Efflux pump inhibitors as a promising adjunct therapy against drug resistant tuberculosis: a new strategy to revisit mycobacterial targets and repurpose old drugs.

Efflux pump inhibitors as a promising adjunct therapy against drug resistant tuberculosis: a new strategy to revisit mycobacterial targets and repurpose old drugs. Expert Rev Anti Infect Ther. 2020 May 20;:1-17 Authors: Rodrigues L, Cravo P, Viveiros M Abstract Introduction: In 2018, an estimated 377,000 people developed multidrug-resistant tuberculosis (MDR-TB), urging for new effective treatments. In the last years, it has been accepted that efflux pumps play an important role in the evolution of drug resistance. Strategies are required to mitigate the consequences of the activity of efflux pumps.Areas covered: Based upon the literature available in PubMed, up to February 2020, on the diversity of efflux pumps in Mycobacterium tuberculosis and their association with drug resistance, studies that identified efflux inhibitors and their effect on restoring the activity of antimicrobials subjected to efflux are reviewed. These support a new strategy for the development of anti-TB drugs, including efflux inhibitors, using in silico drug repurposing.Expert opinion: The current literature highlights the contribution of efflux pumps in drug resistance in M. tuberculosis and that efflux inhibitors may help to ensure the effectiveness of anti-TB drugs. However, despite the usefulness of efflux inhibitors in in vitro studies, in most cases their application in vivo is restricted due to toxicity. In a time when new drugs are needed to fight MDR-TB and extensively d...
Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research

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GENEVA, SWITZERLAND, 6 JULY 2020 – The Stop TB Partnership and Johnson &Johnson – with support from the Global Fund to Fight AIDS, TB and Malaria, and the U.S. Agency for International Development (USAID) – today announced joint efforts to help enable low- and middle-income countries to rapidly scale up use of SIRTURO® (bedaquiline) 100mg tablets in support of new, recently-released World Health Organization (WHO) treatment guidelines. Effective immediately, Johnson &Johnson will make bedaquiline available to Stop TB Partnership’s Global Drug Facility (GDF) at a price of USD$340 per six-...
Source: Johnson and Johnson - Category: Pharmaceuticals Tags: Innovation Source Type: news
In conclusion, we developed a population PK model and assessed target attainment for different ETA regimens. Patients may not be able to tolerate the doses needed to achieve the predefined targets supporting current recommendations for ETA deprioritization. PMID: 32631828 [PubMed - as supplied by publisher]
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Source: International Journal of Infectious Diseases - Category: Infectious Diseases Authors: Source Type: research
We report a case of acquired fluoroquinolone (FQ) resistance under short-course multidrug-resistant tuberculosis (MDR-TB) treatment. The patient was managed at Kabutare hospital, one of the two specialized MDR-TB clinics in Rwanda. A low dose of moxifloxacin was used in the first three critical months. Acquired resistance was identified at the ninth month of treatment, 3 months after stopping kanamycin in a strain initially susceptible only to FQs, kanamycin, and clofazimine. Fluoroquinolone resistance was detected in the same month by deep sequencing as routinely used second-line probe assay and phenotypic drug susceptibi...
Source: The American Journal of Tropical Medicine and Hygiene - Category: Tropical Medicine Authors: Tags: Am J Trop Med Hyg Source Type: research
M. Jaspard et al.
Source: Emerging Infectious Diseases Journal - Category: Infectious Diseases Source Type: research
Publication date: September 2020Source: Journal of Global Antimicrobial Resistance, Volume 22Author(s): Eddie S. Solo, Chie Nakajima, Trevor Kaile, Precious Bwalya, Grace Mbulo, Yukari Fukushima, Sylvia Chila, Nanthan Kapata, Yogendra Shah, Yasuhiko Suzuki
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
Publication date: September 2020Source: Journal of Global Antimicrobial Resistance, Volume 22Author(s): Ibrahim Bitar, Matej Medvecky, Jana Amlerova, Costas C. Papagiannitsis, Jaroslav Hrabak
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
In Madagascar, the multidrug-resistant tuberculosis (MDR-TB) surveillance programme was launched in late 2012 wherein previously treated TB cases and symptomatic MDR-TB contacts (hereafter called presumptive M...
Source: BMC Medicine - Category: Internal Medicine Authors: Tags: Research article Source Type: research
Tuberculosis (TB) is accounted for as one of the most important destructive infectious diseases for humans, which is caused by Mycobacterium tuberculosis. Studies have shown the severe effects of tuberculosis in patients, especially sensitive groups. Emergence and distribution of both multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains have caused failure in the infection eradication. At present, BCG vaccine is the only most effective vaccine for the prevention of TB in childhood but its protection level in pulmonary TB in adult is very variable. Therefore, the need for an appropriate alternative vaccine...
Source: Reviews in Medical Microbiology - Category: Microbiology Tags: BACTERIOLOGY Source Type: research
Abstract Tuberculosis (TB) is a prominent infective disease and a major reason of mortality/morbidity globally. Mycobacterium tuberculosis causes a long-lasting latent infection in a significant proportion of human population. The increasing burden of tuberculosis is mainly caused due to drug and multi drug-resistant. The failure of conventional treatment has been observed in large number of cases. Drugs that are used to treat extensively drug-resistant tuberculosis are expensive, have limited efficacy and with more side effects for longer duration of time and is often associated with poor prognosis. To regulate t...
Source: Current Pharmaceutical Biotechnology - Category: Biotechnology Authors: Tags: Curr Pharm Biotechnol Source Type: research
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