Introduction  

Many researchers believe that respiratory diseases occur due to exogenous factors [1]. Respiratory pathology of children and young people occurs against the background of abiogenic and biogenic factors [2]. Abiogenic factors are unfavorable conditions of nutrition and vital activity, leading to a decrease in the body's resistance. Biogenic factors include various infectious agents, viruses, bacteria, mycoplasmas, chlamydia and fungi, the virulence of which increases against the background of immunodeficiency conditions [3, 4].

It is also believed that respiratory diseases caused by opportunistic viral and bacterial microflora are based on immunodeficiency conditions. Schematically, the formula of respiratory diseases can be shown as follows: stress + immunodeficiency + viruses + bacteria = respiratory disease [5]. Food safety is also an important factor that influence on immunity and can affect the respiratory diseases occurrence [6].

Based on the above, it can be stated that there are a huge number of primary and predisposing factors affecting the development of bronchopulmonary pathology [7]. The wide prevalence of this disease determines the relevance of the study. Antibiotics are most often used in the treatment of patients with bronchopneumonia [8].

In recent years, drugs from the group of fluoroquinolones have been widely used in medical practice [9]. They have high bioavailability, a wide spectrum of antibacterial action, as well as immunomodulatory activity by stimulating the synthesis of immunoglobulins and phagocytosis [10]. In this work, two drugs were used for the treatment of acute nonspecific bronchopneumonia: pefloxacin and erbisol.

Pefloxacin is a broad-spectrum antimicrobial drug from the group of fluoroquinolones. It acts bactericidal. Inhibits the enzyme DNA gyrase of bacteria, as a result of which DNA replication and synthesis of bacterial cellular proteins are disrupted. Gram-negative aerobic bacteria are usually sensitive to pefloxacin: Escherichia coli, Klebsiella spp., Proteus vulgaris., Proteus mirabilis, Enterobacter spp., Neisseria gonorrhoeae, Serratia marcescens, Citrobacter spp., Salmonella spp., Shigella spp. Some intracellular pathogens: Chlamydia spp., Mycoplasma spp. Gram-positive aerobic bacteria: Streptococcus spp., Clostridium perfringens. Moderately sensitive microorganisms: Acinetobacter spp. Gram-negative anaerobic bacteria, Mycobacterium tuberculosis, Bacteroides spp., Spirochaetaceae are resistant to the drug. After intravenous administration, the maximum concentration of the drug in the blood serum is reached within 60 minutes. The half-life is from 7.2 to 13 hours after a single dose. After repeated injections, the half-life is 14-15 hours. Pefloxacin penetrates well into body tissues (bronchial mucosa, bones, heart, spinal fluid, sputum, urine, prostate secretions, bile, peritoneal fluid). It is metabolized in the liver. With normal liver and kidney function, about half of the injected drug is excreted through the kidneys unchanged or in the form of metabolites. About 30% is found in the intestine unchanged and in the form of metabolites [11-13].

Erbisol class preparations contain low-molecular-weight “signaling” fragments of membrane glycoproteins that perform the function of “markers of the physiological state of cells”, which, in case of pathological homeostasis disorders, activate the natural evolutionarily formed controlling systems of the body responsible for finding and eliminating pathological changes in organs and tissues. One of these systems is the immune system. Erbisol contains a complex of natural non-protein low molecular weight organic compounds of non-hormonal origin obtained from animal embryonic tissue; they contain glycopeptides, oligopeptides, nucleotides, amino acids in 0.9% NaCl solution.Specificity of immunomodulatory properties of erbisol class drugs:

• activate M2a macrophages involved in the repair of damaged cells and the regeneration of organs and tissues with the restoration of their functional activity;
• activate killer cells (M1 macrophages; N- and T-killers and cytotoxic T-lymphocytes CD8+) responsible for the destruction of damaged cells unable to regenerate, or abnormal cells (mutant, malignant, virus carriers, etc.) and tissues;
• are immunocorrectors: normalize the activity of Th1- and Th2-lymphocytes and restore the balance of cytokines, thereby harmonizing the state of cellular and humoral immunity, as well as inhibit the course of autoimmune and allergic processes [14-16].

Materials and Methods

The therapeutic and prophylactic effect of the drug pefloxacin both alone and in combination with erbisol was studied for respiratory diseases - bronchopneumonia of piglets. During the experiments, the same feeding and maintenance conditions were maintained.

Before treatment, the animals were comprehensively examined, the diagnosis was established on the basis of clinical signs, laboratory tests, as well as the results of a pathoanatomical autopsy of corpses.

The conclusion about the positive effect of the drugs was given on the basis of complex clinical and laboratory studies. Biochemical, hematological and immunological blood tests were performed before the start of treatment, on the tenth and thirtieth day of observation.

Biochemical studies determined the total protein in the blood serum by the biuretic method, protein fractions by turbidimetric (nephelometric), transaminase activity, copper using BIO-LA-TEST kits [17, 18]. Albumin was found by reaction with bromocresol green, C-reactive protein in the latex agglutination reaction, alkaline phosphatase activity by the ECOSERVICE CLINITEST, total calcium by unified colorimetric, inorganic phosphorus by the molybdenum UV method, glucose by glucose oxidase method [19-21]. Serum carotene was determined by electrocolorimetric express method [22].

Hematological blood tests were carried out on a hematological analyzer "Celly 70", ESR was established by the Panchenkov method, blood smears were stained by Papenheim, differential counting of leukocytes was carried out according to generally accepted methods [23].

The phagocytic activity index (percentage of phagocytic neutrophils) and phagocytic index (average number of microbes phagocytized by one neutrophil) were calculated [24].

Bacteriological flushes from the nasal cavity were collected with sterile cotton swabs into bacteriological tubes with sterile saline solution during the period of maximum manifestation of signs of the disease.

Results and Discussion

The effectiveness of the use of pefloxacin and pefloxacin in combination with erbisol in the acute form of nonspecific bronchopneumonia was carried out on piglets aged 2-3 months. A total of 36 piglets were under observation. All individuals were without pathologies, with average indicators of mass and size.

During the initial examination, there was an increase in temperature to 41 ℃, purulent-catarrhal nasal discharge, piglets were severely depressed, a wet cough that intensified when getting up, appetite decreased, abdominal type difficulty breathing was noted. The pulse is of medium filling, rhythmic, the heartbeat is intensified. The heart tones are muted; the second tone is amplified. During auscultation, wet wheezing and crepitation were heard in sick piglets. When animals were slaughtered in the acute stage of the disease, changes characteristic of serous-catarrhal, catarrhal-purulent bronchopneumonia were detected with lesions mainly in the upper, middle and anterior lobes of the lungs. Bronchial and mediastinal lymph nodes are dark in color, moist. Conditionally pathogenic microflora was isolated from the affected areas of the lungs.

To conduct the experiment, all piglets were divided into three groups of 12 individuals in each group, according to the principle of analogues:

• in the control group of piglets, the disease proceeded naturally;
• The 1st experimental group of piglets was injected with pefloxacin intramuscularly at a dose of 0.5 ml / 10 kg of body weight once a day for 5 days;
• The 2nd experimental group of piglets was prescribed pefloxacin in the same dosage as the animals of the first group, plus erbisol 1 ml subcutaneously every other day three times;
• For fifteen days, body temperature, pulse rate and respiration were measured in sick piglets (Figures 1a-1c).

Daily clinical observations of experienced piglets revealed that as they recovered, the main characteristic symptoms of the disease were minimized (Table 1).

The safety of livestock in the first and second groups was 100%, in the control group one piglet fell on the 10th day. The piglets of the experimental groups were more willing to eat feed and gained more weight than the control ones.

Therapeutic effect of pefloxacin and pefloxacin with erbisol

The therapeutic effect of pefloxacin and pefloxacin in combination with erbisol was studied on sick piglets with acute bronchopneumonia.

Hematological data during treatment are shown in Table 2. Leukocytes in the experimental groups had a good tendency to decrease during the experiment, by the end of which they were approaching the upper limit of the norm, which was not observed in the control group.

The level of erythrocytes by the 10th day of treatment in the control group was higher than in the experimental group on the 2nd experimental by 18.2% and 24.7%, respectively.

Background hemoglobin indicators indicated that hypochromic anemic changes were observed in all groups of piglets. The hematocrit value during the experiment in acute form had a negative dynamic.

The color index in all cases was below normal, which indicates a violation of the ratio between erythrocytes and hemoglobin, and hypochromic anemia in piglets.

In the leukogram, the percentage of basophils, eosinophils and young neutrophils corresponded to the physiological norm. The proportion of rod-shaped neutrophils decreased by 1.4 times by the end of the experiment. In sick piglets, there was a tendency to increase the number of lymphocytes, which indicates the restoration of the leukogram picture.

The results of biochemical studies showed (Table 3) that the concentration of total protein in the blood of piglets of group 1 and group 2 was actively decreasing and by day 30 was lower than the control by 39.4% and 49.5%, respectively. By the end of the experiment, the total protein in the piglets of the experimental groups corresponded to the lower limit of the norm. Albumin in all piglets was below normal.

In the course of research, we note an increase in the level of alpha- and beta-globulins in the control group, while in the experimental groups it practically did not change. Gamma globulins in the experimental groups tend to decrease by 27.6% and 25.7% and correspond to physiological values. In the control, gamma globulins decrease slightly and exceed the norm by 22%.

The activity of alkaline phosphatase exceeds the norm by 2.5-4 times, by the 30th day of the experiment it decreases, but still remains above the norm, which indicates a violation of phosphorus and calcium metabolism.

Piglets have hypocalcemia, characterized by a reduced level of total calcium in the blood (65% of the minimum values of the norm). By the end of the experiment, this level in the experimental groups increased by 53%.

The phosphorus concentration initially corresponds to the physiological norm, and then decreases. This is due to a violation of the calcium-phosphorus ratio, which decreases by 44%, where phosphorus significantly prevails.

Background glucose values are significantly lower than normal, then by the 10th, 30th day they rise and correspond to the normal value, which is confirmed by the normalization of metabolic processes in the piglets' body.

In the acute form, the iron concentration of experimental animals increases and decreases during the experiment, but is within the normal range.

At the beginning of the experiment, the maximum values exceeding the norm by 1.3 times are noted for the level of copper. Then there is a gradual decrease in it, which reaches the norm in the control and experimental groups.

During the experiment, there is a reduced amount of carotene in the blood serum of piglets.

The results of immunological studies are shown in Table 4. Bactericidal activity has a positive trend in group 1 and group 2 and reaches the norm by the 30th day of studies. In the control group, this parameter rises by 7.3% by the 10th day, then decreases by 9.4%.

The phagocytic index decreases in all groups throughout the experiment.

The index of completion of phagocytosis varies slightly. In all groups, there is an increase in the indicator by day 10, and then a decrease by day 30.

The index of completion of phagocytosis in all groups varies slightly.

Lysozyme activity has a positive dynamics of increase in all the studied groups.

We studied the therapeutic efficacy of pefloxacin and pefloxacin in combination with erbisol in comparison with the control group (Table 5).