Extensively drug-resistant tuberculosis pathogen develops further resistance to new antibiotics
Testing antibiotic resistance in a petri dish
Scientists led by the Leibniz Research Center Borstel, the Institute of Microbiology and Laboratory Diagnostics in Gauting, the Institute of Medical Microbiology of the University of Zurich and the German Center for Infection Research (DZIF) have, for the first time, confirmed an extensively drug-resistant strain of Mycobacterium-tuberculosis that has additional resistance to the new antibiotics delamanid and bedaquilin.
Tuberculosis (TB) is still one of the most dangerous infectious diseases worldwide, with over nine million cases and more than one and a half million deaths per year. A major challenge in the fight against TB is the spread of multidrug-resistant (MDR) or extensively drug-resistant (XDR) tuberculosis pathogens in Eastern European and Asian regions. MDR/XDR bacteria have undergone changes in their hereditary information making them resistant even to the most effective tuberculosis drugs.
The new drugs bedaquilin (Sirturo®, Janssen-Cilag, USA) and delamanid (Deltyba®, Otsuka Novel Products, Japan), which were approved for treatment in 2014 and are also effective against MDR tuberculosis pathogens, have therefore raised high hopes. The approval for the antibiotics was fast-tracked due to the enormous demand and a lack of alternative drugs.
However, the ability of tuberculosis pathogens to rapidly adapt has quickly become apparent: about six months later researchers at the University of Zurich reported bedaquilin-resistant tuberculosis bacteria in a young Tibetan who had received the drug for MDR-TB treatment in Switzerland. After treatment failure with bedaquilin, the severely ill patient was treated with delamanid and six other antibiotics. Although the patient initially rapidly improved, the TB recurred two months later. The World Health Organisation Reference Laboratory in Gauting near Munich subsequently conducted further specific antibiotic resistance tests.
The scientists in Gauting, led by the physician Dr Harald Hoffmann, confirmed that alongside the existing bedaquilin resistance, the bacteria had also developed resistance to delamanid. In collaboration with a team led by Prof Stefan Niemann from the Research Center Borstel and Dr Peter Keller from the Institute of Medical Microbiology, University of Zurich, the researchers established that a change in hereditary information has caused the resistance.
“The study illustrates the high adaptability of tuberculosis pathogens. New drugs can quickly be rendered ineffective through changes in hereditary information. Additionally, there is a danger of local and regional MDR-TB outbreaks if this newly acquired resistance is passed on through direct transmission of the pathogen and new infections, explains Stefan Niemann, who coordinates the research field Tuberculosis at the DZIF.
