Instead of antibiotics: how bacteriophages help fight "superinfections"

Instead of antibiotics: how bacteriophages help fight "superinfections"
Instead of antibiotics: how bacteriophages help fight "superinfections"

The coronavirus pandemic has accelerated the growth of antibiotic resistance of bacteria in the human body. As a result, patients who have undergone the disease become at risk of developing "superinfections". Russian doctors and pharmacists see the solution to the problem in improving state vaccination programs and rational use of unique bacteriophage drugs. Alexander Zharnikov, an expert of the Natsimbio holding of the State Corporation Rostec, the head of the project "Development of bacteriophages" of NPO Microgen, Alexander Zharnikov, talks about how to overcome the global tendency to reduce the effectiveness of antibiotics.


Accelerated Impact Bomb

Even before the coronavirus pandemic, antibiotic resistance was among the most serious threats to global public health. WHO has repeatedly announced the growing rate of microbial desensitization to antibacterial drugs and called for "immediate, coordinated and large-scale measures" to prevent a catastrophe.

According to WHO estimates, worldwide antibiotic resistance claims 700,000 patients a year and, if inactive, threatens to reach a mortality rate comparable to oncology within the next 30 years. At the same time, such indicators were calculated even before the start of the pandemic, which provoked a boom in inappropriate antibiotic use.

In April 2021, the Minister of Health of the Russian Federation Mikhail Murashko, speaking at the UN General Assembly, noted that the spread of antimicrobial resistance in Russia is considered at the legislative level as a factor of biological threat, and acknowledged that the deterioration of the situation was seriously affected by the pandemic of the new coronavirus infection.

Due to the protracted crisis caused by COVID-19, mid-term forecasts already contain critical values, and the time that scientists planned to gain by deploying antibiotic resistance programs is rapidly decreasing. But the worst thing is that today doctors have to deal with not one, but two global threats to the health and lives of people at once.


According to doctors working in the "red" zones, a patient with chronic lung diseases entering the hospital with the need to use a ventilator often means the addition of a secondary bacterial infection. The most common of these infections are Klebsiella (Klebsiella), Acinetobacter (Acinetobacter), Pseudomonas aeruginosa (Pseudomonas aeruginosa) and others. These are the so-called hospital infections with pronounced drug resistance.


As Denis Protsenko, the chief physician of the Moscow hospital No. 40 in Kommunarka, told at the congress on the prevention of infections, extremely dangerous bacteria-superinfections are rapidly forming in "covid" patients. Moreover, these are problematic strains with multiple resistance, which limits the possibilities of treatment.

Despite the fact that the concept of "adding" superbugs to the microflora of patients with COVID-19 directly in the hospital is very popular, it is not shared by all practitioners. Some of them believe that the problem is much more complicated and is rooted in the general uncontrolled consumption of antibiotics both in medicine and in animal husbandry.

Therefore, patients admitted to the clinic can themselves act as a kind of reservoir containing and spreading strains of pathogens that are not susceptible to the effect of antimicrobial agents. This view is also confirmed by modern scientific studies that have established a direct relationship between the increasing consumption of antibiotics and the spread of resistance.

Whatever the reasons or their complex, due to the pandemic, the world very quickly moved to a new level of the fight against pathogenic microorganisms. Today, it is necessary to introduce new protocols for the treatment and prevention of infectious diseases, and above all, COVID-19, which will provide not only an increase in the effectiveness of treatment, but also a reduction in the unjustified prescription of antibiotics, as well as, possibly, the use of alternative agents with bactericidal properties.

Finding new methods in the war against superbugs

In 2018, WHO released a report indicating that some of the most common and most potentially dangerous infections in the world, such as Klebsiella pneumoniae, Staphylococcus aureus and pneumococcus pneumoniae, do not respond to medical treatment. And she admitted that the world, more than ever, is in dire need of new ways to combat pathogens of infectious and inflammatory diseases.

Despite the fact that demand usually generates supply, in the situation with the development of new, urgently needed antibiotics, the situation is exactly the opposite. The same WHO states that the volume of investments in the development of antimicrobial drugs has been declining in recent years. Even pharmaceutical giants are scrapping specialized projects due to their unprofitability - with comparable investments, the return on drugs from other groups, for example, oncological ones, is noticeably higher.


So, according to estimates by BARDA (Office of Advanced Biomedical Research and Development under the US Department of Health and Human Services), in 2018, sales of the TOP-10 best-selling drugs ranged from $ 19.9 billion (Humira) to $ 5.7 billion (Stelara). the average revenue from the sale of blockbusters was 8.2 billion. At the same time, the average sales of antibiotics that have recently appeared on the global market in two years did not reach even $ 50 million.

In addition to profitability, there are also problems with technologies - those antibacterial drugs that are currently in development demonstrate an effectiveness that does not exceed the indicators of existing analogues. Against this background, scientists are forced to look for alternative ways. One of them is to enhance the role of immunization.

Vaccine-dependent world

It is a well-known fact that treatment is not only more difficult and more expensive than prevention, but also partially contributes to the emergence of resistant microbes. Timely vaccination prevents infection or re-disease and, as a result, prevents the need to use antibiotics.

As part of the fight against antibiotic resistance, modern medicine offers two ways of vaccination - the expansion of the use of existing drugs and the development of new ones. The effectiveness of the first way is confirmed by the calculations of the WHO. In particular, the organization estimates that if every child in the world is vaccinated against the Streptococcus pneumoniae bacteria that can cause pneumonia and meningitis, a total of 11 million days of antibiotic use per year will be prevented.

Influenza vaccination also contributes significantly to reducing antibiotic consumption. As you know, influenza is one of the most common infections, characterized by the presence of annual seasonal epidemics, which can disable up to half of the country's adult and child population in two to three weeks. With this infection, as with coronavirus, there is a risk of bacterial complications, which entails an increase in antibiotic consumption.

Vaccination prevents the chain of these diseases. For example, according to the results of research by the US National Academy of Sciences, published in 2018, people vaccinated against the flu needed antibiotics 50 percent less often. In Russia, thanks to a well-organized program of mass vaccination of the population in recent years, it has been possible to significantly reduce the incidence of influenza and keep it at a low level. According to Rospotrebnadzor, since 1997, the incidence of influenza in the country has dropped 140 times.


The development of new vaccines for the prevention of bacterial diseases is also helping to reduce the development of resistance. For example, the international medical community is concerned about the spread of multidrug-resistant tuberculosis. New vaccines targeting bacteria such as Staphylococcus aureus, Klebsiella pneumoniae or Clostridium difficile could protect people from diseases that are becoming increasingly difficult to treat.

And, of course, it's hard to imagine a better example of the contribution of vaccination to the fight against antibiotic resistance than today's countering the spread of coronavirus. It is vaccination, when the required coverage is achieved, will ensure the victory over COVID, and as a result, will slow down the increase in antibiotic intake provoked by the virus.

From enemies to assistants

Bacteriophage viruses, natural enemies of bacteria, can become another solution to the problem. Bacteriophage preparations have already saved our country from outbreaks of infectious diseases, for example, from cholera during the Great Patriotic War. In the last decade, they have also been effectively used for the prevention of intestinal infections in emergency zones, for example, in the Irkutsk region and the Far East.

Bacteriophages are interesting in that they act in a targeted manner, in pursuit of the target bacterium, without affecting the rest of the flora of the human body. This avoids the two main risks arising from taking antibiotics - the development of dysbiotic conditions and the growth of drug resistance in bacteria. Among the important features of bacteriophages is the ability to prescribe them to patients with severe chronic diseases and pregnant women, that is, to those categories of the population for whom antibiotics are usually contraindicated.

In Russia, it was possible to isolate and effectively use bacteriophages by the scientists of the Microgen enterprise, which is part of the management system of the Natsimbio holding of the Rostec State Corporation. These drugs are effective in the treatment and prevention of the very problematic causative agents of hospital infections - Klebsiela, Staphylococcus aureus, Pseudomonas aeruginosa and a number of other bacteria. The only production of medicinal bacteriophages in Russia is organized at Mikrogen.

In world practice, bacteriophages are practically forgotten products. The complexity of the bacteriophage selection process discouraged Western scientists and physicians to continue their research and production. On the contrary, Microgen experts managed to preserve the production of bacteriophages and even invest in its development. For example, last year the company created the Biological Resource Center, on the basis of which the collection and storage of an extensive bank of bacterial strains common in Russia is organized. In the collection of the enterprise there are more than 10 thousand strains.

It is expected that this project will expand the scope of application of bacteriophages in Russia, improve production technologies, develop new drugs - now 20 names are being produced, but Russian scientists plan to significantly expand the range and switch to a new format for using bacteriophages.

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