Antibiotic Stewardship Into the Future? the Livestock Industries Livestock Industries Use of Antibiotics in Livestock Constraint

3/08/2012

What has happened since JETACAR?

• Markedly increased awareness Antibiotic stewardship into the • Some vets do not see AMR as a problem – Some see no link between AMR in human future? The Livestock industries medicine and use of antimicrobials in animals Prof Mary Barton • EAGAR played major role in ensuring risks to human health considered in registration University of South Australia process • Post-EAGAR – no medical input

Issues affecting veterinary attitudes Livestock industries

• Perceived lack of action on medical front • Concerns about antimicrobial use largely driven by concerns about • Pilot surveillance program on AMR in E coli , enterococci and residues campylobacter showed relatively little resistance (except pigs) • Antimicrobial use in poultry very restricted • Pilot food surveillance program – again little resistance – 42 day life for meat chickens BUT – Concerns about residues in eggs • MRSA colonisation in vets (771) – Jordan et al. (2011) AVJ 89:152-159. – Do not think antimicrobial resistance is an issue for the industries – Horses only – 21.4% • Pig industry very aware – Mainly horses – 11.8% – Significant disease problems →widespread use of antimicrobials → multi-drug resistant isolates – Cats and dogs – 4.9% Significant research into alternatives – Government and industry – 0.93% – – Pork CRC goal to cease antimicrobial use in 5 years? • Multi-drug resistance enteric bacteria in hospitalised dogs – Darren Trott’s group eg Sidjabat et al (2006) J Antimicrob Chemother 57: 840-848. • Dairy industry ? • Beef industry ?

Use of antibiotics in livestock Constraints and Opportunities

• Commercial products used in food producing • Residues - MRLs animals particularly must be registered • Withholding times for antibiotics • State governments responsible for control of use legislation – Led to banning of streptomycin in food producing animals • Veterinarians can use their judgement – within some limits • Registration process – Off-label use permitted – treatment of a single animal Versus with a product already registered for use in food producing animals • Compounding pharmacies • Nearly all antimicrobials of medical importance – No registration process now S4 (prescription only) – Vet totally on their own

1 3/08/2012

Antibiotics registered for use in Food producing animals Antibiotics registered for use in Food producing animals

Antibiotic Egg layers Meat chickens Pigs Cattle aquaculture Antibiotic Egg layers Meat Pigs Cattle aquaculture aminoglcycosides Spectino Apramcycin Apramcycin Apramycin chickens neomycin Neomycin Neomycin Framycetin lincosamides lincomycin lincomycin lincomycin Lincomycin Spectino Spectino neomycin macrolides Spiramycin erythro Erythro Erytho tylosin spiramycin Spiramycin Oleando amphenicols florfenicol florfenicol ? tylosin kitasamycin Tilmicosin orthosomycins avilamycin avilamycin avilamycin Tiamulin tylosin bambermycins flavophosphol flavophosphol flavophosphol flavophoshol Tilmicosin cephalosporins Ceftiofur penicillins Ampicillin Ampicillin Ampicillin ? Cefuroxime amoxycillin Amoxicillin Amoxicillin Cephalonium Benzyl pen Benzyl pen cephapirin Penethemate Cloxacillin Procaine pen Procaine pen fluoroquinolones polyethers ionophores ionophores ionophores ionophores glycopeptides polypeptides Zn bacitracin Zn bacitracin Zn bacitracin Polymixin quinoxalines olaquindox Zn bacitracin streptogramins virginiamycin virginiamycin virginiamycin virginiamycin Note - gentamicin, fluoroquinolones, Sulph/trimeth yes yes yes glycopeptides, chloramphenicol not registered tetracyclines chlortet Oxyter Oxytet Oxytet ? for use in food producing animals Chlortet Chlor tet

Antimicrobial resistance in livestock Current antimicrobial resistance in isolates livestock isolates • Dairy? Beef? • No fluoroquinolone resistance in E coli and • Pigs – declining resistance in SA studies campylobacter isolates from pigs and poultry • No? ceftiofur resistance Pig isolates 1998 2005 • No gentamicin resistance E coli tetracycline 100% 80% Apramcycin 90% 0% • No virginiamycin resistance in chicken Neomycin 80% 10% enterococci, no van C (let alone van A) Enterococci virginiamycin 90% 10% collected 2008-2009

Barton and Peng (2005) Epidemiology of antibiotic resistant bacteria and genes in piggeries. Report to Australian Pork Ltd.

O157 Antimicrobial susceptibility profiles

Antimicrobial E. coli O:157strain Disturbing trends agent

010 121 123 126 127 129 130 132 138 157 158 159 166 167 169 170 171 174 • Off-label use – not in accord with regulations Ampicillin RRRRRRRRRRRRRRRRRR Ceftiofur ISSSSSSSSSSSIIISSS • Multiple brands of ceftiofur available (no RA Flavomycin RRRRRRRRRRRRRRRRRR for risks to human health) Gentamicin IIIRIIIRRSISRRRIII Neomycin RRRRRRRRRRRRRRRRRR • Ceftiofur advocated for use in pigs Salinomycin RRRRRRRRRRRRRRRRRR Spectinomycin RRRRRRRRRRRRRRRRRR

• Compounding pharmacists… Streptomycin RRRRRRRRRRRRRRRRRR

Tetracycline RRRRRRRRRRRRRRRRRR

Trimethoprim/Sulf RRRRRRRRRRRRRRRRRR

Tylosin RRRRRRRRRRRRRRRRRR

RRRRRRRRRRRRRRRRRR VirginiamycinI = Intermediate Interpreted using NCCLS & DANMAP guidelines R = Resistant S = Susceptible

2 3/08/2012

Example of compounding pharmacy equine list Example from a compounding website Drug Form Strength Quantity amikacin IA & IV injection 250 mg/ml 2, 4, 30 ml azithromycin paste 200 mg/g 500g • VETERINARY chloramphenicol paste 500 mg/g 500g Some of the most commonly prescribed products clarithromycin • Methimazole paste 750 mg/10g 500g, 1 kg Itraconazole doxycycline Paste/powder 500 mg/kg;98% 1 kg;200 g, 1 kg Idoxuridine Chloramphenicol enrofloxacin Paste/powder 3.75 g/10g;100% 500g;1 kg Tacrolimus Trilostane fluconazole paste 300 mg/g 500g Gabapentin itraconazole Paste/lavage/ 400 mg/kg; 1%+DMSO 7%; 400g; 10ml; 30g Hypertonic Saline Hydroxurea ophthalmic oint 1% Cisapride ketoconazole powder USP 100g Aspirin Atropine Sulphate metronidazole paste 500mg/g 250ml; 500ml; 1L Acetazolamide Polymixin B injection 2.5mil IU/15ml 15ml, 90 ml We can even encapsulate your own Tylosin, and we can compound something rifampicin paste 2.5g/10g 500g, 1 kg you may already have into a different strength. Rifampicin, paste 500 mg, 750mg/10g 500g, 1 kg clarithromycin Sulphadimidine, paste 4.5g, 0.9 g/10g 2 kg trimethoprim

Alarm at antibiotics in fish imports An analysis by The Age of ''failed food'' results since Melissa Fyfe and Royce Millar 2010 shows 1050 imported foods, or an average of May 30, 2012 one consignment a day, have not met Australian Antimicrobial use in aquaculture standards. Almost 400 foods were stopped at entry because of micro-organisms such as E. coli , 246 failed Read more: because they contained banned additives or http://www.theage.com.au/national/alarm-at- substances, 228 contained contaminants and 138 • No products registered antibiotics-in-fish-imports-20120529- failed chemical analysis. 1zhfw.html#ixzz1wJbvBldV Chinese food failed the most tests, 13 per cent, followed by food from India, Italy, Japan, South • Permit use of oxolinic acid in goldfish Korea and France. The failed food results included 66 AUSTRALIAN medical experts have raised the alarm instances of Listeria monocytogenes , which can • Salmon and other edible aquaculture products over a rising number of Asian fish imports containing cause pregnant women to miscarry, and eight banned antibiotics. consignments with Vibrio cholerae bacteria, strains Five consignments of fish from Vietnam - including of which can cause cholera. – Clearly off-label use for many years basa fillets, catfish, tilapia and frozen fish cutlets - have been stopped by biosecurity officials this year – Now apparently permits for tetracyclines, because they contained enrofloxacin, an antibiotic florfenicol banned in Australia . Last year, three loads of Vietnamese fish failed tests for banned antibiotics. Anecdotal accounts of use of non-food animal Narelle Clegg, of the federal Agriculture – Department's food safety branch, confirmed a rise in registered products eg nalidixic acid fish imports testing positive for banned antibiotics. ''The trend that we see with fish, and it's generally about antibiotics, is that they are very low levels of residues but they are there nonetheless,'' she said.

Sydney Morning Herald, June 23, 2007 Response of Veterinary Profession THE use of antibiotics on Australia's favourite farmed fish, Atlantic salmon, has risen disturbingly as diseases flare in their sea pens. The increase has raised strong private concerns from the Tasmanian Government, which said it was nearly double the amount expected .... The antibiotics are appearing in wild fish near farms, and the Government has called for an end to the use of one drug, amoxicillin, also used on humans. The $250 million-a-year industry, • 2011 Aust Vet Assoc conference – interested which produces 22,000 tonnes of the fish, is insisting on continued access to antibiotic treatments. From 12 kilograms a year a decade ago, the antibiotics used at salmon and trout farms vets met – mostly academic, regulatory & totalled almost eight tonnes in the first three months this year, according to departmental figures. The Australian Pesticide and Veterinary Medicines Authority permitted the industry to use the most pharm industry with vet public health common antibiotic, oxytetracycline (OTC) and the proprietary medicine, Aquaflor after a risk assessment. "It is disturbing … that the industry has used nearly double the amount of OTC than was anticipated interests in the permit application, " Mr Llewellyn said in a letter to the Tasmanian Salmonid Growers' Association. The farms maintain a holding period to allow antibiotics to pass through the fish before they are harvested, AVA supportive but has no funds but Mr Llewellyn said there was a potential public health impact if OTC entered the human food chain • through consumption of wild fish that might have eaten medicated feed outside pens, or treated salmon that escaped. Salmon also regularly escape from sea pens. In the latest incident, 9000 mature fish swam • Promise to re-vamp “Therapeutic Advisory free of a pen at Strahan last month , triggering an amateur netting spree over the Queen's Birthday long weekend. Mr Llewellyn said a further concern was the use of the human treatment amoxicillin. Group” He threatened to prohibit its use after the state Director of Public Health, Roscoe Taylor, told him of concerns about potential – Current antimicrobial guidelines focus on allergic reactions, and the effect on the drug of antibiotic resistant bacteria already in the sea. therapeutic issues – little public health input

3 3/08/2012

Education of Vets Conclusions

• Aust Vet Assoc conference – veterinary public • Situation better than it was at the time of health Special Interest Group + pharm industry JETACAR • Limited (but increasing ?) interest from vet practitioners) • Greater awareness in industry • Public health and microbiology academics • Most vet practitioners would see pushing AMR, antimicrobial stewardship to client/farmer immediate needs as paramount students – what happens in clinical years or early • Compounding pharmacies a major risk years of practice? • Postgraduate foundations appear to have little • Much depends on attitudes and practices of interest in antimicrobial stewardship graduating veterinarians

4