Detection of Novel Gene Mutations Associated with Pyrazinamide Resistance in Multidrug-Resistant Clinical Isolates in Southern China.

Objective: Pyrazinamide (PZA) is a cornerstone of modern tuberculosis regimens. This study aimed to investigate the performance of genotypic testing of upstream region, and genes to add insights for more accurate molecular diagnosis of PZA-resistant (R)

Methods: Drug susceptibility testing, sequencing analysis of PZA-related genes including the entire operon of () and PZase assay were performed for 448 clinical isolates.

Results: Our data showed that among 448 clinical isolates, 113 were MDR, 195 pre-XDR and 70 XDR TB, while the remaining 70 strains had other combinations of drug-resistance.

Phenotypic and Genotypic Characterization of Streptomycin-Resistant Multidrug-Resistant Clinical Isolates in Southern China.

Streptomycin (STR) is the first antibiotic used in the treatment of tuberculosis (TB) and the earliest antituberculosis drug with acquired resistance developed by The high prevalence of such resistance in many parts of the world limits its use for treating multidrug-resistant (MDR) TB. The aims of this study are to characterize of mutations in , , and genes in MDR isolates originating from southern China and to investigate possible relationship between mutations and strain genotypes for precise diagnosis and treatment. Sequences of , , and genes and the resistance profiles were analyzed for 218 MDR isolates.

Phenotypic and genotypic characterization of levofloxacin- and moxifloxacin-resistant clinical isolates in southern China.

Background: Levofloxacin (LVX) and Moxifloxacin (MXF) are the cornerstones for treatment of multidrug-resistant tuberculosis (MDR-TB). China is one of the highest MDR- and fluoroquinolones (FQ)-resistant TB burdens countries. DNA gyrase encoded by genes is the main target of FQ in (MTB).

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.

Mathematical modelling of the impact of treating latent tuberculosis infection in the elderly in a city with intermediate tuberculosis burden.

Hong Kong is a high-income city with intermediate tuberculosis (TB) burden primarily driven by endogenous reactivations. A high proportion of remote latently infected people, particularly elderly, hinders the effectiveness of current strategies focusing on passive TB detection. In this study, we developed a mathematical model to evaluate the impact of treating latent TB infection (LTBI) in the elderly in addition to current TB control strategies.

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.

Mutation EthA confers co-resistance to prothionamide and ethionamide in both BCG and H37Rv.

Ethionamide (ETA) and prothionamide (PRO) are interchangeably used in tuberculosis (TB) chemotherapy regimens. Subtle discrepancies between biochemical and genetic information on the modes of sensitivity and resistance of isoniazid (INH) and ETA warrants further studies. We report a new mutation - EthA - in Bacillus Calmette-Guérin that corresponds with co-resistance to both PRO and ETA, which to the best of our knowledge has not been reported before.

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.

Does oxidative stress contribute to adverse outcomes in HIV-associated TB?

In HIV infection, oxidative stress is a pronounced phenomenon, with likely links to HIV-related pathologies and the progression of HIV infection per se. TB is an AIDS-defining condition. HIV-associated oxidative stress, like that associated with diabetes mellitus, might adversely impact the outcomes of TB, probably through increased propensity for generation of metabolically dormant mycobacterial persisters, alongside other mechanisms.

Supramolecular strategy for reducing the cardiotoxicity of bedaquiline without compromising its antimycobacterial efficacy.

Bedaquiline (BDQ) is a newly approved anti-tuberculosis drug in treating multidrug-resistant tuberculosis. However, it has very poor aqueous solubility and several case reports have proposed that BDQ has potential risk of cardiotoxicity to patients. In this present study, we have explored into employing host-guest interactions between a synthetic receptor, cucurbit[7]uril (CB[7]), and BDQ aiming to improve the solubility and reduce the inherent cardiotoxicity of BDQ.