Preclinical efficacy testing of new drug candidates

Since the early 1950s, combination chemotherapy has remained the strongest line of defense against the ancient scourge of tuberculosis (TB). Between the years 2000 and 2015 alone, it was estimated that TB treatment averted 39 million deaths among people without HIV infection and, together with antiretroviral therapy, another 9.6 million deaths among people with HIV infection (1). Despite these successes, TB continues to exert a terrible toll on humanity. In 2015, TB was estimated to be the cause of 10.4 million new cases and 1.4 million deaths, making Mycobacterium tuberculosis the leading microbial cause of death in the world (1). The failure to achieve greater control of TB over the past half century is partly attributable to several important limitations of current chemotherapy regimens, including the prolonged treatment durations necessary to prevent relapse after treatment completion and the inability to effectively suppress resistance emergence when treatment is applied on a global scale. These deficiencies are especially notable for current second-line and salvage regimens used to treat drug-resistant TB (2 - 4), which are also complicated by excessive toxicity, poor tolerability, high cost, and the inconvenience of injections, multiple daily doses, and large pill burdens. As a result, shortening or otherwise simplifying regimens to treat TB without sacrificing efficacy is a major goal of TB drug development research (5).