Scientists have developed a new strategy for treating tuberculosis using dry powder aerosols that could be delivered with an inhaler. The researchers from the University of North Carolina School of Pharmacy, Chapel Hill, North Carolina; and Harvard School of Engineering and Applied Sciences, Cambridge, Massachusetts, report their findings in the April 2010 issue of the journal Antimicrobial Agents and Chemotherapy.
Epidemic rates of HIV/TB coinfection as well as emerging multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB strains are contributing to increased TB-associated deaths worldwide. PA-284, a compound capable of being formulated into a dry powder, has not only shown promising activity against MDR and XDR but has also proven safe and effective in patients coinfected with HIV and TB. Previous studies showed that PA-284 was well-tolerated in tablet form, however, side effects such as headache and stomach discomfort were reported. Aerosol delivery of PA-284 directly to the primary site of infection would limit systemic exposure and ultimately eliminate potentially bothersome side effects.
In the study guinea pigs were used to evaluate the effects of PA-284 aerosols on TB infection. One month following infection with TB some guinea pigs received high daily aerosol treatments while others received low daily treatments for 4 weeks. Lung and spleen analysis of guinea pigs receiving the high dose of aerosol PA-284 showed less inflammation, bacterial burden and tissue damage.
"The present studies indicate the potential use of PA-824 dry powder aerosols in the treatment of TB," say the researchers.
(L. Garcia-Contreras, J.C. Sung, P. Muttil, D. Padilla, M. Telko, J.L. VerBerkmoes, K.J. Elbert, A.J. Hickey, D.A. Edwards. 2010. Dry powder PA-824 aerosols for treatment of tuberculosis in guinea pigs. Antimicrobial Agents and Chemotherapy, 54. 4: 1436-1442.)