RU2380113C1 - Method of treating patients with pulmonary tuberculosis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to phthisiology, and can be used in treating the patients with pulmonary tuberculosis. That is ensured by conventional tuberculous therapy. The therapeutic course includes Viferon, rectal suppositories containing 1000000 ME of human recombinant alpha-2 interferon. Viferon is dosed one suppository twice day, every 12 hours, the 1^st to 10^th day - daily and the 11^th to 60^th day - every second day.

EFFECT: therapeutic addition of Viferon in treating tuberculosis in specially developed dose and schedule allows improving clinical effectiveness ensured by reduced abacillation time and closure of decomposition cavities, resolution of infiltrative pulmonary changes.

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Description

The invention relates to medicine, namely to phthisiology, and can be used in the complex treatment of patients with pulmonary tuberculosis.

The problem of treatment of tuberculosis, and especially pulmonary tuberculosis, has attracted special attention of clinicians over the past two decades due to a sharp increase in the incidence of this severe chronic infection and an increase in the number of destructive forms of pulmonary tuberculosis, accompanied by massive excretion of mycobacterium tuberculosis, which are usually resistant to the main anti-tuberculosis drugs. Tuberculosis infection remains a complex socio-economic and biomedical problem. The number of patients with complicated forms has increased both among adults and among children and adolescents. In recent years, tuberculosis is characterized by a tendency to rapid progression, an increase in the number of complications. Often there is a reactivation of latent tuberculosis under the influence of adverse factors.

The leading method in the treatment of pulmonary tuberculosis is antibiotic therapy with anti-TB drugs, which determines the main direction in the future in the fight against tuberculosis (order of the Ministry of Health of the Russian Federation dated March 21, 2003 No. 109). However, many years of experience with the use of anti-tuberculosis therapy indicates an insufficient clinical and radiological effect.

A disadvantage of the known methods of treatment is the rapid emergence of drug resistance of tuberculosis mycobacteria to these drugs, the appearance of various toxic reactions from the liver, gastrointestinal tract and nervous system, and weakening of the immune status. A particularly significant drawback is the lack of bioavailability of drugs in the lung tissue due to extensive fibrotic changes. Significant disadvantages include the development of dysbiotic disorders of the gastrointestinal tract, which leads to a further decrease in immunity. All this makes us look for various new ways to treat pulmonary tuberculosis, which reduce the above disadvantages.

Conducted research of medical, scientific and patent literature identified various methods of treatment of pulmonary tuberculosis.

In the work of A.S. Svistunov and B.V. Pinegin “The use of the immunomodulator lycopide in the complex treatment of pulmonary tuberculosis” (the journal “Problems of Tuberculosis”, 2002, No. 3, p.21-25) describes a method of treating tuberculosis using lycopid .

In the work of S.S. Arshinova and B.V. Pinegin, “Immunomodulators in the treatment of patients with active pulmonary tuberculosis” (Journal of the Treating Doctor, October 2002, No. 10, pp. 36-37), a method for treating pulmonary tuberculosis is described, which provides inclusion in the complex chemotherapy of patients with polyoxidonium.

In the work of G.Yu. Vasilieva and G.S. Balasanyants "Experience in the use of bestim in the complex treatment of infiltrative destructive forms of pulmonary tuberculosis" (Family Doctor magazine, 2003, No. 3, pp. 17-19) describes a method for the treatment of tuberculosis lungs, including in the complex treatment of the bestim immunomodulator.

RF patent No. 2219939 (BIPM No. 36, 2003) protected the “Method for treating tuberculosis”, which provides for the use of the bactericidal bactisporin drug containing a live bacterial culture of Bacillus subtilis 3H as part of complex therapy.

RF patent No. 2253460 (BIPM No. 16, 2005) protected the "Method for the treatment of pulmonary tuberculosis", which provides for the inclusion of zinc sulfate in the treatment regimen, which potentiates the effect of anti-TB drugs.

Application No. 2006127776 (BIPM No. 4, 2008) describes a “Method for the treatment of pulmonary tuberculosis”, including the herbal preparation “Populin” in therapy.

The disadvantage of the above methods is the low effectiveness of treatment in terms of closure of the decay cavities, abacillation and the duration of the clinical manifestations of pulmonary tuberculosis.

The closest in essence and taken as a prototype is the method of treatment of tuberculosis, provided for by the order of the Ministry of Health of the Russian Federation No. 109 dated 03/21/03, "On the improvement of anti-TB measures in the Russian Federation." Standard treatment regimens for patients with tuberculosis, consisting of 2 phases with different tasks:

1. The intensive care phase is aimed at eliminating the clinical manifestations of the disease, maximizing the effect on the mycobacterium tuberculosis population in order to stop bacterial excretion and prevent the development of drug resistance, and to reduce infiltrative and destructive changes in organs;

2. The phase of continued therapy is aimed at suppressing the persisting mycobacterial population. It provides a further reduction in inflammatory changes and involution of the tuberculosis process, as well as restoration of the patient’s functional capabilities.

The disadvantages of this method of treatment are its low efficiency in relation to closing decay cavities, resorption of infiltration and abacillation, prolonged preservation of the clinical manifestations of the disease, the duration of the course of therapy, which leads to the formation of drug resistance of mycobacteria to anti-tuberculosis drugs.

The aim of the invention is to increase the effectiveness of the treatment of pulmonary tuberculosis by reducing the time of abacillation and closing of the decay cavities, resolving the infiltration of changes in the lungs, as well as the disappearance of the clinical manifestations of the disease and reducing the duration of inpatient treatment.

This goal is achieved by prescribing anti-TB therapy according to standard regimens and the Viferon rectal suppository containing 1,000,000 IU of human recombinant interferon alfa-2. The drug is prescribed for one suppository twice a day, with 12-hour intervals, with the first day of treatment, for 10 ^minute a day - every day, from 11 ^th to 60 ^th day - a day.

Included in the composition of the drug Viferon (per. No. 01-11 / 53-06 dated 04/14/06), recombinant human interferon alpha-2 has immunomodulatory activity. When exposed to interferon, there is an increase in the activity of natural killers, T-helpers, cytotoxic T-lymphocytes, phagocytic activity, the intensity of differentiation of B-lymphocytes. The listed properties of interferon allow it to effectively participate in the processes of elimination of the pathogen, preventing possible complications.

A decrease in the level of serum interferon 12 hours after the administration of Viferon makes it necessary to re-introduce it within a day.

Viferon Suppositories provides a simple, safe and painless route of administration. The good absorption of recombinant interferon alpha-2 from an ampoule of the rectum into the blood has been proven in experiment and in practice. At the same time, high concentrations of interferon alpha-2 are created in the blood, which are identical to those for parenteral administration, and systemic and local therapeutic effects are provided.

The practical feasibility of the claimed method is illustrated by examples from clinical practice.

Example 1: patient A., 18 years old, was admitted for inpatient treatment to the Rostov branch of the State Health Care Institution “Tuberculosis Clinical Dispensary” in the Rostov Region for infiltrative tuberculosis S1,2 of the left lung in the phase of decay and contamination, MBT (Mycobacterium tuberculosis) +. The patient's condition upon admission is moderate, the skin is pale, the nutrition is low, tuberculous intoxication phenomena are expressed. Auscultatory in the lungs, vesicular breathing is heard, on the left under the clavicle there are single dry rales. NPV - 18 in 1 minute, blood pressure - 120/80 mm Hg, state of emergency - 76 in 1 minute.

Survey data at admission:

R-grams and T-grams - in S1,2 of the left lung, infiltration of the lung tissue of the focal structure with a decay cavity up to 2.0 cm in diameter, with polymorphic foci around and a wide vascular "path" to the root of the lung.

Blood test - HB - 122 g / l, Er - 3.0 × 10 ¹² / l, L - 7.6 × 10 ⁹ / l, E - 1, P - 7, C - 68, L - 20, M - 4, ESR - 18 mm / hour.

Sputum smear analysis by direct bacterioscopy - CMC (acid-resistant mycobacteria) were found (2-5 in the field of view).

Sputum culture gave rise to 10 colonies of the Office (Mycobacterium tuberculosis).

Mantoux test with 2 TE - 19 mm.

The patient was prescribed treatment according to the claimed method: anti-tuberculosis therapy according to the intensive phase 1 of the standard treatment regimen - streptomycin 1 g, isoniazid 0.6 g, rifampicin 0.6 g, pyrazinamide 1.5 g, multivitamins, vitamin B6 and, simultaneously, from the first day for 10 ^five days - daily, from 11 ^th to 60 ^th day - in a day, the treatment drug Viferon was added, rectal suppositories 1000000 ME (interferon human recombinant alpha-2), one suppository twice daily, with 12 hour intervals.

Data of control examination after 4 months:

R-grams and T-grams - in S1-2 of the left lung, a limited area of pneumosclerosis, single small, medium-intensity foci.

Blood test - HB - 135 g / l, Er - 3.8 × 10 ¹² / l, L - 5.9 × 10 ⁹ / l, E - 1, P - 4, C - 64, L - 26, M - 5, ESR - 6 mm.

Sputum smear analysis by bacterioscopy - no CMC found.

Inoculation of sputum at the office gave a negative result.

Mantoux test with 2 TE - 8 mm.

As a result of treatment according to the claimed method, a positive trend was achieved. The patient's condition improved, the infiltration resolved, the decay cavity was closed, abacillation was achieved, during the treatment she gained 4.5 kg in weight, catarrhal phenomena were not heard. In satisfactory condition, the patient was discharged for outpatient treatment. The duration of inpatient treatment was 126 beds / days.

Example 2: patient M., 49 years old, was admitted for inpatient treatment to the Rostov branch of the State Health Institution “Tuberculosis Clinical Dispensary” in the Rostov Region for infiltrative tuberculosis S10 of the right lung in the phase of decay and contamination, MBT (Mycobacterium tuberculosis) +. The patient's condition at admission is satisfactory, moderate nutrition, temperature - 37.3 ° C. Auscultatory in the lungs was heard vesicular breathing, on the right in the lower sections - dry scattered rales. NPV - 22 in 1 minute, blood pressure - 145/85 mm Hg, state of emergency - 86 in 1 minute.

Survey data at admission:

R-grams and T-grams - in S10 of the right lung, heterogeneous infiltration of the lung tissue of the focal structure of about 6.5 × 5.0 cm with a decay cavity up to 3.5 cm in diameter, polymorphic foci around and in S1-2 of the left lung, wide vascular "path" to the root of the lung.

Blood test - HB - 147 g / l, Er - 4.8 × 10 ¹² / l, L - 8.4 × 10 ⁹ / l, E - 1, P - 9, C - 69, L - 19, M - 2, ESR - 28 mm / hour.

Sputum smear analysis by direct bacterioscopy - CMC found (1-3 in the field of view).

Sputum culture gave rise to 1 large colony of the Office.

Mantoux test with 2 TE - 16 mm.

The patient was prescribed treatment according to the claimed method: anti-tuberculosis therapy according to the intensive phase 1 of the standard treatment regimen - streptomycin 1 g, isoniazid 0.6 g, rifampicin 0.6 g, pyrazinamide 1.5 g, multivitamins, vitamin B6 and, simultaneously, from the first day for 10 ^five days - daily, from 11 ^th to 60 ^th day - in a day, the treatment drug Viferon was added, rectal suppositories 1000000 ME (interferon human recombinant alpha-2), one suppository twice daily, with 12 hourly interval.

Data of control examination after 4 months:

R-grams and T-grams - in S10 of the right lung pneumofibrosis, groups of small, medium intensity foci, the decay cavity is not determined, in S1-2 pneumosclerosis on the left.

Blood test - HB - 146 g / l, Er - 4.8 × 10 ¹² / l, L - 5.6 × 10 ⁹ / l, E - 2, P - 5, C - 62, L - 28, M - 3, ESR - 10 mm.

Sputum smear analysis by bacterioscopy - no CMC found.

Inoculation of sputum at the office gave a negative result.

As a result of treatment according to the claimed method, a positive trend was achieved. The patient's condition improved, the infiltration resolved, the decay cavity was closed, abacillation was achieved, during the treatment she gained 2 kg in weight, catarrhal phenomena were not heard. In satisfactory condition, the patient was discharged for outpatient treatment. The duration of inpatient treatment was 128 beds / days.

Under our supervision, there were 36 patients with pulmonary tuberculosis, out of which 18 people received anti-tuberculosis therapy according to standard regimens (control group). The second group consisted of 18 people (main group). In this group of patients in the treatment of tuberculosis together with the TB treatment from the first day for 10 ^five days - daily, from 11 ^th to 60 ^th day - a day, a drug was added to treatment Viferon, rectal suppositories 1000000 ME (Interferon human recombinant alpha-2), one suppository twice a day, with a 12-hour interval.

A comparative analysis of the treatment results is presented in tables 1 and 2.

Table 1 The dynamics of the clinical manifestations of pulmonary tuberculosis when Viferon is included in the standard therapy regimen, rectal suppositories 1000000 ME (human recombinant interferon alpha-2) Clinical manifestations The main group (n = 18) abs. /% Comparison group (n = 18) abs. /% before treatment after treatment before treatment after treatment Weakness 10 people / 55.6% 2 people / 11.1% 9 people / 50.0% 3 people / 16.7% Rise t ° 9 people / 50.0% 0 people / 0.0% 10 people / 55, b% 2 people / 11.1% Mass deficit 5 people / 27.8% 0 people / 0.0% 4 people / 22.2% 1 people / 5.6% Cough 9 people / 50.0% 1 people / 5.6% 10 people / 55.6% 2 people / 11.1% Sputum 4 people / 22.2% 0 people / 0.0% 3 people / 16.7% 2 people / 11.1% Dyspnea 6 people / 33.3% 1 people / 5.6% 5 people / 27.8% 3 people / 16.7%

As can be seen from table 1, in most patients of the main group, after 4 months of treatment carried out in accordance with the claimed method, the clinical manifestations of pulmonary tuberculosis disappeared, while in the patients of the comparison group the clinical symptoms of tuberculosis persisted.

table 2 The effectiveness of the treatment of pulmonary tuberculosis when Viferon is included in the standard therapy regimen, rectal suppositories 1000000 ME (human recombinant interferon alpha-2) Indicators The main group (n = 18) abs. /% Control group (n = 18) abs. /% Decay cavity closure 12 people / 66.7% 7 people / 38.9% Abacillation 14 people / 77.8% 9 people / 50.0% Resorption of infiltration 12 people / 66.7% 7 people / 38.9% Average bed day 121 178

As can be seen from table 2, as a result of treatment carried out in accordance with the claimed method, in the main group revealed an increase in treatment efficiency: closure of cavities 1.7 times higher, abacillation 1.6 times, resorption of lung tissue infiltration - 1.7 times, a reduction in the time of inpatient treatment by 1.4 times (by 2 months).

Thus, in comparison with anti-tuberculosis therapy according to standard modes, the proposed method for the treatment of patients with pulmonary tuberculosis can improve the effectiveness of treatment by improving the closure of decay cavities, resorption of infiltrative changes in the lungs, and abacillation; and also accelerates the disappearance of the clinical manifestations of the disease, improves the general condition of patients and makes it possible to shorten the length of their stay in the hospital.

Claims (1)

A method of treating patients with pulmonary tuberculosis, providing for anti-tuberculosis therapy according to standard modes, characterized in that from the first day of treatment, for 10 days every day, from 11 to 60 days every other day, Viferon and rectal suppositories containing 1,000,000 are included in the course of treatment ME recombinant human interferon alpha-2, one suppository twice daily, with a 12-hour interval.