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Use of antimicrobials for prevention is a common practice in pig farms, especially in stressful periods that predispose for infectious diseases. Such periods are the time between birth and first lactation, where the cut of the umbilical cord and tail and the trimming of the canines takes place; the ablactation period, where the environment and diet change and the castration of males and vaccinations take place; and finally the fattening period, where overcrowding, inadequate aeration, and low or high temperatures can form a quite stressful environment. For the prevention and treatment of enzootic pneumonia, large quantities of various antibiotics are used, with the most common being ceftiofur, tetracyclines, tiamulin, lincomycin, and enrofloxacin.
Finally, in swine dysentery Brahyspira hyodysenteriae and ileitis Lawsonia intracellularis , lincomycin, tiamulin, macrolides, or tetracyclines are mainly used.
In poultry, antibiotics used for therapeutic reasons are usually administered through water, in contrast to growth-promoting use, where antibiotics are added in feed. Concerns about the extensive use of nontherapeutic agents have arisen after the duplication of the antimicrobial use in aquaculture in the decade — Among them are antibiotics such as sulfonamides, penicillins, quinolones, tetracyclines, and phenicols, which are listed as critically or highly important antimicrobials for human medicine.
Quinolones, tetracyclines, and phenicols are selective for a variety of antimicrobial resistance genes that occur in transposons, plasmids, and integrons that, when mobile, can induce their dissemination. Thermotolerant Campylobacter spp. Although the disease is self-limiting with low mortality, the economic and public health consequences are quite severe, especially in industrialized countries. In contrast to macrolides, resistance to quinolones has emerged during the last 20 years, coinciding with the use of fluoroquinolones mainly enrofloxacin in veterinary medicine.
In addition, the resistance to gentamicin of Campylobacter spp. Salmonella is one of the most important foodborne pathogens. In the case of Salmonellae , the link between antibacterial use and antibiotic-resistant strains at the farm level and the occurrence in humans is well established. This increase in resistance in extended-spectrum cephalosporins is of utmost importance because ceftriaxone is used in severe salmonellosis in children. Bovine strains produce mostly beta-hemolysin, whereas human isolates have the ability to produce alpha-hemolysin. Its widespread use led to the selection of penicillin-resistant strains of S.
Enterococci are commensal bacteria colonizing the intestinal tract of mammals and birds; they are considered indicators of enteric contamination of food and can survive in unfavorable environmental conditions such as high or low temperature, pH, and saline waters. Resistance genes of the ESBL type are mostly plasmid-associated, and therefore can spread among bacteria.
Overdevest et al 89 found a high prevalence of ESBL-coding genes in retail chicken meat Other data show clearly that antibiotic administration to chickens leads to more ESBL-producing bacteria in chicken meat. The possible transport routes between animals and humans are numerous.
Still, the most probable ways of interaction are summarized in transmission through the food chain; 91 through direct or indirect contact with people working in close contact with animals, such as farmers and animal health workers; 92 and through manure contaminated environments and aquaculture. Although the immediate risk from antibiotic-resistant foodborne pathogens is easier to comprehend, perhaps the most perilous situation is the transfer of antimicrobial resistance characteristics through the genetic pool contained in bacteria, bacteriophages, or DNA fragments. According to Rossi et al, 97 horizontal gene transfer, the mechanism by which most bacteria could transfer antibiotic resistance genes, may occur in all matrices.
Still, it is more probable in food categories containing high numbers of microbial cells fermented, minimally processed, or raw foods. This has been shown in vitro by Toomey et al, 98 who have demonstrated the transfer of erythromycin resistance genes from lactic acid bacteria to L.
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In addition, Doucet-Populaire et al 99 report the transfer of tetracycline and erythromycin resistance genes from Enterococcus faecalis to L. Ampicillin resistance has been transferred from Salmonella typhimurium to E. In addition, the transfer of resistance is well documented in bacteria of the same species in the human digestive tract. Therefore, bacteria that contain antimicrobial resistance genes can be an indirect public health hazard, regardless of their pathogenicity, as the available genetic pool of resistance is increased.
The higher burden on human health of antibiotic-resistant foodborne pathogens versus antibiotic-sensitive ones has been well documented. Concerning Salmonella spp. Doyle and Erickson, in a review of emerging pathogens from meat, report selected outbreaks in which increased severity was exhibited, coinciding with the etiological agents being antibiotic-resistant bacteria. In general, the increased severity of infection resulting from antibiotic-resistant bacteria could be summarized as follows:. Delay or failure of treatment. The administration of antibiotics in patients, especially in severe cases, is often given empirically before the results of the antibiogram.
Therefore, antibiotic therapy fails. In some cases, the deterioration of the patient in the relapsed time is fatal. Limited choice of antimicrobials. The available antimicrobials are limited because of the emergence of antibiotic-resistant pathogens. In addition, the increased use of the effective antimicrobials increases the possibility of the appearance of new resistant strains. Selection of suppressed resistant pathogenic strains when antibiotic therapy is administered for treatment of other bacterial diseases.
Coexistence , and possibly increased regulation of pathogenicity genes with resistance genes as a result of selection. The result is the emergence of highly pathogenic strains that are resistant to antibiotics.
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As an example, in S. The human health risks associated with consumption of raw or unpasteurized milk and milk products are well established and have been previously reviewed by Oliver et al. It has been documented that the augmenting appearance of antibiotic-resistant bacteria has led to an increase in foodborne illnesses. Although the number of cases caused by Gram-positive antibiotic-resistant bacteria namely, methicillin-resistant staphylococci and vancomycin-resistant enterococci was comparable to that of Gram-negative bacteria, almost two-thirds of deaths were attributed to Gram negative antibiotic resistant bacteria.
Still, the loss of work days and productivity was not included. For proposing alternatives to antimicrobials, the initial scope of antibiotic usage, namely, therapy, should be considered. Prevention in the form of an immunization program by vaccination could limit the amount of antibiotics needed. In contrast, the cost of vaccination is usually high, and the cross-protection against some pathogens is limited. The low number of the newly discovered Butyricicoccus pullicaecorum isolated from broiler cecum has been positively correlated with inflammatory bowel disease, with the disease reversed after oral administration of the bacterium.
The use of phages is quite intriguing, as they are characterized by specificity and selective neutralization of the pathogen of interest during the lytic phase of their life cycle. Furthermore, the use of phages is compatible with the use of other antimicrobials, as there is no influence between these treatments. Although promising, the use of phages has been limited to treatment of topical infections in humans, neutralization of foodborne pathogens in animals, and control of plant pathogens.
Therefore, the effects of the phages on the microbiota, although expected to be lesser than those of the antibiotics, should be considered. Research on antimicrobial peptides is increasing, and the acquired knowledge is showing the way for future pharmaceutical applications.
Antimicrobial peptides can be an alternative to traditional antibiotics, although some of these have been shown to have toxic effects on mammalian cells. One category of antimicrobial peptides lacking toxicity is the bacteriocins, which are ribosomally synthesized peptides. Nisin A, a bacteriocin produced by lactic acid bacteria, is currently used officially in more than 50 countries, with the US Food and Drug Administration proposing a daily uptake of up to 2. Another possible alternative to antimicrobials is the use of predatory bacteria.
Bdellovibrio and associated organisms show potential in combating pathogenic bacteria in various niches, as they possess a full arsenal of DNases and proteases. The administration of B. Their predation on bacteria is not exhaustive, as a small number of bacteria remain. Although regarded as aerobic, or at least microaerophilic, they can destroy the natural flora of the body cavities.
The global situation concerning antibiotic resistance worldwide is at least alarming. In the present time, the recognition of the importance of antibiotic resistance is almost catholic. Therefore, certain measures have been implied by the states so as to mitigate this problem.
In , the World Health Organization has set the basis for the establishment of measures toward controlling antibiotic resistance. More or less, these basic principles have been followed by both the European Union and the United States of America. The European Union, through the joint report by the European Centre for Disease Prevention and Control and the European Medicines Agency, has also expressed the urge for international cooperation so as to entrench antibiotic resistance.
The White House has recently issued a national strategy plan for combating antibiotic resistance in which the goals issued have also added the necessity of international collaboration. In both the European Union and the United States, the multidisciplinary collaboration is reported to be crucial, as summarized in the One Health initiative.
The stakeholders involved were the national and international health authorities and policy makers, the medical and veterinary communities, the general public, and industry. These messages are reported in Table 3. Priority actions to fight antibiotic resistance: results of an international meeting. Antimicrob Resist Infect Control. Antibiotic-resistant bacteria of animal origin are considered an important contributor to the overall phenomenon of resistance to antibiotics. Although the magnitude of their importance is still under debate, there are certain indications that show a direct link between resistance and antibiotic use in farm animals.
However, this is not the issue: everyone who has used antibiotics has a share in the emergence of resistance, and because the situation is quite alarming, every effort should be made for the reversal of it. Judicious use of antibiotics in animals is a requirement to delay the emergence of bacteria resistant to the still-working antibiotics.
The invention of novel drugs or the use of alternatives to antibiotics should also be encouraged. Still, the increased awareness of the scientific community and the stakeholders in general is both alarming and promising at the same time. The planning of future strategies has already taken place, and in general, it has been agreed on.
Therefore, a combined international action is needed toward the solution of this problem. National Center for Biotechnology Information , U. Journal List Infect Drug Resist v. Infect Drug Resist. Published online Apr 1.
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Vangelis Economou 1 and Panagiota Gousia 2. Author information Copyright and License information Disclaimer. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. This article has been cited by other articles in PMC. Abstract One of the major breakthroughs in the history of medicine is undoubtedly the discovery of antibiotics.
Keywords: antimicrobial resistance, farm animals, food safety, foodborne pathogens, alternatives to antibiotics. Introduction Antimicrobials have been used in human and veterinary medicine for more than 60 years. Antimicrobial use in agriculture, animal husbandry, and aquaculture Antimicrobials have been used in animals for treatment of diseases, for prevention and control of diseases, and also as growth promoters. Table 1 Sales tons of active ingredient of veterinary antimicrobial agents applicable mainly for food-producing animals, including horses, on average per European Union member state between and 22 — Antimicrobial class Tetracyclines Open in a separate window.
Data were derived for cumulative reports involving seven European Union member states in , 25 in , and 26 in Data from the European Medicines Agency.
mevilirono.ga Table 2 Antimicrobial drugs approved for use in food-producing animals actively marketed in the United States between and tons of active ingredient. Drug class Aminoglycosides Antimicrobial resistance in various bacteria of animal origin Campylobacter spp Thermotolerant Campylobacter spp. Salmonella spp Salmonella is one of the most important foodborne pathogens. Staphylococcus spp S. Enterococcus spp Enterococci are commensal bacteria colonizing the intestinal tract of mammals and birds; they are considered indicators of enteric contamination of food and can survive in unfavorable environmental conditions such as high or low temperature, pH, and saline waters.
Modes of spread to humans from farm animals and food The possible transport routes between animals and humans are numerous. Health risks to humans The higher burden on human health of antibiotic-resistant foodborne pathogens versus antibiotic-sensitive ones has been well documented. In general, the increased severity of infection resulting from antibiotic-resistant bacteria could be summarized as follows: Delay or failure of treatment.
Measures to prevent emergence and transmission of antimicrobial-resistant bacteria The global situation concerning antibiotic resistance worldwide is at least alarming. Stakeholders Priority actions Policy makers and health authorities 1. Stop the administration of antibiotics used in human medicine and limit antibiotics to therapeutic use only. It is imperative to reserve the most important classes of antibiotics for humans. Banish, in all countries, the use of antibiotics as growth promoters in animal feed. Regulate the sale of antibiotics for use in human medicine and prohibit over-the-counter sales worldwide.
Have international organizations World Health Organization, European Union develop a charter on good antibiotic stewardship and have all the ministries of health worldwide sign it and commit to respecting it. Human and veterinary health care communities 1. Establish standardized, universal surveillance of antibiotic use and resistance and monitor the emergence and spread of new forms of bacterial resistance. Include, in medical and veterinary school curricula, a solid training in bacterial resistance and the prudent use of antibiotics, and establish on-the-job training programs for health care workers, taking into account the cultural specificities of each country.
General public 1. Develop culturally sensitive awareness campaigns, targeted to the general public, explaining the importance of protecting antibiotics and using them only when absolutely necessary. Provide education about fundamental hygiene, such as handwashing, to prevent the spread of infection. It is imperative to improve sanitation systems to eliminate resistant bacteria in wastewater. Include consumers in the development and implementation of action plans.