Medications for Extensively Drug-Resistant Tuberculosis: Back to the Future?

Abstract

Objective: To reexamine the existing medications for the potential treatment of extensively drug-resistant tuberculosis (XDR-TB), based on susceptibility data, and to identify potential future medications from the literature. Data Sources: Relevant information was identified through a search of MEDLINE (1966–November 2007), PubMed (1955–November 2007), American Search Premier (1975–November 2007), International Pharmaceutical Abstracts (1960–November 2007), Science Citation Index Expanded (1996–November 2007), Cochrane Databases (publications archived until November 2007), and various tertiary sources as listed in the references, using the terms extensively drug-resistant tuberculosis (XDR-TB), ethambutol, pyrazinamide, para-aminosalicylic acid, cycloserine, linezolid, diarylquinoline, nitroimidazopyran, fluoroquinolones, β-lactams, new treatments, and ethionamide alone or in combination regimens. Study Selection and Data Extraction: After identification of the relevant information, the data presented in this article were selected based on clinical relevance and value of information. Data Synthesis: Based on susceptibility data, pyrazinamide, ethambutol, para-aminosalicylic acid, cycloserine, and ethionamide may be used for the treatment of tuberculosis. However, due to the emergence of XDR-TB, many of these agents are no longer successful treatment regimens. We have found limited data supporting potential future use of β-lactams, clarithromycin, and linezolid in resistant TB infections. TMC207, nitroimidazopyran, and SQ109 compounds may also prove to be viable options in the near future for treatment of tuberculosis, especially in cases with resistance to mainstay medications. Conclusions: Extensively resistant tuberculosis appears to be a potentially catastrophic disease if allowed to spread. Due to its resistance profile, very few potentially effective agents are available, calling attention to this growing problem.