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No vacation from tuberculosis: pausing drug therapy encourages resistance

Tuberculosis is no picnic, but taking the required medicines to treat the disease is a long slog: it takes six months, at least, to treat TB. To prevent patients from quitting treatment too soon, many doctors insist on “directly observed therapy”, where patients take their antibiotics under the watchful eye of a medical professional. However, they may also give their patients a weekly 2-day vacation from treatment. Taking a “drug holiday” from TB antibiotics not only offers patients a break from seeing their doctor every day, it can also boost the effectiveness of the drugs and increase patient adherence to the regimen.

But a holiday isn’t always such a good thing, say the authors of a new study. If the antibiotic drugs aren’t well-matched, drug holidays can encourage Mycobacterium tuberculosis to develop resistance to one of the drugs and undermine therapy.

Drusano et al. noted that two antibiotics commonly used together in TB therapy, moxifloxacin and rifampin, have very different half-lives in the body, so when a patient taking both drugs suddenly stops therapy, rifampin is quickly cleared but moxifloxacin hangs around. What effect could that residual moxifloxacin have on M. tuberculosis? Moxifloxacin is a fluoroquinolone, which are known to induce error-prone replication in M. tuberculosis, so the authors were concerned that the low, residual concentrations of moxifloxacin that result from drug holidays could give M. tuberculosis a weekly chance to regrow under conditions that could actually enhance the development of drug resistance. And they were right.

Click on the "source" link above to read more on mBio's blog, mBiosphere...

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