While waiting for new antibiotics: will we have what is so necessary?

Antibiotics are rightly the miracle of modern medicine. Of course, antibiotics are now fairly common. But at the time of its appearance, antibiotics literally changed the world...

It all started in 1928, when the bacteriologist Alexander Fleming, due to a happy occasion, noticed that the growth of Staphylococcus aureus was inhibited on a Petri dish contaminated with mold. A few years later, doctors appeared sulfonamides, and later - more effective beta-lactam antibiotics, chloramphenicol and tetracycline, in the 50s. Last century, the aminoglycosides.

Unfortunately, as scientists discovered more and more antimicrobial agents, no one thought about the need to identify the pathogen, which led to targeted antibiotic therapy. Instead, broad-spectrum antibiotics have become the basis for an unreasonably long and sometimes irrational and inappropriate use of these drugs, which literally save lives. The selective effect that antibiotics can exert on bacteria is also underestimated. Only a few decades passed and it became clear that the overuse of antibiotics only ignited the flames of the natural evolution of the microorganisms that people were trying to kill with antibiotics, contributing to the development of resistance as quickly as possible.

And what do we have now? A huge chasm that continues to grow steadily, separating deadly hospital infections caused by resistant strains of microorganisms from effective antibacterial drugs for their treatment. And hardly change for the better in the near future. Too few new antibiotics that can withstand the huge growth rate of antibiotic resistance in microorganisms.

Doctors are confronted daily with the problem of antibiotic resistance. Patients are now much more at risk of developing an infection than ever. As a result, doctors are now forced to use antibiotics more intensively, and the bacteria in response are also changing rapidly. In addition, the incentive to create new antibiotics is now lost.

Unfortunately, only a few doctors are concerned about the problem of antibiotic resistance and the lack of new effective antibiotics. Most continue to believe that medical scientists, as before, will be able to create new antibiotics as needed. However, very soon, the entire medical community will be faced with a harsh reality, but it will be too late. Infections caused by antibiotic resistant strains are a problem not only for elderly and immunocompromised patients. Under their assault, everyone will give in - friends, relatives, rich and poor. And there will be no drugs to treat them. And everyone will look around looking for the culprits...

So who should be blamed? Arrogant patients who refuse to leave a doctor without a prescription for antibiotics, even if their use is not necessary? Doctors who prescribe antibiotics for viral infections for fear of being misunderstood or accused of ignorance? Farmers who treat animals with antibiotics to stimulate growth and keep them healthy? Pharmaceutical companies who do not wish to invest in the development of new antibiotics? Or regulatory bodies that make it difficult, and sometimes impossible, for a new antimicrobial to enter the market?

And although many are actively researching the causes of the current crisis and discussing ways to resolve it, the facts remain facts:

Ultimately, we will embark on the path to the post-antibiotic era - the era of incurable bacterial infections.

The most serious fatal infections are caused by a group of resistant microorganisms, which the American Society for Infectious Diseases (IDSA) has designated as pathogens "ESKAPE" (from the English word escape - to escape, avoid, escape), because they effectively "avoid" the effects of antibacterial drugs.

Antibiotics have a unique characteristic that sets them apart from all other drugs. Currently effective antibiotics are likely to lose their properties in 15 to 20 years. That is why it is always necessary to create new antibacterial drugs.

Control of the development of new antibiotics has officially existed since the 1950s. Last century. However, it then worked on the principle of "a new microorganism - a new drug", nothing more. Now there are pathogens already resistant to all available antibiotics, and their number will increase exponentially over the next five years.

But the problem is not at all that there are no new antibiotics at the development stage. All have the same mechanisms of action as the antibiotics that are currently in the arsenal of doctors. For example, the new cephalosporins ceftobiprol and ceftaroline are almost identical to cefepime, a drug that has been on the market for a long time. A gram negative microorganism resistant to cefepime will also be resistant to ceftobiprol and ceftaroline.

In 2009, the American Society of Infectious Diseases (IDSA) published the results of an analysis of the arrival of new drugs on the pharmaceutical market for the treatment of infections caused by resistant strains. The data was disappointing. The number of antibacterial drugs in the second or third phase of clinical trials is catastrophically low. From 1983 to 2007 the number of systemic antibiotics approved by the FDA for use decreased by 75%.

Discovering new classes of antibiotics is becoming increasingly difficult. In addition, the large pharmaceutical companies, in turn, have simply lost interest in the antibiotic market due to the fact that the profit from the introduction of new antibiotics into the pharmaceutical market is much less than that of the drugs for treatment of chronic diseases. Antibiotics are drugs that are used only for a short time, only during the period of an infectious disease, while hundreds of thousands of people with chronic illnesses take medication every day for many years. Too much cost is involved in developing and proving the safety and efficacy of the new antibiotic, and even in the case of material and time costs, there is no one hundred percent guarantee that the drug will be approved by regulatory authorities for its use.

Many medical professionals are confused about how the FDA approves new drugs. In fact, this is a serious hurdle that must be overcome before launching the drug on the pharmaceutical market. For example, a pharmaceutical company has developed a new drug for the treatment of community-acquired pneumonia. At the same time, this drug, at the request of the FDA, must undergo clinical studies which would demonstrate its benefits or be comparable to the antimicrobial agents currently available. As the primary endpoint, only a reduction in mortality is considered for all reasons. No other clinical evaluation criteria will be sufficient, for example, a faster start of clinical improvement will not be taken into account. To prove the effectiveness of the new medicine compared to the old one, it will be necessary to include in the study patients whose infections are caused by strains resistant to the reference medicine. It becomes clear that research on such conditions is almost impossible. Unfortunately, such a scenario is not at all a fiction.

The problem is further complicated by the fact that statisticians (and these are people who, as a rule, have never seen and, of course, never treated for pneumonia or any other serious infection) outnumber clinicians at the administrative level, namely that they accept the last decision.

Experts explain IDSA's position as follows: "We only protect the interests of patients. We understand the importance of the FDA's role in the approval process for new drugs, but its position should not be as relentless , it simply "kills" the production of new drugs. There has to be a compromise. There is a saying. The best is the enemy of the good. You can expect perfect results for an infinitely long time, but ultimately they will not get...

According to Dr. Auwaerter, a whole new approach to the development of antibacterial drugs is needed. As an example, he suggests focusing on the anti-TB alliance: "For many years, we did not have new anti-TB drugs at our disposal. To solve this problem, the TB Alliance created, which included scientists, representatives of pharmaceutical companies, charities and government as well as organizations engaged in global health cooperation, forums were opened, funding mechanisms Few new studies "TB drugs. In a remarkably short time to open channels and establish the admission of new drugs. We must now join forces in this way and the means to solve the problem of antibiotic resistance."

IDSA is committed not only to collecting and providing information on antibiotic resistance, but also to proposing effective solutions. In an official letter dated November 20, 2009 to President Barack Obama and Prime Minister Fredrick Reinfeldt, who represents the service of the President of the European Parliament, the IDSA stressed the need to develop 10 new antibiotics by 2020 (10 X '20).

Large-scale and long-term work is planned, the aim of which is to create the infrastructure to ensure the development of new antibacterial drugs, as well as the organization of diagnostic and research initiatives in this field.

Thanks to the joint efforts of the United States and Europe, it is planned to create a special transatlantic commission to resolve the problem of antibiotic resistance, which will monitor the proper use of antimicrobial drugs in the medical and veterinary fields, will take measures to prevent the spread of nosocomial and community infections caused by resistant microorganisms, and develop strategies to establish the reception of new antibacterial drugs in the pharmaceutical market.

We should not "wash our hands" and simply limit the use of antibacterial drugs. We must not forget that not only our patients, but also ourselves are in danger. But nothing will change if we just think about the magnitude, the complexity of this problem, the fact that someone else has to solve it, and there is nothing we can do. Now the FDA is dominated by statisticians who make decisions on drug approval based on numbers, ignoring the opinion of medical practitioners. Together we are a huge group of qualified employees with the right to vote and through joint efforts we will be able to exert significant pressure on the governing bodies and significantly influence their decisions. Of course, it is very important to raise awareness and build the skills of health professionals. In addition, the joint work of political and scientific forces is necessary to determine the extent of the existing problem and its effective solution. The lesson from H1N1 has helped us realize how important it is to always be ready. Unfortunately, we are not sufficiently prepared to deal with the growing resistance to antibiotics.

Take an active position - write letters to the editors of professional medical journals, contact other media, stressing your concern about the situation, don't be afraid to report any gross violations that you have identified. Inform regulators and politicians that the current approach to approving drugs, from which clinicians have been virtually excluded and where statisticians hold leadership positions, is unacceptable. Actively collaborate with pharmaceutical companies. Know that they are not enemies, but that our allies in the fight against the threatening threat increase resistance to drugs. Contact your officials and administration to support the IDSA initiative to develop 10 new antibiotics by 2020.

And be on the lookout. The day is not far when all of humanity will be struck by an overwhelming catastrophe. And it will not happen when it is impossible to perform organ transplant, prosthetic limbs, provide cancer chemotherapy, dialysis, maintain the viability of premature babies and when healthy people start to die after routine surgical procedures or common infections, for which there is no more medicine...