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

Introduction: The purpose of our study was to examine the efficacy and safety of intravenous chemotherapy during intensivetreatment phase in patients with newly diagnosed pulmonary tuberculosis (pulmonary TB). Material and methods: The study involved 92 patients with newly diagnosed pulmonary TB aged between 20 and 68. All patientswith newly diagnosed pulmonary TB and chemosensitive tuberculosis were enrolled in the study. The patients were allocated totwo groups. The first (control) group of 46 patients received standard chemotherapy orally. The second (main) group consistedof 46 patients who were prescribed isoniazid, rifampin, ethambutol by i.v. transfusion, and pyrazinamide orally as a part of thestandard treatment. Results: Symptoms of intoxication and chest manifestations in pulmonary TB patients from the second group were eliminated fasterthan the same symptoms in the group 1. In the group 2, the mycobacterial clearance in sputum smears was reduced more rapidly, and up to2 months it was reached in 37 patients (80.43%), while in the control group in 25 patients (54.35%),p = 0.0066. Destructionhealing and inflitrative change alleviation after 4 months was reached in 38 patients (82.61%) (in control group — 28 (60.87%),(p = 0.0192). No additional negative effects were detected when compared with the control group at any time. Conclusions: Thanks to i.v. chemotherapy, clinical manifestations of the in-patients with pulmonary TB were eliminated faster,severe side effects of anti-TB drugs were not noticed, time of bacterial clearance and healing destruction reduced, healing frequencyof destructions increased and the residual changes decreased

Association of interleukins genes polymorphisms with multi-drug resistant tuberculosis in Ukrainian population

Introduction: Multi-drug resistant tuberculosis (MDR TB) is a significant health problem in some parts of the world. Three major cytokines involved in TB immunopathogenesis include IL-2, IL-4 and IL-10. The susceptibility to MDR TB may be genetically determined. The aim of the study was to assess the association of IL-2, IL-4, IL-10 gene polymorphisms with multi-drug resistant tuberculosis (MDR TB) in Ukrainian population. Material and methods: We observed 140 patients suffering from infiltrative pulmonary tuberculosis (PT) and 30 apparently healthy subjects. The patients were assigned to two groups whether they suffer or do not suffer from pulmonary MDR TB. Interleukin gene (IL) polymorphisms, particularly T330G polymorphism in the IL-2 gene, C589T polymorphism in the IL-4 gene and G1082A polymorphism in the IL-10 gene were studied through polymerase chain reaction. Circulating levels of IL-2, IL-4 and IL-10 in venous blood were estimated using ELISA. Results: Prior to treatment, patients with PT showed significant increase of IL-2 levels and decrease of IL-4 and IL-10 levels compared to apparently healthy subjects. Circulating IL-4 and IL-10 levels were significantly decreased whilst serum IL-2 level was significantly increased in patients with MDR TB compared to non-MDR TB. Low IL-4 and IL-10 secretion and considerable IL-2 alterations were shown to be significantly associated with mutations of homozygous and heterozygous genotypes affecting C589T polymorphism in the IL-4 gene, G1082A polymorphism in the IL-10 gene and T330G polymorphism in the IL-2 gene in patients with PT. Conclusions: Heterozygous genotype and mutations homozygous genotypes gene in polymorphisms determining specified cytokines’ production is a PT risk factor and may lead to disease progression into chronic phase. Heterozygous genotype of aforementioned cytokine genetic polymorphisms was significantly the most frequent in patients with MDR TB

Skuteczność i bezpieczeństwo dożylnej chemioterapii w fazie intensywnego leczenia chorych na świeżo rozpoznaną gruźlicą płuc

WSTĘP: Celem badania była ocena skuteczności i bezpieczeństwa dożylnej chemioterapii w fazie intensywnego leczenia chorych na świeżo rozpoznaną gruźlicę płuc. MATERIAŁ I METODY: Do badania włączono 92 chorych ze świeżo rozpoznaną gruźlicą płuc w wieku 20–68 lat. U wszystkich uczestników badania wykazano wrażliwość na leki przeciwgruźlicze. Chorych przydzielono do dwóch grup: grupa kontrolna złożona z 46 chorych, którzy otrzymali standardowe leczenie doustnie, oraz grupa badana złożona z 46 pacjentów, którzy byli leczeni izoaniazydem, rifampicyną i etambutolem dożylnie i pyrazynamidem podawanym doustnie. WYNIKI: Objawy intoksykacji i objawy oddechowe ustępowały szybciej w grupie leczonej dożylnie w porównaniu z grupą leczoną terapią standardową. U chorych z grupy badanej czas do uzyskania ujemnych wyników badania plwociny był krótszy. Po dwóch miesiącach leczenia negatywny wynik badania plwociny uzyskano u 37 chorych z grupy badanej (80,43%) i u 25 chorych z grupy kontrolnej (54,35%), p = 0,0066. Wygojenie zmian destrukcyjnych i naciekowych po 4 miesiącach leczenia uzyskano u 38 chorych z grupy badanej (82,61%) i u 28 chorych z grupy kontrolnej (60,87%), p = 0,0192. W żadnym z badanych punktów czasowych nie stwierdzono negatywnych efektów leczenia dożylnego w porównaniu z leczeniem standardowym. WNIOSKI: Dzięki chemioterapii dożylnej stosowanej w warunkach szpitalnych u chorych na gruźlicę płuc manifestacje kliniczne ustępowały szybciej, nie obserwowano poważnych zdarzeń niepożądanych, uzyskano skrócenie czasu do negatywizacji wyników badania plwociny i gojenia zmian, odsetek chorych, u których uzyskano ustąpienie zmian destrukcyjnych był wyższy, a odsetek chorych ze zmianami resztkowymi — niższy w grupie leczonej dożylnie.WSTĘP: Celem badania była ocena skuteczności i bezpieczeństwa dożylnej chemioterapii w fazie intensywnego leczenia chorych na świeżo rozpoznaną gruźlicę płuc. MATERIAŁ I METODY: Do badania włączono 92 chorych ze świeżo rozpoznaną gruźlicą płuc w wieku 20–68 lat. U wszystkich uczestników badania wykazano wrażliwość na leki przeciwgruźlicze. Chorych przydzielono do dwóch grup: grupa kontrolna złożona z 46 chorych, którzy otrzymali standardowe leczenie doustnie, oraz grupa badana złożona z 46 pacjentów, którzy byli leczeni izoaniazydem, rifampicyną i etambutolem dożylnie i pyrazynamidem podawanym doustnie. WYNIKI: Objawy intoksykacji i objawy oddechowe ustępowały szybciej w grupie leczonej dożylnie w porównaniu z grupą leczoną terapią standardową. U chorych z grupy badanej czas do uzyskania ujemnych wyników badania plwociny był krótszy. Po dwóch miesiącach leczenia negatywny wynik badania plwociny uzyskano u 37 chorych z grupy badanej (80,43%) i u 25 chorych z grupy kontrolnej (54,35%), p = 0,0066. Wygojenie zmian destrukcyjnych i naciekowych po 4 miesiącach leczenia uzyskano u 38 chorych z grupy badanej (82,61%) i u 28 chorych z grupy kontrolnej (60,87%), p = 0,0192. W żadnym z badanych punktów czasowych nie stwierdzono negatywnych efektów leczenia dożylnego w porównaniu z leczeniem standardowym. WNIOSKI: Dzięki chemioterapii dożylnej stosowanej w warunkach szpitalnych u chorych na gruźlicę płuc manifestacje kliniczne ustępowały szybciej, nie obserwowano poważnych zdarzeń niepożądanych, uzyskano skrócenie czasu do negatywizacji wyników badania plwociny i gojenia zmian, odsetek chorych, u których uzyskano ustąpienie zmian destrukcyjnych był wyższy, a odsetek chorych ze zmianami resztkowymi — niższy w grupie leczonej dożylnie

Interleukin-10 gene polymorphism is associated with multi-drug resistant tuberculosis during the intensive phase of standard chemotherapy

Objective/background: To study whether interleukin (IL)-10 gene polymorphism is associated with multi-drug resistant tuberculosis (MDR TB) during the intensive phase of standard chemotherapy. Methods: The study comprised 170 individuals in Kharkiv region of Ukraine including 74 patients with pulmonary MDR TB (Group 1), 66 patients without MDR TB (Group 2), and 30 healthy donors (Group 3). Serum level of IL-10 was evaluated by enzyme-linked immunosorbent assay (pg/L). Measurements of serum samples were conducted before or during the initial days after hospital admission and after 2 months on antituberculous therapy. Investigations of IL-10 gene polymorphism were performed using restriction analysis of the amplification products of specific regions of the genome. The method of investigation (for the sets real-time) — an allele-specific PCR using intercalating coloring Sybr Green. Polymorphism G1082A of gene IL-10 rs1800896 were genotyped with amplification-refractory mutation system-polymerase chain reaction. Results: In Group 1, the level of IL-10 was (38.01 ± 0.78) pg/L, compared with 43.88 ± 0.70 in Group 2, and 50.25 ± 1.26 in Group 3 (p <0.05 among the groups). In Group 1, 56 (75.68 ± 4.99%) patients had heterozygote GA genotype, 11 (14.86 ± 4.14%) patients had homozygote AA genotype, and seven (9.46 ± 3.40%) patients had homozygote GG genotype. In Group 2, 41 (62.12 ± 5.97%) patients had homozygote AA genotype, 17 (25.76 ± 5.38%) patients had heterozygote GA genotype, and eight (12.12 ± 4.02%) patients had homozygote GG genotype. In Group 3, 17 (56.67 ± 9.05%) healthy donors had homozygote GG genotype, seven (23.33 ± 7.72%) healthy donors had heterozygote GA genotype, and six (20.0 ± 7.30%) healthy donors had homozygote AA genotype (p <0.05 among the groups). Following 2 months antituberculous therapy treatment, there was a significant increase in IL-10 levels in Group 1 (44.58 ± 0.78) and Group 2 (50.59 ± 0.99; p <0.05 between the groups), when compared to the beginning of therapy and after 2 months (p <0.001). Conclusion: Compared to the healthy control group, patients with TB had significantly lower levels of IL-10. This coincided with a greater frequency of heterozygote GA genotype in Group 1 and homozygote AA genotype in Group 2. Further studies are warranted to determine whether a higher number of patients without MDR TB have a causal immunogenetic relationship with IL-10 gene polymorphisms than patients with MDR TB. Standard 2-month TB therapy results in reversal of inflammation characterized by increased IL-10 to a level comparable to that in healthy donors. IL-10 is an immune correlate of treatment outcome and can help to identify a better strategy for TB management. TB chemotherapy may have an immunomodulatory effect of an anti-inflammatory nature

Efficacy and Safety of Intravenous Chemotherapy during Intensive Treatment Phase in Patients with Newly Diagnosed Pulmonary Tuberculosis

Introduction: The purpose of our study was to examine the efficacy and safety of intravenous chemotherapy during intensive treatment phase in patients with newly diagnosed pulmonary tuberculosis (pulmonary TB). Material and methods: The study involved 92 patients with newly diagnosed pulmonary TB aged between 20 and 68. All patients with newly diagnosed pulmonary TB and chemosensitive tuberculosis were enrolled in the 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 and chest manifestations in pulmonary TB patients from the second group were eliminated faster than the same symptoms in the group 1. In the group 2, the mycobacterial clearance in sputum smears was achieved more rapidly, and up to 2 months it was reached in 37 patients (80.43%), while in the control group in 25 patients (54.35%), p = 0.0066. Destruction healing and inflitrative change alleviation after 4 months was reached in 38 patients (82.61%) (in control group—28 (60.87%), (p = 0.0192). No additional negative effects were detected when compared with the control group at any time. Conclusions: Thanks to i.v. chemotherapy, clinical manifestations of the in-patients with pulmonary TB were eliminated faster, severe side effects of anti-TB drugs were not noticed, time of bacterial clearance and healing destruction was shorter, healing frequency of destructions increased and the of 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 2 months 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 ± 0.15 μmol/L; and nitrates, 62.89 ± 1.42 μmol/L (Subgroup 1A: iNOS, 208.40 ± 8.26pmol/min/mgB; nitrites, 5.027 ± 0.17 μmol/L; and nitrates, 59.29 ± 1.79 μmol/L and Subgroup 1B: iNOS, 260.4 ± 8.56pmol/min/mgB; nitrites, 6.371 ± 0.19 μmol/L; and nitrates, 67.36 ± 2.03 μmol/L); 2nd group: iNOS, 286.3 ± 5.92pmol/min/mgB; nitrites, 6.747 ± 0.17 μmol/L; and nitrates, 72.02 ± 1.43 μmol/L (Subgroup 2A: iNOS, 260.9 ± 14.12pmol/min/mgB; nitrites, 5.686 ± 0.20 μmol/L; and nitrates, 66.26 ± 1.89 μmol/L and Subgroup 2B: iNOS, 293.7 ± 6.13pmol/min/mgB; nitrites, 7.059 ± 0.19 μmol/L; and nitrates, 73.72 ± 1.71 μmol/L) versus healthy controls (iNOS, 81.03 ± 2.36pmol/min/mgB; nitrites, 3.83 ± 0.093 μmol/L; and nitrates, 37.98 ± 1.30 μmol/L). After 2 months 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 ± 0.13 μmol/L; and nitrates, 46.65 ± 1.04 μmol/L (Subgroup 1A: iNOS, 125.3 ± 4.5pmol/min/mgB; nitrites, 4.42 ± 0.14 μmol/L; and nitrates, 49.38 ± 1.30 μmol/L and Subgroup 1B: iNOS, 102 ± 3.53pmol/min/mgB; nitrites, 3.93 ± 0.13 μmol/L; and nitrates, 43.26 ± 1.50 μmol/L) and 2nd group: iNOS, 91.4 ± 2.53pmol/min/mgB; nitrites, 3.67 ± 0.09 μmol/L; and nitrates, 35.65 ± 1.06 μmol/L (Subgroup 2A: iNOS, 106.7 ± 5.2pmol/min/mgB; nitrites, 4.04 ± 0.19 μmol/L; and nitrates-40.53 ± 1.83 μmol/L and Subgroup 2B, iNOS, 86.7 ± 2.59pmol/min/mgB; nitrites, 3.56 ± 0.1 μmol/L; and nitrates, 34.22 ± 1.19 μmol/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 2 months 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