The number of multidrug-resistant (MDR) tuberculosis cases officially reported to WHO increased from 29 000 to 53 000 between 2008 and 2010,1 still representing only 18% of the estimated 290 000 patients potentially identifiable if drug susceptibility testing was done in all notified cases of tuberculosis.1
A recent study done in Belarus2 showed a new global record for prevalence of MDR tuberculosis with 35·3% of new patients and 76·5% of previously treated patients diagnosed with the disease. This finding clearly shows how far case mismanagement can affect the chances to control (and eventually eliminate) the disease.1, 2
Unfortunately, since only a quarter of patients with tuberculosis are treated according to established standards and the proportion of treatment success does not exceed 50%,1 extensively drug-resistant (XDR) tuberculosis has already been reported in 77 countries and totally drug resistant cases (ie, Mycobacterium tuberculosis strains with resistance to all known drugs) have been recently described in Italy, Iran, and India.3
The urgent need for new drugs is obvious. The question the tuberculosis community is anxiously posing is whether, in addition to existing drugs,4 the most promising compounds in the development pipeline (delamanid, bedaquiline, and PA-824) are as effective as preliminary studies suggested.1
Gler and colleagues5 and Diacon and colleagues6 provided part of the answer when they reported that delamanid in combination with a background regimen developed according to WHO guidelines,7 is associated with an increase in sputum-culture conversion at 2 months in patients with MDR tuberculosis.
In The Lancet, Andreas Diacon and colleagues8 point to a new direction in tuberculosis treatment with a universal regimen that would be equally effective against Mycobacterium tuberculosis susceptible and MDR strains. Diacon and colleagues assessed the 14-day early bactericidal activity (EBA) of PA-824-moxifloxacin-pyrazinamide. The mean 14-day EBA of this combination (n=13; 0·233 [SD 0·128]) was significantly higher than that of bedaquiline alone (n=14; 0·061 [0·068]), bedaquiline-pyrazinamide (n=15; 0·131 [0·102]), bedaquiline-PA-824 (14; 0·114 [0·050]), but not PA-824-pyrazinamide (n=14; 0·154 [0·040]), and was comparable with standard treatment (ie, rifampicin, isoniazid, and pyrazinamide with streptomycin or ethambutol; n=ten; 0·140 [0·094]), as reported previously.8, 9 Importantly, the addition of pyrazinamide increased the activity of bedaquiline and PA-824.
Diacon and colleagues' study makes several important contributions to the existing body of knowledge. First, treatments seem to be well tolerated and safe, although their study design and sample size does not allow assignment of adverse events to a specific agent.
The exclusion of tuberculosis patients with comorbidities and the poor sample-size-related inferential strength are methodologically justified by the early clinical research phase and underline the need for further trials that enrol more heterogeneous and larger cohorts.