Olena Moshynets: "Today, soldiers who survived on battlefield are dying of generalized sepsis. But they can be saved"
The unexpected appeal on social media from an unfamiliar soldier was surprising. He did not ask for help in raising money for some much-needed items, did not want to talk about injustice or a problem that could only be solved by publicity. He only needed the contacts of the heroine of one of my publications, a microbiologist from the Institute of Molecular Biology and Genetics Olena Moshynets.
At the time, we did a big interview with her about bacterial resistance to antibiotics and how to fight it.
It turned out that Yurii was a fighter who had been seriously wounded at the front and had been in hospital for about 9 months, where doctors had been trying to treat an infection that was resistant to all antibiotics without success. Naturally, I helped the soldier contact Olena, hoping that she and her team could still help.
Since our previous interview, her approach to treating multidrug-resistant infections has been tested in practice. In particular, the experimental therapy was carried out at the Amosov National Institute of Cardiovascular Surgery, Romodanov Institute of Neurosurgery, Scientific and Practical Center for Endovascular Neuro-Radiotherapy of the National Academy of Medical Sciences of Ukraine, Kyiv City Clinical Hospital #6, Oxford Medical, Kyiv Regional Hospital, and some others.
The work of the team led by Moshynets was also supported by the National Research Foundation of Ukraine, which provided funding.
WE BELIEVE WE HAVE MADE A DISCOVERY IN THE TREATMENT OF RESISTANT INFECTIONS
- As for this soldier who was looking for you through me. As far as I remember, he had a severe leg injury, and doctors performed osteosynthesis. What happened to him and why did he develop such a severe infection?
- At the time I got involved, he had a severe long-term infectious history. As a result, osteomyelitis developed, that is an infectious complication in the bone. Such a disease is generally very difficult to treat because the bone itself is inert, it is poorly protected from infection, and it does not tolerate antibiotics. We applied our therapeutic approach, administered anbiotic therapy under constant laboratory control, and in a few days the condition improved.
- How long did the treatment last in total?
- It took a long time, but the positive result was already apparent after 10 days.
- So soon? After 9 months in hospital?
- Yes. We had a case where an almost hopeless patient started to improve on the second day. This was also a military man who had already had ventilator-associated pneumonia, abdominal wound infection and sepsis during his 8-day stay in the hospital in Dnipro. All these complications were caused by a combined microflora, and in particular, Klebsiella. The microflora was multidrug-resistant and did not react to therapy. The entire treatment took a little over two weeks, and improvement occurred within the first day.
- Can you tell us about your method?
- Let's try it. As we studied the problem, we concluded that the combination of two antibiotics, old proven ones that are available on the Ukrainian market, leads to two very interesting phenomena.
First, we destroy the biofilm that develops at the site of the infection. Last time we talked in detail about this feature of bacteria. Clinicians do not yet understand this. However, any infectious process, wherever it is localized, up to generalized sepsis, is always a process associated with the formation of a biofilm in the focus. Thus, any therapy that is aimed at destroying the biofilm, even if it is not aimed at destroying the bacteria directly, but at least at destroying, breaking down, loosening the biofilm, will significantly improve the patient's condition.
And secondly, it turned out that this "anti-biofilm" antibiotic of ours causes a restructuring of the cell wall in Gram-negative bacteria. And this leads to a change in their antibiotic resistance profile. Simply put, if we have a Klebsiella that is resistant to everything, then the use of an antibiotic that destroys the biofilm develops its sensitivity to a second drug that we use as an additional component of therapy.
- So it's always the same drug?
- Yes. That is why we believe that we have discovered by finding a universal solution to the problem of Klebsiella infections resistant to all available antibiotics. So far, on all the strains we have encountered and in all the patients who have undergone our experimental therapy, it has been effective, and the pathogen itself has disappeared and has not "returned" over time.
Besides the fact that we destroy the biofilm and change the resistance profile, this combination has a very fast antibacterial, bactericidal effect. That is why we see bright positive dynamics in patients on the first, second, and third day of therapy. That is, we are not talking about therapy for months, as is now, unfortunately, the case.
2-3 DAYS IN HOSPITAL IS ENOUGH
- If a person gets a persistent infection again after treatment, will treatment be easier?
- Of course, reinfection is possible, and the therapy does not protect the patient in the future, but this regimen can be used as many times as necessary.
- In fact, you take a hopeless patient and get him back on his feet with drugs that are no longer used by many?
- That's right, we get involved when the situation is worse than ever and use antibiotics to which this resistant flora is not officially sensitive. And if everything is done correctly, if the patient does not have catheters, foreign bodies or, for example, metal structures, the infection will not return.
- What if you can't do without these metal structures?
- In this case, you will have to replace them with new, clean ones. The problem with such structures is that an antibiotic will not be able to remove the infection on them.
- How can you catch such a complex infection?
- It can be acquired during almost any inpatient procedure - an injection, catheter insertion, even a doctor's examination. As a rule, such hospital flora is much more malignant, aggressive, and resistant to antibiotics. If we talk about the specific case of our military man, he has developed resistance to all known antibiotics.
- As I understand it, it is better not to stay in the hospital?
- There is a direct correlation between the time spent in the hospital and the chance of getting a multidrug-resistant infection. But from my experience, two or three days is enough. Ideally, our hospitals should separate patient flows so that people with multidrug-resistant infections do not infect other patients. Unfortunately, this is almost impossible now, there are not enough hospitals.
- Your method is new, few people know about it yet, and even fewer will risk using it because it has not been officially approved in protocols. What can doctors do now when they meet a patient who does not respond to any drug?
- There are no generally accepted therapeutic solutions for such patients, and no recommendations either.
- By "no decision" do you mean that there is no officially approved protocol?
- There is no decision at all! There are some recommendations. In particular, in the latest order of the Ministry of Health of Ukraine dated 23.08.2023 No. 1513 on the rational use of antibacterial drugs, there is a cautious recommendation to prescribe a combination of two very expensive antibiotics, the cost of which is not covered by the medical care package and, most importantly, the effectiveness of which has not been tested on Ukrainian patients.
And we already know how much our Klebsiella strains differ genetically from, for example, Polish strains. By the way, our Ministry of Health would also know about this if they finally introduced molecular genetic epidemiological monitoring of antibiotic resistance in Ukraine. Our Polish colleagues from the National Polish Reference Center at the National Medical Institute (Warsaw, Poland) have studied 50 Ukrainian post-war Klebsiella and shared with us the disappointing results.
Therefore, in general, official evidence-based medicine cannot offer anything reliable to such a patient. But I cautiously hope that as a result of, in fact, collective international 20-year research by various groups of scientists, we have found such a solution. This is a very ambitious statement, but the truth is that so far all the patients who have been treated with the antibacterial regimen that we have developed in our team have responded positively to this therapy.
THE MOST MODERN ANTIBIOTICS DO NOT WORK
- What about developed countries? Do they also have no solutions for treating complex hospital infections?
- The world is searching for new antibiotics. But those that appear are insanely expensive, and some that are already available in the world are not yet available in Ukraine. For example, a very expensive siderophore cephalosporin (cefiderocol). But even they prove to be ineffective in contact with our hospital strains.
There are reports from Germany, where our military was treated with this expensive cefiderocol, that it does not always work either. Moreover, an article was published in which they studied 6 samples of infections (isolates) from Ukrainian patients, and 4 of them were already resistant to this, a completely new antibiotic that is not yet available in Ukraine.
- It sounds scary.
- I think that Ukraine is now leading the world as a territory where there is a terrible selection of resistance to everything, including the latest antibiotics, which are now available only in developed countries. As a result, we have sharply worsened the situation with antibiotic resistance throughout Europe. That is why Ukraine is being urged to pay more attention to the problems of infection control, which we have been ignoring for a long time.
- In general, this is the area of responsibility of epidemiologists. Their number has been seriously rightsized, but they are there, and, hypothetically, they should work in every hospital.
- You're right, but the epidemiological service was taken off, and as a result, we found ourselves in an absolute epidemiological dead end concerning antibiotic resistance. On the one hand, there is no one to conduct an investigation, and on the other hand, from my experience with some officials, I see that there is no such task.
- One of the tools for such control used to be bacteriological laboratories that were supposed to operate in every hospital. Do you know how they are doing today?
- They exist, but not in every hospital. There is a requirement to have a microbiology service that would perform competent cultures, not a bacteriological laboratory. In other words, a hospital can sign a contract with such a laboratory and everyone is happy with it. However, if you take the culture and send it to work in 6-7 hours, the result is likely to be wrong. In addition, if you do not have your own laboratory at hand, you will not be culturing even a difficult patient every day, you will already be counting money, which is what is actually happening.
- If your treatment regimen is already known, why hasn't the Ministry of Health included it in its recommendations, at least for soldiers who are in a hopeless condition?
- In the two years of large-scale war, we have not yet developed recommendations on antibiotic therapy for the military. There is no protocol for the treatment of multidrug-resistant infections, i.e. those still sensitive to 1-2 antibiotics, and all resistant infections. There are no national recommendations on what to do with patients in such cases.
- But there are European and global protocols.
- Yes, in severe cases, as I said, they use quite expensive drugs that we do not have. However, there is still no universal "golden antibiotic", and we are now leaving the average doctor, the average surgeon or intensive care physician, the anesthesiologist, face to face with the problem.
And today, people who survived the battlefield are dying of generalized sepsis. These are young, strong people, they can die of sepsis for weeks. Even in this situation, many doctors do not cooperate with us because they are afraid of responsibility for using experimental therapy that is not officially recommended. And I understand them well. And higher organizations do not notice this problem.
IF YOU CAN TREAT FOR $20 THOUSAND, WHY SAVE MONEY?
- Tell me, do you have any publications about this work in Western journals?
- Of course, our team considers it a priority to publish in serious journals in order to be heard. In recent years, we have published articles discussing the antibiotic film strategy for the treatment of Gram-negative infections. We show in a series of experiments that our approach works. We also talk about the practical application of the method, because it is not easy to nurse such a patient, it is always a dedicated job of a doctor.
- What is the reaction of foreign doctors to your work?
- So far, it is cautious. People do not trust simple solutions to such difficult, complex problems. Fortunately, they don't have as many patients as we do. In addition, they have access to the most modern, expensive antibiotics. So, of course, if it is possible to treat a patient for 20 thousand dollars, and insurance covers this treatment, then there is no need to save money.
- You said that some of our patients are already resistant to the latest antibiotic. How do they treat them in this case? I mean, in the West?
- That is a very good question! I recently found an interesting article in a very reputable magazine where the British treated our Ukrainian patient for a Ukrainian post-war hospitalized multi-infection of his left limb. The patient had been injured by a ballistic missile and then developed a multiple infection as a result of treatment in Ukrainian hospitals. He was treated with the aforementioned cefiderocol and many other advanced antibiotics in combination. Eventually, the patient's leg was amputated.
And "our" patient, as we remember, saved his leg. And I wrote to the author of the article on an emotional wave that we have other experience in treating such patients and referred to our recently published article with this protocol, and the doctor immediately replied that he had seen our article and even referred to it as "an example of the necessity to be innovative to overcome some of these resistance patterns" and we are proud of it!
- Ukraine is not the first country, unfortunately, in the Third World, where there is a war. Have the countries of Asia or Africa, where wars occur frequently, not faced the problem of antibiotic resistance? In theory, international organizations should have developed recommendations on this problem.
- Indeed, in Syria, we have also seen a surge in antibiotic resistance. But there are several nuances here. Firstly, the conflict in Syria was earlier than the war in Ukraine, and the infectious situation was somewhat better. Time is not in our favor here.
And secondly, of course, Ukrainian medicine is better than Syrian medicine. According to the articles I've seen, the mortality rate was higher there, and patients spent less time in the hospital. Our patients are stabilized better, they survive more often after being wounded. Unfortunately, the longer a patient stays in the hospital, the more resources there are for the development of multidrug antibiotic resistance.
There is one more point. This is Ukraine's proximity to the European Union. The wounded Syrians infected with such strains did not get to Europe. Because in fact, we learned about the antibiotic resistance disaster from European scientific periodicals, you know? And each time these publications are more and more emotional. And Ukraine continues to pretend that nothing is happening.
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Indeed, the Ministry of Health officials see the problem of antibiotic resistance only in self-medication, unlawful prescription and non-compliance with the medication regimen. Perhaps this is true on a global scale because, unlike Ukraine, rich countries are doing well with infection control in hospitals.
Unfortunately, Olena Moshynets' group will no longer be able to continue the research. This year, the National Research Foundation of Ukraine rejected the application because the doctors who tested the method in practice are not formally scientists, although they have significant scientific articles. So the group is putting this project on hold for now.
But I hope that military medics will learn about the method and adopt it. At least in cases where there is no other solution.
Tetiana Halkovska, Censor. NET
