Antibiotic resistance: a threat to humanity

In 1945, three scientists from the UK – Fleming, Flory and Chain received the Nobel Prize in Physiology or Medicine for the discovery of penicillin – the first antibiotic that helped humanity fight infections. Its availability during the Second World War allowed to save the lives of many: only among soldiers, the mortality rate due to the addition of a bacterial infection during wounds decreased from 18 to 1%. Penicillin also gave civilians a chance to survive in previously almost hopeless cases. With the help of an antibiotic, they began to successfully treat syphilis, pneumonia, tuberculosis, diphtheria and even gangrene. ^[1].

Today in the line of antibiotics there is not only the legendary penicillin. For almost a century, more than fifteen different groups of such drugs have appeared, not only with antibacterial, but also antifungal, antitumor effects. This breadth of choice and extended spectrum of action helps fight infections. But along with the availability of antimicrobial agents, a new problem has arisen – the resistance of bacteria to antibiotics. It is called the term “antibiotic resistance”. Without proper measures, the situation can grow to critical proportions, and then humanity will face a serious threat to life – even minor injuries and common infectious diseases will become deadly.

It is important to understand that antibiotic resistance only occurs in microorganisms, not in humans. But it is we who are at risk, because when infected with antibiotic-resistant bacteria, the treatment of the infection becomes much more complicated.

Why does antibiotic resistance occur?

Microorganism resistance to antibiotics has been named by WHO as one of the ten most serious problems of modern medicine. It also has a negative impact on the global economy, as the treatment of patients becomes lengthy and expensive. In addition, the terms of hospitalization of the patient are delayed, and this hits his pocket. Understanding what lies at the heart of the problem, you can look for solutions.

There are two types of antibiotic resistance in bacteria: congenital and acquired. The first one is based on the complete absence of the target microorganism of the action of an antibacterial agent or its inaccessibility due to inactivation by enzymes or low permeability. The second type of resistance occurs in several situations:

1. By contact with antibiotics.
2. Due to mutations in chromosomal DNA, which modifies the protein structure of bacteria.
3. During transformation with the formation of mosaic genes.
4. With horizontal gene transfer.

Acquired antibiotic resistance manifests itself through five mechanisms of protection against the action of antibiotics:

• blocking an antibacterial agent by a microbial cell;
• destruction of the antibiotic by enzymes that destroy the structure of the active substance;
• getting rid of the substance that has entered the cell with the help of special “pumps” in the walls;
• leveling the effect of antimicrobial agents, that is, microorganisms “develop” ways to bypass their main action, for example, blocking the production of useful substances;
• disguise. Microbes use this defense mechanism to prevent antibiotics from recognizing certain parts of them (targets), thereby preventing the drugs from fully acting on them. ^[2].

Antibiotic inactivation by enzymes is the most common mechanism. It occurs due to the synthesis of enzymes that can either destroy the drug or modify it. Also, under the action of enzymes, the affinity of targets can change, which blocks the binding of the antibiotic to them.

An interesting fact: a similar defense mechanism works against most groups of antibacterial agents.

The second most common mechanism for the manifestation of antibiotic resistance is masking – a change in the structure of targets that allows microbes to become invisible to the active substance of the drug. Its occurrence is possible by one of two mechanisms. In the first case, spontaneous gene mutations are “guilty”, which change the structure of target molecules. What is important: such resistance is not transmitted by horizontal gene transfer. The second mechanism, on the contrary, is associated with HGT (horizontal gene transfer). It is the products of these genes that are capable of causing modification of the target molecule. ^[3].

How do we contribute to the emergence and spread of antibiotic resistance

Despite the fact that resistance to antibiotics occurs in microorganisms, humanity is directly involved in this. Many factors contributing to the emergence of such a problem are associated precisely with the wrong actions of a person.

One of the main causes of antibiotic resistance is self-medication. Patients independently prescribe antibacterial drugs for themselves, even with a common cold. Antibiotics are often used to treat viruses, the right dosage is incorrectly selected, the required frequency of administration and the desired course of treatment are not taken into account. Many patients, after improvement, reduce the medication to 1 time per day instead of 2-3 or stop therapy altogether. All this reduces the concentration of the antibiotic in the body at a time when not all bacteria have died. And some microorganisms can not only survive in such conditions, but also become resistant to the action of an antibacterial drug.

And this is not the only factor that provokes antibiotic resistance. Its occurrence and distribution is also associated with:

• poor health care delivery system. In particular, patients with infectious diseases may be in the same room, and it is possible that resistant bacteria are present in the body of one of them;
• use of antibiotics in animal husbandry. As a result, such products can end up in human food, and due to the presence in the body of even low concentrations of substances to fight bacterial infections, resistance can occur;
• irresponsible prescribing of antibiotics by healthcare professionals. Some doctors sin this by writing a prescription for such drugs just in case. ^[4].

How critical is the situation with antibiotic resistance in the world

Although it was only in the 21st century that antibiotic resistance was declared a menacing situation, the problem has been around for a long time. Resistant bacteria appeared almost immediately after the discovery and use of penicillin. But today the scale of the spread of antibiotic resistance has seriously increased. And the WHO explains this by the coronavirus pandemic, during which almost all patients with serious complications were prescribed antibiotics. Contributed to the development of resistance and frequent mutations of the virus that causes COVID ^[5].

However, even without the coronavirus, the situation was critical. More and more infections are becoming deadly due to the expansion of their antimicrobial resistance. Thus, Klebsiella pneumoniae, which is resistant to antibiotics of the carbapenem group, has been found in almost all regions of the world. These are medicines of the last reserve, that is, they are almost the only hope for the recovery of patients. But K. pneumoniae is a bacterium that is the main cause of nosocomial infections (in newborns, patients in intensive care units), so the possibility of effective treatment is very important.

Another example is the antibiotic resistance of E. coli to the group of fluoroquinolones (ciprofloxacin, ofloxacin, and others) used to treat urinary tract infections. As the data show, treatment is ineffective in almost half of patients. While colistin (known as polymyxin E) has only recently been targeting these two types of resistant bacteria, there are already reports of a number of regions where colistin-resistant bacteria have been found. Thus, it can be argued that there is actually nothing to treat infections caused by these bacteria. And these are just a few examples of the danger of antibiotic resistance, because there are still such dangerous diseases as gonorrhea, tuberculosis and more. In 2018 alone, half a million cases of antibiotic resistance to rifampicin were detected in TB patients. And without explanation, it is clear how this threatens humanity.

What can be done

The solution to the situation with bacterial resistance to antibiotics in human hands. It is most likely impossible to completely get rid of this problem, but it can be slowed down and even reduced.

At the patient level, antibiotic resistance can be prevented by:

• refusal of self-medication;
• careful adherence to the antimicrobial treatment regimen prescribed by the doctor;
• vaccinations that can protect against serious diseases;
• careful hygiene, mandatory disinfection of wounds, scratches;
• responsible attitude towards your health.

Bacterial resistance to antibiotics must also be tackled at the physician and healthcare facility level. To do this, specialists are obliged not to prescribe antimicrobial agents, unless there is a serious need for this. Doses, frequency of administration, course of treatment should be selected with special attention, emphasizing the patient on strict adherence to it.

In healthcare facilities, the spread of infections between patients should be prevented, so it is necessary to ensure that there is no contact, including at the level of the clinic.

It is also necessary to deal with the problem of antibiotic resistance at the state level. To do this, it is worth stimulating and funding medicine, a field of scientific research, in a timely manner, so that doctors and scientists can develop new effective antimicrobial agents and explore ways to bypass bacteria. ^[6].

Over the past few years, the world health organizations have been dealing with the situation with the resistance of microorganisms to the action of antibiotics. Since 2020, the “World Antimicrobial Awareness Week” has been actively held (from November 18 to 24). It has been introduced since 2015, but used to have a slightly different name. Such an event is a worldwide campaign aimed at informing about the problem of resistance, as well as ways to prevent it. ^[7].

And in 2015, at the session of the World Health Assembly, the Global Action Plan to Combat Antibiotic Resistance was adopted, the strategic goals of which were:

1. Optimizing the use of antimicrobial agents.
2. Raise awareness of bacterial resistance to antibiotics.
3. Reducing the number of transmission of infection through the creation of appropriate sanitary and hygienic conditions and preventive measures.
4. Accumulation of knowledge and data through surveillance and research.
5. Preparation of business cases for systematic investments in the study and development of new drugs ^[8].

No one can give accurate predictions of how quickly and effectively the problem can be dealt with. But efforts must be made by all links, starting from ourselves. Flemming saved humanity by discovering penicillin, now the task is to preserve the ability to treat patients even from the most complex infections.

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