Drug-resistant Tuberculosis Therapy Research Articles

Mediastinal Lymphadenopathy Complicating into a Bronchonodal Fistula and Lung Abscess Formation – Rare Manifestation of Drug-resistant Tuberculosis

Pulmonary tuberculosis (TB) sometimes involves regional lymph nodes like mediastinal lymph nodes. These may resolve spontaneously or on treatment; or they may enlarge and result in various complications such as extrinsic bronchial inflammation, ulceration, or rarely erode through the bronchial wall. This erosion is seen radiologically as mediastinal widening or lymphadenopathy with atelectasis and consolidation termed “epituberculosis.” This is more frequently encountered in infants than older children and extremely rarely in adults. We hereby describe a rare case of a 14-year-old girl with mediastinal lymphadenopathy complicating into a bronchonodal fistula and lung abscess formation. A diagnosis of pulmonary rifampicin-resistant TB was obtained on repeated testing of sputum for GeneXpert. The patient was started on appropriate drug-resistant TB therapy and completed therapy successfully.

Baseline glycated hemoglobin and potassium level correlated with pretreatment QT-corrected interval among patients with diabetic drug-resistant tuberculosis.

Bedaquiline is a core drug with an optimized background regimen for treating drug-resistant tuberculosis (DR-TB) patients. One of the adverse effects of bedaquiline is QT-corrected (QTc) interval prolongation. TB patients with diabetes mellitus (DM) are more likely to develop QTc interval prolongation during TB treatment than those without DM. This study aimed to correlate baseline electrolyte levels (potassium, calcium, and magnesium), thyroid-stimulating hormone (TSH), body mass index (BMI), blood glucose, glycated hemoglobin (HbA1c), and pretreatment QTc interval among patients with diabetic DR TB who received regimens containing bedaquiline. It was a prospective study with a cross-sectional design. Blood samples, BMI, and electrocardiogram were collected at baseline before starting the regimen for DR-TB. Pearson correlation was used to correlate between baseline electrolyte level, TSH, BMI, complete blood count, blood glucose, HbA1c, and pretreatment QTc interval. Seventy-two DR-TB patients met the inclusion criteria, half with DM. The blood glucose and HbA1c were significantly higher in patients with DM. Pretreatment QTc interval was similar between the two groups. Levels of calcium, magnesium, TSH, blood glucose, and BMI were not correlated with pretreatment QTc interval. There was a correlation between baseline potassium and HbA1c levels with pretreatment QTc interval (P < 0.05; r = 0.357 and r = -0.376, respectively). Baseline potassium level correlates with the pretreatment QTc interval in those without DM. Baseline HbA1c and potassium levels correlate with pretreatment QTc interval among DR-TB patients with DM. Our study indicates the importance of monitoring HbA1c and potassium levels during DR-TB therapy containing bedaquiline for early detection of QTc prolongation.

Rare adverse effects of anti tuberculous therapy − a case series

Tuberculosis is prevalent throughout the world and is a major public health problem in most developing countries. Standardized and directly observed treatment under NTEP (National Tuberculosis Elimination Programme) is currently recommended for drug-sensitive pulmonary tuberculosis in India. It is generally well tolerated, with few minor side effects. Severe side effects necessitating discontinuation of therapy are rare with standard TB treatment regimens. Drug-resistant tuberculosis (DR-TB) has become more common in recent years, posing a challenge to global efforts to control the disease. Therapy for DR-TB has been associated with many adverse effects. Therefore, close monitoring of patients on DR-TB therapy is necessary to ensure that adverse effects of drugs are recognized early by healthcare personnel and treated accordingly. This will improve drug compliance and, hence, treatment goals. Here we report three cases of tuberculosis who had unusual adverse effects while receiving anti-tuberculous medication, prompting drug discontinuation.

Challenging Treatment of Drug-Resistant Tuberculosis during Pregnancy: A Case Report

Introduction: Globally, drug-resistant tuberculosis (TB) still has a high number of cases. Pregnant women are one of the high-risk populations for TB infection, especially multidrug resistance (MDR)/Rifampicin resistance (RR) TB. Physiological differences in pregnant women and the safety of the fetus make drug resistance TB treatment challenging. Case: A 20-year-old woman was 22 weeks pregnant while undergoing the third month of the late phase for short-regimen. Thus, Kanamycin was one of her early phase treatment combinations during the first trimester of pregnancy. After we consulted with other departments, especially the obstetric department, we decided not to change her regimen. Her chief complaint before treatment was cough with white sputum and fluctuated shortness of breath for two months. The patient only experienced minor side effects in the early treatment phase. The patient was cured of MDR TB on 8 October 2020 at 34 weeks of gestation. Her baby was born on 10 November 2020 at 37 weeks without congenital abnormality. Observation for her baby continued by the pediatric department. The last follow-up of her baby in the middle of 2022 found no abnormality in the child’s growth and development. Conclusion: Drug-resistant TB therapy in pregnant women requires the collaboration of a multidisciplinary team to consider the benefits and risks of the therapy based on gestational age and disease severity.

Between Curing and Torturing: Burden of Adverse Reaction in Drug-Resistant Tuberculosis Therapy.

Drug-resistant tuberculosis (DR-TB) requires prolonged and complex therapy which is associated with several adverse drug reactions (ADR). The burden of ADR can affect the quality of life (QoL) of patients that consists of physical, mental, and social well-being, and influences the beliefs and behaviors of patient related to treatment. This article reviews the burden of ADR and its association with QoL and adherence. We used PubMed to retrieve the relevant original research articles written in English from 2011 to 2021. We combined the following keywords: “tuberculosis,” “Drug-resistant tuberculosis,” “Side Effect,” “Adverse Drug Reactions,” “Adverse Event,” “Quality of Life,” “Adherence,” “Non-adherence,” “Default,” and “Loss to follow-up.” Article selection process was unsystematic. We included 12 relevant main articles and summarized into two main topics, namely, 1) ADR and QoL (3 articles), and 2) ADR and therapy adherence (9 articles). The result showed that patients with ADR tend to have low QoL, even in the end of treatment. Although it was torturing, the presence of ADR does not always result in non-adherence. It is probably because the perception about the benefit of the treatment dominates the perceived barrier. In conclusion, burden of ADR generally tends to degrade QoL of patients and potentially influence the adherence. A comprehensive support from family, community, and healthcare provider is required to help patients in coping with the burden of ADR. Nevertheless, the regimen safety and efficacy improvement are highly needed.

Anti-Tubercular Activity of Substituted 7-Methyl and 7-Formylindolizines and In Silico Study for Prospective Molecular Target Identification.

Novel series of diversely substituted indolizines were designed, synthesized, and evaluated for their in vitro anti-mycobacterial activity against H37Rv and multi-drug-resistant (MDR) strains of Mycobacterium tuberculosis (MTB). Many compounds exhibited significant inhibitory activity against MTB H37Rv strains. Indolizines 2d, 2e, and 4 were also found to be active against MTB clinical isolates with multi-resistance to rifampicin and isoniazid. Indolizine 4 was identified as the most promising anti-mycobacterial agent, displaying minimum inhibitory concentration (MIC) values of 4 and 32 μg/mL against H37Rv and MDR strains, respectively. Furthermore, an in silico study was carried out for prospective molecular target identification and revealed favorable interactions with the target enzymes CYP 121, malate synthase, and DNA GyrB ATPase. None of the potent molecules presented toxicity against peripheral blood mononuclear (PBM) cell lines, demonstrating their potentiality to be used for drug-sensitive and drug-resistant tuberculosis therapy.

Antiretroviral switching and bedaquiline treatment of drug-resistant tuberculosis HIV co-infection

Bedaquiline, a potent new therapy for drug-resistant tuberculosis, results in improved survival including in HIV patients with multidrug and extensively drug-resistant tuberculosis. In line with WHO recommendations, in South Africa and other low-income and middle-income settings, antiretroviral therapy is switched from generic fixed-dose combination efavirenz-containing regimens to twice-daily nevirapine with separate companion pills because of interactions between efavirenz and bedaquiline. Early data suggest a signal for low antiretroviral therapy adherence after this antiretroviral therapy switch. Mortality and other tuberculosis-specific benefits noted with bedaquiline treatment in multidrug and extensively drug-resistant tuberculosis HIV might be compromised by HIV viral failure, and emergent antiretroviral resistance. Programmatic responses, such as adherence support and dual pharmacovigilance, should be instituted; antiretroviral therapy initiation with fixed-dose combinations without bedaquiline drug interactions should be strongly considered.

Clinical characteristics and therapeutic effect of drug-resistant tuberculosis in children

Objective: To explore the clinical characteristics of drug-resistant tuberculosis (TB) in children and to study the effectiveness of second-line anti-TB therapy for children and to examine the incidence of adverse drug reactions. Method: Retrospective research was conducted. The clinical records of children in West China Second Hospital diagnosed as drug-resistant TB from January 2010 to June 2014 were investigated.The clinical characteristics and risk factors were analyzed retrospectively. Treatment effect at discharge was examined as a short-term outcome indicator to evaluate the effectiveness of second-line anti-TB therapy and the incidence of adverse drug reactions. χ(2) test was used. Result: Forty-six patients were diagnosed as drug-resistant TB in 443 children infected with TB, with a 10.4% resistance rate. The 46 children included 26 male and 20 female patients, aged from one month and 28 days to 17 years and 5 months, with the average age (8.4±4.5) years, >7 to 14 years old patients as the biggest part(25 patients, 54.3%). Among the 46 children, 20 patients(43.5%)had close contact with TB patients, of whom 12 patients (60.0%) contacted with family members (including parents, brothers and sisters and grandparents living together) and 8 patients(40.0%) contacted with patients from outside family (such as relatives or neighbors). Moreover, 11 cases (23.9%) were under initial treatment and 35 cases (76.1%) were retreated.From 2010 to 2014, the number of cases of initial and retreated patients had no significant difference(0 and 1, 1 and 13, 4 and 7, 4 and 11, 2 and 3 cases, χ(2)=3.255, P=0.196). Among retreated patients, 31.4% (11/35) had irregular treatment before.Until discharge, the effective rate was 87.0% (40/46), while the incidence rate of adverse drug reaction was 10.9%(5/46). Conclusion: The therapy for drug-resistant TB is effective and the incidence of adverse drug reaction is relatively low.

Occurrence and clinical management of moderate-to-severe adverse events during drug-resistant tuberculosis treatment: a retrospective cohort study.

ObjectivesTo determine the incidence of symptomatic moderate-to-severe adverse events during treatment of drug-resistant tuberculosis, and to compare their risk and outcomes by patients’ human immunodeficiency virus (HIV) co-infection status.MethodsWe conducted a retrospective cohort analysis of patients treated for drug-resistant tuberculosis between January 2008 and February 2010. Routinely, clinicians monitored and managed patients’ response to treatment until its completion. Any symptomatic adverse event observed by the clinician or reported by the patient was recorded in the standard patient treatment booklet of the National Tuberculosis and Leprosy Programme. There were 18 symptomatic adverse events routinely monitored. Depending on the nature of the medical intervention needed, each was graded as mild, moderate or severe. Data were extracted from the patient treatment booklet using a structured form, then descriptive, bivariate and Cox proportional hazard analysis performed, stratified by patients’ HIV infection status. Statistical associations were done at the 5% level of significance and reported with 95% confidence intervals.ResultsFifty seven (57) patients with drug-resistant tuberculosis were identified, 31 (53%) of whom were HIV co-infected. The cumulative incidence of moderate-to-severe adverse events was 46 events in 100 patients. HIV co-infected patients experienced more moderate-to-severe adverse events compared with the HIV uninfected patients (median 3 versus 1 events, p = 0.01). They had a four-fold increase in the cumulative hazard of moderate-to-severe adverse events compared with the HIV uninfected patients (HR = 4.0, 95% CI 1.5 – 10.5). Moderate-to-severe adverse events were the main determinant of a clinician’s decision to reduce the dose or to stop the suspected offending medicine (RR = 3.8, 95% 1.2-11.8).ConclusionsModerate-to-severe adverse events are common during drug-resistant tuberculosis therapy. They are more likely to occur and to persist in HIV co-infected patients than in HIV uninfected patients. Clinicians should employ various strategies for preventing drug-induced patient discomfort and harm, such as reducing the dose or stopping the suspected offending medicine. Managers of tuberculosis control programmes should strengthen pharmacovigilance systems. We recommend a more powered study for conclusive risk-factor analysis.Electronic supplementary materialThe online version of this article (doi:10.1186/2052-3211-7-14) contains supplementary material, which is available to authorized users.

Use of Anti-Retroviral Therapy in Tuberculosis Patients on Second-Line Anti-TB Regimens: A Systematic Review

IntroductionUse of antiretroviral therapy (ART) during treatment of drug susceptible tuberculosis (TB) improves survival. However, data from HIV infected individuals with drug resistant TB are lacking. Second line TB drugs when combined with ART may increase drug interactions and lead to higher rates of toxicity and greater noncompliance. This systematic review sought to determine the benefit of ART in the setting of second line drug therapy for drug resistant TB.MethodsWe included individual patient data from studies that evaluated treatment of drug-resistant tuberculosis in HIV-1 infected individuals published between January 1980 and December of 2009. We evaluated the effect of ART on treatment outcomes, time to smear and culture conversion, and adverse events.ResultsTen observational studies, including data from 217 subjects, were analyzed. Patients using ART during TB treatment had increased likelihood of cure (hazard ratio (HR) 3.4, 95% CI 1.6–7.4) and decreased likelihood of death (HR 0.4, 95% CI 0.3–0.6) during treatment for drug resistant TB. These associations remained significant in patients with a CD4 less than 200 cells/mm3 and less than 50 cells/mm3, and when correcting for drug resistance pattern.LimitationsWe identified only observational studies from which individual patient data could be drawn. Limitations in study design, and heterogeneity in a number of the outcomes of interest had the potential to introduce bias.DiscussionWhile there are insufficient data to determine if ART use increases adverse drug interactions when used with second line TB drugs, ART use during treatment of drug resistant TB appears to improve cure rates and decrease risk of death. All individuals with HIV appear to benefit from ART use during treatment for TB.

Drug-resistant Tuberculosis

Drug-resistant Mycobacterium tuberculosis (TB) infection represents a serious and growing problem. For patients infected or suspected of being infected with multidrug or extensively drug-resistant TB, several medications have to be given simultaneously for prolonged periods. Here, we review the literature on treatment and monitoring of adverse effects of pediatric drug-resistant TB therapy in a high resource, low TB burden setting.