Mycobacterium abscessus strain variability in preclinical drug development: does it really matter?

Background: New treatment options for Mycobacterium abscessus infections are urgently needed. Since a correlation between MICs and clinical outcomes is not clearly established, potency of novel drugs needs to be evaluated using additional in vitro drug activity assays. Preclinical drug activity assays generally use the M.

Relative Contributions of the Novel Diarylquinoline TBAJ-876 and its Active Metabolite to the Bactericidal Activity in a Murine Model of Tuberculosis.

Background: TBAJ-876 is a next-generation diarylquinoline. In vivo, diarylquinoline metabolites are formed with activity against Mycobacterium tuberculosis. Species-specific differences in parent drug-to-metabolite ratios might impact the translational value of animal model-based predictions.

A laboratory perspective on biofilm culture, characterization and drug activity testing.

is an emerging opportunistic pathogen causing severe pulmonary infections in patients with underlying lung disease and cystic fibrosis in particular. The rising prevalence of infections poses an alarming threat, as the success rates of available treatment options are limited. Central to this challenge is the absence of preclinical models that accurately mimic conditions and that can reliably predict treatment outcomes in patients.

Unraveling antibiotic resistance mechanisms in Mycobacterium abscessus: the potential role of efflux pumps.

Objectives: Mycobacterium abscessus is an opportunistic respiratory pathogen in patients with underlying lung disease. It is infamously known for its low treatment success rates because of its resistance to multiple classes of antibiotics. Further insight into M.

Delamanid or pretomanid? A Solomonic judgement!

Given the low treatment success rates of drug-resistant tuberculosis (TB), novel TB drugs are urgently needed. The landscape of TB treatment has changed considerably over the last decade with the approval of three new compounds: bedaquiline, delamanid and pretomanid. Of these, delamanid and pretomanid belong to the same class of drugs, the nitroimidazoles.

Predictive Modeling to Study the Treatment-Shortening Potential of Novel Tuberculosis Drug Regimens, Toward Bundling of Preclinical Data.

Background: Given the persistently high global burden of tuberculosis, effective and shorter treatment options are needed. We explored the relationship between relapse and treatment length as well as interregimen differences for 2 novel antituberculosis drug regimens using a mouse model of tuberculosis infection and mathematical modeling.

Methods: Mycobacterium tuberculosis-infected mice were treated for up to 13 weeks with bedaquiline and pretomanid combined with moxifloxacin and pyrazinamide (BPaMZ) or linezolid (BPaL).