The resistance of microorganisms, bacterial pathogens, to antimicrobials is a global problem in both healthcare and veterinary medicine. It is believed that the main reason for the emergence and spread of antimicrobial resistance in humans is the transfer of antibiotic resistant strains of microorganisms or genes, determinants of resistance, through products of animal origin from productive animals to humans. Thus, the main way of antimicrobial resistance containment is to restrain and minimize it through the prudent use of antibiotics in veterinary medicine, especially those that are critically important for productive animals. In addition, some classes of antibacterial substances and antibiotics, that are widely used in humane medicine, are used in veterinary medicine. The need to use and preserve these important therapeutic agents is relevant from the point of view of the concept «One Health». The article provides a list of all antibacterial substances used by productive animals for their importance in veterinary medicine, developed by a special group of experts of the World Organisation for Animal Health (OIE). Any antimicrobial agent authorized for use in veterinary medicine for productive animals, in accordance with the criteria for quality, safety and efficacy as defined in Section 6.9 of the Terrestrial Animal Health Code, is considered to be important for veterinary medicine. All the antimicrobial substances used for productive animals are divided in this list on critical, very important and important for veterinary medicine. Attention was also drawn to the peculiarities of the use of critical antimicrobial agents in veterinary medicine, especially those recognized as critical in humane medicine. These include aminoglycosides, cephalosporins of the 3rd and 4th generation, fluoroquinolones, glycopeptides, macrolides, some penicillins and polymyxins. The article also describes the classification of critical antimicrobials by the European Medicines Agency (EMA) and the Panel of Experts on Antimicrobials (AMEG) of the WHO based on the risk profile for humans through the development of antimicrobial resistance after application to productive animals. Such an assessment will give veterinary practitioners an important justification when they make decisions about the clinical treatment of bacterial infections and the responsible appointment of antimicrobial therapy. This will help to reach the balance among the achievement of the effectiveness of antimicrobial therapy of productive animals, reducing of the selective pressure on the development of antibiotic resistance and ensuring of a high level of human health.
У статті представлені результати вивчення чутливості бактерій-ізолятів, збудників гострої бактеріальної інфекції дихальних шляхів у молодняка великої рогатої худоби, до фторхінолонового антибіотика «третього покоління» данофлоксацину. Так, мінімальна інгібуюча концентрація данофлоксацину для ізолятів Staphylococcus aureus становила 0,32 ± 0,052 мкг/см3 (n=20), а для Streptococcus pneumoniае – 0,29 ± 0,064 мкг/см3 (n=10). Застосування у терапевтичних дозах нового антимікробного препарату на основі данофлоксацину Данофлокс 2,5% (розчин для ін’єкцій) викликало клінічне одужання у телят, хворих на гостру бактеріальну інфекцію дихальних шляхів, що було підтверджено результатами загального аналізу крові хворих тварин після проведеної антибіотикотерапії. Дослідження імунологічних та біохімічних показників крові показали відсутність негативного впливу препарату на імунний захист та фізіолого-функціональний стан організму молодняка великої рогатої худоби.
In the article a literature review of scientific papers on the topic of antimicrobial resistance of bacteria of the family Pasteurellaceae, pathogens of respiratory diseases in pigs and cattle, is presented. The main mechanisms of the development of Pasteurellaceae resistance to β-lactam antibiotics are the synthesis of β-lactamases by bacteria, what are able to break the beta-lactam ring, thereby inactivating β-lactams, or alteration of the penicillin-binding proteins structure. Other mechanisms, such as reduced permeability of the outer membrane or the process of active removal of antibiotics from the bacterial cell (efflux), are very rare. Resistance among Pasteurellaceae to β-lactams is often associated with plasmids. Eflux and ribosomal protection are the main mechanisms for the development of resistance of Pasteurellaceae to tetracyclines. At least nine tetracycline resistance genes (tet genes) have been identified in bacteria of the genus Pasteurella, Mannheimia, Actinobacillus and Haemophilus, what encode these processes. Resistance to aminoglycosides and aminocyclitols is mainly caused by enzymatic inactivation of antibiotics, as well as through mutations in chromosomal genes. Many plasmids carry genes of resistance to aminoglycosides, causing resistance to antibiotics of other groups. Chemical modification of a ribosomal target by rRNA methylases and mutations in ribosomal proteins are the main resistance mechanisms of bacteria of the family Pasteurellaceae to macrolides. Many gram-negative bacteria have a natural resistance to macrolide antibiotics. The development of lincosamide resistance is influenced by methyltransferase 23S rRNA, active efflux proteins, enzymatic inactivation and chromosomal mutations. Resistance of bacteria of the family Pasteurellaceae to chloramphenicol is caused mainly by enzymatic inactivation, while the emergence of resistance to fluorophenicol is associated with the efflux of an antibiotic from a bacterial cell. Plasmids carrying phenicol resistance genes were detected in isolates of P. multocida, M. haemolytica, A. pleuropneumoniae and H. parasuis. Usually the level of bacteria sensitivity of the genus Pasteurella, Mannheimia, Actinobacillus and Haemophilus to quinolones is quite high. Resistance to quinolones mainly occurs due to mutational alterations in chromosomal genes, and may also be in consequence of the export antibiotics from the cell by membrane proteins or thanks to qnr genes of plasmids. The main mechanism of resistance to sulfonamides and trimethoprim is both plasmid-mediated and mutation-induced production of altered dihydropteroate synthetase and dihydrofolate reductase with reduced affinity with these antimicrobials. Monitoring of antibiotic resistance with the determination of its mechanism phenomenon will facilitate the choice of an effective agent of etiotropic therapy of respiratory diseases of cattle and pigs caused by bacteria of the family Pasteurellaceae.
Bacterial intestinal infections are one of the main diseases in pigs of different ages. Bacterial diseases of the pig digestive tract lead to significant economic losses due to high mortality, reduced growth, treatment and prevention costs. The main bacterial intestinal infections of pigs are anaerobic enterotoxemia (clostridiosis), colibacillosis, intestinal salmonellosis, dysentery, proliferative enteropathy (ileitis). Anaerobic enterotoxemia of pigs is an acute toxic-infectious disease mainly of newborn piglets, caused by pathogenic bacteria of the genus Clostridium and characterized by hemorrhagic-necrotic inflammation of the intestinal mucosa, diarrhea and toxicosis. Swine colibacillosis is an intestinal infection caused by the enterotoxigenic Escherichia coli, which is able to produce enterotoxins that locally affect the intestines of pigs, causing diarrheal syndrome. Intestinal salmonellosis is a factorial infection. The causative agents are enteropathogenic salmonella (mainly Salmonella enterica serotype typhimurium), which cause inflammation and necrosis of the small and large intestine, leading to diarrhea, which may be accompanied by generalized sepsis. Dysentery is a severe enteroinfection of pigs caused by the anaerobic bacterium Brachyspira hyodysenteriae, characterized by fever, debilitating mucohemorrhagic diarrhea and dehydration, leading to high mortality among animals. Proliferative enteropathy is a sporadic disease of pigs caused by Lawsonia intracellularis. The acute form of ileitis, known as proliferative hemorrhagic enteritis, is characterized by intestinal hemorrhage and sudden death, and usually occurs in pigs older than 4 months. Diarrhea in piglets can also be caused by enterococci (Enterococcus spp.) and chlamydia (Chlamydia suis). Enterococcal bacteria cause diarrhea in newborn piglets, and intestinal chlamydia infections are mostly common in rearing piglets, and it is believed that most intestinal infections caused by chlamydia are subclinical. The literature review regarding the etiology, pathogenesis and clinical diagnosis of major bacterial intestinal infections in pigs is presented in the article.
The objective of the research was to study the antimicrobial activity of danofloxacin, the third-generation fluoroquinolone antibiotic, against bacteria, pathogens of acute respiratory infection in pigs. Samples of nasal excretions were selected from clinically sick weaned piglets with acute respiratory infection for microbiological investigation. The sensitivity test, carried out by the disc-diffusion method, showed a high level of the microflora sensitivity of the inflammatory exudate to danofloxacin. Bacteria Streptococcus suis and Bordetella bronchiseptica have been isolated and identified from biomaterial by generally accepted microbiological methods. The degree of antimicrobial activity of danofloxacin against isolated strains of microorganisms was established by determination the minimum inhibitory concentration (MIC) of danofloxacin for isolated bacteria by consecutive dilutions in a liquid nutrient medium. The MIC average of danofloxacin for Streptococcus suis isolates (n = 20) was 0.33 ± 0.082 μg/ml and for Bordetella bronchiseptica isolates (n = 8) – 0.21 ± 0.044 μg/ml. The obtained results showed a high level of bacteriostatic activity of danofloxacin regarding bacterial isolates, pathogens of acute respiratory infection in pigs. Danofloxacin, like other fluoroquinolones, is a critical antimicrobial substance for veterinary medicine. Therefore, chemotherapeutic agents based on this antibiotic can serve as a drug of choice for empirical treatment of pigs with acute respiratory infections of bacterial etiology. To right choose an effective agent for etiotropic therapy and minimize the selection of resistant strains of microorganisms, the antimicrobial susceptibility of isolated bacteria should be pre-established.
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