Tuberculosis is a tough disease. Once infected, you're committed to months of a hodge-podge of medications (yes, i used the word hodge-podge) with varying side effects. What we've settled on is a standard four-drug regimen, using four drugs mostly to prevent against the development of resistance, a phenomenon that I'll talk about in a later post. This standard course of therapy is riddled with compliance issues, making a shorter, more tolerable regimen in everybody's best interests. And finding new drugs has been incredibly difficult.
So it's refreshing to see this study from Brazil, where they randomized treatment-naive patients to 8 weeks of either ethambutol, the standard, or moxifloxacin, a fluoroquinolone antibiotic that we know works against TB, in addition to the classic three-drug regimen. They then finished the 6 months of therapy with the standard two-drug regimen. They excluded patients with HIV requiring antiretroviral therapy and patients whose initial culture grew out a multi-drug resistant organism, among other things. The findings are striking.
At 8 weeks of treatment, patients in the moxifloxacin group had an 80% culture negative rate, compared with 63% in the ethambutol group, with the difference noticeable even at the 1 week point. There were no significant differences for adverse events.
Intensive treatment of TB was initially 18 months, then 9 months, then 6 months, where it is now. If a shorter course of therapy with moxifloxacin is compared with a longer course and these results hold, then we may be looking at an even shorter course of therapy, a significant change. If moxifloxacin's effects are in just killing a bunch of TB at the very beginning and leaving the slow-growing bugs to persist, then you'd expect a difference in relapse rates, which there wasn't in the study, although it may not have been a big enough study to detect a difference in a relatively rare finding.
The major goal for TB therapy globally is simplification: with this, you'll achieve resistance control, be able to manage disease in the community and not only in the major centres, and get more people completing their treatment regimen. This may be a step towards that goal.
Conde, M., Efron, A., Loredo, C., De Souza, G., Graça, N., Cezar, M., Ram, M., Chaudhary, M., Bishai, W., & Kritski, A. (2009). Moxifloxacin versus ethambutol in the initial treatment of tuberculosis: a double-blind, randomised, controlled phase II trial The Lancet, 373 (9670), 1183-1189 DOI: 10.1016/S0140-6736(09)60333-0
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