Multidrug-resistant tuberculosis.

Tuberculosis (TB) remains the foremost cause of death by an infectious disease globally. Multidrug-resistant or rifampicin-resistant TB (MDR/RR-TB; resistance to rifampicin and isoniazid, or rifampicin alone) is a burgeoning public health challenge in several parts of the world, and especially Eastern Europe, Russia, Asia and sub-Saharan Africa. Pre-extensively drug-resistant TB (pre-XDR-TB) refers to MDR/RR-TB that is also resistant to a fluoroquinolone, and extensively drug-resistant TB (XDR-TB) isolates are additionally resistant to other key drugs such as bedaquiline and/or linezolid.

The intersecting pandemics of tuberculosis and COVID-19: population-level and patient-level impact, clinical presentation, and corrective interventions.

The global tuberculosis burden remains substantial, with more than 10 million people newly ill per year. Nevertheless, tuberculosis incidence has slowly declined over the past decade, and mortality has decreased by almost a third in tandem. This positive trend was abruptly reversed by the COVID-19 pandemic, which in many parts of the world has resulted in a substantial reduction in tuberculosis testing and case notifications, with an associated increase in mortality, taking global tuberculosis control back by roughly 10 years.

High-dose rifapentine with or without moxifloxacin for shortening treatment of pulmonary tuberculosis: Study protocol for TBTC study 31/ACTG A5349 phase 3 clinical trial.

Introduction: Phase 2 clinical trials of tuberculosis treatment have shown that once-daily regimens in which rifampin is replaced by high dose rifapentine have potent antimicrobial activity that may be sufficient to shorten overall treatment duration. Herein we describe the design of an ongoing phase 3 clinical trial testing the hypothesis that once-daily regimens containing high dose rifapentine in combination with other anti-tuberculosis drugs administered for four months can achieve cure rates not worse than the conventional six-month treatment regimen.

Methods/design: S31/A5349 is a multicenter randomized controlled phase 3 non-inferiority trial that compares two four-month regimens with the standard six-month regimen for treating drug-susceptible pulmonary tuberculosis in HIV-negative and HIV-positive patients.

Direct Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis by Use of PCR Sequencing.

An in-house-developed sequencing assay for analysis of pyrazinamide (PZA) resistance was evaluated using 162 archived complex (MTBC) isolates with phenotypic PZA susceptibility profiles that were well defined by analysis of Bactec MGIT 960 PZA kit and PZase activity data. Preliminary results showed 100% concordance between sequencing and phenotypic PZA drug susceptibility test (DST) results among archived isolates. Also, 637 respiratory specimens were prospectively collected, and 158 were reported as MTBC positive by the Abbott Realtie MTB assay (96.

Metformin as a host-directed therapeutic in tuberculosis: Is there a promise?

To complement the development of new or repurposed drugs for improving the treatment outcomes of drug-susceptible and drug-resistant tuberculosis, current insight also focuses on the use of host-directed therapy. Metformin, a drug often used in the management of type 2 diabetes mellitus, has attracted attention by virtue of its favourable activity as an adjunctive agent against tuberculosis, discovered through laboratory and clinical studies. To definitively establish its role as a host-directed therapeutic in tuberculosis, more preclinical and clinical research is still required to better delineate its mechanism(s) of action and optimal clinical use.

Genetic susceptibility to Tuberculosis: Interaction between HLA-DQA1 and age of onset.

Several genome-wide association studies (GWAS) identified new single nucleotide polymorphisms (SNPs) with susceptibility to Tuberculosis (TB). However, many of them were not replicated across ethnic groups. The cause of this phenomenon of genetic heterogeneity is uncertain.

Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis.

Background: Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis.

Methods: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016.

New drugs and regimens for tuberculosis.

Since standardized rifampin-based first-line regimens and fluoroquinolone-based second-line regimens were used to treat tuberculosis (TB), unfortunately without timely modification according to the drug resistance profile, TB and drug-resistant disease are still important public health threats worldwide. Although the last decade has witnessed advances in rapid diagnostic tools and use of repurposed and novel drugs for better managing drug-resistant TB, we need an appropriate TB control strategy and a well-functioning health infrastructure to ensure optimal operational use of rapid tests, judicious use of effective treatment regimens that can be rapidly tailored according to the drug resistance profile and timely management of risk factors and co-morbidities that promote infection and its progression to disease. We searched the published literature to discuss (i) standardized versus individualized therapies, including the choice between a single one-size-fit-all regimen versus different options with different key drugs determined mainly by rapid drug susceptibility testing, (ii) alternative regimens for managing drug-susceptible TB, (iii) evidence for using the World Health Organization (WHO) longer and shorter regimens for multidrug-resistant TB and (iv) evidence for using repurposed and novel drugs.

Oxidative Stress and First-Line Antituberculosis Drug-Induced Hepatotoxicity.

Hepatotoxicity induced by antituberculosis drugs is a serious adverse reaction with significant morbidity and even, rarely, mortality. This form of toxicity potentially impacts the treatment outcome of tuberculosis in some patients. Covering only first-line antituberculosis drugs, this review addresses whether and how oxidative stress and, more broadly, disturbance in redox homeostasis alongside mitochondrial dysfunction may contribute to the hepatotoxicity induced by them.

Recent controversies about MDR and XDR-TB: Global implementation of the WHO shorter MDR-TB regimen and bedaquiline for all with MDR-TB?

Tuberculosis (TB) is now the biggest infectious disease killer worldwide. Although the estimated incidence of TB has marginally declined over several years, it is out of control in some regions including in Africa. The advent of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) threatens to further destabilize control in several regions of the world.

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis.

Global tuberculosis incidence has declined marginally over the past decade, and tuberculosis remains out of control in several parts of the world including Africa and Asia. Although tuberculosis control has been effective in some regions of the world, these gains are threatened by the increasing burden of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. XDR tuberculosis has evolved in several tuberculosis-endemic countries to drug-incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis).