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Global Health and Tropical Medicine

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Why thioridazine in combination with antibiotics cures extensively drug-resistant Mycobacterium tuberculosis infections.

Thioridazine (TDZ) in combination with antibiotics to which extensively drug-resistant Mycobacterium tuberculosis (XDR-TB) is initially resistant yields a cure. This is due to the fact that TDZ enhances the killing of intracellular M. tuberculosis by non-killing macrophages, inhibits the genetic expression of efflux pumps of M. tuberculosis that extrude antibiotics prior to reaching their intended targets, and inhibits the activity of existing efflux pumps that contribute to the multidrug-resistant phenotype of M. tuberculosis.
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Thioridazine: an old neuroleptic effective against totally drug resistant tuberculosis

Globally, tuberculosis infections continue to increase their resistance to antibiotics. Multidrug resistant tuberculosis infections (MDR TB) have progressed to extensively drug resistance status (XDR TB) and the latter have evolved in some parts of the world to totally drug resistant (TDR TB) infections.
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Phenothiazines, bacterial efflux pumps and targeting the macrophage for enhanced killing of intracellular XDRTB

Phenothiazines have their primary effects on the plasma membrane of prokaryotes and eukaryotes. Among the components of the prokaryotic plasma membrane affected are efflux pumps, their energy sources, energy providing enzymes such as ATPases, and genes that regulate and code for permeability aspects of the bacterium.
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Thioridazine cures extensively drug-resistant tuberculosis (XDR-TB) and the need for global trials is now!

Thioridazine (TDZ) has been shown to have in vitro activity against multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis, to promote the killing of intracellular MDR and XDR strains and to cure the mouse of antibiotic-susceptible and -resistant pulmonary tuberculosis (TB) infections.
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Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Staphylococcus aureus.

BACKGROUND:
Antimicrobial resistance mediated by efflux systems is still poorly characterized in Staphylococcus aureus, despite the description of several efflux pumps (EPs) for this bacterium. In this work we used several methodologies to characterize the efflux activity of 52 S. aureus isolates resistant to ciprofloxacin collected in a hospital in Lisbon, Portugal, in order to understand the role played by these systems in the resistance to fluoroquinolones.
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About GHTM

GHTM is a R&D Unit that brings together researchers from IHMT with a track record in Tropical Medicine and International/Global Health. It aims at strengthening Portugal's role as a leading partner in the development and implementation of a global health research agenda. Our evidence-based interventions contribute to the promotion of equity in health and to improve the health of populations.

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