RU2849173C1 - Method for preventing pseudomonas gastroenteritis in piglets - Google Patents

Abstract

FIELD: veterinary medicine.

SUBSTANCE: method is characterised in that it provides for the introduction of streptomycin and levomycetin into the feed at a dose of 2.5 mg/kg of live body weight twice a day for 7 days.

EFFECT: use of the invention will prevent pseudomonoic gastroenteritis in piglets.

1 cl, 4 tbl

Description

The proposed invention relates to veterinary medicine and can be used for the prevention of pseudomonas gastroenteritis in piglets.

Various antibacterial agents are known for the prevention of gastroenteritis in piglets: tetracyclines, oxamycins, macrolides and fluoroquinolones, as well as immunoglobulin-C [Use of allogenic immunoglobulin-C for the treatment of gastrointestinal diseases in piglets / A.G. Shakhov, V.I. Lesnykh, E.G. Polozhenko, Yu.N. Brigadirov, S.I. Chaika, N.P. Zuev. - Voronezh, 1990. - 4 p. - (IL / Voronezh CNTI, No. 362-90)].

In connection with the spread of infectious diseases caused by pathogens of not only bacterial but also viral nature, composite preparations containing antimicrobial and antiviral components are becoming widespread [RU 2118529 C1, A61K 31/00, 10.09.1998: Veterinary drug "Tricaptol" for the treatment of gastroenteritis in young farm animals].

For the treatment and prevention of gastroenteritis in piglets, it is recommended to use vitamin preparations A, E, C and cyanocobalamin [Sevryuk I.Z. Prevention of immune deficiencies and diarrhea in young animals / I.Z. Sevryuk // Ecological problems of pathology, pharmacology and therapy of animals: International coordination meeting. - Voronezh, 1997. - P.346-348]. Compositions of nitazole, sulfonamides and antibiotics have found wide application [Shabunin S.V. / Therapy and prevention of gastrointestinal diseases of bacterial etiology in piglets with combinations of nitazole with sulfonamides and antibiotics / S.V. Shabunin, P.A. Parshin // Ecological problems of pathology, pharmacology and therapy of animals: International coordination meeting. 1997. - P.369].

Fradisin and tylosin tartrate have therapeutic efficacy in gastroenteritis of piglets [SU 681598 A1, A61K 31/00, A61P 31/00, 23.03.1981; Antipov V.A. Technical preparations of antibiotics - effective therapeutic and prophylactic agents for veterinary medicine and animal husbandry / V.A. Antipov, V.S. Grishkevich // Collection of scientific papers "Pharmacology and toxicology of new drugs and feed additives in veterinary medicine". - Leningrad, 1990. - P. 171-173; Antipov V.A. Drug for the treatment and prevention of gastroenteritis and bronchopneumonia in pigs / V.A. Antipov, A.G. Shakhov // Certificate for rational proposal of the State University of Veterinary Medicine of the USSR dated 10.06.1986. - No. 439-11/2015].

A drug is known for the prevention and treatment of infectious diseases of pigs with signs of gastroenteritis using fradisin, a macrolide antibiotic [Description of the invention to the author's certificate SU 681598 A1, A61K 31/00, A61P 31/00 / O.A. Gavrilova, A.M. Makukhina, A.G. Rezvykh et al., 1981], which is the closest analogue of the claimed invention.

However, the use of fradisin for the prevention of infectious diseases of pigs and the treatment of sick animals requires its daily administration with feed in the amount of 0.2-0.4 kg per 1 ton for prevention and 0.4-4.0 kg per 1 ton for treatment, respectively.

Tylosin tartrate (the active ingredient of fradisin) is one of the preparations of microbiological synthesis. Compared to fradisin, it has a higher antimicrobial activity against gram-positive and gram-negative microflora [Bukhanov V.D. Therapy and prevention of swine dysentery / V.D. Bukhanov // Abstract of a Cand. Veterinary Science Dissertation, Moscow, 1986. - 24 p.; Zuev N.P. Production and development of antimicrobial compositions based on tylosin-containing preparations / N.P. Zuev, V.D. Bukhanov // Proceedings of the First Congress of Veterinary Pharmacologists of Russia, 21-23.06.2007. - RAAS VNIVIPFiT, Voronezh, 2007. - P.311-316].

The disadvantages of streptomycin are: a narrow spectrum of activity against microorganisms that cause gastroenteritis in piglets, and the rapid development of resistance to it in pathogens.

The objective of the invention is to increase the effectiveness of streptomycin in the prevention of gastroenteritis in piglets of bacterial (pseudomonal) etiology.

The solution to the problem allows us to:

1. Expanding the spectrum of antimicrobial action of drugs against microbes that cause gastroenteritis in piglets before establishing a bacteriological diagnosis, or in case of mixed infection, when the pathogens of the microbial association have different sensitivity to antibacterial drugs.

2. To prevent the development of toxic effects by achieving a faster and more complete effect with the simultaneous administration of two or more drugs in smaller than usual course doses.

3. Potentiation of the antibacterial effect due to the synergism of the components of the composite drug.

4. Prevention or reduction of the possibility of the emergence of acquired drug resistance in pathogenic microorganisms.

Based on the above requirements, aminoglycoside (streptomycin) and drugs with a broader spectrum of action that are better than those obtained by chemical synthesis, which include chloramphenicol, are promising for the creation of composite antibacterial agents with a broad spectrum of action. I.E. Mozgov // Pharmacology. - M .: Agropromizdat, 1985. - Pp. 338-341; Bukhanov V.D. Therapy and prevention of swine dysentery / V.D. Bukhanov // Abstract of Cand. Sci. (Veterinary Science) Dissertation, Moscow, 1986. - 24 p.; Zuev N.P. Production and development of antimicrobial compositions based on tylosin-containing drugs / N.P. Zuev, V.D. Bukhanov // Proceedings of the First Congress of Veterinary Pharmacologists of Russia, 21-23.06.2007. - RAAS VNIIVIPFIT, Voronezh, 2007. - P.311-316].

The latest inventions in the field of prevention and treatment of secondary gastroenteritis in piglets are: COMPOSITE PREPARATION FOR THE PREVENTION AND TREATMENT OF GASTROENTERITIS IN PIGLETS (2412702, (02/27/2011), COMPOSITE PREPARATION FOR THE TREATMENT OF GASTROENTERITIS IN PIGLETS WITH DYSENTERY (2593804, (10.08.2016); COMPOSITE PREPARATION FOR THE TREATMENT OF YERSINIA-INDUCED GASTROENTERITIS IN PIGLETS (Patent No. 2810702 dated 28.12.2023).

However, there is no information in the literature or publications on composite preparations for the prevention of pseudomonas gastroenteritis in piglets. Therefore, the objective of the invention was to develop an effective method for the prevention of pseudomonas gastroenteritis in piglets. A synergistic combination of streptomycin and chloramphenicol in a 1:1 ratio is effective for the prevention of pseudomonas gastroenteritis in piglets, while reducing the recommended doses and reducing the toxicity of the components of the composite preparation. This composition is effective in preventing pseudomonas gastroenteritis in piglets when administered enterally at a dose of 2.5 mg/kg of each per 1 kg of live body weight twice daily for 7 days.

The technical result of the invention is that a synergistic combination of streptomycin and chloramphenicol and a method developed on this basis for the prevention of pseudomonas gastroenteritis in piglets, comprising the active ingredient streptomycin and the synergist chloramphenicol in a 1:1 ratio, are administered enterally at a dose of 2.5 mg/kg of live body weight of streptomycin and 2.5 mg/kg of live body weight of chloramphenicol twice daily for 7 days. The invention enhances the prophylactic efficacy of the method for the prevention of pseudomonas gastroenteritis in piglets and prevents the development of resistance to it in the pathogens causing pseudomonas gastroenteritis in piglets.

Examples of specific implementation.

Laboratory studies have enabled us to determine the optimal component ratios in the composite product being developed for their antimicrobial activity against bacteria that play a role in the etiology of pseudomonas gastroenteritis in piglets. The results are presented in Table 1.

Table 1

Antimicrobial activity of a composition of streptomycin with chloramphenicol Type of microorganism Pseudomonas aeruginosa Minimum bacteriostatic concentration (MBC), μg/ml: Streptomycin 46 Levomycetin 44 Compositions of streptomycin with chloramphenicol 1:1 10 2:1 12 3:1 14 Fractional inhibitory concentration (μg/ml) in a 1:1 ratio Streptomycin 0.1 Levomycetin 0.1 FIC-compound index 0.2

As the data in this table show, the most effective proportion of the components of the composite drug, which potentiates the antimicrobial activity of the composition, is the ratio of streptomycin and chloramphenicol 1:1.

The fractional inhibitory concentration (FIC) of streptomycin against Pseudomonas aeruginosa during the interaction of streptomycin with chloramphenicol was 0.1; chloramphenicol - 0.1; the FIC index of the compound was 0.2; which predetermines the prospects for using this composition.

Table 2

Prevention of adaptation of the microorganism causing pseudomonas gastroenteritis in piglets Bacteriostatic concentration of streptomycin, μg/ml of nutrient medium containing chloramphenicol Background (MBK after the first passage) After 30 passages on nutrient media containing chloramphenicol Pseudomonas aeruginosa Pseudomonas aeruginosa 46 46

From the data in Table 2 it is evident that the antimicrobial activity of streptomycin against the causative agents of pseudomonas gastroenteritis in piglets does not change even after 30 passages.

We then studied the prophylactic effect of the composite drug on reproduced pseudomonas infections in white mice with enteral administration of the composite drug at a rate of 2.5 mg/kg of the mass of each of its ingredients, with the determination of the drug protection index, the results of which are presented in Table 3. Animals in the control group did not receive medication.

Table 3.

Study of the antimicrobial activity of the composite drug in vivo No. Name of groups Palo Survived Protection index Composite preparation Streptomycin Levomycetin Composite preparation Streptomycin Levomycetin Composite preparation Streptomycin Levomycetin 1 Control 7 7 7 3 3 3 2 The drug and infection after three hours 1 2 2 9 8 8 88 71 71 3 Infection and drug at the same time 2 3 3 8 7 7 71 57 57 4 Infection and after three hours the drug 4 5 5 6 5 5 50 28 28 5 Infection plus twice daily medication 3 4 4 7 6 6 57 43 43

The use of the composite preparation (streptomycin plus chloramphenicol) in vivo showed (Table 3) that the protective indices of the composite preparation, streptomycin and chloramphenicol separately when applied 3 hours before infection of white mice were 88, 71 and 71%, respectively, against pseudomonas infection; with a single administration of the preparations simultaneously with infection, it was lower and was 71, 57 and 57%. The protection index decreased with a single application of the preparations 3 hours after infection to 50, 28 and 28 percent. Administration of the preparations simultaneously with infection and 7 hours after it, and their subsequent administration for 7 days twice a day provided a protective index against pseudomonas infection of 57, 43 and 43%. The original cultures were reisolated from the blood of the heart, liver, kidneys and spleen of dead animals.

Thus, administration of the composite drug and its components, streptomycin and chloramphenicol, 3 hours before infection provides the highest efficacy against the studied pseudomonas infection. A single administration of the drugs simultaneously with infection and 3 hours afterward results in a reduced efficacy. Therefore, the prophylactic effect of the drugs is most effective.

From the data in Table 4 it is evident that the prophylactic efficacy of the composition of streptomycin plus chloramphenicol when given with feed for 7 days twice a day at a dose of 2.5 mg/kg of live weight of each of the components of the composition is higher than that of the original drugs separately.

The results of the study of the prophylactic efficacy of the composite drug for pseudomonas gastroenteritis in piglets are presented in Table 4.

Table 4.

Comparative prophylactic efficacy of the developed method for pseudomonas gastroenteritis in piglets Group Streptomycin plus chloramphenicol Streptomycin Levomycetin Number of healthy animals at the beginning of the experiment, heads. 20 20 20 The number of piglets infected with pseudomonas gastroenteritis by the end of the experiment, heads. 1 3 3 Preventive effectiveness, % 95 85 85

The obtained data indicate that the prophylactic effectiveness of the developed method using a composite drug increases due to the synergistic interaction of streptomycin and chloramphenicol, as well as the expansion of the antimicrobial activity of streptomycin and the prevention of the development of resistance to this composition in the microorganism - the causative agent of pseudomonas gastroenteritis in piglets.

Claims (1)

A method for the prevention of pseudomonas gastroenteritis in piglets, characterized by the fact that it includes the introduction of streptomycin and chloramphenicol into the feed at 2.5 mg/kg of live body weight each 2 times a day for 7 days.