First Resistance to a New Generation of Tuberculosis Drugs
Swiss TPH The drugs Bedaquiline and Delamanid belong to a new generation of tuberculosis drugs administered for the treatment of multidrug-resistant tuberculosis. Yet, for the first time, scientists from the Swiss Tropical and Public Health Institute (Swiss TPH) and the University of Zurich detected resistance against these two antibiotics. Treating multidrug-resistant tuberculosis becomes a huge challenge, the researchers in the renowned New England Journal of Medicine say.
Recently, the regulatory authorities in the US and Europe approved the antibiotics Bedaquiline and Delamanid for the treatment of multidrug-resistant TB as part of a fast-track approval. In case study researchers from the Swiss Tropical and Public Health Institute (Swiss TPH) and the University of Zurich now detect first resistance against the two drugs.
Dramatic case history
In 2010 a Tibetan migrant in Switzerland was diagnosed with multidrug-resistant tuberculosis and immediately hospitalised. A therapy consisting of four different antibiotics remained ineffective. Only the new drug Bedaquiline showed temporarily satisfying results. In 2013 the patient was considered cured and released from hospital. But only five months later he suffered a relapse and was hospitalised again. After an unsuccessful treatment with seven different antibiotics, the patient was also given the new antibiotic Delamanid. But after a few weeks, TB bacteria developed resistance against this new drug. Only the partial removal of the lungs could save the patient’s life.
Rapid spread of multidrug-resistant tuberculosis
Researchers from the Swiss TPH analysed the whole genomes of the TB bacteria over the whole treatment period of three years. They show how quickly TB bacteria develop resistance against new antibiotics. In order to prevent resistance, a whole cocktail of new antibiotics would be necessary. „The treatment would have been more successful if we had administered the two antibiotics together“, says Sebastien Gagneux from Swiss TPH and co-author of the study. Together the antibiotics would possibly have eliminated all the bacteria and also hampered resistance. But it is still unknown whether or not a combined administration would cause serious side effects.
Neglected tuberculosis research
It is not only that TB bacteria quickly develop resistance against new drugs. Over decades there were no funds released for research and development of new drugs and vaccines against tuberculosis. The disease was considered a problem of developing countries. But it is no longer. Multidrug-resistant tuberculosis is quickly multiplying in Eastern European countries and more and more diagnosed also in Switzerland. “That such a disease can hardly be cured in Switzerland worries me”, says Gagneux.
Tuberculosis remains a global thread. The disease is easily transmitted from humans to humans by coughing. Multidrug-resistant tuberculosis quickly spreads in Eastern European countries, in Africa as well as Asia. New drugs and vaccines are urgently needed to fight the disease.
Acquired Resistance to Bedaquiline and Delamanid in Therapy for Tuberculosis.
Guido V. Bloemberg, Peter M. Keller, David Stucki, Andrej Trauner, Sonia Borrell, Tsogyal Latshang, Mireia Coscolla, Thomas Rothe, Rico Hömke, Claudia Ritter, Julia Feldmann, Bettina Schulthess, Sebastien Gagneux, and Erik C. Böttger. New England Journal of Medicine 373: 20, 2015. DOI: 10.1056/NEJMc1506878