How do you prevent development of antibiotic resistance when suffering from tuberculosis?

Tuberculosis bacilli grow slowly, and grow inside human cells[1] . Slow growth tends to make bacteria intrinsically less susceptible to antibiotics, and being inside a host cell makes it more difficult to achieve a high, therapeutically-effective dose of an antibiotic. To add to the challenge, resistance to some of the most effective anti-TB antibiotics (like rifampin) can arise by single-base mutations in the bacterial genome. Given these factors, it’s not surprising that resistance often emerges during the course of treatment.

The development of resistance is best prevented by multi-drug therapy. Here are the current CDC/IDSA guidelines (in part):

Abbreviations: DOT, directly observed therapy; EMB, ethambutol; HIV, human immunodeficiency virus; INH, isoniazid; PZA, pyrazinamide; RIF, rifampin.

From Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis | Clinical Infectious Diseases | Oxford Academic

If the molecular targets of action for each of the antibiotics used are distinct, then the probability of resistance emerging against all of them goes down exponentially, at least in theory.

The other big factor in the emergence of resistance is compliance. Therapy is long and intensive and relatively expensive – $15,000 in the US and $250 in low-income countries[2] . Patients will start to feel better long before the infection is eradicated, and thus be tempted to skip doses or discontinue therapy. Directly-observed therapy – in which a health-care worker hands you the meds and watches you take them – is an effective means of improving compliance. It also adds substantially to the cost of therapy.

TB was once the leading killer of adults in North American and European cities[3], but declined steeply in the 19th century, long before the discovery of antibiotics or even of Mycobacterium tuberculosis. Nobody really knows why[4] . We rely on antibiotics now to control the spread of TB. If antibiotics begin to fail, we could be in big trouble.

Footnotes

[1] https://www.ncbi.nlm.nih.gov/pmc…

[2] Costs to Health Services and the Patient of Treating Tuberculosis: A Systematic Literature Review

[3] http://www.resmedjournal.com/art…

[4] Historical declines in tuberculosis in England and Wales: improving social conditions or natural selection?