From the bedside to the bench and back.
The shroud of silence was the most difficult to handle. This is how Nina Khanna from the University Hospital Basel felt in the days just before the NCCR AntiResist was made public. The physician is currently at the forefront of the NCCR. Together with her team, she manages the patient samples without which the project would not move forward.
She almost abandoned all hope, when it took so long for an answer to come. But then in December, when approval for the NCCR AntiResist was granted, all the more was Nina Khanna’s joy. “However, we were initially sworn to secrecy and it wasn’t easy to hide my delight.”The medical doctor and Professor of Infectious Diseases at the University Hospital Basel is responsible for the clinical part of the NCCR.
Nina Khanna has already been working with the infection biologists from the Biozentrum for several years. This started when Dirk Bumann became the Faculty Representative for her PhD students. Later, joint projects arose, they discussed their work and developed new ideas together. “Since Dirk was very interested in the clinical side of things, I took him on the hospital round with me and showed him which pathogens and resistances cause problems in the clinic,” recalls Nina Khanna. “The great thing about the NCCR is that we can bridge the gap between basic research and clinical work. As a practicing physician, it would be immensely difficult to carry out basic research at the high level achieved at the Biozentrum.” In her opinion, the various disciplines are necessary in order to successfully run such a large and ambitious project. Shared with all in the NCCR, she has a great vision: “To uncover yet unknown targets or discover novel therapies and then to test them in the clinic, that would really be great. We are open as to whether we ultimately find a normal antibiotic treatment, a phage therapy or a way to intervene in bacterial communities.”
Nina Khanna started with her project even before the NCCR was launched, because everything is based on her work. She and her team provide the clinical samples and the data for basic research. They are responsible for bringing other hospitals and partners on board and for coordinating the whole thing. “We take specimens from lung secretions and urine, and take biopsies when patients undergo surgery. It is crucial, that we get the samples directly from the patients to study the environment in which the bacteria survive.” This work requires approval from the Ethics Committee, well-trained staff who are familiar with the exact procedures and know how to collect the samples, and a study nurse who coordinates everything. Nina Khanna also deals with antibiotic resistance in clinical routine. But in comparison with the worldwide epidemiology, such resistance does not occur very frequently at the University Hospital in Basel. Gram-negative bacteria, which are often resistant to many antibiotics, are not a local problem. It is rather patients from abroad who bring the multi-resistant pathogens with them. “We have patients from Thailand, Colombia and the Balkan countries. When they come to us from other hospitals, they also introduce resistant pathogens collected from there,” reports Nina Khanna. “We certainly come into contact with resistant bacteria every week but can successfully treat most infections with a broad spectrum of commonly used antibiotics. In cases of very serious infections, we sometimes have to request emergency antibiotics or new, not yet approved drugs.”
Nina Khanna experiences quite often that patients die from an infection. But this is not due to ineffective antibiotics but rather because the infection is already in a late stage. The pathogen has already spread throughout the patient’s body. Should the germ find its way into the blood circulation, it can lead to circulatory collapse and multiple organ failure, often with a fatal outcome. Especially at risk are individuals with a weakened immune system, including patients who have undergone chemotherapy or a transplantation. And also being elderly, diabetic or having serious injuries from an accident are risk factors for a life-threatening infection.
Prof. Nina Khanna is a research group leader at the Department of Biomedicine and senior physician in the Clinic for Infectious Diseases and Hospital Epidemiology at the University Hospital Basel. She studied medicine at the Universities of Fribourg and Basel and subsequently worked as a postdoc at the University of Würzburg. In 2012, she became the Deputy of the Infection Biology research lab, which she took over as the Head two years later. In 2017, she was appoin- ted to Titular Professor for Infectious Diseases.
The Gram-positive bacterium Staphylococcus aureus causes most of the problems in the hospital,” emphasizes Nina Khanna. “It causes persistent infections that we can only manage with surgery. Although the antibiotic itself is effective, an operation is required to reach the site of infection.” Resistant pathogens are also a problem for patients with cystic fibrosis. In this hereditary metabolic disease, the lungs produce viscous mucus, which is a perfect breeding ground for germs. As those affected, often consequently suffer from chronic pulmonary infections, they are frequently treated with antibiotics for extended periods, which in turn promotes the development of resistance.
Basically, most pathogens met in daily hospital life are sensitive to antibiotics. But for patients infected with multi-resistant bacteria special protective measures come into force. “For this, it is of course important to know exactly how the pathogen is transmitted. All these measures lie in the responsibility of the Hospital Hygiene department. In my daily work, I am not concerned about getting infected,” says Nina Khanna. “Considering, however, the current developments in antibiotic resistance, there is no doubt that we urgently need to find new antibiotics. The NCCR is an important step in this direction.»