Antimicrobial properties «Lipin» inhalation use in children with asthma

Анотація

Introduction. Problems of modern pharmacotherapy of bronchial asthma (BA) in children is largely reduced to the establishment of effective dosage forms that provide the delivery of drugs in the bronchopulmonary system without affecting other organ systems. A promising area in addressing the causal treatment of asthma in children is the use of the formulation «Lipin», which is a liposome, arising by self-assembly of amphiphilic lipid complexes.

Material & methods. The study of antimicrobial properties «Lipin» on microorganisms isolated from sputum in 135 children are hospitalized in the pulmonology department of GU «Children's Hospital road» Kharkiv about asthma in the period of exacerbation. Age was surveyed children from 5 to 14 years on average - 11 ± 0,12 years. The diagnosis of bronchial asthma (BA) is set according to GINA guidelines. The treatment groups were representative, rondomizirovany by age, sex, severity of the disease. Patients with asthma in all forms (atopic, non-atopic, mixed) and severity (mild, moderate, severe) received basic asthma treatment according to the Ministry of Health of Ukraine № 4.01.12-8.1178 order dated 14.12.2009, which was supplemented by liposomal formulation «Lipin» inhalation through an ultrasonic nebulizer in age dosage. All drugs used in accordance with instructions for their use, approved by the Ministry of Health of Ukraine. Microbiological examination of sputum was performed by conventional methods: for seeding solid or liquid nutrient medium, followed by isolation and isolates microscopy, biochemical and serological identification. Identification of the isolates was performed according to the position of the Ministry of Health USSR order number 535 and respectively toksonomicheskih determination tests bacteria Burgi. The antimicrobial activity of the preparation «Lipin» was determined by the level of the minimum inhibitory concentration (MIC) - twofold serial dilution method in medium Mueller-Hilton, the minimum bactericidal concentration (MBC) - was carried out on crops of solid growth medium by the method of S. Navashin. Statistical analysis of the results was performed using Exel applications, Statgrafics-5 with the definition average value (M) and standard error (m). The obtained data were statistically processed by parametric mathematical statistics (t-Student criterion) when  0,05.

Results & discussion. While recognizing the authority of the International (GINA, 2012) and a national protocol on the principles of asthma therapy in children, it should be noted that the recommended therapy is mainly focused on the achievement of symptomatic and pathogenetic effects. In principle this is not considered part of the microbial factor not only in the induction, but also burdening the pathogenesis and clinical course of the disease in children. In this connection, studies on the effect of non-allergic (infectious) factors on the development of asthma as a multi-stage, sequential pathological process and the development of additional methods of basic therapy is relevant and allows individualized therapy protocols in relation to the etiological factors of the disease.

The study showed that in the sputum of children with asthma in all forms of the disease were determined by the following organisms: S. pyogenes, S. aureus, E.coli, Pr. Mirabilis, Ps. aeruginosa. In 29.6% of children with asthma from sputum were sown Association: S. aureus + S. pyogenes; S. aureus + E. coli; S. aureus + Ps. aeruginosa; S. aureus + Pr. Mirabilis. The use of corticosteroids in treatment of asthma in children contributes to the activity of biological and pathogenic properties of indigenous, transient and exogenous microflora, mainly by reducing its control alfeolyarnymi phagocytic macrophages. As a result, the activation of pathogenic and conditionally pathogenic microflora, leading to the development of processes in dysbiotic bronchopulmonary system and disbionty on a new bio-based implement relapse. From this it follows that even effective sanitation agents in bronchopulmonary system, the traditional routes of administration of antibacterial drugs, properly selected, taking into account the sensitivity of pathogens to them, does not prevent it from subsequent reinfection relevant pathogens located in the throat and in the bronchopulmonary system. One way to solve this problem is to use as the dosage form liposomes, which are limited microvolumes arising by self-assembly of amphiphilic lipid complexes. The basis of selection of such a drug we used in the clinic used liposomal preparation «Lipin» inhalation at dosages of age through an ultrasonic inhaler in addition to basic therapy recommended by GINA (2012) in two stages. The first stage is achieved by using «Lipin» in 135 children with asthma, aged 5 to 14 years in acute inhalation through an ultrasonic nebulizer in age dosage of 5-10 mg / kg, depending on the age of one inhalation 2 times a day for 7-10 days in children with asthma. This is the effect of biocompatibility with enzymatic and immunological systems of the body, it is anti-microbial and anti-inflammatory effect «Lipin» due to their constituent natural phospholipids - phosphatidylcholine. The second stage of antimicrobial therapy for supporting sanitizing effect is based on the ability to «Lipin» in saline to accumulate on the damaged parts of mucous bronchopulmonary tree and provide prolonged antimicrobial effect and thus prevent the proliferation of pathogenic and opportunistic microorganisms. Comparison of the spectrum of antimicrobial activity of liposomal drug «Lipin» in saline to microorganisms isolated from the sputum of an inhalation after treatment showed that antimicrobial activity «Lipin» advantageously provides bactericidal effect against pathogenic and conditionally pathogenic microorganisms. It should be noted that this formulation does not have a significant impact on the indigenous microflora of the mucous bronchial tree. Conclusions. 1. BA in children is characterized by a complex structure combining etiologic gram-positive, gram-negative microorganisms, fungi of the genus Candida, and their associations, isolated from sputum and can be defined as the induction and relapse. 2. Liposomal preparation «Lipin» inhalation through the use of an ultrasonic nebulizer has a direct bactericidal effect on pathogenic and opportunistic pathogenic microorganisms isolated from the sputum of children suffering from asthma in the period of exacerbation (MIC - 2,12-3,43 mcg/ml, MBC - 3,41-12,6 mcg/ml). 3. «Lipin» pronounced bactericidal effect is in direct proportion to the dose of the drug used and the time of its effects on the microorganisms isolated from the sputum of children suffering from asthma. 4. Inhaler use liposomal drug «Lipin» at a dose of 5.10 mg / kg body weight per inhaled three times a day for 8-10 days causes bactericidal activity against Gram positive, Gram negative microorganisms and fungi of the genus Candida, isolated from the sputum children with asthma.