scholarly journals The Therapeutic potential of interferon-gamma in tuberculosis

ADMET & DMPK ◽  
2022 ◽  
Author(s):  
Svetlana A. Berns ◽  
Julia A. Isakova ◽  
Polina Pekhtereva
Keyword(s):  
Interferon Gamma ◽  
Clinical Efficacy ◽  
Therapeutic Potential ◽  
Therapeutic Option ◽  
Multidrug Resistant ◽  
Recent Experimental Data ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Complex Therapy

Tuberculosis is one of the critical health problems worldwide. The search for ways to improve the results of tuberculosis treatment and overcome drug resistance lies in understanding the pathogenesis of the development of the infectious process. The interferon system, particularly the role of interferon-gamma, has been identified as the main link in the immune response in tuberculosis. The clinical efficacy of interferon-gamma has been studied and evaluated in clinical trials since the end of the last century. There was obtained evidence of the clinical efficacy of interferon-gamma as part of complex therapy. Recent experimental data make it possible to consider interferon-gamma as a promising therapeutic option for the treatment of multidrug-resistant tuberculosis as part of complex therapy worthy of further studies.  

Lung Resection for Multidrug-Resistant Tuberculosis

2005 ◽  
Vol 13 (2) ◽  
pp. 172-174 ◽  
Author(s):  
Rishen Naidoo ◽  
Anu Reddi
Keyword(s):  
Lung Resection ◽  
Postoperative Mortality ◽  
Multidrug Resistant ◽  
Cure Rate ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Traditional Drug ◽  
Localized Disease ◽  
Cure Rates

The emergence of multidrug-resistant tuberculosis poses a serious challenge to traditional drug therapy. In view of the relapse rate of up to 50% following medical management, there has been renewed interest in the role of surgery for this problem. We report our experience with lung resection for this condition. Over a 5-year period, resection was performed in 23 patients who were diagnosed with multidrug resistance after completing a course of standard chemotherapy and at least 3 months of second-line therapy. Pneumonectomy was performed in 17 patients and lobectomy in 6. There was no operative or postoperative mortality. Major complications developed in 4 patients (17.4%): 2 had post-pneumonectomy empyema and 2 underwent rethoracotomy for bleeding. Ten patients were sputum positive preoperatively, and only 1 remained positive after surgery. The patients were put on appropriate chemotherapy and followed up for 18 months. The cure rate was 95.6%. Pulmonary resection can be considered as an important adjunct to medical therapy in carefully selected patients: those who have localized disease with adequate pulmonary reserve, or who have multiple previous relapses, or whose sputum remains positive after 4 to 6 months of appropriate medical treatment. Surgery offers high cure rates with acceptable morbidity and mortality.

scholarly journals Interferon-Gamma Improves Macrophages Function against M. tuberculosis in Multidrug-Resistant Tuberculosis Patients

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Taj Ali Khan ◽  
Humaira Mazhar ◽  
Shamim Saleha ◽  
Hamid Nawaz Tipu ◽  
Niaz Muhammad ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Multidrug Resistant ◽  
Human Interferon ◽  
Peripheral Blood Mononuclear ◽  
Infected People ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Background. Mycobacterium tuberculosis (M. tuberculosis) that causes tuberculosis (TB) kills millions of infected people annually especially multidrug-resistant tuberculosis (MDR-TB). On infection, macrophages recognize the mycobacteria by toll-like receptor (TLR) followed by phagocytosis and control of mycobacteria. In addition, macrophages also secrete IL-12 to induce IFN-γ production by T, which, in turn, increases the phagocytosis and oxidative burst. Individuals with defects in innate or adaptive immunity exhibit increased susceptibility to M. tuberculosis. Understanding these immunologic mechanisms will help in TB control. We aimed to investigate the immunopathologic mechanisms in MDR-TB and role of recombinant human interferon-gamma (rhIFN-γ). Study Design and Methods. Monocyte-derived macrophages (MDMs) were generated from peripheral blood mononuclear cells of MDR-TB patients and healthy subjects and were investigated for immunologic response by ELISA and flow cytometry. Results. Different functional and molecular anomalies were observed in macrophages. In addition, a defective immune response to M. tuberculosis from the patient’s MDMs was characterized, which in turn improved by pretreatment with rhIFN-γ. Conclusion. This work highlights the fact that rhIFN-γ improves macrophages function against M. tuberculosis and treatment of patients with poor responsiveness to TB therapy may be needed in future to include IFN-γ as adjuvant therapy after the full characterization of pathological and molecular mechanisms in these and in other more multidrug-resistant TB patients.

Role of Treatment Cost on Transmission of Multidrug-Resistant Tuberculosis Into Iran

2015 ◽  
Vol 61 (6) ◽  
pp. 1029-1030 ◽  
Author(s):  
Abed Zahedi Bialvaei ◽  
Hossein Samadi Kafil ◽  
Mohammad Asgharzadeh
Keyword(s):  
Treatment Cost ◽  
Multidrug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis

scholarly journals Patients’ Perception of a Community Pharmacist-Managed Multidrug-Resistant Tuberculosis Program in Peru: A Public Health Perspective

2017 ◽  
Vol 8 (3) ◽  
pp. 11 ◽  
Author(s):  
Sean O'Brien ◽  
Jacy Downey
Keyword(s):  
Public Health ◽  
Community Pharmacist ◽  
Community Pharmacists ◽  
Multidrug Resistant ◽  
Perceived Barriers ◽  
The Public ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Objectives: The primary objective is to investigate the public’s perception about the role of the community pharmacist in Peru’s directly observed treatment, short course (DOTS) program. The secondary objective is to assess perceived barriers that would prevent the public from utilizing community pharmacists in order to identify future opportunities for community pharmacists to increase adherence to multidrug-resistant tuberculosis (MDR-TB) therapy. Design: Qualitative study comprised of an 8 close-ended survey questionnaire. Setting: Healthcare clinics established by a medical mission group in Lima and surrounding communities, Peru, from July 13 to July 27, 2015. Participants: Patients 15 years of age and over who sought healthcare at the clinics. Main outcome measures: Public’s perception about the role of the community pharmacist in Peru and barriers that would prevent the public from seeking a community pharmacist. Results: Out of the 445 patients approached, 438 patients completed the survey, resulting in a 98% response rate. More than half (52%) of the respondents were likely to seek a community pharmacist to assist them in completing a MDR-TB medication regimen. Almost half (48%) of the respondents felt comfortable with assistance of a community pharmacist in completing an MDR-TB regimen. The physician was the first health care professional that was contacted for all medical situations, including drug-related questions (61%). Lack of privacy in the pharmacy (53%) and busyness of the pharmacists (52%) were the top perceived barriers for asking community pharmacists questions. Conclusion: This study highlights the need for pharmacist participation in Peru’s DOTS program. Furthermore, this investigation has identified several issues of concern related to current community pharmacy practice in Peru. Therefore, future efforts may be necessary to address these identified areas of opportunity to promote the community pharmacist’s role in health screening, drug therapy monitoring, and counseling to decrease the public health burden of MDR-TB. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received), employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents or royalties.   Type: Original Research

scholarly journals STUDI FENOMENOLOGI : DUKUNGAN TERHADAP KEPATUHAN MINUM OBAT PADA PENDERITA TUBERCULOSIS DENGAN MULTIDRUG-RESISTANT

2021 ◽  
Vol 8 (1) ◽  
pp. 12-20
Author(s):  
Murwanti Murwanti
Keyword(s):  
Health Services ◽  
Community Involvement ◽  
Sampling Technique ◽  
Phenomenological Approach ◽  
Multidrug Resistant ◽  
Spiritual Support ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Background: Tuberculosis is an infectious disease if the patient does not complete therapeutic treatment can cause multidrug-resistant tuberculosis (MDR-TB). The role of the environment is needed to support treatment.The study aims to explore more deeply the family's support for medication adherence in patients with multidrug-resistant tuberculosis (TBC-MDR). Method: This type of research is qualitative using a descriptive phenomenological approach, in-depth interviews of 5 participants based on purposive sampling technique. Results: The results of the study found the role of the family towards TB-MDR patients manifested in emotional, physical, instrumental, and spiritual support. emotional support consists of positive and negative emotional. Community involvement after counseling was supportive but there were some who could not accept even families of MDR-TB sufferers were also shunned. The role of health services is to convey information, prepare medicines, supervise, motivate treatment, remind check schedules, refer to more complete facilities when needed, visit homes and ensure patients take medication if unable to come to the public health service. Conclusion: This study found 3 main themes, namely the role of comprehensive family, community involvement and the role of health services in mentoring TB-MDR patients.

scholarly journals Solid Lipid Nanoparticles as Formulative Strategy to Increase Oral Permeation of a Molecule Active in Multidrug-Resistant Tuberculosis Management

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1132
Author(s):  
Antonella Obinu ◽  
Elena Piera Porcu ◽  
Sandra Piras ◽  
Roberta Ibba ◽  
Antonio Carta ◽  
...  
Keyword(s):  
Solid Lipid Nanoparticles ◽  
Oral Absorption ◽  
Antitubercular Activity ◽  
Multidrug Resistant ◽  
Lipid Nanoparticles ◽  
Particle Size Range ◽  
Solid Lipid ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis

The role of mycobacterial efflux pumps in drug-resistant tuberculosis has been widely reported. Recently, a new compound, named SS13, has been synthesized, and its activity as a potential efflux inhibitor has been demonstrated. In this work, the chemical–physical properties of the SS13 were investigated; furthermore, a formulative study aimed to develop a formulation suitable for oral administration was performed. SS13 shows nonintrinsic antitubercular activity, but it increases the antitubercular activity of all the tested drugs on several strains. SS13 is insoluble in different simulated gastrointestinal media; thus, its oral absorption could be limited. Solid lipid nanoparticles (SLNs) were, therefore, developed by using two different lipids, Witepsol and/or Gelucire. Nanoparticles, having a particle size (range of 200–450 nm with regards to the formulation composition) suitable for intestinal absorption, are able to load SS13 and to improve its permeation through the intestinal mucosa compared to the pure compound. The cytotoxicity is influenced by the concentration of nanoparticles administered. These promising results support the potential application of these nanocarriers for increasing the oral permeation of SS13 in multidrug-resistant tuberculosis management.

Safety and Efficacy of Delamanid in the Treatment of Multidrug-Resistant Tuberculosis (MDR-TB)

2013 ◽  
Vol 5 ◽  
pp. CMT.S11675 ◽  
Author(s):  
Stephen K. Field
Keyword(s):  
Multidrug Resistant ◽  
Phase Iii ◽  
Drug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Improved Outcomes ◽  
Resistance Patterns ◽  
Mdr Tb ◽  
Phase Iii Study

Globally, the incidence of tuberculosis (TB) is declining but the proportion of drug-resistant cases has increased. Strains resistant to both isoniazid and rifampin, and possibly other antibiotics, called multidrug-resistant (MDR), are particularly difficult to treat. Poorer outcomes, including increased mortality, occur in patients infected with MDR strains and the costs associated with treatment of MDR-TB are substantially greater. The recent recognition of MDR-TB and strains with more complex resistance patterns has stimulated the development of new TB medications including fluoroquinolones, oxazolidinones, diarylquinolines, nitroimidazopyrans, ethylenediamines, and benzothiazinones. Bedaquiline, a diarylquinoline, was approved for the treatment of MDR-TB in 2012. Addition of delamanid to WHO-approved treatment improved outcomes for MDR-TB and for extensively drug-resistant TB in a large randomized, controlled phase II clinical trial and is undergoing evaluation in a large international phase III study. This review will focus on MDR-TB and the role of delamanid in its treatment.

scholarly journals Gyrase Mutations Are Associated with Variable Levels of Fluoroquinolone Resistance in Mycobacterium tuberculosis

2016 ◽  
Vol 54 (3) ◽  
pp. 727-733 ◽  
Author(s):  
Maha R. Farhat ◽  
Karen R. Jacobson ◽  
Molly F. Franke ◽  
Devinder Kaur ◽  
Alex Sloutsky ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Open Reading Frames ◽  
Fluoroquinolone Resistance ◽  
Test Results ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Disease Mutations ◽  
The Individual ◽  
Selection Of

Molecular diagnostics that rapidly and accurately predict resistance to fluoroquinolone drugs and especially later-generation agents promise to improve treatment outcomes for patients with multidrug-resistant tuberculosis and prevent the spread of disease. Mutations in thegyrgenes are known to confer most fluoroquinolone resistance, but knowledge about the effects ofgyrmutations on susceptibility to early- versus later-generation fluoroquinolones and about the role of mutation-mutation interactions is limited. Here, we sequenced the fullgyrAandgyrBopen reading frames in 240 multidrug-resistant and extensively drug-resistant tuberculosis strains and quantified their ofloxacin and moxifloxacin MIC by testing growth at six concentrations for each drug. We constructed a multivariate regression model to assess both the individual mutation effects and interactions on the drug MICs. We found thatgyrBmutations contribute to fluoroquinolone resistance both individually and through interactions withgyrAmutations. These effects were statistically significant. In these clinical isolates, severalgyrAandgyrBmutations conferred different levels of resistance to ofloxacin and moxifloxacin. Consideration ofgyrmutation combinations during the interpretation of molecular test results may improve the accuracy of predicting the fluoroquinolone resistance phenotype. Further, the differential effects ofgyrmutations on the activity of early- and later-generation fluoroquinolones requires further investigation and could inform the selection of a fluoroquinolone for treatment.

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