Antituberculosis Therapy In Patients Research Articles

Prevalence of vitamin D deficiency and the effect of vitamin D3 supplementation on response to anti-tuberculosis therapy in patients with extrapulmonary tuberculosis

BackgroundWe aimed to assess serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations in extrapulmonary tuberculosis (EPTB) patients and to evaluate the effect of vitamin D3 supplementation on their treatment course.MethodsSerum 25(OH)D3concentrations were measured in 47 newly diagnosed EPTB patients and 42 controls. Vitamin D-deficient EPTB patients were randomly assigned to receive 50,000 IU of vitamin D3 (cholecalciferol) orally once a week for 6 weeks (total 300,000 IU), followed by maintenance doses of 1000 IU a day besides anti-TB drugs or the first line anti-TB treatment only. Follow up serum 25(OH)D3 concentrations were measured after 3 months of starting vitamin D3 supplementation. Both groups were evaluated for clinical, laboratory, and radiological outcomes after treatment.ResultsSerum 25(OH)D3 concentrations were significantly lower among TB cases (17.1 ± 5.5 nmol/L) compared to healthy controls (51.8 ± 27.3 nmol/L), and vitamin D deficiency was observed in all EPTB patients (n = 47). Patients in VD3 supplementation group had significantly higher weight gain and serum albumin level at 2 months and end of treatment, higher hemoglobin concentration at the end of treatment, significantly lower CRP and ESR at 2 months and at the end of treatment. In cases with TB pleurisy, a significant higher rate of full resolution of pleural fluid after 6 months of anti-TB treatment and shorter treatment duration were noted compared to the other group.ConclusionsVitamin D deficiency is prevalent in EPTB patients, in whom, vitamin D supplementation is a useful adjunctive therapy to anti-TB drugs and improves treatment course.

The role of melatonin in the formation of tuberculotic inflammation, forecast regarding the influence on the effectiveness of treatment in the conditions of the COVID­-19 pandemic (literature review)

Objective — to study the role of melatonin in the formation of tuberculous inflammation and the prospects of its influence on increasing the effectiveness of treatment in the conditions of the COVID-19 pandemic, by conducting an analysis of information from available sources of literature on the selected topic.
 Materials and methods. The research was carried out for the period from December 2021 to September 2022. Access to various full-text and abstract databases was used as the main source of research.
 Results and discussion. A large number of studies carried out so far prove the connection between the influence of melatonin and tuberculosis inflammation, since tuberculosis infection can be associated with seasonal changes in the immune system, and these processes are correlated and accompanied by fluctuations in the level of melatonin. Th1-type specific cellular immunity is responsible for protective immunity in tuberculosis, while the Th2-type response underlies the progressive nature of inflammation. T-lymphocytes and macrophages have been shown to have receptors for melatonin, and they are also target cells for its immunomodulatory function. Melatonin has been shown to regulate gene expression of several immu­nomodulatory cytokines, including TNF-α, transforming growth factor-β, and macrophage stem cell factor.Thus, the conducted narrowly differentiated analysis based on available literature sources allows us to predict that melatonin can stimulate the Th1 immune response in TB and may have an immunoprotective effect on the Th1-type subtype of the delayed-type immune response during the acute phase of mycobac­terial inflammation.
 Conclusions. The analysis of the tuberculosis situation in Bukovina indicates a tendency towards an increase in the incidence rate in 2021 compared to 2020. The same dynamics are maintained in the first half of 2022. At the same time, no significant changes in the mortality rate were found. The above analysis of the main indicators of epidemiology indicates the sufficient importance of the problem of tuberculosis for the coming years, and therefore, the search for methods of increasing the effectiveness of the treatment of this pathology, especially under the conditions of multiple and extended drug resistance, is an important task of modern phthisiology. The analysis of the available data base accumulated to date on the role of melatonin in the pathophysiology of the formation of an inflammatory reaction in the lungs and its influence on the clinical course and effectiveness of anti-tuberculosis therapy is a promising scientific direction of research. The appointment of melatonin along with traditional methods of treatment of tuberculosis can have a positive effect on increasing the effectiveness of anti-tuberculosis therapy in patients with the pulmonary form of tuberculosis.

Problems of anti-tuberculosis therapy in patients on hemodialysis

The objective: to determine possibility of prescribing and safety of various anti-tuberculosis drugs and their combinations as part of a therapeutic or preventive course of anti-tuberculosis therapy (ATBT) in patients with end-stage chronic kidney disease (CKD) receiving hemodialysis replacement therapy in the settings with high prevalence of drug resistant strains of Mycobacterium tuberculosis.Subjects and Methods. 42 patients receiving hemodialysis replacement therapy were followed-up by Central Tuberculosis Research Institute: of them, 31 (73.8%) had active tuberculosis and 11 (26.2%) had residual post-tuberculous changes in the respiratory organs. During the follow-up, the nature and severity of adverse reactions to anti-tuberculosis drugs were assessed.Results. In the patients with end-stage CKD suffering from respiratory tuberculosis, drug resistant strains prevailed – 68.2%. Some of adverse events developed when taking anti-tuberculosis drugs were as follows: deterioration of uremia in 20.5% of cases, cardiovascular complications – in 17.9%, and neurotoxic reactions – in 15.4%. Progression of uremia occurred more often in the followed-up patients taking anti-tuberculosis drugs versus hepatotoxic reactions (p = 0.02). When treating tuberculosis patients with end-stage CKD, isoniazid was discontinued due to adverse events in 12.8% of cases and pyrazinamide in 12.8% of cases, other drugs were discontinued less frequently. Compilation of individual regimens of anti-tuberculosis drugs with the consideration of drug susceptibility testing results, contraindications, and concomitant diseases made it possible to provide an adequate anti-tuberculosis therapy for patients with end-stage CKD with tuberculosis infection in 92.9% of cases for a period of more than 6 months.

ЕФЕКТИВНІСТЬ ЛІКУВАННЯ ТУБЕРКУЛЬОЗУ ЛЕГЕНЬ В ЗАЛЕЖНОСТІ ВІД ГЕНОТИПУ CYP3A4

Among the factors that can influence the course and effectiveness of the treatment of pulmonary tuberculosis (TB) the genetic characteristics of patients play an important role. It is established that cytochrome (CYP) 3A4/5 is involved in metabolism of more than 30 % of xenobiotics. Consequently, the activity of this enzyme is greatly influenced by responsible genes, such as CYP3А4. The aim of the study was the investigation of prognostic value of CYP3A4 polymorphism on the course and effectiveness of anti-tuberculosis therapy in patients with pulmonary TB. Materials and methods. Using PCR method, a detection of polymorphism of CYP3A4*1B, CYP3A4*1G genes, which determine the activity of CYP3A4 enzyme, was performed in 105 patients with newly diagnosed pulmonary TB. We have revied medical records at the beginning and at the end of inpatient treatment and considered the form, extent, regression rate of TB-lesions, and the rate of smear-positive cases. A statistical analysis of study data, expressed in absolute or relative values, was done using Pearson’s chi-squared test. Results: It was established that out of 105 enrolled TB-patients 84 individuals (80,0%) carried the genotype of “rapid metabolizers” (RA), the rest – 15 (14,3%) and 6 (5,7%) individuals were “intermediate metabolizers” (IM) and “slow metabolizers” (SM) correspondently. According to CYP3A4 genotype in patients with SM and IM the bi-lateral lesions as well as the processes of pulmonary destruction and dissemination, as well as smearpositiveness occurred more frequently than in RM. For example, in IM group the dissemination was observed almost two times more frequently than in RM (Р<0,05; χ2=4,44). At the end of the in-patient treatment in SM remaining TB-infiltrates observed more often, while the resolution of consolidation registered more rarely (66,7%) than in IM and RM (81,0% and 80,0%, correspondently). Also, in SM the TB infiltrates remained more often than in RM (33,3% versus 8,3%, Р<0,05; χ2=4,44). At the same time in IM the smear-positive status remained more often than in other groups. Conclusion. Genotypes of “intermediate metabolizers” and “slow metabolizers” according to CYP3A4 genes were associated with unfavorable pulmonary disease both at initiation and at the end of in-patient phase of the TB treatment. Identification of CYP3A4 genotype in pulmonary TB patients allows allocation of the groups of high risk of unfavorable TB course. Key words: pulmonary tuberculo

Efficacy assessment of modern regimens of preventive antituberculosis therapy in patients basically treated with TNF-α inhibitors

Background. Biological agents, especially anti-tumor necrosis factor blocking agents, frequently are used to treat autoimmune inflammatory rheumatic diseases. Due to their negative impact on immune system and high risk of reactivation of latent tuberculosis infection all the patients must be well examined before initiation of an anti-tumor necrosis factor therapy (ATNFT).
 Purposes and tasks. An estimation of efficiency of preventive anti-tuberculosis therapy (PATT) with patients undergoing ATNFT.
 Methods and materials. In the research took part 128 patients, suffering from different inflammatory rheumatic diseases, whom was planned anti-tumor necrosis factor therapy. In 62 cases were found the indications for prescription PATT for 4 weeks before initiation of biological therapy and from 8 to 20 weeks after.
 Results. An active tuberculosis has been developed in 8 cases, the process was similar to tuberculosis and human immunodeficiency virus. The factors of risk were the prescription adalimumab and infliximab, impaired glucose tolerance, diabetes type 2 and drunkenness abuse.
 Conclusion. The existing preventive anti-tuberculosis therapy is not able to preclude the development of tuberculosis in all cases and needs to be optimized.

Clinical Characteristics and Treatment Outcomes of Definitive Versus Standard Anti-Tuberculosis Therapy in Patients with Tuberculous Lymphadenitis.

Although it is necessary to culture Mycobacterium tuberculosis from tuberculous lymphadenitis (TBL) patients for definitive therapy, based on the drug-sensitivity test (DST), substantial cases remain culture-negative. Limited data are available regarding the treatment outcomes after standard anti-tuberculosis therapy in culture-negative TBL. The aim of this study was to compare the recurrence rates between definitive anti-tuberculosis therapy, based on DST and standard anti-tuberculosis therapy in culture-negative TBL. A multicenter retrospective cohort study was performed from 2011 to 2015 in South Korea. The study population was divided into two groups according to treatment type. A total of 234 patients with TBL were analyzed, who were treated with definitive (84 patients) and standard anti-tuberculosis (150 patients) therapy, respectively. During a 28.0 (24.0–43.0) month follow-up period, nine cases (3.8%) had recurrence of TB after treatment completion. The recurrence rate was not significantly different between the two groups (2/84, 2.4% in definitive anti-tuberculosis therapy group versus 7/150, 4.7% in standard anti-tuberculosis therapy group, p = 0.526). The recurrence in all nine cases was diagnosed as clinical recurrence rather than microbiological recurrence. Therefore, culture-negative TBL can be treated with standard anti-TB medication, although DST is not available but clinically stable after initiation of treatment.

Evaluation of metformin in combination with rifampicin containing antituberculosis therapy in patients with new, smear-positive pulmonary tuberculosis (METRIF): study protocol for a randomised clinical trial

IntroductionShorter duration of treatment for the management of drug-susceptible pulmonary tuberculosis (TB) would be a significant improvement in the care of patients suffering from the disease. Besides newer drugs and...

Medication errors with antituberculosis therapy in an inpatient, academic setting: forgotten but not gone.

Tuberculosis, an infectious disease caused by the bacteria Mycobacterium tuberculosis, has significant public health implications. Despite the decreasing prevalence of tuberculosis cases and the availability of well-established treatment guidelines, errors with antituberculosis medications remain a concern as clinician experience with the infection has waned and the goal of eradicating tuberculosis has remained unfulfilled. Whereas inappropriate use of other anti-infective classes has been extensively studied, the evaluation of medication errors associated with antituberculosis therapy has been limited to a small number of studies conducted more than two decades ago. This study evaluated the prevalence of inpatient medication errors with antituberculosis therapy in patients with suspected or confirmed tuberculosis disease. All admitted patients treated with at least one antituberculosis medication between July 2010 and June 2013 were evaluated for inclusion in the retrospective study. Multidrug antituberculosis regimens were reviewed for medication errors, which were categorized as dosing errors, drug interactions, omission of therapy and inappropriate continuation of therapy in the presence of drug toxicity. Appropriate management was determined in accordance with the national guidelines for the treatment of tuberculosis, as well as guidelines on the use of antiretroviral agents for patients with both human immunodeficiency virus (HIV) infection and tuberculosis disease. The impact of infectious diseases and pulmonary consultation on the prevalence of medication errors was also examined. More than half of all study patients (44/72, 61%) experienced at least one medication error associated with antituberculosis therapy. Dosing errors were the most common type of medication error identified and were predominantly related to weight-based dosing. Seven dosing errors were related to drug interactions between rifamycins and antiretroviral therapy in HIV-infected patients. Medication error rates were similar between patients receiving consultation from infectious diseases and/or pulmonary specialties and those without consultation. The large majority of antituberculosis medication errors (56/66 errors, 85%) remained uncorrected during the patient's hospital admission. Medication errors associated with antituberculosis therapy remain a common occurrence in the current clinical practice setting. Greater vigilance when prescribing medications for tuberculosis disease is needed.

Optimal Duration of Daily Antituberculosis Therapy before Switching to DOTS Intermittent Therapy to Reduce Mortality in HIV Infected Patients: A Duration-Response Analysis Using Restricted Cubic Splines.

Compared with thrice-weekly intermittent antituberculosis therapy (ATT), the use of daily ATT during the intensive phase has shown improved survival in HIV infected patients with tuberculosis. However, the optimal duration of daily ATT before initiating intermittent ATT is not well known. In this study, we analysed the mortality of HIV-related tuberculosis according to the duration of daily ATT before switching to thrice-weekly ATT in patients who completed at least two months of treatment in an HIV cohort study. Statistical analysis was performed using Cox proportional hazard models. To relax the linearity assumption in regression models and to allow for a flexible interpretation of the relationship between duration of daily ATT and mortality, continuous variables were modelled using restricted cubic splines. The study included 520 HIV infected patients with tuberculosis and 8,724.3 person-months of follow-up. The multivariable analysis showed that the mortality risk was inversely correlated with the duration of daily ATT before switching to intermittent therapy during the first 30 days of ATT but, after approximately 30 days of treatment, differences were not statistically significant. The results of this study suggest that daily ATT should be given for at least 30 days before switching to intermittent ATT in HIV infected patients with tuberculosis.

Genetic polymorphisms in metabolic enzymes and susceptibility to anti-tuberculosis drug-induced hepatic injury.

We examined the relationships between N-transacetylase 2 (NAT2), cytochrome P450 (CYP) 2E1 enzyme, glutathione S-transferase M1, T1 (GSTM1/GSTT1) gene polymorphisms, and anti-tuberculosis drug-induced hepatic injury (ADIH). A one-to-one matched case-control study was carried out using clinical data. NAT2, CYP2E1, GSTM1, and GSTT1 polymorphisms were identified in 173 pairs of research subjects. Statistical analysis was performed to determine risk factors of ADIH. The results showed that low body mass index and alcohol consumption were risk factors of ADIH, with odds ratios of 6.852 and 3.203, respectively. The frequencies of NAT2 slow acetylator, CYP2E1 -1259G>C, -1019C>T wild-type, and the GSTM1 null genotype were higher in the case group than in the control group, with odds ratios of 2.260, 2.696, 4.714, and 2.440, respectively. GSTT1 was not found to be related to ADIH. Interactive analysis showed that NAT2 slow acetylator and the GSTM1 null genotype were mutually synergistic, while an antagonistic relationship was observed between the CYP2E1 wild-type genotype and the other 3 genetic types. The risks of hepatic injury were higher after anti-tuberculosis therapy in patients carrying the NAT2 slow acetylator, CYP2E1 -1259G>C, -1019C>T wild-type, and GSTM1 null genotype.

Role of Quantiferon TB gold assays in monitoring the efficacy of antituberculosis therapy

RationaleThe impact of antituberculous treatment on (IFN)-γ response to mycobacterial tuberculosis antigens have been widely investigated but the results have been controversial. Aim of workTo evaluate the role of Quantiferon TB gold assays as one of the interferon-gamma release assays (IGRAs) for monitoring the efficacy of antituberculosis therapy in patients with active disease. Subjects and methodsThirty patients with active pulmonary TB were enrolled in this cross-sectional study where they were subjected to history taking, clinical examination, chest X-ray, direct smear examination of sputum samples for AFB using Ziehl–Neelson stain performed on three visits; up on enrollment, 2 and 6months later. Lowenstein Jensen medium cultures of sputum samples were done for isolation of Mycobacterium tuberculosis on first visit. All patients in the study group were subjected to QuantiFERON-TB Gold estimation on the three visits. ResultsThe mean sensitivity and specificity of QFT-G test was 85.9% and 62.6% respectively. Using χ2 analysis, there was a statistically significant association between QFT-G results and culture results upon enrollment and Acid fast bacilli positivity on second and third visits. Studying the changes in QFT-G results throughout the whole study period revealed a statistically significant decrease in number of QFT-G positive cases from 24/29 patients (82.8%) at first visit to 4/25 patients (16%) at the third visit. All 21/25 patients (84%) who became QFT-G negative at the end of the study had a complete clinical and microbiological recovery of the TB disease. ConclusionThe analysis of QFT-G assay results showed that in the majority of our TB patients there was a correlation between clinical treatment outcome and changes of IFN-γ response to M. tuberculosis-specific antigens.

Antituberculosis therapy in patients with hepatitis B viral infection

Tuberculosis (TB) and Hepatitis B virus (HBV) infections are quite common in the developing world especially South Asia. As both are so common, co-infection is not very uncommonly encountered in clinical practice. However, since anti-tuberculosis therapy (ATT) can be hepatotoxic in around 10% of patients, the occurrence of hepatotoxicity can complicate management especially in the presence of already compromised liver function due to HBV. Therefore, co-infection of TB and HBV is an important public health issue. Unfortunately the regional and National hepatology societies of South Asia have not bothered to provide any guidance in this matter. This article reviews the epidemiology and management of co-infection with Tuberculosis (TB) and Hepatitis B virus (HBV) and the hepatotoxicity due to ATT.

Serial Testing of T-SPOT.TBAssays with Anti-Tuberculosis Therapy in Patients with Extrapulmonay Tuberculosis

Serial Testing of T-SPOT.<i>TB</i>Assays with Anti-Tuberculosis Therapy in Patients with Extrapulmonay Tuberculosis

This issue of Acta

This issue of Acta

Supraclavicular lymph node tuberculosis presenting with immune thrombocytopenic purpura

Supraclavicular lymph node tuberculosis presenting with immune thrombocytopenic purpura

Leptin Levels in Various Manifestations of Pulmonary Tuberculosis

Background. Proinflammatory cytokines are prime candidates as causative agents of the metabolic changes that eventually result in tuberculosis-associated weight loss. Microbial products and cytokines such as TNF and IL-1 increase leptin expression dose dependently in adipose tissue. Leptin plays an important role in cellular immunity. Objectives. In this study, we investigated serum leptin and TNF-α levels before and after antituberculosis therapy in patients with active pulmonary tuberculosis (TB). Methods. Twenty five in patients with active pulmonary TB and 18 healthy controls participated in the study. Leptin and TNF-α levels were measured before treatment and six months after the treatment and they were compared with the control group. Body mass index (BMI) and chest X-rays before and after the treatment were also evaluated. Results. The leptin levels before and after the treatment were 1.66±1.68 ng/mL and 3.26±3.81 ng/mL, respectively. The leptin levels of tuberculous patients were significant than in healthy patients (P < .05). The BMI was 19.36 ± 2.55 kg/m2 before the treatment and 22.87 ± 3.13 kg/m2 after the treatment. The TNF-α level was 23.19±12.78 pg/mL before the treatment and 15.95±6.58 pg/mL after the treatment. There was no correlation between leptin and TNF-α levels. Leptin levels were low in patients who had sequela lesion on chest radiographs. Conclusion. Leptin levels are suppressed in tuberculous patients and low leptin levels may contribute to increased susceptibility to infection and recovery with sequela lesions.

Reconstitution of Immune Responses to Tuberculosis in Patients With HIV Infection Who Receive Antiretroviral Therapy

s: To assess the restoration of immune responses to tuberculosis, as manifested by secretion of T-helper type 1 cytokines (interferon [IFN]-gamma, interleukin [IL]-12, and IL-2) and T-helper type 2 cytokines (IL-10), in HIV-positive patients who receive antiretroviral therapy (ART). Prospective cohort study. University hospital. Ten HIV-positive patients, all naïve to ART and all about to start ART for clinical indications, and 11 healthy, HIV-negative control subjects. Assessment of T-cell proliferation and cytokine production after administration of ART to patients with HIV infection. All patients had a negative tuberculin skin test result at baseline and were anergic. Highly active ART reduced the viral load to very low levels in all patients within a short time after starting therapy. Blood samples were drawn every 2 months after starting therapy, and continued for 1 year while the patients continued to receive ART. There were trends toward increased proliferation of peripheral blood mononuclear cells (PBMCs) in response to Mycobacterium tuberculosis-specific stimuli, but these were delayed until several months of ART had elapsed. Similar trends were noted in relation to the secretion of IFN-gamma. Neither PBMC proliferation nor IFN-gamma secretion reached levels seen in healthy control subjects. No consistent trends in IL-2, IL-10, or IL-12 production were noted. ART restores immune responses to M tuberculosis, although this restoration is delayed and does not reach levels seen in healthy, HIV-negative control subjects. These results may explain in part the phenomenon of paradoxic reactions to antituberculosis therapy in patients with HIV infection. A larger study in which patients are followed up for a longer period of time will allow the magnitude and timing of this reconstitution to be more precisely defined.