Clinical antibiotic resistance

2021-06-23 02:50 PM

Therefore, therapeutic resistance is a relative concept, related to the magnitude of the effect and is dose-dependent, i.e. the minimum inhibitory concentration in vitro and at the site of infection.

Some concepts

When treating an infected patient with antibiotics, here, there exists an interrelationship of 3 components, namely: Antibiotics - Body - Bacteria.

Therefore, if antibiotic treatment fails, we need to consider this failure from all three factors above.

In the relationship between bacteria and antibiotics, resistance is understood as the ability of bacteria to resist antibiotics and therapeutic chemicals.

We should distinguish between biological resistance and therapeutic resistance. Biological resistance are individuals of a species that, by acquiring genetic characteristics, are less susceptible than other individuals of the same species. These biologically resistant individuals are not necessarily resistant to treatment, as treatment resistance is primarily based on treatment outcomes.

Therefore, treatment resistance is a relative concept, related to the magnitude of the effect and depends on the dose, i.e. the minimum inhibitory concentration (MIC) in vitro and at the site of infection. It depends on the drug concentration achievable and the effect of the drug on the physicochemical parameters measured at the site of infection. A pathogen that exhibits resistance at low concentrations is likely to be susceptible at higher concentrations.

Resistance classification

There are two types of false resistance and true resistance.

Fake resistance

Pseudo-resistance is the manifestation of resistance but is not intrinsic, ie not due to genetic origin.

For example, the phenomenon of bacterial resistance when located in large pus-filled abscesses or surrounded by necrotic tissue, antibiotics do not penetrate the inflammatory and pathogenic bacteria, so the drug does not promote its effect. This is the case when there is an obstruction that causes the circulation to stagnate.

Or when the bacteria are in a resting state (not multiplying, not metabolizing), they are not affected by drugs that inhibit the biosynthesis of substances, for example, the bacilli are in the tuberculosis cave.

Therefore, when the body's immune system is impaired or the function of macrophages is limited, the body is not able to eliminate the inhibited bacteria from the body; so when there are no more antibiotics they recover and grow again.

True resistance

There are two types, natural resistance and acquired resistance.

Natural resistance: Some bacteria are not affected by certain antibiotics, for example, Pseudomonas is not affected by penicillin or staphylococcus is not affected by colistin. Non-walled bacteria such as Mycoplasma will not be affected by antibiotics that inhibit wall biosynthesis, such as beta-lactams.

Acquired Resistance: Due to an inherited event of mutation or acquisition of a resistance gene that causes a bacterium to go from zero to becoming resistant.

Resistance genes are located on chromosomes and/or bacterial plasmids and/and on transposons.

What is interesting is the selective effect of antibiotics: When antibiotics are widely used and especially in insufficient doses, antibiotics are the factors that create selective pressure and retain resistant strains of bacteria; it can also be a trigger for induced mutations in bacteria, not only creating more and more resistance but also increases resistance levels (this is what we are used to). roughly called "greasiness" of the drug).

The spread of resistant bacteria

A bacterium has a resistance gene, that gene will be transmitted vertically (vertical) to the next generation through cell multiplication (division). In addition, through different forms of genetic transport such as transformation, transduction, conjugation and transposition, resistance genes can be transmitted horizontally (horizontal) from one cell to another; even from the cell of one bacterial species to the cell of another (if the resistance gene is on the R - plasmid), for example from dysentery to E. coli, or from E. coli to bacteria typhoid bacteria.

In the microbial population (communities of bacteria belonging to the normal microflora in humans): Under the effect of antibiotics, resistant individuals are selected, retained and developed into resistant strains of bacteria; resistant strains of bacteria continue to be selected and replaced susceptible strains, making bacteria more and more resistant to antibiotics.

In the macrobiotic population (humans, animals): Through transmission (through the air, food, dust, tools...) resistant bacteria are transmitted from person to person or from animals to people.

In the race between human efforts to invent new antibiotics and bacterial resistance to antibiotics, bacteria have so far won. Therefore, to promote effectiveness and prevent antibiotic-resistant bacteria, we must implement a strategy of safe and rational use of antibiotics.

Resistance mechanism

Resistance genes create resistance by:

Reduces plasma membrane permeability, eg resistance to tetracycline, oxacillin; the resistance gene produces a protein that puts on the membrane, preventing the antibiotic from entering the cell; or incapacitated transmembrane transport by blocking the carrier proteins and antibiotics from entering the cell.

Altering the target: Because a structural protein or a nucleotide on the 30S or 50S subunit of the ribosome is altered, the antibiotic does not bind to the target (eg, streptomycin, erythromycin) and therefore fails to exert its effect use.

Generation of isoenzymes that have no affinity for antibiotics any longer, so the effects of antibiotics are ignored, for example, resistance to sulfamide and trimethoprim.

Generating enzymes: Enzymes produced by resistance genes can:

Changes in the chemical structure of the antibiotic molecule, rendering the antibiotic ineffective, for example, acetylation or phosphorylation or adenylation of aminoxides or chloramphenicol.

Destruction of the chemical structure of the antibiotic molecule, for example, β-lactamase, makes the β-lactam antibiotics ineffective.

An antibiotic-resistant bacterium is usually due to a combination of the above separate principles, for example, Gram-negative bacteria that are resistant to β-lactams are due to the production of β-lactamases plus decreased ability to bind PBPs penicillin-binding) and reduced plasma membrane permeability.