Project Antibiotics
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Antiobiotics used in food industry, impact of antibiotics on human health
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Project Antibiotics
- 1. University of agricultural sciences and veterinary medicine, Cluj-Napoca Faculty of Animal Science and Biotechnologies Antibiotics used in food industry , Impact of antibiotics on human health Presented by: Igor Balta BIA IV - 2016
- 2. 1. What Is an antibiotic? 2. Use of them in animals and humans 3. History of discovery of antibiotics 4. Current uses of antibiotics in livestock 5. Classification of antibiotics 6. Pharmacodynamics/ Pharmacokinetics 7. Origin of antimicrobial classes 8. Modes and targets of antibiotics 9. Frequently occurred diseases treated by antibiotics 10. Brands of important antibiotics 11. lAntibiotics used in agriculture, food animals, aquaculture 12. Benefits in poultry 13. What is Antibiotic/ Antimicrobial resistance? 14. Level of knowledge of antibiotics in the world 15. Alternatives to antibiotics 16. Summary of antibiotics used in the world 17. Drug resistant bacteria (AMR) 18. Human and animal antibiotics often overlap 19. Bibliography
- 3. What is an antibiotic? • An antibiotic is a substance produced by microorganism, that has the capacity ,to selectively inhibit or kill other microorganisms (Paul Vuillemin 1941) • An antimicrobial is a broader term, reffering to any substance that can affect microbial life, including synthetic and semi-synthetic compounds and substances without selective toxicity ( e.g Biocides) • Antibiotics are not effective against viruses such as the common cold or influenza, and their inappropriate use allows the emergence of resistant organisms.
- 4. Use of antimicrobials in humans • Antimicrobials/Antibiotics are (should be) used in humans mainly to kill or inhibit bacteria that cause disease and infection. • In the US, there are 150 million outpatient prescriptions for antibiotics every year. Centers for Disease Control and Prevention (Atlanta US) estimates that about 1/3 of these are unnecessary.
- 5. Use of antimicrobials in Animals • Therapeutic use: - To treat sick animals. • Prophylactic/meta- phylactic use: -To prevent infection in animals. • Growth promoters (when antimicrobials are used as a supplement in animal feed in sub-therapeutic concentrations (prohibited in the EU)): -To improve feed utilization , production and enhance economic returns to farmers. -Control of chronic diseases in intensively-reared animals.
- 6. History of discovery of antibiotics https://ugc.futurelearn.com/uploads/assets/61/1b/611b1dc5-3039-4c33-af42-2cd23db0d654.png
- 9. Classification of Antibiotics/antimicrobials • Based on chemical structure • Based on target organisms - Antiviral - Antibacterial - Antifungal - Antiparasitic • Based on antimicrobial activity - Bactericidal - Bacteriostatic • Spectrum of activity - Narrow - Broad Note: Sulfonamides are both antiparasitic and antibacterial
- 10. Bactericidal antimicrobials • Penicilins • Cephalosporins • Fluoroquinolones • Glycopeptide • Monobactams • Carbapenems • Bactericidal drugs are recommended for : Life threatening infections where the immune system is unable to remove bacteria eg. Endocarditis/ Immunocompromised patients.
- 11. Bacteriostatic antimicrobials • Tertacyclines • Sulphonamides • Macrolides • Chramphenicol • Trimethropin
- 15. Pharmacodynamics (PD) • Mechanisms for killing or inhibit growth • Time dependent / concentration dependent • MIC – minimum inhibitory concentration • MBC – minimum bactericidal concentration
- 19. https://www.coursera.org/learn/antimicrobial-resistance/lecture/TRlqj/lecture-2-antimicrobials-and-antimicrobial-action (Gram negative) Stops Folic acid metabolism
- 27. Antibiotics used in Agriculture
- 28. Uses of antimicrobial drugs in food animals • Antimicrobials are very beneficial in reducing morbidity and mortality due to bacterial diseases • These drugs are administered therapeutically to individual sick animals, or to entire groups where some animals are sick and additional cases are expected • They are also administered prophylactically in feed, water, or by injection, to prevent disease in animals at high risk of disease (e.g. after transport or mixing) • In cattle, poultry and swine, antimicrobials are also administered in feed for growth promotion and increased feed efficiency • Some antimicrobial classes are unique to veterinary medicine or human medicine; however, most classes are used in both fields • Some antimicrobials used in humans are administered routinely to large numbers of animals, either for control/prophylaxis, or for growth promotion http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/pubs/amr-ram_final_report-rapport_06-27-eng.pdf
- 29. Beef Pneumonia and diarrhoea are major infectious diseases, and cattle are often individually or mass medicated with an ionophore to promote growth, and some are fed tylosin (a macrolide) or oxytetracycline to control liver abscesses. Individual animal injections with therapeutic levels of penicillin, tetracycline, ceftiofur (third generation cephalosporin), tilmicosin (a macrolide), florfenicol (a derivative of chloramphenicol), or trimethoprim/ sulfadoxine are occasionally administered on beef cow- calf operations and, more frequently, in feedlots
- 30. Poultry Many broiler rations contain antimicrobial drugs, including ionophores and sulfonamides, to prevent coccidiosis. Several antimicrobials are approved for growth promotion and feed efficiency in broilers, turkeys, and layers (e.g., bacitracin, bambermycin, chlortetracycline, penicillin, virginiamycin. Chicks may be injected prophylactically with gentamicin or ceftiofur ( poults only) to prevent yolk-sac infections ( omphalitis ) and vaccine injection-site abscesses. Treatment of individual sick birds is not generally practical, and nearly all medications are administered to entire flocks through feed or water. Escherichia coli infections, leading to cellulitis and septicemia, are major disease problems in poultry, but other diseases caused by bacteria and mycoplasma are prevented, treated, and controlled with antimicrobials.
- 32. http://farm6.static.flickr.com/5548/11327609753_2ab514feaa_m.jpg https://projects.ncsu.edu/project/poultryhealth/fletcher/gross-histo-links/images-gross-histo/cellulitis-histo-4. Lymphocytes accumulating around blood vesels Lymphocytes - part of the acute inflammation
- 35. Swine After weaning, most pigs receive antimicrobials in “starter rations” or water when they are most vulnerable to infectious disease caused by viruses, mycoplasma, and bacteria. This may be related to the stress of weaning or movement within the production unit. Antimicrobials in greatest use include tetracyclines , tylosin , and sulfamethazine or other sulfas. Pneumonia is an important problem in swine production, and antimicrobials are used to treat and prevent clinical cases and outbreaks (i.e., ceftiofur , sulfonamides, tetracyclines , tiamulin) . Bacterial diarrhoea caused by Escherichia coli may be treated with gentamicin, apramycin, and neomycin. Swine dysentery, caused by Brachyspira hyodysenteriae , and ileitis ( enteropatia suina ), caused by Lawsonia intracellularis , may be treated with lincomycin , tiamulin , or macrolides.
- 36. Dairy Most calves are separated from their dams at birth and housed separately in hutches or pens to control infection. Diarrhoea and pneumonia are important diseases of dairy calves. Antimicrobials may be administered orally (i.e., tetracyclines, penicillins, sulfonamides) or by injection (i.e., ceftiofur) for treatment or prophylaxis. Lactating dairy cows receive few if any antimicrobials in their feed because of the need to avoid drug residues in the milk. However, mastitis caused by a variety of bacteria is an important problem in the industry and is responsible for most antimicrobial use. Clinical cases in individual lactating cows may be treated by intra-mammary infusion (administered directly into the udder). To prevent and treat mastitis, antimicrobials may be routinely infused into the udder at the start of the nonlactating period (“drying-off” period), often to the entire herd. Most mastitis pathogens are Gram-positives (e.g., Streptococcus) and are treated with penicillins, cephalosporins, erythromycin, and oxytetracyclines.
- 37. Aquaculture Salmonids are the predominant aquaculture species in Europe and Canada. No antimicrobials are registered for growth-promotion purposes, and only four are licensed for therapy. Treatments are administered in the feed to the entire group of fish in the tank or pen. Oxytetracycline is used most frequently, but potentiated sulfonamides (sulfadiazine/trimethoprim, sulfadimethoxine/ormetoprim) and florfenicol are also administered . The primary bacterial diseases of concern in salmon and trout culture are septicemias caused by various bacterial pathogens, namely Aeromonas salmonicida, and Renibacterium salmoninarum . However, there are now licensed vaccines for all of these and many other common bacterial pathogens of fish, all of which are highly efficacious and have resulted in a significant decrease in antimicrobial use in aquaculture. Most antimicrobial treatments are administered to juveniles (Sheppard, 2000)
- 38. • Not only residues of antibiotics remain in fish products, but the antibiotics used in fish feed can remain in the aquatic environment for an extensive period of time, through excretion, exerting selective pressure and spreading rapidly through water systems. • Indeed, some suggest 70-80 percent of antibiotics given to fish are excreted into water. There are regulatory controls around maximum residue levels in place in some regions already, for example Europe. • Use of antibiotics in aquaculture and its impact on the environment is a growing concern amongst scientists, yet quantifying the amount of use and how much is being disseminated into the environment is very difficult. Aquaculture
- 39. Sheep Мastitis is one of the most important and frequent diseases requiring antimicrobial treatment. In lambs, pneumonia and coccidiosis are common indications for treatment. The use of antimicrobial drugs in feed is not common. Some sheep receive 61 prophylactic injections (e.g. post-lambing) with oxytetracycline or other drugs. For treatment of infections such as mastitis and pneumonia, ceftiofur, florfenicol or tilmicosin may be used.
- 40. Benefits of Antibiotics Benefits of growth promoters Livestock and poultry producers are interested in any practice that promotes animal growth or an increase in productive efficiency. The following benefits are claimed: 1. Increased productive and feed efficiency, thereby improving producer margins and yielding cheaper foods for consumers. A shortened days-to-market interval, thus lowering interest costs and allowing more productive cycles per unit of time; 2. Increased efficiency of feed yields less waste and potentially reduces the environmental impact; 3 Reduced incidence of disease (even though this is not an explicit claim for growth promotion or feed efficiency, therefore it is an indirect benefit.
- 41. Definitions of AMR Real word – clinical definition - Resistance is the ability of a bacterial strain to survive or grow during antimicrobial treatment. Research – genetic definition - Resistance is defined by the presence of a genetic change (mutation on gene), i.e a resistance determinant. Laboratory – microbiological definition - Resistance is the ability to survive or grow or higher antimicrobial concentrations than most other bacterial strain the same species
- 42. Antibiotic Resistance Transmission through the Food Chain Consumers may be exposed to resistant bacteria via contact with or consumption of animal products—a far-reaching and more complex route of transmission. For example, Alexander et al (2010). showed that drug-resistant Escherichia coli was present on beef carcasses after evisceration and after 24 h in the chiller and in ground beef stored for 1 to 8 days. Others isolated ciprofloxacin-resistant Campylobacter from 10% to 14% of consumer chicken products. MRSA has been reported to be present in 12% of beef, veal, lamb, mutton, pork, turkey, and game samples purchased in the consumer market in the Netherlands, as well as in cattle dairy products in Italy . Likewise, extensive antibiotic resistance has been reported for bacteria, including human pathogens, from farmed fish and market shrimp. https://ugc.futurelearn.com/uploads/files/69/6f/696f36a1-112f-48be-8a2b-fe065cb82401/Clin._Microbiol._Rev.-2011-Marshall-718-33.pdf
- 44. https://ugc.futurelearn.com/uploads/files/e8/4d/e84dd759-0325-4769-997d-2bbf10d1fc9a/2-2013-508.pdf
- 45. • In animal farming • In the community • In healthcare facilities • Through travel © European Centre for Disease Prevention and Control
- 46. • In animal farming • In the community • In healthcare facilities • Through travel
- 47. • In animal farming • In the community • In healthcare facilities • Through travel
- 48. • In animal farming • In the community • In healthcare facilities • Through travel https://ugc.futurelearn.com/uploads/files/cd/a9/cda91840-8c97-4464-a510-94a9355186e5/Selection_and_spread_MP.pdf
- 49. How antibiotic resistance can be transmitted from animals to people • Direct contact with infected animals: farm workers : Handling pigs and poultry and working in a farm environment puts people at risk of picking up resistant bacteria from the animals’ bodies or their faeces. • Consumption of food contaminated with resistant bacteria (for example, the potentially food-poisoning Salmonella, Campylobacter and E coli ) Contamination of meat generally results from faecal material getting onto the carcase during the slaughter and evisceration process (guts are removed). Infected meat can also contaminate other foods in domestic or restaurant/catering kitchens. • Resistant bacteria can be transferred in water, soil and air. Animals excrete a significant amount of the antibiotics, making their manure a potential source of both antibiotics and AR bacteria which can enter soil and groundwater. • In the US, tetracycline-resistance genes have been found in groundwater samples 250 metres downstream from the slurry lagoon of a pig farm and appeared to have spread among the local soil microbes. • In the Netherlands, 14% of people living near turkey farms where the growth-promoter avoparcin was used were found to carry enterococcal bacteria resistant to vancomycin, a closely related and important human drug. • Enterococcal bacteria resistant to three important types of drugs used to treat people (all of which are used in poultry production) have been found on the surfaces of cars driving behind a poultry transport truck and in the air inside the car. http://www.fao.org/fileadmin/user_upload/animalwelfare/antibiotics_in_animal_farming.pdf
- 52. Use antibiotics wisely. How? • See a health care professional for diagnosis and do not demand antibiotics, instead ask if other possible ways for relief are available. • Do not self-medicate with antibiotics or use leftover medicines from a previous illness. • Follow treatment directions if you are prescribed a course of antibiotics.
- 53. Why • Antibiotic use accelerates development and spread of resistant bacteria. • Furthermore, taking antibiotics is associated with risks, including side effects such as diarrhea, allergic reactions and colonization of resistant bacteria in the body. Therefore, antibiotics should be used only when needed. • Many infections, such as the common cold or the flu, are caused by viruses and can not be treated by antibiotics. • Also, some bacterial infections can be taken care of by your immune system and do not require antibiotics. Since different antibiotics are used for different bacterial infections, the choice of therapy is complicated and requires medical training. Old medicines can have lower activity and fail to work.
- 57. ALTERNATIVES TO ANTIBIOTICS Before antibiotic The human immune system protects our bodies from intruding microorganisms, such as pathogenic bacteria and viruses. Antibodies are protein structures that are naturally produced by our immune system and function by specifically recognizing and neutralizing foreign organisms or molecules. s were discovered, infectious diseases were treated with “serum therapy” which in practice meant that antibodies were transferred from immune individuals to infected patients. Although the treatment was rather effective, it was at that time associated with toxic side effects. Now, industrially produced antibodies are considered an interesting and presumably safe future alternative to antibiotics and technical advances have made it possible to produce purified antibodies with low toxicity. However, the curative effect of antibodies decreases as the infection progresses, which means that they need to be administered as early as possible upon infection. Antibacterial antibodies will therefore best be used in combination with conventional antibiotics, or as prophylaxis. Thus, even if useful antibodies eventually will reach the market, the need for effective antibiotics will remain. Antibodies targeting Clostridium difficile, Staphylococcus aureus and Pseudomonas aeruginosa are in the drug-development pipeline. Antibodies
- 58. Probiotics • Probiotics contain live microorganisms that exert health benefits on the host upon consumption. • The positive effects are obtained through restoration or maintenance of the host’s normal flora, which averts colonization of pathogenic bacteria. • Clinical trials of novel probiotics that specifically aim to treat or prevent diarrhea caused by Clostridium difficile are ongoing. • Probiotics prevent or treat local infections, primarily of the gut, and cannot substitute antibiotics as a treatment of more severe bacterial infections.
- 59. Vaccines Prevention of infectious diseases through vaccination has been practiced for centuries. During vaccination, dead or attenuated bacteria or viruses are injected into the blood stream, which triggers the production of memory cells that produce antibodies. The antibodies will protect us from disease the next time these specific bacteria or viruses enter our bodies. There are currently many effective vaccines against both viral and bacterial diseases on the market, but there is still a problem with vaccine coverage, particularly in low- and middle-income countries. For example, despite the existence of an effective vaccine against the bacterium Streptococcus pneumoniae, it has been estimated that hundreds of thousands of children under the age of five die each year in infections caused by this bacterium. Global coverage of the Streptococcus pneumoniae vaccine would save many lives and would substantially reduce the need for antibiotic treatment in children. Novel vaccines against Clostridium difficile and Staphylococcus aureus are currently in the drug- development pipeline.
- 60. Phage therapy Phages, or bacteriophages, are viruses that infect bacteria, they can also be genetically engineered for selection of specific characteristics. The principle of phage therapy is that these very host-specific viruses are introduced during an active bacterial infection and selectively kill the pathogenic bacteria. This treatment strategy has been applied, primarily in Eastern Europe during the 20th century, but is somewhat controversial in scientific and medical communities. For example, the phages must be able to immediately kill the bacteria(be lytic) and their exact host range, biology and pharmacology needs to be determined before they can be used as therapeutics. Phages have low inherent toxicity but do partly consist of proteins, which may trigger a human immune response. When phages are administered, they will multiply once they have infected their host bacteria, which means that they will evolve in our bodies. A disadvantage of phage therapy is the potential of promoting emergence of phage-resistant bacterial pathogens. Since phages are very host specific, phage therapy will not affect then normal flora of humans. A clinical trial evaluating the applicability of phage therapy for the treatment of Pseudomonas aeruginosa-induced burn infections is ongoing.
- 61. Antimicrobial peptides • Antimicrobial peptides are parts of plants and animals’ natural defense against various microorganisms, bacteria included. • The peptides generally target and disrupt the bacterial cell membrane, which results in cell lysis and bacterial death. • Antimicrobial peptides have a broad spectrum and could in theory be used against a variety of bacterial infections. The peptides have a rapid action and bacteria are potentially less prone to develop resistance against them, when compared to conventional antibiotics. • On the other hand, they are instable and could potentially lose their antimicrobial properties quickly when entering our bodies. Also, antimicrobial peptides often exhibit cytotoxic effects on human cells and have therefore primarily been evaluated as topical treatments for local infections. • An antimicrobial peptide product targeting Pseudomonas aeruginosa is in the drug- development pipeline. https://ugc.futurelearn.com/uploads/files/26/c0/26c01652-ee10-458e-943d-db6d0f15972d/Factsheet_Alternatives_ABx.pdf
- 67. Antibiotic use in food animals can result in resistant Campylobacter that can spread to humans. Resistant Campylobacter are common in many countries and cause illness in travelers. Ciprofloxacin and azithromycin res. http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf Campylobacter spreads from animals to people through contaminated food, particularly raw or undercooked chicken and unpasteurized milk. Infections may also be acquired through contact with animals and by drinking contaminated water.
- 68. Salmonella spreads from animals to people mostly through food. Antibiotic use in food animals can result in resistant Salmonella, and people get sick when they eat foods contaminated with Salmonella. Key measures to prevent resistant infections include: • Avoiding inappropriate antibiotic use in food animals. • Tracking antibiotic use in different types of food animals. • Stopping spread of Salmonella among animals on farms. • Improving food production and processing to reduce contamination. • Educating consumers and food workers about safe food handling practices.
- 69. Salmonella serotype Typhi spreads from one person to another through food or water contaminated with feces. Typhoid fever is common in developing countries lacking safe water and adequate sanitation. Most U.S. cases are associated with travel to those countries. Sometimes the source is a carrier who is no longer ill, but is still infected. Key measures to prevent the spread of resistant infections include: • Vaccinating people traveling to countries where typhoid fever is common. • Consuming safe food and water when traveling in those countries Improving access to clean water and sanitation for people living in those countries. • Reporting changes in resistance to people who diagnose and treat patients with typhoid fever. • Investigating cases of typhoid fever to identify and treat carriers.
- 70. Shigella spreads from one person to another in feces through direct contact, or through contaminated surfaces, food, or water. Antibiotic use in humans can result in resistant Shigella and hasten further spread. Key measures to prevent resistant infections include: • Promoting thorough and frequent hand washing with soap, especially in child care centers, elementary schools, restaurants, and homes with small children. • Using antibiotics to treat more severe Shigella infections and managing milder infections with fluids and rest. ■ Reporting changes in resistance to healthcare providers. • Detecting and controlling outbreaks of Shigella infections. • Educating consumers and food workers about safe food handling practices.
- 71. Human and animal antimicrobials often overlap Humans and animals are often affected by similar, or even the same, pathogens. Therefore it stands to reason that many of the antimicrobials used to treat these infectious diseases are similar. Indeed many antimicrobials that are used in animals and in aquaculture, are important for human use. Some of these are used in animals for growth promotion, as well as therapeutically to treat sick animals, including tetracyclines and macrolides.
- 72. IS THIS A PROBLEM FOR HUMAN HEALTH? What does the existing literature say? With human use of antibiotics it is widely accepted that there is a correlation between use and resistance. Countries or areas that use more antibiotics, often have higher rates of resistant bacteria, meaning infections are harder to treat. The link between the use of antibiotics in animals and resistant infections in humans, however, is more contentious and normally focuses on the likelihood that resistant bacteria in animals, created by the selection pressures of antibiotic use, will be transferred to humans. This transfer could potentially happen through direct contact with an animal, from consumption of undercooked or unpasteurised animal products, or via the spread of resistant bacteria into environmental reservoirs, which may then transmit resistance genes to human bacteria, or come into contact with humans directly.
- 73. Resistance to fluoroquinolones linked to the global poultry industry • The fluoroquinolones are classified by the WHO as critically important antibiotics for human medicine, and their effectiveness needs to be protected . One of the main fluoroquinolones in human medicine is ciprofloxacin (brand name Cipro), which is a first line drug for treatment of severe Salmonella and Campylobacter infections in adults. It is also effective against plague, anthrax, and potential biological weapons. • Poultry are ‘a major source of human exposure to fluoroquinolone resistance via food’, according to EFSA’s Panel on Biological Hazards. • Enrofloxacin (brand name Baytril), a fluoroquinolone drug related to ciprofloxacin, is used worldwide in the poultry industry. Baytril is authorised in the UK for treatment only, for respiratory and digestive system infections in pigs, cattle and poultry, including calves and piglets, and is administered to poultry in drinking water. • In 2006, the European Medicines Agency came to similar conclusions to the FDA’s: that in countries around the world the ‘introduction and subsequent use [of fluoroquinolones for animal use] has been followed by the emergence of antimicrobial resistance in bacteria of food-producing animals and subsequently spread of resistant zoonotic bacteria to humans’, particularly Campylobacters. • Unlike the US, the EU still permits the use of enrofloxacin in poultry production. As noted above, the use of fluoroquinolones may well also be increasing the spread of MRSA in farm animals.
- 74. Consumers are concerned about the safety of foods. Individuals should not suffer any threat from food, in case of litigation , people must alert the farming industries, to the need to ensure that animal products are safe and healthy for consumers. The aim should be to produce a product with no residues and with minimum levels of bacteria that have no acquired antibiotic resistance. Controls on animal usage will not resolve the current problems in human medicine, but may well help to extend the useful life of any new classes of antibiotics, if and when they are introduced.