TB: It's Still a Treatment Challenge

A recent review published in the New England Journal of Medicine examined the principles of tuberculosis treatment, current approaches, areas of uncertainty, and persistent challenges to combatting the disease. C. Robert Horsburgh, Jr., MD, of Boston University, and colleagues published a review article regarding the treatment of tuberculosis on November 26, 2015.

Tuberculosis has been a concern since before people began keeping records. Even in today’s age of modern medicine, 1.5 million people die from the disease each year. According to the review, “standard treatment now consists of a 2-month induction phase with at least isoniazid, rifampin, and pyrazinamide, followed by a 4-month consolidation phase with at least isoniazid and rifampin.” During the induction phase, two sets of bacteria are killed, the first one quickly, and the second which has been classified as persistent.

However, the researchers note, “Despite the usefulness of this conceptual model, there are some important unexplained observations.” After the first two months of drug therapy, most patients appear to be cured, yet many must still complete the additional four months of therapy in order to avoid relapse. The problem is that there is no way to identify those will or will not relapse without the extra drugs, which means at least some people are being overtreated.

The last 10 years have seen a great change in how tuberculosis is diagnosed. “Although culture remains the standard for both diagnosis and drug susceptibility testing, molecular DNA-based diagnostics have become widely available and permit both rapid diagnosis and preliminary assessment of drug susceptibility.” Faster diagnosis allows for faster treatment.

Still, the 6-month treatment plan is long compared to the standard treatments for other infectious diseases, and 3-13% of patients experience hepatotoxic effects, 15% have adverse drug reactions, and 7.7% of those result in hospitalization, disability or death. Additionally, between 16 and 49% of patients do not complete the full 6-month treatment for a wide variety of reasons from adverse drug reactions to stigma, or the patient’s belief they are cured.

Multidrug-resistant (MDR) tuberculosis presents additional, complicated issues. “Whenever possible, the initial treatment regimen should be individually tailored according to the results of drug susceptibility testing of the M. tuberculosis isolate from the patient.” There are still many questions and opportunities to improve the treatment of tuberculosis. Faster, more accurate molecular testing to assess drug resistance, better tools for understanding how the drugs penetrate in order to develop individualized treatment plans, and the development of new drugs will all contribute to “less toxic, radically shorter regimens of curative treatment.”