Updates

"Tuberculosis (TB) has long been, and remains, the most important infectious killer of human beings. Worldwide, the current disease burden is 15 million active cases per year. Standard treatment consists of isoniazid, rifampin, and pyrazinamide for 2 months, followed by intermittent rifampin and isoniazid for 4 months. In case of resistance to isoniazid, initial therapy also includes ethambutol, which is continued until isoniazid susceptibility is documented. To ensure compliance, therapy is ideally administered as directly observed therapy. However, analysis of a series of 11 clinical trials has raised important questions about the effectiveness of directly observed therapy.¹ Moreover, the extended duration of the standard “short course” chemotherapy complicates treatment, especially in resource poor countries, and may result in poor compliance that can lead to the development of drug resistance. Despite completion of therapy, morbidity is still considerable and recurrence occurs commonly.^2,3 Outcomes are especially poor in extra-pulmonary TB. Given these problems, new ways to shorten the duration of chemotherapy and to reduce the emergence of drug resistance are badly needed. The first obvious approach has been the development of newer anti-TB drugs. The second approach has been the application of the sciences of microbial pharmacokinetics/pharmacodynamics (PK/PD) and pharmacometrics to both old and new drugs. Finally, improved understanding of the molecular mechanisms of drug resistance may allow us to block these processes and preserve the efficacy of old and new drugs. In this 3-part series, recent..."