New experimental drugs for the treatment of tuberculosis

Abstract

New antitubercular agents are needed for two main purposes: to further simplify therapy (through reductions in the number of medicaments used, the number of doses administered, and the duration of treatment required), thus facilitating supervision and improving compliance, and to combat resistant mycobacteria. Reduction in the number of medicaments has been achieved by combining two or more drugs in a single tablet while retaining a degree of bioavailability similar to that of the single components. The adverse effects observed with once-weekly high doses of rifampin have limited the development of widely spaced intermittent regimens of treatment. For this reason new rifamycins have been developed that are as active as rifampin against mycobacteria but that also offer the advantage of high and prolonged serum levels and thus have the potential for once-weekly administration. The in vitro and in vivo properties of these drugs have been studied. Three classes of drugs show promise for the treatment of drug-resistant tuberculosis: spiropiperidyl rifamycin, the fluoroquinolones, and combinations of beta-lactam agents and beta-lactamase inhibitors.