Treatment Of Drug-sensitive Tuberculosis Research Articles

Exfoliated dermatitis and hepatitis to first line Anti-Tubercular Therapy with treatment of Drug-Sensitive Tuberculosis with second line Anti-Tubercular Therapy: a roller coaster ride

The Adverse Drug Reactions (ADRSs) to Anti-Tubercular Therapy (ATT) have been reported from 8% to 85% worldwide, while the prevalence of ADRSs to 1st line ATT from India reported 2.3% to 17%, with more during the intensive phase and daily regime. However, cutaneous ADRSs related to ATT are less commonly seen. Common cutaneous ADRSs are maculopapular rash, urticarial, erythema multiforme, exfoliative dermatitis, and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Among the 1st line ATT, pyrazinamide is the most common cause at 2.38%, and isoniazid is reported the least at 0.98%. Exfoliated dermatitis is rarely seen with 1st line ATT therapy limited to some case reports and case series.

Management of Isoniazid Monoresistant Tuberculosis

lsoniazid (INH) is one of the main first-line drugs used for the treatment of active tuberculosis (TB) and latent TB infection because it has bactericidal capabilities and a good level of safety. The presence of TB germs that are resistant to INH will reduce the effectiveness of TB treatment. The treatment mix for INH monoresistant TB patients is a combination of rifampicin (R), isoniazid (H), pyrazinamide (Z), ethambutol (E), and levofloxacin (Lfx) or R-H-Z-E-Lfx given for 6 months. If a health facility provides loose TB medication, the patient can be given a combination of treatment without INH (R-Z-E-Lfx). In conditions where the Lfx drug cannot be used because there is severe intolerance (serious adverse events) or there are contra indications, the treatment given is the R-H-Z-E combination for 6 months. Clinical monitoring for patients with INH monoresistant TB follows the same principles as treatment of drug-sensitive TB. In conclusion, the treatment guide for INH monoresistant TB patients is a combination of rifampicin (R), isoniazid (H), pyrazinamide (Z), ethambutol (E), and levofloxacin (Lfx) or R-H-Z-E-Lfx for 6 months.

Update: Diagnostics and treatment of pulmonary tuberculosis

Molecular diagnostic tools have changed the approach to the detection of Mycobacterium tuberculosis and associated drug-resistance substantially. PCR-based technologies allow a more rapid detection with higher diagnostic sensitivity in pulmonary and extrapulmonary specimens. However, a real point of care test, which needs minimal technical resources remains missing. Genome sequencing technologies are currently changing tuberculosis drug resistance testing, and for some questions are replacing phenotypic drug resistance testing, based on culture.New evidence on treatment for drug-sensitive tuberculosis allows shortening of treatment to 4 months, or in selected cases even to 2 months based on the use of fluoroquinolones, high dose rifamycins and newly developed TB medicines.Such developments will very likely simplify the management of tuberculosis, although prevention remains the most important pillar of any tuberculosis related public health strategy.

Study of gene patterns for Rifampicin in LPA, which were discordant in CBNAAT in the state of Telangana, India

Introduction: Among the first line drugs used for treatment of Drug Sensitive Tuberculosis, Rifampicin plays a crucial role. Hence it is important to know the resistance of Rifampicin using molecular technologies like CBNAAT and line probe Assay. However, a diagnostic dilemma occurs when there is discordance in result of rifampicin resistance at periphery and in higher laboratories like Intermediate Reference Laboratory (IRL). Aims and objectives: To study various patterns of Gene for rifampicin that is demonstrated in probes of Line Probe Assao for First line –Line Probe Assay, which showed discordance with CBNAAT at periphery. Methodology: A retrospective observational study was conducted from 1st January 2021 to 31st December 2021 for all those samples which showed rifampicin discordance. Result: A total of 203 results were found discordant in Rifampicin. The resolution for rifampicin discordance is resolved using the NAAT facility at (IRL). Most of the resolution occurred in concurrence with result of Rifampicin in field. Eight of them gave inconclusive results (MTB not detected) Conclusion: It is very important to understand the gene patterns in LPA for providing appropriate regimen to the patients.

Modelling of a drug resistant tuberculosis for the contribution of resistance and relapse in Xinjiang, China

Tuberculosis has been prevalent in Xinjiang with severe drug resistance situation. It is unclear that which Mycobacterium tuberculosis (M.tb) infections (drug sensitive or drug resistant) most affected the tuberculosis incidence, how to identify the relative contribution of primary and acquisition resistance attributable to drug resistant tuberculosis incidence and relapse percentage in drug sensitive M.tb infection in Xinjiang. In this paper, a dynamical transmission model of drug resistant tuberculosis with fast/slow progression (both in drug sensitive and drug resistant M.tb transmission) and relapse is addressed by incorporating acquisition resistance and primary resistance. Theoretically, it is proved that the disease free equilibrium is globally asymptotically stable when the basic reproduction number $ \mathcal{R}_0\leq1 $, whereas the disease is uniformly persistent, and there exists at least one endemic equilibrium if $ \mathcal{R}_0>1 $. The model is fitted to the newly monthly tuberculosis cases infected by drug sensitive and drug resistant M.tb from 2017 to 2018 in Xinjiang by carrying out Markov chain Monte Carlo algorithm, and it is identified that the contribution percentages of drug sensitive and drug resistant M.tb infections separately reach 80.07% and 19.93% among incident cases of tuberculosis, which illustrates that drug sensitive M.tb transmission is a predominant cause of tuberculosis prevalence in Xinjiang during 2017-18. Moreover, it is estimated that primary rather than acquisition resistance accounts for 74.88% of all incident drug resistant tuberculosis, and the mean relapse percentage is approximately 0.5% but increasing month by month in 2017-18. Our results suggest that early diagnosis and screening (including new tests and drug regimens) and thorough treatment of drug sensitive tuberculosis are the more effective measures in controlling tuberculosis transmission in Xinjiang.

Pancytopenia and Pulmonary Tuberculosis: A Case Report

Background: Hematopoietic system is seriously affected by tuberculosis. It exerts a dazzling variety of hematological effects involving both cell lines and plasma components [1]. Anemia and leukopenia are not unusual with tuberculosis (TB), but pancytopenia is rare [2]. Findings: In this report, we described a case of a 42 years man presenting bleeding and pancytopenia; bacteriological pulmonary TB was established by genotypic rapid test and treatment following the WHO guidelines on drug-sensitive TB treatment. Patient recovered entirely with the WHO recommended regimen associated with general and local treatment of the bleeding. Conclusion: This case report emphasizes the importance of always suspecting tuberculosis in a tuberculosis-endemic area, even when the clinical manifestations are atypical, like pancytopenia and also of properly investigating the differential diagnosis. Even though prognosis seems to be less good, actual treatment regimen is still effective.

Rifampicin impairs adipogenesis by suppressing NRF2-ARE activity in mice fed a high-fat diet

Prolonged treatment with rifampicin (RFP), a first-line antibacterial agent used in the treatment of drug-sensitive tuberculosis, may cause various side effects, including metabolic disorders. The nuclear factor (erythroid-derived 2)-like 2 (NFE2L2, also known as NRF2) plays an essential regulatory role in cellular adaptive responses to stresses via the antioxidant response element (ARE). Our previous studies discovered that NRF2 regulates the expression of CCAAT-enhancer-binding protein β (Cebpb) and peroxisome proliferator-activated receptor gamma (Pparg) in the process of adipogenesis. Here, we found that prolonged RFP treatment in adult male mice fed a high-fat diet developed insulin resistance, but reduced fat accumulation and decreased expression of multiple adipogenic genes in white adipose tissues. In 3 T3-L1 preadipocytes, RFP reduced the induction of Cebpb, Pparg and Cebpa at mRNA and protein levels in the early and/or later stage of hormonal cocktail-induced adipogenesis. Mechanistic investigations demonstrated that RFP inhibits NRF2-ARE luciferase reporter activity and expression of NRF2 downstream genes under normal culture condition and in the early stage of adipogenesis in 3 T3-L1 preadipocytes, suggesting that RFP can disturb adipogenic differentiation via NRF2-ARE interference. Taken together, we demonstrate a potential mechanism that RFP impairs adipose function by which RFP likely inhibits NRF2-ARE pathway and thereby interrupts its downstream adipogenic transcription network.

Antimicrobial usage at a large teaching hospital in Lusaka, Zambia.

Antimicrobial resistance is a growing global health concern. Antimicrobial stewardship (AMS) curbs resistance rates by encouraging rational antimicrobial use. However, data on antimicrobial stewardship in developing countries is scarce. The objective of this study was to characterize antimicrobial use at the University Teaching Hospital (UTH) in Lusaka, Zambia as a guiding step in the development of an AMS program. This was a cross-sectional, observational study evaluating antimicrobial appropriateness and consumption in non-critically ill adult medicine patients admitted to UTH. Appropriateness was defined as a composite measure based upon daily chart review. Sixty percent (88/146) of all adult patients admitted to the general wards had at least one antimicrobial ordered and were included in this study. The most commonly treated infectious diseases were tuberculosis, pneumonia, and septicemia. Treatment of drug sensitive tuberculosis is standardized in a four-drug combination pill of rifampicin, isoniazid, pyrazinamide and ethambutol, therefore appropriateness of therapy was not further evaluated. The most common antimicrobials ordered were cefotaxime (n = 45), ceftriaxone (n = 28), and metronidazole (n = 14). Overall, 67% of antimicrobial orders were inappropriately prescribed to some extent, largely driven by incorrect dose or frequency in patients with renal dysfunction. Antimicrobial prescribing among hospitalized patients at UTH is common and there is room for optimization of a majority of antimicrobial orders. Availability of certain antimicrobials must be taken into consideration during AMS program development.

Patient predictors of poor drug sensitive tuberculosis treatment outcomes in Kyiv Oblast, Ukraine.

Background: Ukraine has high rates of poor treatment outcomes among drug sensitive tuberculosis (DSTB) patients, while global treatment success rates for DSTB remain high. We evaluated baseline patient factors as predictors of poor DSTB treatment outcomes. Methods: We conducted a retrospective analysis of new drug sensitive pulmonary TB patients treated in Kyiv Oblast, Ukraine between November 2012 and October 2014. We defined good treatment outcomes as cure or completion and poor outcomes as death, default or treatment failure. We performed logistic regression analyses, using routine program data, to identify baseline patient factors associated with poor outcomes. Results: Among 302 patients, 193 (63.9%) experienced good treatment outcomes while 39 (12.9%) failed treatment, 34 (11.3%) died, and 30 (9.9%) defaulted. In the multivariate analysis, HIV positive patients on anti-retroviral therapy (ART) [OR 3.50; 95% CI 1.46 - 8.42; p 0.005] or without ART (OR 4.12; 95% CI 1.36 - 12.43; p 0.01) were at increased risk of poor outcomes. Alcohol abuse (OR 1.81; 95% CI 0.93 - 3.55; p 0.08) and smear positivity (OR 1.75; 95% CI 1.03 - 2.97; p 0.04) were also associated with poor treatment outcomes. Conclusions: High rates of poor outcomes among patients with newly diagnosed drug sensitive TB in Kyiv Oblast, Ukraine highlight the urgent need for programmatic interventions, especially aimed at patients with the highest risk of poor outcomes.

Drug resistant TB spine in a two year old child: A case report

Spinal tuberculosis (TB) is a disease of high morbidity that is associated with deformity and neurological sequelae, especially in growing children. Children diagnosed with spinal TB need to be monitored closely for clinical improvements. Previous history of antituberculous therapy (ATT), poor adherence to previous ATT, contact with persons having known drug-resistant (DR) TB, or clinical worsening despite regular ATT are strong indicators for the diagnosis of DR TB of the spine. We report a case of spinal DRTB in a two year old child with no previous history of ATT and contact with a person on irregular treatment for drug sensitive TB that did not show regression of the spinal lesions despite standard ATT.

Rifampicin Bioavailability in Fixed-Dose Combinations for Tuberculosis Treatment: Evidence and Policy Actions

Purpose: The pharmacokinetics (PK) of anti-tuberculosis drugs, including their bioavailability (BA), significantly impacts the efficacy and effectiveness of tuberculosis (TB) treatment regimens. Rifampicin, one of the most important drugs in the treatment of drug-sensitive tuberculosis, has been used increasingly in fixed-dose combinations (FDCs). This paper reviews and analyzes available data on BA and PK of rifampicin with a focus on FDCs, from published studies and reports. Methods: Using PubMed as the primary database, Cochrane and other relevant databases, a systematic review of literature was conducted to identify studies on the bioavailability and efficacy of rifampicin in FDCs versus single drug formulations. A number of keywords including “bioavailability”, “rifampicin”, “fixed dose combinations”, and “pharmacokinetics” were used in various combinations. The search covered the period 1980 to 2016. Priority was given to articles on rifampicin bioavailability in fixed dose combinations used in the program setting, and human studies that used the World Health Organization (WHO) approved BA/PK protocol and sample size (≥22 patients). Findings: More than 450 original peer-reviewed articles, reviews and reports, were assessed for this analysis. Eleven papers, which included data from high-TB-burden countries (South Africa, India, and China), raised significant concerns about rifampicin bioavailability within FDCs; the authors of the studies discussed multiple factors associated with low bioavailability, including drug formulation and quality, storage environment, patient factors, and concomitant diseases. Implications: Recent studies and reviews point to the problem of low bioavailability of rifampicin in fixed dose combinations. However, in the field, it remains a hidden or unrecognized factor leading to poor treatment outcomes. It is difficult to study the issue thoroughly unless there is awareness among TB program personnel of its existence, and adequate laboratory and research support is available to national tuberculosis programs (NTPs). In stemming the tide of tuberculosis multi-drug resistance (MDR) and extensive drug resistance (XDR), it is paramount to ensure that rifampicin bioavailability is adequate in FDCs, and to detect and address any deviation from recommended target ranges. There is a need for strategies to minimize the undesirable clinical effects of reduced rifampicin bioavailability in FDCs, and for effective utilization of quality-assured drugs within NTPs programs; these can help NTPs support effective case management in line with the international TB care standards, while taking into consideration the factors affecting drug absorption and therapeutic concentration.

New drugs to treat difficult tuberculous and nontuberculous mycobacterial pulmonary disease.

Treatment of drug-sensitive tuberculosis (TB) is effective, whereas that of multidrug-resistant and extensively drug-resistant TB as well as nontuberculous mycobacterial (NTM) disease are less so. Therapy in general requires good adherence to potentially toxic drug regimens over prolonged periods. Poor adherence is associated with resistance development and poor outcome. This review will present promising new treatments, both new drugs and regimens, for difficult mycobacterial pulmonary infections. A number of new and repurposed drugs including bedaquiline, delamanid, pretomanid, linezolid and clofazimine, and drug regimens, such as the The Evaluation of a Standard Treatment Regimen of Anti-tuberculosis Drugs for Patients With MDR-TB (STREAM) trial regimens, are currently progressing from basic research through clinical trials.

Efficacy of pyrazinoic acid dry powder aerosols in resolving necrotic and non-necrotic granulomas in a guinea pig model of tuberculosis.

New therapeutic strategies are needed to treat drug resistant tuberculosis (TB) and to improve treatment for drug sensitive TB. Pyrazinamide (PZA) is a critical component of current first-line TB therapy. However, the rise in PZA-resistant TB cases jeopardizes the future utility of PZA. To address this problem, we used the guinea pig model of TB and tested the efficacy of an inhaled dry powder combination, referred to as Pyrazinoic acid/ester Dry Powder (PDP), which is comprised of pyrazinoic acid (POA), the active moiety of PZA, and pyrazinoic acid ester (PAE), which is a PZA analog. Both POA and PAE have the advantage of being able to act on PZA-resistant Mycobacterium tuberculosis. When used in combination with oral rifampicin (R), inhaled PDP had striking effects on tissue pathology. Effects were observed in lungs, the site of delivery, but also in the spleen and liver indicating both local and systemic effects of inhaled PDP. Tissue granulomas that harbor M. tuberculosis in a persistent state are a hallmark of TB and they pose a challenge for therapy. Compared to other treatments, which preferentially cleared non-necrotic granulomas, R+PDP reduced necrotic granulomas more effectively. The increased ability of R+PDP to act on more recalcitrant necrotic granulomas suggests a novel mechanism of action. The results presented in this report reveal the potential for developing therapies involving POA that are optimized to target necrotic as well as non-necrotic granulomas as a means of achieving more complete sterilization of M. tuberculosis bacilli and preventing disease relapse when therapy ends.

Patient predictors of poor drug sensitive tuberculosis treatment outcomes in Kyiv Oblast, Ukraine

Background: Ukraine has high rates of poor treatment outcomes among drug sensitive tuberculosis (DSTB) patients, while global treatment success rates for DSTB remain high. We evaluated baseline patient factors as predictors of poor DSTB treatment outcomes. Methods: We conducted a retrospective analysis of new drug sensitive pulmonary TB patients treated in Kyiv Oblast, Ukraine between November 2012 and October 2014. We defined good treatment outcomes as cure or completion and poor outcomes as death, default (lost to follow up) or treatment failure. We performed logistic regression analyses, using routine program data, to identify baseline patient factors associated with poor outcomes. Results: Among 302 patients, 193 (63.9%) experienced good treatment outcomes while 39 (12.9%) failed treatment, 34 (11.3%) died, and 30 (9.9%) were lost to follow up. In the multivariate analysis, HIV positive patients on anti-retroviral therapy (ART) [OR 3.50; 95% CI 1.46 – 8.42; p 0.005] or without ART (OR 4.12; 95% CI 1.36 – 12.43; p 0.01) were at increased risk of poor outcomes. Frequent alcohol use (OR 1.81; 95% CI 0.93 - 3.55; p 0.08) and smear positivity (OR 1.75; 95% CI 1.03 - 2.97; p 0.04) were also associated with poor treatment outcomes. Conclusions: High rates of poor outcomes among patients with newly diagnosed drug sensitive TB in Kyiv Oblast, Ukraine highlight the urgent need for programmatic interventions, especially aimed at patients with the highest risk of poor outcomes.

Patient predictors of poor drug sensitive tuberculosis treatment outcomes in Kyiv Oblast, Ukraine

Background: Ukraine has high rates of poor treatment outcomes among drug sensitive tuberculosis (DSTB) patients, while global treatment success rates for DSTB remain high. We evaluated baseline patient factors as predictors of poor DSTB treatment outcomes. Methods: We conducted a retrospective analysis of new drug sensitive pulmonary TB patients treated in Kyiv Oblast, Ukraine between November 2012 and October 2014. We defined good treatment outcomes as cure or completion and poor outcomes as death, default (lost to follow up) or treatment failure. We performed logistic regression analyses, using routine program data, to identify baseline patient factors associated with poor outcomes. Results: Among 302 patients, 193 (63.9%) experienced good treatment outcomes while 39 (12.9%) failed treatment, 34 (11.3%) died, and 30 (9.9%) were lost to follow up. In the multivariate analysis, HIV positive patients on anti-retroviral therapy (ART) [OR 3.50; 95% CI 1.46 – 8.42; p 0.005] or without ART (OR 4.12; 95% CI 1.36 – 12.43; p 0.01) were at increased risk of poor outcomes. Smear positivity (OR 1.75; 95% CI 1.03 - 2.97; p 0.04) was also associated with poor treatment outcomes. Conclusions: High rates of poor outcomes among patients with newly diagnosed drug sensitive TB in Kyiv Oblast, Ukraine highlight the urgent need for programmatic interventions, especially aimed at patients with the highest risk of poor outcomes.

Patient predictors of poor drug sensitive tuberculosis treatment outcomes in Kyiv Oblast, Ukraine

Background: Ukraine has high rates of poor treatment outcomes among drug sensitive tuberculosis (DSTB) patients, while global treatment success rates for DSTB remain high. We evaluated baseline patient factors as predictors of poor DSTB treatment outcomes. Methods: We conducted a retrospective analysis of new drug sensitive pulmonary TB patients treated in Kyiv Oblast, Ukraine between November 2012 and October 2014. We defined good treatment outcomes as cure or completion and poor outcomes as death, default or treatment failure. We performed logistic regression analyses, using routine program data, to identify baseline patient factors associated with poor outcomes. Results: Among 302 patients, 193 (63.9%) experienced good treatment outcomes while 39 (12.9%) failed treatment, 34 (11.3%) died, and 30 (9.9%) defaulted. In the multivariate analysis, HIV positive patients on anti-retroviral therapy (ART) [OR 3.50; 95% CI 1.46 – 8.42; p 0.005] or without ART (OR 4.12; 95% CI 1.36 – 12.43; p 0.01) were at increased risk of poor outcomes. Alcohol abuse (OR 1.81; 95% CI 0.93 - 3.55; p 0.08) and smear positivity (OR 1.75; 95% CI 1.03 - 2.97; p 0.04) were also associated with poor treatment outcomes. Conclusions: High rates of poor outcomes among patients with newly diagnosed drug sensitive TB in Kyiv Oblast, Ukraine highlight the urgent need for programmatic interventions, especially aimed at patients with the highest risk of poor outcomes.

THE EFFECTIVENESS OF TREATMENT OF DRUGSENSITIVE TUBERCULOSIS, COMBINED WITH HIV INFECTION, IN THE TB FACILITY OF THE FEDERAL PENITENTIARY SERVICE

Goal: The effectiveness of treatment of drug-sensitive tuberculosis, combined with HIV infection in the TB facility of the Federal Penitentiary Service. Materials and methods. 81 men with drug-sensitive tuberculosis with HIV co-infection. Age: from 20 to 49. Results. In 50% of patients with drug-susceptible tuberculosis, co-infected with HIV in a TB institution of the Federal Penitentiary Service, bacterial excretion will be stopped by microscopy and sowing for 3 and 2 months using first-line or combination first-line and second-line anti-tuberculosis drugs in the initial regimen, respectively. The decay cavities will be closed for 5 months with initial treatment only first-line anti-tuberculosis drugs and 3 months for initial treatment with a combination of first-line and second-line anti-tuberculosis drugs.

Is there randomized controlled trial evidence to support the treatment of drug-sensitive tuberculosis with fluoroquinolones?

Is there randomized controlled trial evidence to support the treatment of drug-sensitive tuberculosis with fluoroquinolones?

Pulmonary Tuberculosis--Is Surgery still Necessary?

Tuberculosis is still one of the most common infectious diseases along with HIV and malaria and therefore represents a serious problem in the health sector. Due to immigrants and refugees, the disease is also present in Europe. The global increase of multidrug resistant tuberculosis leads to a highly significant and current importance of sufficient therapeutic measures. In recent years, this fact has led to a reevaluation of surgical therapy in the context of an interdisciplinary and multimodal treatment of multidrug resistant tuberculosis. In addition, despite an effective treatment of drug sensitive tuberculosis with antibiotics, there are still indications for surgery in the treatment of tuberculosis. Beside massive hemoptysis as an emergency indication for surgical intervention, secondary complications of tuberculosis such as aspergilloma, chronic hemoptysis, pneumothorax, bronchopleural fistula and destroyed lung remain indications for surgery. The indication for surgery should always be made in a multimodal therapeutic approach by an interdisciplinary team, taking patient age and functional analysis into account. Effective antibiotic therapy should be performed before and after surgery in order to achieve a sustained treatment success.

Recomendaciones de GESIDA/Secretaría del Plan Nacional sobre el Sida para el tratamiento de la tuberculosis en adultos infectados por el virus de la inmunodeficiencia humana (actualización enero de 2013)

This consensus document was prepared by an expert panel of the Grupo de Estudio de Sida (GESIDA [Spanish AIDS Study Group]) and the Plan Nacional sobre el Sida (PNS [Spanish National AIDS Plan]). The document updates current guidelines on the treatment of tuberculosis (TB) in HIV-infected individuals contained in the guidelines on the treatment of opportunistic infections published by GESIDA and PNS in 2008. The document aims to facilitate the management and treatment of HIV-infected patients with TB in Spain, and includes specific sections and recommendations on the treatment of drug-sensitive TB, multidrug-resistant TB, and extensively drug-resistant TB, in this population. The consensus guidelines also make recommendations on the treatment of HIV-infected patients with TB in special situations, such as chronic liver disease, pregnancy, kidney failure, and transplantation. Recommendations are made on the timing and initial regimens of antiretroviral therapy in patients with TB, and on immune reconstitution syndrome in HIV-infected patients with TB who are receiving antiretroviral therapy. The document does not cover the diagnosis of TB, diagnosis/treatment of latent TB, or treatment of TB in children. The quality of the evidence was evaluated and the recommendations graded using the approach of the Grading of Recommendations Assessment, Development and Evaluation Working Group.