Speaker
Description
Background and objectives: Tuberculosis (TB) is the leading bacterial cause of human death worldwide. The proportion of antibiotic resistant Mycobacterium tuberculosis (Mtb) strains is increasing. The aim of this study was to analyze the effect of an orally administered anti-TB drug candidate - benzothiazinone (BTZ) - 043 on Mtb induced granulomas.
Material and Methods: Eighteen guinea pigs were infected s.c. with 1x10^3 Mtb H37Rv. Starting 14 d after infection, subgroups (n=6, each) were orally treated with BTZ-043, isoniazid, and vehicle, respectively, daily for 28 d. On day 42 after infection, animals were euthanized and a complete autopsy with macroscopic assessment of lesions was conducted. Fixed (4 % formaldehyde) tissue samples and granulomas were processed by histochemical and immunohistochemical methods. Stained tissue sections were scanned as whole-slide images to allow quantification and statistical testing of lesion parameters.
Results: The extent of subcutaneous granulomas and the proportion of necrosis were significantly reduced in BTZ-043-treated guinea pigs compared to vehicle controls. Systemic spread with granuloma genesis in other organs did not occur in this group. A highly significant reduction in mycobacterial load in subcutaneous granulomas, draining lymph nodes and spleen was demonstrated.
Conclusions: BTZ-043 is a promising antibiotic and showed significant efficacy in the guinea pig model of TB after only 28 days of oral administration.
Keywords
BTZ-043, guinea pig, Mycobacterium tuberculosis, MDR-TB, treatment, new antibiotics
Registration-ID code | 450 |
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Junior Scientist Status | No, I am not a Junior Scientist. |
Professional Status of the Speaker | Postdoc |
Primary author
Co-authors
External references
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