In vitro, PA-824 exhibits the high activity against multidrug-resistant clinical isolates from Asia (India and South Korea) and from throughout the United States (MIC < 1 μg/ml) and is equally active against the drug-sensitive and multidrug-resistant isolates of M. tuberculosis (MICs range, 0.039 to 0.531 μg/ml).A recent study shows that single-nucleotide polymorphisms of PA-824 resistance genes (fgd1 [Rv0407] and ddn [Rv3547]) don't significantly affect the PA-824 MICs (≤ 0.25 μg/ml).

In the rapid tuberculosis mouse model, PA-824 shows significant anti-microbial activity in a dose-dependent manner: at 50 mg/kg, PA-824 in MC produces a more than 1-log reduction of the CFU in the lungs; at 100 mg/kg it produces about a 2-log reduction, and at 300 mg/kg it produces a 3-log reduction. Furthermore, long-term treatment of PA-824 at 100 mg/kg in cyclodextrin/lecithin also leads to the reduction of the bacterial load below 500 CFU in the lungs and spleen.PA-824 exhibits time-dependent anti-microbial activity in a murine model of tuberculosis with a maximal observed bactericidal effect of 0.1 log CFU/day over 24 days.

(S)-Tedizolid

5-hydroxypyrazine-2-carboxylic acid

Actinomycin D

AHAS inhibitor

Amikacin

Amikacin hydrate

Amoxicillin

Amoxicillin sodium

Amoxicillin trihydrate