XDR tuberculosis

Back ground: Drug resistant tuberculosis is alarmingly on the rise especially in developing countries. Skeletal tuberculosis accounts up to 10% of all extra pulmonary tuberculosis. World Health Organisation (WHO) has not formulated guidelines for the management of Multi-drug resistant skeletal tuberculosis. Results: A retrospective analysis of patients treated for musculoskeletal tuberculosis was done, to study drug resistance patterns. The outcome was assessed both clinically and radiologically...

Owing to the spread of multidrug resistance (MDR) and extensive drug resistance (XDR), there is a pressing need to identify potential targets for the development of more-effective anti-M. tuberculosis (Mtb) drugs. PafA, as the sole Prokaryotic Ubiquitin-like Protein ligase in the Pup-proteasome System (PPS) of Mtb, is an attractive drug target. Here, we show that the activity of purified Mtb PafA is significantly inhibited upon the association of AEBSF (4-(2-aminoethyl) benzenesulfonyl fluoride) to PafA residue Serine 119 (S119)...

BACKGROUND: Mycobacterium tuberculosis drug resistance is a major challenge to the use of standardized regimens for tuberculosis (TB) therapy, especially among previously treated patients. We aimed to investigate the frequency and pattern of drug resistance among previously treated patients with smear-positive pulmonary tuberculosis at the Korle-Bu Teaching Hospital Chest Clinic, Accra. METHODS: This was a cross-sectional survey of mycobacterial isolates from previously treated patients referred to the Chest Clinic Laboratory between October 2010 and October 2013...

SETTING: B.J.Wadia Hospital,Mumbai OBJECTIVE:: The prevalence and type of DR-TB was evaluated pre and post-2013 and outcome was studied. DESIGN: Descriptive retrospective study. Children were defined as having DR-TB on the basis of GeneXpert or LPA and/or drug susceptibility testing(DST) of MTB grown on culture or from contact's DST. RESULTS & CONCLUSION: The prevalence of DR-TB was 110 out of 1145 cases (9.6%) which showed an increase, compared to 5...

AIMS: Pyrazinamide (PZA) is an important component of first-line tuberculosis (TB) treatment because of its distinctive capability to kill subpopulations of persister Mycobacterium tuberculosis (MTB). The significance of PZA can be understood by its inclusion in the most recent World Health Organization-recommended multidrug-resistant (MDR) TB regimen. Very little information is available about the prevalence of PZA-resistant TB from geographically distinct regions of high burden countries, including Khyber Pakhtunkhwa (KPK), Pakistan, because drug susceptibility testing (DST) of PZA is not regularly performed due to the complexity...

Little is known about the impact of comorbidities on multidrug resistant (MDR) and extensively drug resistant (XDR) tuberculosis (TB) treatment outcomes. We aimed to examine the effect of human immunodeficiency virus (HIV), diabetes, chronic kidney disease (CKD), alcohol misuse, and smoking on MDR/XDRTB treatment outcomes. We searched MEDLINE, EMBASE, Cochrane Central Registrar and Cochrane Database of Systematic Reviews as per PRISMA guidelines. Eligible studies were identified and treatment outcome data were extracted...

The Ukraine ranks among the top twenty countries with the highest number of multi-drug resistant (MDR), and extensively drug resistant (XDR) Mycobacterium tuberculosis (MTB) cases in the world. However, little is known of the genetic diversity, i.e., resistance signatures in clinical isolates from this region. We analyzed seven of most prevalent MDR/XDR antibiotic resistance conferring genes from clinical isolates ( N = 75 ) collected from geographically diverse Ukrainian oblasts and its southern Crimean peninsula...

BACKGROUND: Excellent treatment outcomes have recently been reported for patients with multi/extensively drug-resistant tuberculosis (M/XDR-TB) in settings where optimal resources for individualised therapy are available. OBJECTIVE: To ascertain whether differences remain in treatment responses between patients with M/XDR-TB and those with non-M/XDR-TB. METHOD: Patients with TB were prospectively enrolled between March 2013 and March 2016 at five hospitals in Germany...

Despite the low expensive and effective four-drug treatment regimen (isoniazid, rifampicin, pyrazinamide and ethambutol) was introduced 40 years ago, TB continues to cause considerable morbidity and mortality worldwide. In 2015, the WHO estimated a total of 10.4 million new tuberculosis (TB) cases worldwide. Currently, the increased number of multidrug-resistant (MDR-TB), extensively-drug resistant (XDR-TB) and in some recent reports, totally drug-resistant TB (TDR-TB) cases raises concerns about this disease...

Tuberculosis (TB) remains a major health problem worldwide. The infectious agent, Mycobacterium tuberculosis, has a unique ability to survive within the host, alternating between active and latent disease states, and escaping the immune system defences. The extended duration of anti-TB regimens and the increasing prevalence of multidrug- (MDR) and extensively drug-resistant (XDR) M. tuberculosis strains have created an urgent need for new antibiotics active against drug-resistant organisms and that can shorten standard therapy...

With the growing body of knowledge on the contribution of efflux activity to Mycobacterium tuberculosis drug resistance, increased attention has been given to the use of efflux inhibitors as adjuvants of tuberculosis therapy. Here, we investigated how efflux activity modulates the levels of efflux between monoresistant and multi- and extensively drug resistant (M/XDR) M. tuberculosis clinical isolates. The strains were characterized by antibiotic susceptibility testing in the presence/absence of efflux inhibitors, molecular typing, and genetic analysis of drug-resistance-associated genes...

Multidrug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) has emerged as global health threat, causing millions of deaths worldwide. Identification of new drug candidates for tuberculosis (TB) by targeting novel and less explored protein targets will be invaluable for antituberculosis drug discovery. We performed structure based virtual screening of eMolecules database against a homology model of relatively unexplored protein target: the α-subunit of Tryptophan synthase (α-TRPS) from Mycobacterium tuberculosis essential for bacterial survival...

BACKGROUND: Growth-based drug susceptibility testing (DST) is the reference standard for diagnosing drug-resistant tuberculosis (TB), but standard time to result (TTR) is typically ≥ 3 weeks. Rapid tests can reduce that TTR to days or hours, but accuracy may be lowered. In addition to the TTR and test accuracy, the cost of a diagnostic test may affect whether it is adopted in clinical settings. We examine the cost-effectiveness of rapid diagnostics for extremely drug-resistant TB (XDR-TB) in three different high-prevalence settings...

BACKGROUND: The emergence of extensively drug-resistant tuberculosis (XDR-TB) has raised public health concern for global TB control. Although multi drug-resistant tuberculosis (MDR- TB) prevalence and associated genetic mutations in Morocco are well documented, scarce information on XDR TB is available. Hence, the evaluation of pre-XDR and XDR prevalence, as well as the mutation status of gyrA, gyrB, rrs, tlyA genes and eis promoter region, associated with resistance to second line drugs, is of great value for better management of M/XDR TB in Morocco...

Tuberculosis (TB) remains a major global health problem and ranks as the second leading cause of death among deaths caused by infectious diseases worldwide. Although the availability of short-course regimens as first-line anti-tuberculosis drugs, the emergence of drug-resistant Mycobacterium tuberculosis strains pose a major challenge to the prevention and control efforts of national tuberculosis programs (NTPs). M. tuberculosis changes its cellular environment with the mechanisms that have been evolved since prehistoric times...

PURPOSE OF REVIEW: Multidrug-resistant (MDR) tuberculosis (TB) and extensively drug-resistant (XDR)-TB epidemics are key obstacles towards TB control and elimination. RECENT FINDINGS: Diagnosis of MDR/XDR-TB is difficult and requires several weeks. New diagnostic tools are being tested and proposed allowing for shorter time to diagnosis and reduced delays in starting an adequate treatment regimen. MDR/XDR-TB treatment strategies are currently on an evolving stage...

Tuberculosis (TB) remains as one of the leading killer infectious diseases of humans. At present, the standard therapeutic regimen to treat TB comprised of multiple antibiotics administered for a minimum of six months. Although these drugs are useful in controlling TB burden globally, they have not eliminated the disease. In addition, the lengthy duration of treatment with multiple drugs contributes to patient non-compliance that can result in the development of drug resistant strains (MDR and XDR) of Mycobacterium tuberculosis (Mtb), the causative agent of TB...

After decades of relative inactivity, a large increase in efforts to discover antitubercular therapeutics has brought insights into the biology of Mycobacterium tuberculosis (Mtb) and promising new drugs such as bedaquiline, which inhibits ATP synthase, and the nitroimidazoles delamanid and pretomanid, which inhibit both mycolic acid synthesis and energy production. Despite these advances, the drug discovery pipeline remains underpopulated. The field desperately needs compounds with novel mechanisms of action capable of inhibiting multi- and extensively drug -resistant Mtb (M/XDR-TB) and, potentially, nonreplicating Mtb with the hope of shortening the duration of required therapy...

Mycobacterium tuberculosis, the causative agent of tuberculosis disease, is one among the deadliest pathogens in the world. Due to long treatment regimen, HIV co-infection, persistence of bacilli in latent form and development of XDR and TDR strains of Mtb, tuberculosis has posed serious concerns for managing the disease, and calls for discovery of new drugs and drug targets. Using a computational pipeline involving analysis of the structural models of the Mtb proteome and an analysis of the ATPome, followed by a series of filters to identify druggable proteins, solubility and length of the protein, several candidate proteins were shortlisted...

Multidrug-resistant (MDR) and extensive drug-resistant (XDR) tuberculosis (TB) are significant health problems throughout the world. Although the main treatment is medical, adjunctive surgical resection may increase the chance of cure in selected patients with MDR-TB or XDR-TB. This study aimed to present a case series of patients who underwent surgical resection for MDR-TB.Between March 2008 and November 2011, surgical resection was performed on 54 patients including 34 with MDR-TB and 20 with XDR-TB at the Departments of Surgery of Shanghai Public Health Clinical Center (Shanghai), Henan Chest Hospital (Henan), and Anhui Chest Hospital (Henan)...