More research needed to fight multidrug-resistant TB

One third of the world's population is infected with tuberculosis (TB) and despite valiant efforts to combat it, TB continues to pose a serious threat to individuals and public health around the world. In recent years the fight got harder as a new strain of multidrug-resista...

One third of the world's population is infected with tuberculosis (TB) and despite valiant efforts to combat it, TB continues to pose a serious threat to individuals and public health around the world.

In recent years the fight got harder as a new strain of multidrug-resistant tuberculosis (MDR-TB) has created a serious new threat. New research may have the answer to fighting this new strain of TB, but more research is needed to optimise the recommended treatment. The study was funded in part by the TB PAN-NET ('Pan-European network for the study and clinical management of drug resistant tuberculosis') project, which has received almost EUR 11 million under the Health Theme of the EU's Seventh Framework Programme (FP7).

According to an international research group called the Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB, the use of newer drugs, a greater number of effective drugs, and a longer treatment regimen may be associated with improved survival of patients with MDR-TB. Their research was published in PLOS Medicine.

In 2010, 8.8 million people fell ill with TB and 1.4 million people died from it making it the second greatest killer worldwide due to a single infectious agent. More than 95 % of these deaths occur in low and middle-income countries leading many in the first world to believe that they are safe. In fact, no country has eradicated the disease and according to statistics from the World Health Organization (WHO), in Europe alone TB causes 49 new cases and kills 7 people every hour.

Global efforts to control TB however are being challenged by the emergence of strains that are resistant to several antibiotics including isoniazid and rifampicin, the two most powerful, first-line (standard) anti-tuberculosis drugs. The treatment of MDR-TB is lengthy, toxic, expensive and has mostly resulted in poor outcomes for patients. Importantly, the optimal treatment regimens for MDR-TB have not been determined and, to date, there have been no randomised controlled trials of treatments for MDR-TB.

In some countries, it is becoming increasingly difficult to treat MDR-TB. Treatment options are limited and recommended medicines are not always available. In some cases even more drug-resistant tuberculosis is developing. Extensively drug-resistant TB, XDR-TB, is a form of MDR-TB that responds to even fewer available medicines.

The researchers from the Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB pooled data on outcomes of 9 153 patients from 32 centres to find out more about the most effective way of treating MDR-TB. What the researchers discovered was that the use of certain drugs, the use of four or more effective drugs, and the duration of treatment were associated with successful patient outcomes.

From this the authors were able to conclude that 'this individual patient data meta-analysis of 9 153 patients suggests that treatment of MDR-TB should include a later generation quinolone, and ethionamide or prothionamide. In patients who have not received second-line drugs before, the optimal number of likely effective drugs appears to be at least four in the initial intensive phase, and at least three in the continuation phase. The duration of therapy associated with highest odds of success was 7-8.5 months for the initial intensive phase, and 25-27 months for total duration.

Despite this, the authors urge caution in interpreting the results due to the limitations in the methods and type of data used in the study. The authors note: 'In view of the serious limitations of these observational data, these findings should be considered to have highlighted several important questions for future clinical trials. These questions include the role and choice of injectables (medications that have to be given by injection), the optimal duration of an injectable and total therapy, and the potential value of later generation quinolones as well as certain group 4 and group 5 drugs.'For more information, please visit: PLOS Medicine http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001300 WHO Tuberculosishttp://www.who.int/topics/tuberculosis/en/