Antibiotics in livestock farming

Changed on: 28.07.2016
Zwei Kühe vor Trinktrog auf der Weide
caption
Two cows at a drinking trough on pasture land

There is evidence of a link between the use of antibiotics and the prevalence of antimicrobial resistances. The more antibiotics in a particular substance group are used on humans or animals, the more bacterial pathogens resistant to this particular substance will be found at a later date. Resistance against antimicrobial drugs presents a health risk to the population, may result in the longer duration of medical conditions in patients, lead to higher public health expenses and have adverse economic repercussions on society (1).

More information
Zwei Kühe vor Trinktrog auf der Weide
caption
Two cows at a drinking trough on pasture land

There is evidence of a link between the use of antibiotics and the prevalence of antimicrobial resistances. The more antibiotics in a particular substance group are used on humans or animals, the more bacterial pathogens resistant to this particular substance will be found at a later date. Resistance against antimicrobial drugs presents a health risk to the population, may result in the longer duration of medical conditions in patients, lead to higher public health expenses and have adverse economic repercussions on society (1).

More information

Campylobacter

The use of the fluoroquinolone Enrofloxacin as a therapeutic drug in poultry farming is said to be one cause of the occurrence of Ciprofloxacin-resistant campylobacter. Campylobacter jejuni is believed to be the most important bacterial pathogen causing gastroenteritis throughout Europe. The European Food Safety Agency (EFSA) confirmed chicken meat as the main source for campylobacteriosis in humans in January 2011 (9). The poultry formula of Enrofloxacin was licenced as veterinarian drug in Austria in August 1989, at a time when resistance rates for gyrase inhibitors (test substance at the time: nalidixic acid) in human campylobacter isolates were under 3%.

There was a sharp rise in resistance in human campylobacter isolates to Ciprofloxacin parallel to the increased use of Enrofloxacin as an inadvertent consequence of the poultry hygiene directive to prevent the spread of salmonella that came into effect on 1 January, 1992. A total of 16.9 % of all campylobacter isolates tested had already formed resistance to Ciprofloxacin in 1992 and even 22.1 percent in 1993. By 2011 (data up to and including August), 65 % of all human campylobacter isolates had developed resistance to Ciprofloxacin (Image 1). This development in resistance levels is similar to events in poultry production (10, 11). Isolates taken from sick children (gyrase inhibitors are not allowed to be used on children) could not be differentiated from isolates taken from other age groups in terms of Ciprofloxacin resistance (12).

Even though antibiotics should not normally be used to treat campylobacteriosis, the EMA still draws the following conclusion: "Infections in humans with fluoroquinolone and macrolide resistant Campylobacters have resulted in increased risk of hospitalisation and complications" (13). Resistance increases in humans as a result of Enrofloxacin use in animals could also be observed elsewhere; this was the reason why the poultry license for Enrofloxacin was revoked in the USA (14). In countries such as Australia and New Zealand, which never approved the use of enrofloxacin in animal production, the resistance rates in human Campylobacter isolates remain unchanged at under 3% (15).

High-level fluorquinolone resistance in campylobacter can be traced back almost completely to a mutation in that segment of the gyrA gen that encodes the subunit A of the DNA gyrase (16). In contrast to the enterobacteriaceae situation, only one mutation is required in campylobacter to acquire complete Ciprofloxacin resistance. This explains why resistance rates to Ciprofloxacin are considerably lower in salmonella. There were “only” 19 Ciprofloxacin resistant human salmonella isolates in Austria in 2010, as well as nine strains that were resistant to third-generation Cephalosporines (17).

E.coli

E.coli

Monitoring resistance to 3rd generation Cephalosporines in E. coli

Third and fourth generation Cephalosporine resistance levels have become an increasing problem in human medicine, in particular in the case of E. coli. The monitoring of the 3rd generation Cephalosporine resistance in E.coli is an indicator for the detection of extended spectrum betalactamases (ESBL). While 100 % of human isolates tested as part of a monitoring were fully sensitive in 2001, more than 7 % of isolates are ESBL formers at present (18,19). Additionally, Ciprofloxacin resistance in human E.coli isolates rose from 6.9 % to above 20 % over the same period.

A plasmid-bound resistance mechanism towards gyrase inhibitors was described for E.coli for the first time in 2002 (20). These plasmids can also transmit resistances to 3rd generation Cephalosporines (21). These phenomena could explain the frequent presence of ESBL formers in poultry isolates and E.coli isolates taken from poultry in Austria, where 3rd generation Cephalosporines are not used in the poultry sector (Table 1). Abroad, the massive (legal and illegal) use of Ceftiofur in poultry farming is considered a significant cause (22,23). Several recent studies point to raw poultry meat having causal significance as a source of human E.coli infections, in particular for infections of the urinary tract (24-28).In 2009, the Danish food agency concluded: "food derived spread of ESBL-producing bacteria may be the origin in at least some of the human cases" (29).

The Panel on Biological Hazards (BIOHAZ) of the European Food Safety Agency (EFSA) recommended the development and implementation of specific measures to control raw poultry, pork and beef in August 2008, prioritising measures to combat resistance to gyrase inhibitors and 3rd and 4th generation Cephalosporines in poultry meat farming, in particular (30).
There are still controversial debates over the exact relevance of raw poultry meat as a vehicle of antibiotic-resistant pathogens in humans. Raw meat as a source of Methicillin-resistant staphylococcus aureus ST398 seems to play only a minor role in Austria, as opposed to other countries (31,32). Not only this, but doctors can draw on several new antibiotic substance groups as a backup for multi-resistant, gram-positive bacteria.

Impact of Resistance

Impact of Resistance

Petrischale

Resistance to betalactamase antibiotics caused by the creation of extended spectrum beta-lactamases (ESBL) and (fluoro)quinolone resistance represent resistance characteristics that limit therapeutic options in human and veterinary medicine dramatically. Resistant Campylobacter, Escherichia coli and Salmonella enterica occur in various animal species, the environment, animal feed and foodstuffs, as well as in humans and are transmitted among and between them. However, the significance for human health and the transmission mechanisms of resistant bacteria and resistant genes of diverse origin are not well understood, despite the large number of studies on resistance. The research venture "RESET – ESBL and (Fluoro)Quinolone RESistance in EnTerobacteriaceae" is attempting to characterise isolates of different origin occurring currently, as part of the German initiative "Research Platform for Zoonoses" (33). Data from the various research foci in the fields of epidemiology, molecular genetics and pharmacy should go into a concept for risk assessment. Recommendations on improving the control of resistant bacteria -- ESBL and plasmid-mediated quinolone resistance (PMQR) carrying E.coli and S. enterica in particular -- should be designed, based on these results.  A ban on the use of Enrofloxacin in poultry farming is foreseeable in the European Union in the near future. Individual EU Member States have already decided to reduce the overall use of antibiotics considerably in animal-based food production (34).

Although the slogan "Most of the problems with resistance in human medicine are correlated to use of antimicrobials in humans" is still true, it is undisputed that antimicrobial resistance is also of importance in foods of animal origin (35, 36). At present, the progressing resistance of human-pathogenic bacteria to antimicrobials represents a problem that requires the commitment of all the parties involved (human and veterinary medicine, primary animal production, food processing and food preparation) to take responsibility in their respective fields to keep the development and spreading of antimicrobial resistances at bay.

ESBL-producing E.coli from animal-based food in Austria

Samples ESBL-producing E. coliESBL-producers in percent
Chicken meat with skin471838,3
Chicken meat without skin311135,5
Chicken liver4125
Chicken meat total823036,6
Minced meat mixed1600
Minced beef2813,6
Minced pork2713,7

Table 1: extended spectrum betalactamases (ESBL)-producing in E. coli from animal-based food (Austria, 2011) (Springer B., Giftiger Samstag, Wien 2. Juli 2011)

Foodstuffs

Foodstuffs

A total of 500 samples (pork, beef, salad, fish/seafood, eggs) taken from food retailers were examined in 2013. ESBL producing and ciprofloxacin-resistant enterobacteriaceae, as well as MRSA, could be detected in pork and beef samples, in particular. However, the detection rate of ESBL producing and ciprofloxacin-resistant enterobacteriaceae was considerably lower than that in poultry. The enterobacteriaceae (mainly E.coli) often showed co-resistances to sulfonamides and tetracyclines. The MRSA from the pork and beef samples was standardised and could be allocated to “livestock associated MRSA”. ESBL formers, ciprofloxacin-resistant enterobacteriaceae or MRSA could only be detected in individual cases in the fish and seafood specimens tested (tests included import products). Most positive samples came from imported iridescent shark fillets. Only one in 100 Austrian salad products tested positive for a ciprofloxacin-resistant E.coli isolate. The egg contents examined all tested negative. None of the 500 food samples tested positive for carbapenemase-producing enterobacteriaceae (37).

Resistant bacteria in poultry products

The contamination rate of poultry products with resistant bacteria was studied in 2012, examining a total of 200 poultry meat samples from food retailers. The study showed high contamination levels in poultry with ESBL-producing, AmpC-producing or Ciprofloxacin-resistant enterobacteriaceae. It could be shown that the isolates would also be co-resistant to sulphonamides and tetracycline by determining the minimal inhibitor levels for different classes of antibiotics. Methicillin-resistant staphylococcus aureus (MRSA) was only found in one turkey meat sample. Carbapenemase-producing enterobacteriaceae was not found (37).

Recommended Literature

Recommended Literature

  1. Empfehlung des Rates vom 15. November 2001 zur umsichtigen Verwendung antimikrobieller Mittel in der Humanmedizin (2002/77/EG).
  2. Allerberger F, Apfalter P, Burgmann H, et al. ABSantibioticstewardship im Niedergelassenen Bereich. 2.edt., ABSGROUP, Wien, 2011.
  3. Musch A (2009) GERMAP 2008. Chemotherapie Journal 18 (1): 27-30.
  4. Moulin G, Cavalie P, Pellanne I, et al. (2008) A comparison of antimicrobial usage in human and veterinary medicine in France from 1999 to 2005. Journal of Antimicrobial Chemotherapy 62: 617-625.
  5. Liebrich S (2011) Gefährliche Keime aus dem Stall: Der Missbrauch von Antibiotika in der Massentierhaltung bedroht die Gesundheit von Verbrauchern.  Süddeutsche Zeitung, 20.09.2011, Seite: 17.
  6. Kadenbach K (2011) SPÖ-Europaabgeordnete warnt vor zunehmender Resistenz unddaraus folgenden Gesundheitsgefahren in Europa. OTS0056 5 II 0290 SPK0001 AI Mi, 28.Sep 2011.
  7. Allerberger F., H. Würzner (1998) Antibiotika in der Nutztierhaltung. Mitt Österr Sanitätsverwaltung 99:3-8.
  8. Pugh M (2002) The EU precautionary bans of animal feed additive antibiotics. Toxicology Letters 128: 35-40. 
  9. European Food Safety Authority. Jahresbericht 2010. ISSN 1725-5775.
  10. Feierl G, Pschaid A, Sixl B, Marth E (1994) Increase of ciprofloxacin resistance in Campylobacter species in Styria, Austria. Zentralbl Bakteriol. 281(4):471-474.
  11. Feierl G, Leitner E, Gehrer M, et al.(2011) Epidemiology of campylobacteriosis and trends of resistance in Austria. 16th International Workshop on Campylobacter, Helicobacter and Related Organisms; AUG 28-SEP 1, 2011; Vancouver, Canada [Poster No. 239].
  12. Jelovcan S, Springer B (2010) Resistenzbericht Campylobacter – Daten aus dem Human-, Lebensmittel- und Veterinärbereich. Resistenzbericht Österreich AURES 2009, pp.100-110. 
  13. COMMITTEE FOR MEDICINAL PRODUCTS FOR VETERINARY USE (CVMP) 2006. REFLECTION PAPER ON THE USE OF FLUOROQUINOLONES IN FOOD-PRODUCING ANIMALS IN THE EUROPEAN UNION: DEVELOPMENT OF RESISTANCE AND IMPACT ON HUMAN AND ANIMAL HEALTH. EMEA.
  14. Davidson DJ. In the matter of enrofloxacin for poultry: withdrawal of approval of Bayer Corporation‘s new animal drug apllication 1 (NADA) 140-828 (Baytril). In: FDA Docket no.00N-1571; 2004.
  15. Butzler JP (2005) Campylobacter from obscurity to celebrity. Clin. Microbiol. Infect. 11: 341 – 342.
  16. Aarestrup F M, Engberg J (2001) Antimicrobial susceptibility of thermophilic Campylobacter. Vet. Res. 32: 301-310.
  17. Kornschober C, Orendi U (2011) Nationale Referenzzentrale für Salmonellen – Jahresbericht 2010. BMG Newsletter bmg.gv.at/cms/home/attachments/0/9/7/CH1305/CMS1299590600940/jb_salmonellen_2010_04032011.pdf
  18. Apfalter P, Fluch G (2010) Antibiotikaresistenz bei ausgewählten invasiven Infektionserregern. Resistenzbericht Österreich AURES 2009, pp.100-110.
  19. Huemer HP, Eigentler A, Aschbacher R, Larcher C (2011) Dominance of CTX-M group 1 beta-lactamase enzymes in ESBL producing E. coli from outpatient urines in neighbouring regions of Austria and Italy. Wien Klin Wochenschr. 123:41-44)
  20. Wang M, Tran JH, Jacoby GA, et al. (2003) Plasmid mediated quinolone resistance in clinical isolates of Escherichia coli from Shanghai, China. Antimicrob Agents Chemotherapy. 47:2242-2248.Cheung TK, Chu YW, Chu MY, et al. (2005) Plasmidmediated resistance to ciprofloxacin and cefotaxime in clinical isolates of Salmonella enterica serotype Enteritidis in Hong Kong. J Antimicrob Chemother. 56: 586-589).
  21. Dutil L, Irwin R, Finley R, et al. Ceftiofur resistance in Salmonella enterica serovar Heidelberg from chicken meat and humans, Canada. Emerg Infect Dis 2010; 16(1):48-54.
  22. Health Council of the Netherlands. Antibiotics in food animal production and resistant bacteria in humans. The Hague: Health Council of the Netherlands, 2011; publication no. 2011/16E.
  23. Overdevest Im Willemsen I, Rijnsburger M, et al. (2011) Extended-Spectrum ß-Lactamase Genes of Escherichia coli in Chicken Meat and Humans, the Netherlands. Emerg Infect Dis 17 (7):1216-1222.  
  24. Smet A, Martel A, Persoons D, et al. (2009) Comparative analysis of extended-spectrum-{beta}-lactamase-carrying plasmids from different members of Enterobacteriaceae isolated from poultry, pigs and humans: evidence for a shared {beta}-lactam resistance gene pool? J Antimicrob Chemother. 63(6): 1286-1288.
  25. Smet A, Martel A, Persoons D, et al. (2009) Broad-spectrum betalactamases among Enterobacteriaceae of animal origin: molecular aspects, mobility and impact on public health. FEMS Microbiol Rev. 34(3): 295-316.
  26. Dierikx C, van Essen-Zandbergen A, Veldman K, et al. (2010) Increased detection of extended spectrum beta-lactamase producing Salmonella enterica and Escherichia coli isolates from poultry. Vet Microbiol. 145(3-4): 273-278.
  27. Leverstein-van Hall MA, Dierikx CM, Cohen SJ, et al. (2011) Dutch patients, retail chicken meat and poultry share the same ESBL genes, plasmids and strains. Clin Microbiol Infect. 17(6): 873-880.
  28. Jensen VF, Hammerum AM (2010) DANMAP 2009 - Use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, foods and humans in Denmark. ISSN 1600-2032.
  29. EFSA Panel on Biological Hazards (BIOHAZ) Panel (2008) Foodborne antimicrobial resistance as a biological hazard - Scientific Opinion of the Panel on Biological Hazards. Question No EFSA-Q-2007-089. www.efsa.europa.eu/en/efsajournal/doc/765.pdf
  30. Feilhauer B.: Bestimmung der Besiedelungsrate von Geflügel und Geflügelprodukten durch Staphylococcus aureus respektive MRSA. Bachelorarbeit, FH Johanneum, Studiengang Biomedizinische Analytik. Graz, 2009
  31. van Cleef BAGL, Monnet DL, Voss A, et al. (2011) Livestock-associated methicillin-resistant Staphylococcus aureus in humans, Europe. Emerg Infect Dis 17:502-505.
  32. Benninger G (2011) Zoonosen: Bekannte und neue Infektionskrankheiten – eine Herausforderung für die Forschung an der Schnittstelle von Human- und Veterinärmedizin. DZKF 5/6: 1-6.
  33. Minister van Landbouw, Natuur en Voedselkwaliteit. Brief aan Stuurgroep Antibioticaresistentie Dierhouderij. 16-4-2010.
  34. COMMITTEE FOR MEDICINAL PRODUCTS FOR VETERINARY USE (CVMP) 2006. Infections in humans with fluoroquinolone and macrolide resistant Campylobacters have resulted in increased risk of hospitalisation and complications.
  35. World Health Organization (1997) The Medical Impact of the use of antimocrobials in food animals. Report of a WHO Meeting, Berlin, Germany, 13-17 October 1997, WHO/EMC/ZOO/97.4.
  36. Austrian Federal Ministry of Health and Women’s Affairs: AURES - der österreichische Antibiotikaresistenzbericht
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