Antibiotic resistance: why take them accurately?

Antibiotics (from the Greek anti - against, bios - life) are natural, but also synthetically produced drugs that have the ability to act on bacteria, slowing their growth and destroying them.

Their discovery revolutionized the treatment of bacterial diseases and contributed significantly to the reduction of mortality from infectious diseases.

Historical milestones in antibiotic treatment

"Sometimes one finds what one is not looking for."
(Alexander Fleming)

In 1988, German scientist E. Freudenreich isolated bacterial secretions for the first time and discovered their antibacterial properties.

The most famous antibiotic, penicillin, is still considered to be the greatest discovery. Its discoverer was a Scottish physician, Alexander Fleming, who first discovered a bacteria-killing substance he named lysozyme in 1921.

In 1928, Fleming went on holiday and left a petri dish with a bacterial culture on his desk.
By the time he returned, the dish had grown a mould with a ring of bacteria around it. He repeated the process.
He identified the mould as Penicillium notatum and the antimicrobial as penicillin.

The first antibiotics were originally natural substances derived from fungi or other bacteria. In the mid-1930s, sulfonamides were added.

Research into new antibiotics is expensive and unsuccessful

In the 1960s, a number of new antibiotics with different mechanisms of action were created by chemical synthesis.

In the 1970s, a turning point occurred because, as antibiotics were developed, bacterial resistance began to develop as a result of their large quantities and hence overuse.

Unfortunately, in the same period, pharmaceutical companies lost interest in developing new drugs because of the cost of research.

Annual research costs around USD 5 billion! In addition, up to 80% of substances fail efficacy and safety tests.

How do antibiotics work?

Antibiotics are substances that slow the growth of microorganisms or kill them completely.

They are produced by the bacteria or fungi themselves, as in the case of penicillin.

Nowadays, mostly synthetic derivatives with a strong antimicrobial effect and at the same time minimal toxicity for humans are used.

Mechanism of action of antibiotics

Antibiotics act on bacteria in several ways.

They retard their growth and fusion, slow down the synthesis of proteins and nucleic acids by bacteria and disrupt the bacterial membrane.

1. Slowing down cell wall synthesis - the cell wall is vital to the bacterium, so disrupting it kills the microbe
2. disruption of the bacterial membrane - disruption of the bacteria's cytoplasmic membrane results in the leakage of certain substances important for its survival
3. slowing down protein synthesis - affects the process of peptide chain elongation (protein products)
4. slowing down nucleic acid synthesis - prevents nucleic acid fusion

Their effect is evaluated by their minimum inhibitory concentration (MIC). This is the determination of the smallest possible concentration of an antibiotic that is able to slow down the growth and multiplication of bacteria.

Another important value is the determination of the post-antibiotic effect (PAE). This is the period of time it takes for the microorganisms to stop multiplying, in simple terms the duration of the effect of the drug.

Interesting:
The PAE is a very important value. By the time the effect of one ingested tablet is over, administration of a second one is necessary. Most antibiotics are therefore given once every 12 or once every 24 hours. If a drug is delayed or forgotten, the bacteria builds up resistance to that drug - it becomes resistant!

What antibiotics are we familiar with?

Based on their mechanism of action, antibiotic drugs can be divided into several groups.
They are standardly divided according to their chemical structure.

Table with the division of ATBs by chemical structure:

What adverse reactions can be expected when taking ATBs?

Biological effects of the drug on the organism are the most common. They are caused by a change in the natural microflora in a particular organ. They can be observed on the skin and mucous membranes, but also on internal organs (intestine - diarrhoea).

Allergic reactions are another common reaction to drugs and therefore to ATBs. They are caused by hypersensitivity of the organism to a particular substance (active substance, excipient) and its hyperactive response. They are most common with ATBs of the penicillin series.

Poisoning (intoxication) by an antibiotic can occur inadvertently, but also intentionally. This happens when high doses of the drug are ingested, but also when the individual has a higher sensitivity to the drug. The patient develops different symptoms depending on the dose of the drug. In some cases, permanent consequences occur (e.g. liver damage, kidney damage).

Antibiotic resistance tends to increase

Resistance of a bacterium to an antibiotic can be primary or secondary.

The reason for primary resistance is the genetic insensitivity of the pathogen to a particular antibiotic. This means that the bacterium is naturally resistant to that drug.

Secondary resistance arises during improper treatment with an ATB or as a result of previous use of an ATB. It is an acquired adaptation of the microorganism.
Around the drug, predominantly resistant bacterial strains are selected.

Types of bacterial resistance:

1. Penicillin-type resistance - occurs after long-term use of penicillin-type ATBs.
2. streptomycin type of resistance - observed with rapid emergence of highly resistant bacterial strains (streptomycin, erythromycin)

Basic mechanisms of resistance:

• limited penetration of the ATB into the bacterial cell
• change in target structure, change in receptor
• metabolic changes in the bacterial cell
• inactivation of the antibiotic due to inhibition of certain enzymes

Bacterial resistance - a new threat

The increasing resistance of bacterial pathogens to antibiotic treatment - bacterial resistance to ATBs - is one of the most important health threats of the 21st century.

It is becoming not only a health but also an economic problem. Even the basic measure of tying drugs to prescription has not prevented it.

Already in 2017, the World Health Organization released a list of bacteria with the highest rates of resistance to available drugs, for which it is essential to invent new antibiotics.

Some new antibiotics are currently approved, while others are undergoing clinical trials. The aim is to advance the treatment of resistant and difficult-to-manage infections.

Interesting: the most resistant bacteria include Acinetobacter baumanii, Pseudomonas aeruginosa, Enterobacteriaceae, Enterococcus faecium, Staphylococcus aureus, MRSA.

Reasons for bacterial resistance:

1. Ignorance and incorrect use of antibiotics by the patient himself.
2. blindly administering antibiotic treatment by a doctor without prior blood tests - problem with health insurance

How can we defend ourselves?

To prevent the bacteria from becoming resistant to the antibiotic and subsequently prolonging the disease or making it worse, the doctor's choice of medicine is important in the first place.

The second priority is the correct use of the medicine by the patient.

• Before treatment, the patient should have a blood sample taken to determine to which of the wide range of ATBs the pathogen causing his disease is sensitive.
• Subsequent to the blood draw, the treatment itself is administered to the patient at a sufficient dose.
• Adherence to the PAE is important in treatment, i.e. each tablet must be given at the correct time according to the doctor's orders.
• It is good to combine ATB with probiotics (they protect the intestinal microflora, which is disturbed by the drug).
• The treatment must be finished completely, even if the patient feels better.
• During treatment, rest and increased fluid intake are important.
• The patient should be in a home environment, not exposed to excessive sunlight.

Caution:
Some patients wonder why their head, muscles and joints hurt or why their temperature is elevated when they are taking the ATB correctly.
ATBs destroy the infection itself. However, they do not affect the symptoms of the disease until the bacteria is completely killed and the symptoms resolve on their own.
Symptoms should be treated separately with pain medication, temperature medication, or medication for diarrhea and vomiting.
The time intervals for taking each medication should be observed, as they vary according to the specific medication.