SURFACTANT

A multicomponent system of cellular and non-cellular elements whose structural and functional unity ensures normal respiratory biomechanics.

To characterise the condition of the surfactant system, three degrees of impairment have now been identified:

1.Insignificant.

2.Expressed.

3.Widespread.

At the heart of the disturbances occurring in the surfactant system of the lungs in tuberculosis are processes involving an increase in the permeability of the air-blood barrier:

1.Surfactant damage on the alveolar surface.

2.Altered metabolism and damage to A2.

3.Disruption of mechanisms for removal of waste surfactant from the alveoli.

THE STAGES OF INTERACTION BETWEEN MBT AND THE MACRO-ORGANISM.

The first is characterised by the progressive multiplication of MBT in the absence of a specific T- lymphocyte response and lasts for 2 to 3 weeks.

The second occurs after the formation of mature T lymphocytes and is characterised by a stabilisation of MBT growth.

This is usually followed by a decompensation stage, which coincides with the destructurisation of the lymphoid masses and the appearance of necrotic changes in the lungs. The vaccine effect may be due to a shortening of the first phase of the process.

The definition of drug sensitivity or drug resistance is based on a population- based approach, which implies different degrees of resistance in a pool (different population) of microbial cells. Drug resistance is assessed in quantitative terms, such as 'minimum inhibitory concentration' (MIC).

RESISTANCE

– that degree in part of the microbial population that predetermines treatment failure in most cases.

It is generally accepted that 10% of resistant strains in the entire microbial population of a patient can have a pathogenetic effect.

In phthisobacteriology, this is 1%, or 20 colony- forming units (CFU), for first-line antituberculosis drugs (DAAs). This proportion of the microbial population is capable of displacing the initial population after one month and forming a nidus.

THE TRUE NATURAL SUSTAINABILITY

– a permanent species trait of microorganisms associated with the absence of a target of action of the AB or inaccessibility of the target due to initially low permeability of the cell wall, enzymatic inactivation of substances or other mechanisms.

ACQUIRED RESISTANCE

– the property of individual strains, which is genetically determined, to remain viable at concentrations of AB that inhibit the growth of the bulk of the microbial population.

THE MOLECULAR MECHANISMS OF MBT

STABILITY:

1.AB inactivation (enzymatic).

2.Modification of the target of action (change in the spatial configuration of the protein due to a mutation of the corresponding section of the genome).

3.Hyperproduction of the target, leading to a change in the agent-target ratio and release of part of the bacterial life support proteins.

4.Active elimination5 of the drug from the microbial cell

(effluent) due to the activation of stress defense mechanisms.

5.Alteration of the permeability parameters of the external MBT structures, blocking the ability of AB to penetrate the cell.

6.Activation of a "metabolic shunt" (metabolic bypass).

TYPES OF DRUG RESISTANCE.

1.Primary drug resistance - in MBT strains isolated from patients who have not received specific therapy or have been treated for one month or less.

2.Acquired drug resistance is among first-time patients as a result of treatment failure.

Mono-drug resistance - resistance to one of the drugs, but sensitivity to the other drugs is maintained.

Multidrug resistance - resistance to isoniazid and rifampicin at the same time (regardless of the presence of resistance to the other drugs).

Superresistant - multiple drug resistance combined with resistance to fluoroquinolones and one of the injectable drugs (kanamycin, amikacin, capriomycin).