Cord thrombophlebitis. Description of the development of clinical signs

Drug-resistant tuberculosis, as in the case of ordinary tuberculosis, is caused by Koch's bacillus. But there are differences in the disease, and there are many of them. For example, drug-resistant TB is a stronger and more resistant form than the common disease. This is also expressed at the stage of treatment, when drugs intended for ordinary tuberculosis are ineffective before LUT. The disease itself is severe and worsens every year.

Recently, there have been a considerable number of LUT forms, which are growing unhindered. If earlier this type of disease arose as a misuse of drugs and inconsistencies in treatment, now such a diagnosis haunts literally every second patient who first visits a phthisiatrician.

Patients at risk

Diseases can be experienced by people with such infections and diseases:

• persons who have been diagnosed with AIDS infection syndrome;
• people who are addicted to drugs and alcohol;
• members of the public who have problems with immunodeficiency and reduced immunity;
• people who do not have permanent residence and live in zones of complete or partial unsanitary conditions;
• persons imprisoned in prisons and pre-trial detention centers. A large number of accumulations of various people can lead to the spread of the disease. Also, an important role is played by the wrong method of treatment in places of deprivation of will.
• people who have previously fallen ill and are undergoing treatment, but who do not have real results in the recovery process.

The main symptoms of the disease include the following manifestations:

• chronic course of the disease, which have frequent exacerbations;
• if the x-ray shows not small tuberculous foci, but large stripes;
• tuberculosis can easily interact with bacterial or private diseases and infections, since sputum contains a huge amount of microbacteria.

Causes of drug-resistant tuberculosis

The first of the causes of infection with drug-resistant tuberculosis can be attributed to the infection of one person from another who has this disease. The second group involves infection during treatment. That is, people who have the usual form of tuberculosis can get some kind of mutation due to improper use of drugs or their ineffectiveness on the disease and its focus.

Due to the treatment, the composition of bacteria could change, which create a mutation and do not continue to take the usual forms of prevention. But along with ordinary bacteria, there will always be those that have defects and do not perceive medicines as a threat. If we take into account the fact that at least one hundred million bacteria are simultaneously located in only one focus of tuberculosis, then mutational forms of infectious bacteria are also necessarily located in them. It is they who will be resistant to all drugs known in the world.

If the healing process goes in the right direction and no errors are allowed, then the mutational bacteria will not play any role. Again, with improper treatment, if: the courses of treatment were completed ahead of time, the drugs were received in small doses, the drugs were chosen incorrectly or the combination of drugs did not meet the standards, there are more bacteria of the wrong content in relation to ordinary, not so dangerous bacteria. As a result, the disease develops much faster and the forms of bacteria acquire a viable appearance, which helps them to multiply rapidly.

Signs of LUT during treatment

The patient begins to cough with phlegm. It can also be expectoration accompanied by blood leakage, excessive sweating, a sharp decrease in weight, a feeling of weakness. The doctor will be able to tell the difference between LUT even before receiving the bacterial susceptibility test.

It is worthwhile to understand that conventional drugs that treat simple type tuberculosis are not cured, since mutated bacteria are no longer susceptible to drugs. The doctor determines further treatment individually. Since the specialist should find out the individual structure of the patient, as well as see the threshold of his sensitivity to drugs. The course of treatment can last from a six-month examination to two years of therapy. The chances of getting rid of such an ailment are approximately 50-80%, depending on the patient's condition.

Remember that most reserve drugs are toxic, so they can provoke side effects that lead to long-term anguish for the patient. Sometimes doctors also resort to surgery during treatment, that is, they cut out part of the infected lung.

But the basic principles of treatment remain the same:

1. continuity of treatment
2. its duration,
3. the use of various types of drug combinations.
4. control by medical professionals.

Sensitive to this drug are those strains of mycobacteria for which this drug is critical concentration (stability criterion) has a bactericidal or bacteriostatic effect.

Resilience (resistance) is defined as a reduction in sensitivity to such an extent that a given strain of mycobacteria is able to multiply when exposed to a drug at a critical or higher concentration.

Along with the concepts of sensitivity and resistance to anti-tuberculosis drugs, terms are also used that define the quantitative and qualitative aspects of drug resistance.

Characteristics of drug-resistant tuberculosis

Acquired (secondary) resistance- these are cases of tuberculosis when MBT strains turn from susceptible to resistant phenotypes during or after a course of chemotherapy. Ineffective chemotherapy of tuberculosis contributes to the selection of drug-resistant MBT mutants.

The presence of acquired resistance is suspected in patients with a history of indications for treatment with anti-TB drugs for 1 month or more, while initially it was known that this MBT strain was sensitive to anti-TB drugs at the beginning of therapy.

Primary resistance. In some cases, in patients with initial examination, MBT strains are detected that have a pronounced resistance to one or more anti-tuberculosis drugs.

Primary resistance occurs when a person is infected with MBT while already resistant to one or more anti-TB drugs.

Combined resistance. The definition adopted by the World Health Organization summarizes primary and acquired resistance to determine its prevalence.

Monoresistance. MBT strains are resistant to only one of the five first-line anti-TB drugs (rifampicin, isoniazid, ethambutol, pyrazinamide, streptomycin).

Multidrug resistance (MDR) MBT to the action of isoniazid and rifampicin simultaneously, with or without the presence of resistance to any other anti-tuberculosis drugs.

Polyresistance(complex combination resistance) is the resistance of the office to any two or more anti-tuberculosis drugs without simultaneous resistance to isoniazid and rifampicin.

Multidrug-resistant Mycobacterium tuberculosis, or multidrug-resistant tuberculosis (MRI) is the most dangerous form of bacterial resistance at present. MRI is a major concern in tuberculosis control in many countries.

Since the 1990s, there have been several outbreaks of MRI in various regions of the world as a result of the misuse of anti-TB drugs. Usually, MRI occurs in chronic tuberculosis, the absence of the effect of the standard chemotherapy regimen proposed by the WHO, or other treatment regimens, and constitutes a significant proportion of TB patients with acquired resistance.

Criteria for drug resistance

The level of resistance of this strain as a whole is expressed by the maximum concentration of the drug (the number of micrograms per 1 ml of nutrient medium), at which the reproduction of mycobacteria is still observed (by the number of colonies on solid media).

For various drugs, a certain concentration is established (critical), having clinical significance, in which reproduction of mycobacteria sensitive to this drug is still observed.

To determine the drug resistance of mycobacteria, the most common method is the method of absolute concentrations on dense egg nutrient medium Lowenstein-Jensen.

Drug-resistant microorganisms able to multiply at such a content of the drug in the environment, which has a bacteriostatic or bactericidal effect on sensitive individuals.

MBT properties

1) Reproduction occurs rather slowly, cell division occurs in 20-24 hours. On liquid nutrient media at tº 37 C º, visible growth appears on the 5-7th day, on solid nutrient media - on the 14-15th day.

2) Possess sustainability:

to the effects of environmental factors, are not afraid of the cold (survive at a temperature of -269˚ C.),

to high concentrations of acids, alkalis, alcohols (acid resistance).

3) Differ great vitality, i.e. can retain their pathogenic properties in:

- dried sputum in the dark, without access to sunlight, for 10-12 months,

- indoors, on the pages of books, clothes, furniture, walls up to 3-4 months,

- street dust up to 2 weeks,

- damp earth from 4 to 12 months.

- water up to 5 months,

- butter - up to 8 months, cheese - up to 7 months.

Direct sunlight has a detrimental effect on the ICD, under the influence of which they die in a few hours.

Dying fast:

at boiling (after 15 min.),

from exposure to UV radiation, bleach, chloramine, iodine, formalin. For disinfection, preparations containing chlorine in high concentrations are used.

In a dry heat cabinet - at tº 100 C º, they die after 45 minutes.

4).Exhibit variability and adaptability to adverse effects.

The variability of the ICD manifests itself in the following forms:

- Morphological variability

- Variability to dyes

- Biological variability - an increase or decrease in virulence for a complete loss of virulence.

Morphological variability appears in the form polymorphism, i.e., the ability to form different forms. They may completely or partially lose their cell membrane (the so-called L forms) and become inaccessible to the action of drugs or natural human defense mechanisms.

This allows mycobacteria to exist imperceptibly for years and decades in the conditions of a living organism, but at the same time there is a constant danger that they will again transform into ordinary mycobacteria and cause a recurrence of tuberculosis.

Atypical forms of MBT can cause human and animal diseases that are indistinguishable from the clinical, radiological and morphological manifestations of tuberculosis. Such diseases are called mycobacteriosis.

Tuberculosis diagnosis is based on the data of clinical, histological, microbiological studies, evaluation of the results of tuberculin tests and test therapy. Of these methods, the most reliable is the detection of Mycobacterium tuberculosis (MBT), while the rest are informative only in combination. Modern microbiological diagnosis of tuberculosis consists of several main groups of tests aimed at:
identification (detection) of the pathogen;
determination of drug resistance;
typing of Mycobacterium tuberculosis.

Bacterioscopic methods. Detection of the pathogen begins with the simplest and fastest bacterioscopic methods: light microscopy with Ziehl-Neelsen staining and fluorescent microscopy with fluorochrome staining. The advantage of bacterioscopy is the speed of obtaining the result, but its possibilities are limited due to low sensitivity. This method is the most economical and is recommended by the World Health Organization as the main method for identifying infectious patients.
Cultural studies. Cultural studies are recognized as the "gold standard" for detecting MBT. In Russia, egg media are used for inoculation of pathological material: Levenshtein-Jensen, Finn-II, Mordovsky, etc. To increase the percentage of mycobacteria isolation, inoculation of pathological material is carried out on several media, including liquid ones, which makes it possible to satisfy all the cultural needs of the pathogen. Crops are incubated
up to 2.5 months, in the absence of growth by this time, the culture is considered negative.
biological assay method. The most sensitive method for detecting MBT is considered to be the biological test method - infection of guinea pigs highly sensitive to tuberculosis with diagnostic material.
Molecular genetic diagnostics. The development of molecular biology has significantly improved the detection efficiency of mycobacteria. The basic method of molecular genetic research is polymerase chain reaction(PCR) aimed at detecting the DNA of mycobacteria in the diagnostic material. PCR gives exponential amplification of a specific DNA region of the pathogen: 20 cycles of PCR lead to an increase in the content of the original DNA by 1 million times, which makes it possible to visualize the results by agarose gel electrophoresis. The role of molecular diagnostics in clinical practice is increasing as the number of patients with poor bacterial excretion increases. However, in establishing a diagnosis, PCR results are complementary and should be compared with clinical examination, radiography, smear microscopy, culture, and even response to specific treatment.

MBT drug resistance:

primary (in untreated patients);

secondary (with inadequacy of therapy).

Allocate monoresistance (to one drug),

polyresistance (to 2 or more),

· multi-resistance (drug-to-HR) - to isoniazid, rifampicin.

It is multiresistance or multiple drug resistance (MDR) of the causative agent of tuberculosis that has epidemiological and clinical significance in modern conditions.

The clinical significance of identifying patients with MDR tuberculosis is that this category of patients is characterized by:

The high prevalence of the process

The progressive course of the disease

immunodeficiency,

Lack of effect from ongoing standard chemotherapy.

An important sign of MBT variability. is resistance to one or more anti-tuberculosis drugs. Types of drug resistance:

Primary - MBT resistance to anti-tuberculosis drugs (ATP) in patients with tuberculosis who have not previously received specific therapy.

Initial - MBT resistance to anti-TB drugs in patients with tuberculosis who could previously receive them. Includes

primary and not identified acquired.

Acquired (secondary) resistance in patients who have previously received specific therapy.

Monoresistance - resistance to one drug.

Polyresistance - resistance to two or more anti-TB drugs, but not to a combination of isoniazid and rifampicin.

Multiple - -//- + combination of isoniazid and rifampicin

Cross (complete and incomplete)

The main mechanisms for the development of drug resistance

I. Mutation

2. Selection

Therefore, at least 4 drugs are used for chemotherapy; if the drug = 40 mcg / ml and the MBT is stable, which should be excluded.

Methods for determining drug resistance

1 .Classic: -md proportions

m-d stability coefficient - m-d absolute concentrations

2.Expedited:

Radiometric m-d of the VAS GES system

3. Promising: -molecular-genetic.

MDR tuberculosis is the resistance of pathogenic microorganisms to the tuberculosis drugs used. This variety of pathological process is considered the most dangerous due to the lack of effective treatment options for patients. As a result, the disease is actively progressing and can lead to disastrous consequences.

Where does sustainability come from?

The resistance of microorganisms is most of all revealed when using powerful medicines: Rifampicin and Isoniazid. The drugs are among the primary therapeutic options that can overcome the activity of a viral infection of tuberculosis.

The formation of stability is carried out in several situations:

1. Incorrectly selected therapy of the disease. It is necessary to take a comprehensive approach to the treatment of the disease, it is recommended to use several options for antibiotics at once. In this case, the options are set depending on the nature of the course of the pathological process and the form of the disease.
2. Preliminary completion of therapeutic measures. The duration of therapy should be at least six months. The absence of manifesting symptomatic signs and improvement in general well-being is not an indicator for discontinuation of medication.
3. Interruption of prescribed treatment. Such a violation occurs due to the lack of necessary control over the conduct of therapy.

Today, drug resistance occurs in all countries of the world. Mycobacteria can be transmitted to healthy people with weak immune systems, in places with a large number of people, especially in medical institutions, places of detention and nursing homes.

Varieties of a stable form of the disease

Drug resistance of the body is divided into primary and acquired forms. The first variety is strains of patients who have not previously received therapy, or treatment was incomplete (interrupted). In this case, patients belong to the group of initial resistance. If deviations are detected in the process of carrying out therapeutic measures for one month or longer, then the pathology is characterized as acquired.

Depending on the structure of drug resistance, the stability of the disease to one type of medicine is distinguished (while sensitivity to other options is preserved) and multidrug resistance in tuberculosis. There is a so-called super-resistance that can lead to death.

Known for XDR tuberculosis - extensive drug resistance. It represents the inability to use numerous anti-tuberculosis drugs. The process occurs as a result of illiterately selected therapy, most often this occurs due to self-selection of drugs.

Elimination of pathology

The effectiveness of therapy depends on the stage of development of the disease. The timing of the treatment also plays an important role. Medical specialists are obliged to take a responsible approach to the choice of drugs, taking into account the individual characteristics of the patient. Preference is given to complex treatment with the use of various antibiotics.

• adhere to a strictly established treatment regimen, when using traditional medicine recipes, it is imperative to inform the physician about this;
• the patient is obliged to take medications in a clearly defined period of time;
• it is important to protect a person from foci of exposure to harmful microorganisms, this will prevent the occurrence of relapses;
• the patient should carefully monitor the state of the immune system.

In the case of diagnosing the most resistant variant of tuberculosis, the patient is recommended to use several treatment regimens at once.

In the absence of the necessary therapeutic effect from the first-line drugs, second-line drugs are prescribed. They are a backup. Medicines are administered intravenously. The most common drugs include Levofloxacin, Cycloserine, Ethionamide.

Before prescribing medication, the patient undergoes a special test. It allows you to establish the sensitivity of the body in relation to antibiotics. It is acceptable to use the third treatment regimen. It is applied in certain clinical situations. Clarithromycin, Amoxiclav and Meropenem are considered to be in demand. This option is considered relevant in the case of diagnosing multidrug resistance in relation to drugs of the first two groups.