Abstract | OBJECTIVES: Assessment of the activity of thioridazine towards Mycobacterium tuberculosis (Mtb), in vitro and in vivo as a single drug and in combination with tuberculosis (TB) drugs. METHODS: The in vitro activity of thioridazine as single drug or in combination with TB drugs was assessed in terms of MIC and by use of the time-kill kinetics assay. Various Mtb strains among which the Beijing genotype strain BE-1585 were included. In vivo, mice with TB induced by BE-1585 were treated with a TB drug regimen with thioridazine during 13 weeks. Therapeutic efficacy was assessed by the change in mycobacterial load in the lung, spleen and liver during treatment and 13 weeks post-treatment. RESULTS: CONCLUSIONS:
Thioridazine is bactericidal towards Mtb in vitro, irrespective the mycobacterial growth rate and results in enhanced activity of the standard regimen. The in vitro activity of thioridazine in potentiating isoniazid and rifampicin is not reflected by improved therapeutic efficacy in a murine TB-model.
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Authors | Gerjo J de Knegt, Marian T ten Kate, Dick van Soolingen, Rob Aarnoutse, Martin J Boeree, Irma A J M Bakker-Woudenberg, Jurriaan E M de Steenwinkel |
Journal | Tuberculosis (Edinburgh, Scotland)
(Tuberculosis (Edinb))
Vol. 94
Issue 6
Pg. 701-7
(Dec 2014)
ISSN: 1873-281X [Electronic] Scotland |
PMID | 25621361
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antitubercular Agents
- Drug Combinations
- isoniazid, pyrazinamide, rifampin drug combination
- Pyrazinamide
- Thioridazine
- Isoniazid
- Rifampin
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Topics |
- Animals
- Antitubercular Agents
(administration & dosage, pharmacology, therapeutic use)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Drug Combinations
- Drug Therapy, Combination
- Female
- Isoniazid
(pharmacology, therapeutic use)
- Mice, Inbred BALB C
- Microbial Sensitivity Tests
(methods)
- Microbial Viability
(drug effects)
- Mycobacterium tuberculosis
(drug effects, growth & development)
- Pyrazinamide
(pharmacology, therapeutic use)
- Rifampin
(pharmacology, therapeutic use)
- Stem Cells
(drug effects)
- Thioridazine
(administration & dosage, pharmacology, therapeutic use)
- Tuberculosis
(drug therapy)
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