Personal stories: Roger Brüggemann and Rob ter Heine
RadboudUMC is the large academic hospital of Radboud University in Nijmegen. We spoke with Rob ter Heine and Roger Brüggemann, pharmacists at RadboudUMC, about the biomarker of SensUs 2018, their vision on biosensing, the importance of personal dosing, and about the future of healthcare and SensUs.
Who are we?
I am Roger Brüggemann, a hospital pharmacist and clinical pharmacologist at the Radboud University Medical Center in Nijmegen, the Netherlands. My work focuses on antibiotics and the treatment of fungal diseases. In our research group HIV, Hepatitis C and TBC are also researched. I became a hospital pharmacist and clinical pharmacist because it connects chemistry with patients. The interactions with doctors and the complex care of hospitalized patients seemed the most beautiful challenge to me. My main task is to predict the behavior of medicines like antibiotics and to look how we can improve these therapies for individuals.
My name is Rob ter Heine, I am specialized in making computer models for the prediction of drug behavior and graduated as a hospital pharmacist and clinical pharmacologist. I have been working at the RadboudUMC Nijmegen for three years to improve the treatment of infectious diseases. In this way, I contribute to improving medical care in a scientific way. Our work can be applied at any moment, i.e. a solution we came up with last week could be used today. At the Radboud UMC Nijmegen I act as an expert for mathematical modelling with applications in multiple medical fields.
We look at what happens to patients during their stay in, for example, the Intensive Care and by doing research we try to contribute to an optimal treatment of each individual patient. We work in a so called “stewardship” with our department, which is a collaboration between microbiologists, infectiologists and pharmacists who predict the future of resistance to medicines. We know the drugs, the analytical tools, the patients and the pathogens. An important drug we monitor is for example vancomycin, the antibiotic that SensUs 2018 focuses on.
“The consequence of antibiotic resistance is simply death.”
When patients cannot be treated adequately they die, so antibiotic resistance is very dangerous. When penicillin and, later, other antibiotics were discovered and developed, the doctors thought that they had the perfect tool to keep people alive and society stopped investing in the development of new antibiotics.
Nowadays, companies do not take the risk anymore to develop new drugs. We believe that good measurements can be part of the solution, in order to give every patient his or her optimal dose. The majority of antibiotic resistance originates from disciplines like livestock farming and agriculture. So in a way eating meat enlarges the problem of antibiotic resistance. Moreover, with increasing global air traffic we foresee a doomsday scenario: micro-organisms travelling between continents without any therapies to counter the diseases that they cause.
“We are a bit like Sherlock Holmes.”
Nowadays you hear about outbreaks of Vancomycin-Resistant Enterococcus (VRE) and Vancomycin Intermediate Staphylococcus Aureus (VISA) in the Netherlands. These are big problems in many countries. In Nijmegen we prevent such outbreaks in the best possible way: by retaining the transmission of antibiotic resistant strains between individuals and by optimizing the dose of antibiotics.
Vancomycin is used in critically ill patients. It is a last-resort drug for which we know the optimum concentration. By measuring drug concentrations we try to give patients the right dose: the dose kills the bacteria but does not damage the kidneys. This right dose depends strongly on the individual patient.
The measurement of vancomycin concentrations requires a vast network of trained nurses, professional laboratories and corresponding specialists. In our laboratories we have different machines for different antibiotics, for vancomycin we use immuno-assays and ultrasensitive mass spectrometers. We use these machines at least twice a day to measure vancomycin.
Many things can go wrong in this process from sample to answer, so we do have some setbacks from time to time. The time required for the whole dose-adjustment process of general antibiotics of a patient is approximately three days, however, there is a large spread. Treating physicians simply do not have the time to wait for results. Most of the time we look if the patient is doing well and if not we take a blood sample and diagnose the morning after. For vancomycin testing, the turnaround time is about 6 to 12 hours.
Treatment of Patients
“I just visited a newborn who lies on the intensive care for an infectious disease.”
Some people come to the hospital for specific infections that have escalated, while others get infected while being in the hospital. These infections can occur spontaneously, by contact or in the hospital by the environment.
As clinical pharmacologists we investigate pharmacokinetics and pharmacodynamics, i.e. the effect of drugs on pathogens, in order to give patients the best possible treatment. We study current practices and have discovered that a lot can be improved. In the intensive care approximately 40% of all patients is not being treated with the adequate exposure. This is something we try to solve.
We can only tune vancomycin concentrations using an infusion. If the kidneys of a patient do not function anymore the patient holds a lot of fluid, from which his or her body will literally swell. This affects the distribution of the drug and is important for the calculations we perform. Other difficulties could be human mistakes. An example is a nurse taking blood from the same infusion as where he or she dosed vancomycin in the first place. This could lead to a drug concentration of approximately 180 mg/L while 20 mg/L is the general target concentration. We find it essential that everyone involved in measuring drug concentrations should be qualified in all terrains. Therefore, we try to find optimal therapies for individual patients to prevent these possible problems.
The patients’ critical conditions can lead to septic shocks. These shocks block renal perfusion which causes great damage to the kidneys. These patients always get vancomycin, which could result in a downward spiral: first the kidneys stop working, vancomycin will not be cleared anymore by the kidneys, as a result the drug concentration rises and the kidneys get damaged more than before. As pharmacist we see the biggest challenge in the recovery of those critical patients.
Currently, we have patients in the OPAT (Outpatient Antibiotic Treatment). These patients are treated with vancomycin at home by using elastomeric infusion. However, controlling the vancomycin dose affects patients’ social lives immensely. These patients need to visit the hospital often and therefore have limitations in their daily life. Furthermore, the pharmacokinetic behavior of vancomycin is heavily regulated by hemodynamic changes. It would be very helpful to have a biosensor in order to track these rapid changes.
We think that biosensors for vancomycin would be very helpful especially for specific tissue concentration measuring and for critically ill patients. Not only the speed of receiving test results, but also getting direct feedback is beneficial. The biosensors could be helpful as rapid tests, but more ideal would be to integrate the biosensors in catheters and receive online results. If we could measure in specific locations, for example inside an infected knee, that would also be very valuable. Admission to hospitals is getting more and more expensive, and being in a hospital brings the risk of acquiring other infections. So, the ideal situation is to treat patients outside of the hospital rather than by long stays in the hospital.
“SensUs could cause a revolution in personalized care.”
We think that biosensing is the future of medical care. Measuring drug concentrations could cause major improvements for both patients and medical professionals. We cannot wait until the future of biosensing is here. We think that SensUs can help to realize personalized care and also make it known in society. We are strong supporters of your mission!