Title: Drug-resistant Tuberculosis - where next?

Tjip van der Werf

University of Groningen, Netherlands


Dr. van der Werf studied Medicine at the Groningen University, Netherlands and graduated as an MD in 1980. He worked as a tropical doctor in Ghana where he first was exposed to challenges in TB treatment. After his PhD thesis (1991) on studies in TB and Buruli ulcer at the University in Groningen, he joined the University Medical Center Groningen as a board certified Chest Physician. His clinical and scientific interests include critical care and infectious diseases including TB and Buruli ulcer. In 2006, he was appointed as full professor in Infectious Diseases. As of November 2018, he had published 340 articles in PubMed; 26 PhD students graduated under his supervision; his H factor was 37.


Tuberculosis (TB) control is severely hampered by the emerging threat of drug resistance. BCG, although the most widely used vaccine, has not been shown to impact on the global TB epidemic. Only few novel drugs that have become available, and most of the treatment components consist of repurposed drugs (new generation quinolones, linezolid and clofazimine) while two of the injectable agents have recently been withdrawn because of their associated risk of poor outcome. Many patients in highly burdened settings drop out because of the toxicity and long duration of 2nd line drug treatment.

An overview will be presented of the current evidence to treat drug-resistant TB; the issue of drug exposure to individualize treatment based on an algorithm that includes therapeutic drug monitoring; the potential to fine tune treatment based on pharmacokinetic and pharmacodynamic modeling; and the potential of host targeted treatment components, attempts to prevent sequelae including early case finding and prevention of scar formation, as well as therapeutic vaccination. A recent break-through opening the way to develop biomarkers as surrogate endpoints to speed up vaccine development will be discussed.

The need to collaborate between all stake holders including public health, microbiologists, public and private care providers and drug providers will be addressed, as well as the need to integrate management for co-infections with HIV and hepatitis B/C. Finally, knowledge gaps to improve treatment outcome will be discussed.

Audience take away:

•    The emerging threat of drug resistant TB 
•    The essentials of pharmacokinetic/pharmacodynamic modeling to reduce toxicity, and to enhance efficacy, in order to improve TB treatment outcome
•    The importance of collaborative networks with all stakeholders involved
•    Thinking outside the box – considering therapeutic vaccines, integrate pharmacological en microbiological data to improve treatment outcome; combine hard and soft skills to improve adherence and improve outcome
•    The model presented applies to a wider spectrum of chronic conditions. The research presented illustrates how collaborative research can improve patient   outcome. 
•    We foster a research agenda focused on the weakest link in the chain leading to improved outcome.