNOS activity may serve as additional diagnostic criteria to differentiate MDR-TB from nonresistant TB in patients with relapsed and newly diagnosed TB. Easily assessed NO-related markers can also serve as predictors of treatment outcome because patients with drug-susceptible strains had lower NO output approaching levels found in controls.