Multiple Drug Resistant Pulmonary Tuberculosis Research Articles

Strategy of the Host-Directed Therapy for Tuberculosis: the Importance of Interferon-Gamma in the Pathogenesis and Therapy of Tuberculosis Infection

The review analyzes of 69 publications and discusses treatment of drug-resistant tuberculosis from the standpoint of the influence on immune mechanisms that limit progression of inflammation and damage to lung tissue. Interferon-gamma is the most significant cytokine in tuberculosis infection pathogenesis. The article describes genotypic and phenotypic features of interferon-gamma production in various clinical forms of pulmonary tuberculosis. It presents the data supporting the therapeutic use of recombinant interferon-gamma and results of its clinical use as adjuvant treatment additionally to chemotherapy. It demonstrates the prospects for immunotherapy with Ingaron, the drug manufactured in Russia, for patients with multiple drug-resistant pulmonary tuberculosis.

Evaluation of the effectiveness of immunomodulator BI-V in the complex therapy of children and adolescents with multiple drug-resistant pulmonary tuberculosis

BACKGROUND. The feasibility of combining antimycobacterial therapy (AMBT) with bedaquiline (Bdq) and delamanid (Dlm) with non-specific immunomodulator BI-V in children and adolescents with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/Rif-TBP) needs to be studied.
 OBJECTIVE. To find out the effectiveness of the use of complex AMBT with Bdq and Dlm with non-specific immunomodulator BI-V in children and adolescents with MDR/Rif-TBP.
 MATERIALS AND METHODS. Children and adolescents with MDR/Rif-TBP at the initial stage of AMBT were given BI-V (BIVEL, Slovenia) as a non-specific immunomodulator. The patients were divided into two groups: 1st – 20 patients who received Bdq + Dlm + levofloxacin (Lfx) + linezolid (Lzd) + clofazimine (Cfz); 2nd ‒ 28 patients whose complex treatment included BI-V (Вdq + Dlm + Lfx + Lzd + Cfz + BI-V). BI-V was prescribed from the age of 3 years at 5 ml suspension once a day during 24 days
 RESULTS. The use of BI-V against the background of individualized regimens of AMBT in children and adolescents with MDR/Rif-TBP increased the effectiveness of treatment, contributed to the disappearance of symptoms of intoxication, the resolution of infiltration foci and the healing of decay cavities in system of immune protection, which contributed to the shortening of the inpatient stage of treatment, while maintaining a high therapeutic effectiveness (“cured” ‒ 92.8 %) and the formation of small residual changes in the lungs in the majority (89.3 %).
 CONCLUSIONS. When using combined complex AMBT with Bdq, Dlm and BI-V, high therapeutic efficiency was observed in most patients (92.8 %).

Epidemic Patterns and Effectiveness of Treatment of Tuberculosis Patients with Different Drug Resistance Profiles in the Republic of Tajikistan

The objective: study of the burden and effectiveness of treatment of multiple drug resistant pulmonary tuberculosis (MDR TB) with different chemotherapy regimens in the Republic of Tajikistan.Subjects and Methods. To achieve this objective, the prevalence of drug resistant tuberculosis in 2009–2020 was studied by analyzing statistical documents on drug resistant tuberculosis, official reporting data from the Center for Medical Statistics and Republican TB Control Center by the Ministry of Health and Population Social Welfare of the Republic of Tajikistan.Results. The analysis of official statistics indicates a stable trend towards a decrease in tuberculosis incidence from 2014 to 2019, annually on average up to 1% – from 60,8 to 56,5 per 100,000 population. During the pandemic in 2019–2020, this trend increased, according to statistics the incidence made 39.7 per 100,000 population. From 2014 to 2019, tuberculosis mortality also declined steadily from 3,9 to 2,2 per 100,000 population. During the pandemic in 2019–2020, a rapid decline was noted – from 2,2 to 1,4, while in 2020–2022, it decreased from 1,4 to 1,0 per 100,000 population. From 2013 to 2020 treatment success reached 90%. The detection of drug resistant tuberculosis is close to 900 cases per year, and more than 90% of them were covered with treatment. In 2018–2020, successful treatment of drug resistant tuberculosis increased from 72,5% to 80,6% due to the introduction of new and repurposed anti-tuberculosis drugs.

Tolerability and Efficacy of Chemotherapy Containing Bedaquiline in Patients with Multiple Drug Resistant Pulmonary Tuberculosis

The objective: to evaluate safety and efficacy of bedaquiline in the treatment of patients with multiple drug resistant tuberculosis (MDR-TB).Subjects and Methods. Clinical data of 523 patients above 18 years old registered for MDR TB treatment as per regimen 4 were retrospectively analyzed. HIV-negative patients were selected and divided into two groups by the use of bedaquiline in the chemotherapy regimen.Results. In MDR TB treatment regimen containing bedaquiline, adverse reactions were observed in 95.7% of cases, the majority of them (65.2%) were of mild or moderate degree of severity. In 30.4% of such cases, bedaquiline was temporarily discontinued (mostly due to hepatotoxic reactions). No cardiotoxicity was observed as a response to bedaquiline, the median corrected QT interval made 413 ms, the maximum value was 438 ms. Adding bedaquiline to the regimen resulted in faster (in the first 3 months of treatment) and more frequent (in 94.7%) sputum conversion by culture (in the regimens with no bedaquiline, it was achieved in 63.8% of cases, p = 0.019). Treatment with regimens containing bedaquiline was effective in 82.61% of patients, while regimens with no bedaquiline were effective in 65.2% of cases, p = 0.085.

Tuberculosis Cutis Orificialis of the Oral Cavity in a HIV Positive Patient with Pulmonary Tuberculosis

Tuberculosis cutis orificialis is a rare form of cutaneous tuberculosis. The article presents 5 clinical cases of tuberculosis cutis orificialis of the oral cavity and lips that were described in publications. We present our own clinical case of successful treatment of tuberculosis cutis orificialis of the oral cavity, red border of the lips and skin of the lower lip against the background of multiple drug resistant pulmonary tuberculosis in a HIV positive patient. The case was especially difficult due to a long diagnostic search (10 months), severe immunosuppression, and drug resistance of Mycobacterium tuberculosis.

Treatment of multiple drug resistant pulmonary tuberculosis in a diabetic patient with renal allograft

The article describes a clinical case of treatment of multiple drug resistant tuberculosis in the patient with type 1 diabetes mellitus who had received a kidney transplant (from his mother) 3 years before tuberculosis was diagnosed due to diabetic nephroangiosclerosis and the development of end-stage chronic renal disease. Pulmonary tuberculosis developed while taking immunosuppressive drugs, it manifested by an infiltrate with destruction of lung tissue in the upper lobe of the left lung, infiltrative tuberculosis of the left upper lobe and segmental bronchi, bacterial excretion confirmed by microscopy and culture. The strain of tuberculosis was resistant to 5 drugs including isoniazid and rifampicin. The chemotherapy regimen included pyrazinamide, capreomycin, levofloxacin, ethionamide, cycloserine, and paraaminosalicylic acid. Glomerular filtration rate was monitored every month. The full course of anti-tuberculosis chemotherapy (556 doses) was effectively completed, glomerular filtration by that time was 77.0 ml/min. Stable sputum conversion was achieved (confirmed by sputum culture), the cavity was healed, and some areas of pneumosclerosis and single solid foci persisted.

УРОВЕНЬ МОЧЕВОЙ КИСЛОТЫ В СЫВОРОТКЕ КРОВИ У БОЛЬНЫХ ВПЕРВЫЕ ВЫЯВЛЕННЫМ ТУБЕРКУЛЕЗОМ ЛЕГКИХ С МНОЖЕСТВЕННОЙ ЛЕКАРСТВЕННОЙ УСТОЙЧИВОСТЬЮ ВОЗБУДИТЕЛЯ

The level of uric acid in blood serum was investigated in 134 new patients suffering from multiple drug resistant pulmonary tuberculosis (78 men and 56 women). The tests were performed by admission to hospital and then repeated in 1, 2, 3, 4, 5, 6, 7 and 8 months of treatment. Prior to chemotherapy the increased uric acid level was observed in 28.2% of men and 37.5% of women. During treatment with pyrazinamide uric acid level increased in this category of patients in 1 month after treatment start and further it went down; however it was above normal during the whole course of treatment. Monitoring of uric acid level in the patients with initially normal rates has shown that the primary increase of uric acid was observed during the whole course of chemotherapy (8 months) and more often during the first 2 months of treatment both in men and women.

Morphological signs of inflammatory activity in different clinical forms of drug-resistant pulmonary tuberculosis

to determine whether the activity of tuberculous inflammation is associated with different clinical forms of drug-resistant pulmonary tuberculosis. The material taken from 310 patients operated on in 2010-2015 were retrospectively examined. The patients underwent economical lung resections of limited extent (typical and atypical ones of up to 3 segments) for circumscribed forms of tuberculosis with bacterial excretion. A study group consisted of 161 (51.9%) patients with drug-resistant variants of pulmonary tuberculosis. A control group included 149 (48.1%) patients with preserved susceptibility of Mycobacterium tuberculosis to anti-TB drugs. The activity of specific changes in tuberculosis was morphologically evaluated in accordance with the classification proposed by B.M. Ariel in 1998. The highest activity of fourth-to-fifth degree specific inflammation, including that outside the primary involvement focus, was obtained in the drug-resistant pulmonary tuberculosis group due to the predominance of patients with cavernous and fibrous-cavernous tuberculosis versus those in whom the susceptibility to chemotherapeutic agents was preserved. A macroscopic study showed that the primary lesion focus had a median size in one-half of the all the examinees; but large tuberculomas, caverns, and fibrous caverns over 4 cm in diameter were multiple and detected in the drug-resistant pulmonary tuberculosis group. Multidrug resistance was observed in more than 60% of the patients with fibrous-cavernous pulmonary tuberculosis, extensive drug resistance was seen in those with cavernous tuberculosis, which is an aggravating factor. The data obtained from the morphological study of the intraoperative material can specify the clinical form of tuberculosis and evaluate the efficiency of preoperative specific therapy. The highest activity of specific inflammation was observed in patients with multiple drug-resistant pulmonary tuberculosis, the prevalence of third-to-fourth degree specific changes was seen in those with multiple and extensively drug-resistant tuberculosis. The findings suggest that the activity of tuberculous inflammation is associated with different clinical forms of drug-resistant tuberculosis and with a spectrum of drug resistance.

ОСОБЕННОСТИ ТУБЕРКУЛЕЗА У РЕБЕНКА С СОПУТСТВУЮЩЕЙ ПАТАЛОГИЕЙ

The clinical case demonstrated the intermittent course of primary tuberculosis caused by multiple drug resistant mycobacteria in 8 year old child with concurrent disorders of CNS and locomotor apparatus and living in the social institution of the closed type. The disease was detected in 2 years after the early period of primary tuberculous infection and administered preventive treatment by two anti-tuberculosis drugs. The disease was diagnosed during examination due to aspiration pneumonia with expressed clinical manifestations. Treatment of aspiration pneumonia and multiple drug resistant pulmonary tuberculosis was successfully completed.

The Functional Assessment of Patients With Pulmonary Multidrug-Resistant Tuberculosis

Tuberculosis (TB) remains an important public health problem worldwide, as its residual lesions result in functional and quality of life impairments. Few studies have investigated multiple-drug-resistant pulmonary TB (MDR-TB), and the literature regarding the functional parameters of this group of patients is scarce. Functional characterization may point to the need for post-treatment intervention measures that optimize the quality of life in patients with MDR-TB. Thus, this study sought to analyze the respiratory function, functional capacity, and quality of life of patients who were treated for MDR pulmonary TB. This study investigated a cross-sectional cohort of MDR-TB patients who underwent drug treatment for at least 18 months. Patients who had associated diseases (human immunodeficiency virus [HIV], severe heart disease, and hypertension) or disabilities that prevented them from walking were excluded. The subjects underwent the following assessments: forced spirometry, a chest radiograph, the 6-min walk test, a bioelectrical impedance analysis, maximal inspiratory and expiratory pressures, and a health-related quality of life questionnaire. Eighteen patients who met the eligibility criteria were enrolled. Spirometric evaluation showed that 78% of the subjects had abnormal patterns. The maximal respiratory pressures were significantly decreased in all subjects, despite the fact that their nutritional status was within the normal range. The distance completed in the 6-min walk test was less than expected in 72% of the subjects. All of the subjects who were evaluated had residual lesions, and 78% reported a worsening in their quality of life. In conclusion MDR-TB cured subjects exhibit impaired respiratory function and a mildly reduced functional capacity and quality of life, suggesting that a portion of these patients may require a pulmonary rehabilitation approach.

Subpopulation structure of regulatory Т-cells of blood in patients with multiple drugresistant pulmonary tuberculosis

Subpopulation structure of regulatory T-cells of peripheral blood in patients with newly diagnosed pulmonary tuberculosis depending on the clinical form of disease and sensitivity of Mycobacterium tuberculosis to anti-tuberculosis drugs have been analyzed in this work. It has been shown that in formation immune suppression at infiltrative, dissemination and fibrosis-cavity pulmonary tuberculosis the leading part play natural regulatory CD4+ CD25+ Foxр3+ -T-lymphocytes. Thus increase of their number in blood at drug-resistance and drugsusceptible patients. It has been demonstrated that in patients with fibro-cavernous and infiltrative form of the disease and drug-resistance pulmonary tuberculosis the number of CD4+ CD25- Foxр3+ -regulatory T-cells were increasing.

Intrathoracic muscle flap transposition in the treatment of fibrocavernous tuberculosis.

Conventionally, pulmonary resection with thoracoplasty is used to treat fibrocavernous complication of pulmonary tuberculosis. This operation is usually bloody, time-consuming with complicated postoperative course. To prevent massive blood loss and preserved pulmonary function, a more simplified operative procedure, cavernostomy combined intrathoracic muscle flap transposition was used and the outcome was evaluated in this study. Retrospective review. Between December 1989 and June 1996, a total of ten patients with fibrocavernous pulmonary tuberculosis were managed using cavernostomy combined with intrathoracic muscle flap transposition. Five of them had concomitant aspergilloma within the cavity while three had multiple drug resistant pulmonary tuberculosis. The muscle flap was used to plombage the cavity and reinforce the closure of bronchopleural fistula after cavernostomy. Six postoperative complications occurred in five patients, including reformation of cavity (2), bronchopleurocutaneous fistulae (3), and postoperative bleeding (1). The success or failure of intrathoracic muscle flap transposition on patients with fibrocavernous tuberculosis was significantly correlated with the size of the cavity (194.0+/-11.2 vs. 283.0+/-44.6 cm(3), P=0.016) and the number of bronchopleural fistulae (1.6+/-0.4 vs. 4.0+/-0.4, P=0.008). There was no operative death and in long term follow-up, there was no recurrence of hemoptysis or deterioration of pulmonary function in the successful group of patients. Cavernostomy combined with intrathoracic muscle flap transposition can be used to treat well-selected fibrocavernous pulmonary tuberculosis patients, except on patients with large size cavity, multiple bronchopleural fistulae or multiple drug resistance tuberculosis.

Multiple drug resistant pulmonary tuberculosis — Fourteen years experience in Buenos Aires, Argentinia

Multiple drug resistant pulmonary tuberculosis — Fourteen years experience in Buenos Aires, Argentinia

A case of resistant tuberculosis

We report a case of multiple drug-resistant pulmonary tuberculosis, in which treatment with two second line chemotherapy regimens was inadequate. Despite in-vitro sensitivity to ciprofloxacin the patient remained sputum positive with Mycobacterium tuberculosis after 11 months.