A phase II study has shown that the new antibiotic moxifloxacin, in combination with other drugs, could shorten the time needed to cure tuberculosis by several months. The findings are reported in Article in this week's edition of The Lancet, written by Professor Richard E Chaisson, Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA, and colleagues.
The development of new drug regimens for tuberculosis is an urgent global health priority. Although so-called short-course treatment can effectively cure drug-susceptible tuberculosis in 6 months, a large proportion of patients in whom tuberculosis is diagnosed do not complete a course of treatment. New drugs that shorten the duration of tuberculosis treatment would substantially reduce the likelihood of disease recurrence and death caused by inadequate therapy. Additionally, since every year there are 500 000 reported cases of tuberculosis caused by strains of Mycobacterium tuberculosis that are resistant to the key first-line drugs isoniazid and rifampicin, agents that are active in multidrug-resistant tuberculosis are also needed. Moxifloxacin is a promising new antibiotic that could add to the effects of existing antituberculosis drugs.
In this randomised controlled trial assessed 170 tuberculosis-positive patients at one hospital in Rio de Janeiro, Brazil. All were receiving a standard of combination of first line tuberculosis drugs, and were then randomised to receive as the fourth drug in their regimen either moxifloxacin 400mg with an ethambutol placebo (85 patients), or ethambutol (15-20 mg/kg) plus moxifloxacin placebo (85 patients) five days per week for eight weeks. Ethambutol is widely used in tuberculosis treatment but has very little activity, and was used as a control. The endpoint of the study was the proportion of patients whose sputum culture tested negative by week eight. The researchers found that, at week eight, 80% of moxifloxacin patients tested negative, compared with 63% in the ethambutol group. A total of 16 adverse events (eight in each group) were reported in 12 patients, with only one being deemed as related to the study drug.
The authors say: "The results of our trial have substantial implications for future trials. First, the improved culture conversion rates found after 8 weeks in the experimental group suggest that moxifloxacin, in combination with other first-line antituberculosis drugs, could shorten the time needed to cure tuberculosis by several months. Because treatment default is directly related to the duration of treatment, a reduction in the duration of tuberculosis therapy would substantially improve outcomes. Additionally, shorter regimens for tuberculosis treatment would reduce workloads for overburdened tuberculosis control programmes, especially in high-incidence countries. Second, the demonstration of moxifloxacin's antimycobacterial activity shows that this agent can be used to treat tuberculosis caused by organisms with resistance to first-line antituberculosis agents, such as isoniazid and rifampicin."
They conclude that clinical trials are now underway to assess whether shorter courses of moxifloxacin-containing regimens can cure tuberculosis as well or better than the current 6-month regimen.
In an accompanying Comment, Dr Hans L Rieder, International Union Against Tuberculosis and Lung Disease, Switzerland, says: "What is needed, and is perhaps in reach, is a regimen [for uncomplicated multidrug-resistant tuberculosis] that is well tolerated, of reasonably short duration, without an unacceptably high frequency of adverse drug effects, and thus an effective treatment. Such a regimen will be deliverable at intermediate rather than specialised central levels in low-income countries."
The lead Editorial in this week's Lancet says discusses the Stop TB Partners Forum happening now in Beijing (April 1), at which ministers from the countries most affected by MDR/XDR-TB* are meeting to discuss strategies for drug-resistant infection. The Editorial says: "To succeed they will need to build consensus, establish political will, and secure sustainable funding... At a time when many US$ billions are spent on failing institutions, the underfunding by $1•6 billion a year for tuberculosis is shameful, particularly when each dollar spent on care generates $15 in productivity."
It concludes: "Attitudes to tuberculosis must change among health professionals and the public. Laboratories and clinicians need to follow best practice in diagnosing, reporting, and managing the disease—and they need to have the tools to do so. Additionally, efforts to control tuberculosis should engage communities to reduce stigma, support care, and develop local solutions. The meeting being held in China this week must be an inflexion point in our collective response to tuberculosis."
Professor Richard E Chaisson, Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA T) +1-410-955-1755 E) rchaiss@jhmi.edu
Dr Hans L Rieder, International Union Against Tuberculosis and Lung Disease, Switzerland T) +41 31 829 4577 / +41 79 321 9122 E) TBRieder@tbrieder.org
Lancet Press Office T) +44 (0) 20 7424 4949 E) pressoffice@lancet.com
For full Article, Comment, and Editorial see: http://press.thelancet.com/tb.pdf
Notes to editors: *MDR = multidrug-resistant, XDR= extensively drug-resistant
Journal
The Lancet