Antibiotic-resistant pathogens are becoming an increasing problem, especially in hospitals. Infected patients must be isolated as soon as possible. However, appropriate methods for testing patients upon admission to hospital and isolating them if necessary are still lacking. A young biotechnology company from Baden-Württemberg called SpinDiag GmbH has developed a cost-effective method for the rapid testing of microbial resistance in normal hospital wards without the need for comprehensive equipment. Product development and clinical approval are underway, and market launch is planned for late 2019.
Resistance to antibiotics is a perfectly normal and completely natural reaction of bacteria to toxic substances in their environment. For a long time, this property was not a particularly serious problem, because enough alternative drugs were available in the event of certain drugs not working. However, the long-term and inappropriate application of antibiotics in humans and animals has in fact led to the cultivation of drug-resistant microorganisms. As a result, many pathogens have become resistant to treatment with existing antibiotics. Problem-causing pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) are on the rise notably in hospitals where infection with drug-resistant bacteria can become life-threatening in patients with certain pre-existing diseases.
A way of identifying whether patients admitted to hospital are carrying drug-resistant pathogens therefore needs to be found in order to prevent the spread of antibiotic-resistant bacteria, especially in the hospital environment. These patients could then be specifically treated in isolation. Bacterial resistance tests are available on the market, but it can take up to two days before results are available. Moreover, in combination with all the safety measures that need to be put in place, such tests are far too expensive for routinely examining a large number of people, or even all patients that are admitted to hospital. Hence only patients believed to be carrying antibiotic-resistant pathogens are currently being tested.
Six scientists from the Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. in Freiburg became aware of this problem quite some time ago and decided, in April 2016, to establish a company called SpinDiag GmbH. Their aim is to combat antibiotic-resistant bacteria using a cheap and simple test for identifying bacterial resistances. “At Hahn-Schickard, over the last few years we have developed a variety of on-site solutions for investigating bacteria and viruses, and many doctors have said that they would like to have a rapid hospital test to hand,” says Dr. Daniel Mark, one of the six founders and managing director of the Freiburg biotechnology start-up.
“That's exactly what we came up with,” emphasizes Mark. “And once we had developed the rapid hospital tests we wanted to bring them to market through our own company. Test development is now complete, but we do not yet have a product. We are focusing on this now. It is estimated that in Germany alone, half a million patients are infected every year. Although only a small fraction of these patients is infected by antibiotic-resistant bacteria, this number is gradually increasing and becoming a serious problem. This is why we want our test to become a tool that can be used at hospital point of entry to find out what is being allowed in, so to speak. Patients carrying antibiotic-resistant bacteria can be isolated and appropriate hygiene measures put in place immediately.”
Current practice is to take a swab sample, cultivate the bacteria and then investigate the culture for the presence of resistant bacteria. It usually takes several days for results to be available. Moreover, such laboratory examinations are very expensive. “With the rapid test we have developed, the swab sample is applied directly to a disposable plate that looks like half a CD and analysed in a shoe box-size CD-player-like device within 30 minutes,” says the company founder explaining the principle of the SpinDiag test. “The reagents are released by the rotational movements of the sample carrier and a complete PCR1 – from sample preparation and mixing to aliquoting – is carried out.”
In the test carrier that is being processed in an analytical device developed by SpinDiag’s cooperation partner, Qiagen Lake Constance GmbH, the minute amounts of liquid reagents flow into microfluid channels. The methodology in which reactions are carried out with the help of centrifugal forces is called centrifugal microfluidics. Twenty-five resistance-specific real-time PCRs take place in parallel on the platform developed by SpinDiag. The device also detects fluorescent signals. A positive signal indicates that the sample contains resistance genes.
“Our method enables such a large number of tests because all steps, no matter how complex, are carried out by the device completely automatically,” says Mark. “The test is very simple to perform, and this was very important to us. No previous experience or special diagnostic equipment is required. The test carrier is simply inserted into the device and the results are available within 30 minutes. The ideal scenario would be for these devices to be available in all hospital wards, so that the least amount of time possible is lost before the test result is available.” The resistance genes covered by the SpinDiag test were chosen jointly with national reference centres in Germany and Belgium. “The 25 bacterial resistances covered by our test provide a very high level of safety. Although the test does not cover all bacterial resistances, we are certain that it covers the most common and most dangerous ones,” says Mark.
Such a multiplex test will cost approximately 20 euros per patient. “This definitely pays off for hospitals,” says the scientist. “We have done some sample calculations with an expert on clinical-economic models. An outbreak of infection due to an unidentified drug-resistant pathogen or the unnecessary isolation of a patient are both more expensive than the treatment and isolation of only those patients diagnosed with drug-resistant bacteria. Our test is fast, broad and affordable – we think that this is unique.”
Results are available within half an hour. “Then a decision can be made as to whether the patient has to be treated in isolation,” says the physicist. “In the event of a positive result, further examinations will be carried out. Our rapid test helps us exclude the risk of infection with drug-resistant pathogens caused by a patient. Above all, it is about implementing appropriate hygiene measures quickly, not about making a decision on the type of treatment that has to be initiated."
According to Mark, the preliminary work for the rapid test is very well secured with patents. He comments: “Although Hahn-Schickard is a SpinDiag shareholder and we are still using some of Hahn-Schickard's infrastructure, we are now completely independent.” The company founders do not want to return to pure research work. Mark says: “Running your own company is fun. We really enjoy being independent. And things are going quite well.” Over the next two weeks the company will be hiring two more employees.
Until the end of the year, the scientists will be busy completing product development. The resulting prototype will be used to start the marketing authorisation process in early 2018. Market launch is planned for the end of 2019, initially in Germany, Austria and Switzerland, before the company eventually places the system on the market throughout the EU, while simultaneously initiating the authorisation process for marketing the product in the USA.
1 Polymerase chain reaction (editor's note)