12 October 2022 12:18

Resistance: What to do when antibiotics don’t work?

Researchers compare the spread of antibiotic-resistant hospital infections to an epidemic. As a result of complications caused by drug-resistant infections, more than a million patients worldwide die each year. In the future, the number will only increase.

How to fight infections that are not affected by any antibiotic? Is there a way to overcome complications? What should be done so that humanity does not return to the Middle Ages? Researchers from the Institute of Molecular Biology and Genetics (IMBG) of the National Academy of Sciences of Ukraine are looking for answers to these questions. Their project ‘Development of combined therapy for severe Klebsiella pneumoniae-associated nosocomial infections to overcome their antibiotic resistance’ became a winner in the call ‘Support for Research of Leading and Young Scientists’ of the National Research Foundation of Ukraine. And although grant funding is currently suspended (the funds are directed to the defense of the country), researchers continue their work.

Olena Moshynets, PI of the project and a senior researcher at the Institute, has been fighting hospital infections for several years. Especially with the most dangerous polyresistant infection Klebsiella pneumonia (also called Friedlander’s bacillus). This infection is extremely toxic and resistant to almost all antibiotics. Unfortunately, there is a lot of Klebsiella in hospitals, intensive care units, maternity wards, etc.

Olena’s research group was many times faced the situation when a patient had a multi-resistant hospital infection (not sensitive to any of antibiotics), and doctors gave up: said that they can do nothing, there are no protocols for treatment.

“There are no official data on mortality from complications caused by resistant infections in our country,” says the researcher. “But people (thousands of patients!) die from these infections. It is necessary to solve this problem, to count cases of antibiotic resistance (every month, in every hospital), to draw up national protocols, to conduct elementary trainings for doctors…

Of course, it is necessary to solve the problem of resistance comprehensively: to monitor sterility in intensive care units; search for new drug combinations that would be effective against hospital-acquired infections; develop new antibiotics. And if creating a new antibiotic is long and expensive, finding effective combinations of existing drugs is quite possible.”

Such a scheme of combination of antibiotics was developed by the researchers of the IMBG of the National Academy of Sciences of Ukraine. The combination of drugs was tested on research models in the laboratory – biofilms, biomimetic models of wound surfaces, etc. (Biofilms are supracellular bacterial formations where an infection can ‘chronize’, –  author’s note).

«We proved that the new combination of drugs affects both the infection and its biofilm state,” Ms. Olena continued. “The scheme includes non-toxic antibiotics, each of which is ineffective against Klebsiella alone, but their combination yields an excellent result.”

The researchers cooperate with Amosov National Institute of Cardiovascular Surgery, Kyiv Regional Clinical Hospital, and private hospitals, and have good treatment results.

“We overcome the infection with the help of two pharmacological molecules and human immunity,” explains Olena. “As a result of the action of antibiotics, Klebsiella (on the biofilm level) becomes vulnerable to the immune system. Thus, antibiotics together with immunity overcome this infection. We have had patients who seemed to have no chance of recovery, but thanks to our scheme, they survived. Moreover, polyresistant Klebsiella disappeared and there were no recurrences.”

In addition to the new scheme, researchers are also working with other components of the fight against resistant infections. A few years ago, for example, they helped to preserve the diagnostic laboratory at Kyiv Regional Clinical Hospital. (The researchers were supported by the authorities of the Kyiv Regional Administration). “The former director just wanted to close the laboratory. But who would do the bacterial contamination tests in the surgical and resuscitation wards then?” says the researcher. “It is the microbiological service in hospitals and clinics that should examine from surfaces in a medical institution, and control aseptic methods, in particular, check the effectiveness of disinfectants used in the hospital.”

By the way, the project PI has a negative attitude to the decision to sell antibiotics by prescription. “It’s like we’re showing the world that we’re doing something, we’re responding to a problem,” says Olena Moshynets. “But in fact, this is a transfer of responsibility to patients. I have not come across cases of resistance among outpatients, but there are a lot of them in hospitals. In addition, in the conditions of war, it can be difficult to find a doctor who would give a prescription.”

According to the microbiologist, it is also necessary to create additional recommendations and training programs for doctors regarding the interpretation of antibiotic charts. Unfortunately, many drugs are sensitive to Klebsiella etc vitro (in a test tube) and are not sensitive in vivo (in the body). Explanatory work on aseptic methods is also needed (each patient with polyresistance should have a separate bathroom at least).  

With the NRFU grant funding, the researchers purchased modern equipment – an isilatuion box, a device for conducting PCR reactions in real time, a photometer, a thermostat, and reagents. This equipment will remain at the institute and will be used in future research.

Before the war, the researchers had managed to complete 70-80% of the tasks planned. Today, despite the suspension of grant funding, they continue their work. Of course, experiments that require expensive reagents cannot be carried out yet. Therefore, they process data, prepare articles, and disseminate the results of their work at conferences of clinical microbiologists in Ukraine and Europe.

“We have a very good, young team,” Olena added. “We work in a friendly and harmonious way, in wartime we support each other.”

Olena Moshynets lives in Buchansky District. She says that in the first days she experienced a deep shock, especially when the enemy came close. “I thought: “How is this possible in the 21st century?”, “Why is this happening?”… But I did not feel despair.” The researcher is confident that it`s necessary to persistently do what you can. Moreover, the results of her team’s work (effective drug combinations) are very necessary for patients both clinics and military hospitals.

Svitlana GALATA

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