Multidrug-resistant tuberculosis (MDR-TB) is an increasing challenge for the treatment of TB. Currently existing drugs for the treatment of MDR TB are only moderately potent, show restrictions with absorption or oral bioavailability, and have toxicity profiles that make patient management difficult. Current international guidelines for the treatment of MDR-TB include at least one second-line agent administered by injection. There are two important classes of injectable drugs: the aminoglycosides (amikacin and kanamycin) and the polypeptide capreomycin. Capreomycin is specifically recommended for use in cases of known or suspected resistance to the aminoglycosides. Capreomycin also seems to have activity against non-replicating persister bacilli, unlike aminoglycosides. The drug is painful to receive by injection and is associated with severe systemic side effects, including nephrotoxicity and ototoxicity. The goal of this project is to develop novel formulations or modifications of capreomycin that can be orally administered, maintain efficacy, possibly decrease adverse events (nephrotoxicity and ototoxicity), and used as part of a drug regimen for the treatment of MDR-TB.
