Antibiotic Resistance

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1 Antibiotic Resistance The Role of the Veterinary Profession Dr Michael Lintott BVSc MANZCVS

2 Antibiotics - literal translation Against Life Antibacterials Antifungals Antivirals Anthelmintics

3 Plan to cover. Other.biotic resistance. What is Antibiotic Resistance?? Veterinary concerns and principles of use Clinical cases Veterinary Guidelines to Prescription

4 Anthelmintic Resistance in NZ FEC Reduction test Resistance to an anthelmintic was inferred when there was <95% reduction in FEC 7-10 days after treatment.

6 What is the Current Situation in NZ? Only 36% of farms have no resistance for all anthelmintics tested. Resistance to more than one anthelmintic family was evident on 13% of farms. Resistance to all three active families - ivermectin, levamisole and albendazole on 8% of farms. Multi drug resistant parasites are rare but multiple resistance is common.

7 Haemonchus contortus barbers pole worm

9 Plan to cover. Other.biotic resistance. What is Antibiotic Resistance?? Veterinary concerns and principles of use Clinical cases Veterinary Guidelines to Prescription

10 If you think you understand anti-microbial resistance, it hasn t been explained properly to you Loneragan, G (2013) Did This Come from That? Antibiotic resistance and the science behind knowing the unknowable. National Institute for Animal Agriculture Antibiotics Symposium, Bridging the Gap Between Animal Health and Human Health, Kansas City, Mo, 13 November.

11 What is Antibiotic Resistance? Antibiotic resistance in bacteria is either an inherent (naturally occurring) or acquired ability to withstand treatment with one or more antibiotics. If bacteria are resistant then the diseases they may cause cannot be cured or controlled by treatment with antibiotics, or there may be few effective drug choices.

13 What Causes Antimicrobial Resistance? Antibiotic resistance can be caused by any of the following: A naturally occurring (or acquired via genetic mutation) capability to withstand treatment without any previous exposure to the antibiotics Previous exposure to the antibiotics Transfer of resistance from other bacteria (pathogenic or non-pathogenic) that have already acquired resistance.

14 The relentless race Clatworthy AE, Pierson E & Hung DT. Nature Chemical Biology 2007;3:

16 Current theories on AMR and reservoirs are in fact, incredibly complex Currently, little or no quantification of importance of different routes ( except human) Therefore: difficult to quantify benefit of any intervention

Recent Media Attention Kiwi contracts superbug resistant to every antibiotic New Zealand Herald, 19 November 2013.

17 Recent Media Attention Kiwi contracts superbug resistant to every antibiotic New Zealand Herald, 19 November CDC warns of future catastrophic antibiotic resistance New Scientist, 17 September Superbug spreads further in community New Zealand Herald, 29 April Antibiotic resistance as big a risk as terrorism Britain s Chief Medical Officer, March Antibiotic misuse by vets fuelling rise of superbugs The Times (London), 19 February Antibiotic-resistant bacteria are everywhere Science Nordic, January 24, 2015 Antibiotic resistance now 'global threat', WHO warns, BBC News, 30 April 2014

18 Call to punish GPs over antibiotics BBC News 18 August 2015 Professor Mark Baker, NICE: "People who overuse antibiotics are creating a problem for patients with lifethreatening infections" GP Dr Simon Bowers: "There are people who think the snotty nose they've got needs antibiotics and needs them now" The National Institute for Health and Care Excellence's Prof Mark Baker said 10 million prescriptions a year in England were inappropriate. He said regulators need to deal with overprescribing doctors who failed to change their ways. The Royal College of GPs said the call was "counterproductive and unhelpful".

19 Press Release: NZ Veterinary Association Friday, 6 March 2015 Vets play key role in judicious use of antimicrobials Yesterday, fast food restaurant McDonald s announced that it will only source animals raised without antibiotics that are important to human health, highlighting the key role veterinarians play in judicious use of antimicrobials to combat the rise of antimicrobial resistant bacteria.

21 Antimicrobial resistance is a key priority for the NZVA and we are working alongside MPI and other industry partners to develop a national strategy to address this global concern. Dr Dennis Scott, Chair of the New Zealand Veterinary Association Anti-microbial Resistance Working Group We recognise that use of antimicrobial medicines for treating disease in humans and animals has seen major improvements in human and animal health, and in quality of life, for over more than half a century. They must continue to effectively treat bacterial infections as they are critical in guarding and supporting the health and welfare of humans and animals. All veterinarians have a role to play in ensuring the careful use of antimicrobials so that they will remain effective for treating infections.

NZVA Media Release Tuesday 21 July 2015 Veterinarians set antibiotic goal for animals By 2030 New Zealand Inc will not need antibiotics for the maintenance of animal health and wellness, New Zealand

22 NZVA Media Release Tuesday 21 July 2015 Veterinarians set antibiotic goal for animals By 2030 New Zealand Inc will not need antibiotics for the maintenance of animal health and wellness, New Zealand Veterinary Association (NZVA) President Dr Steve Merchant said today. With sharply increasing levels of resistance to antibiotics worldwide, we want animals and, by extension, humans to enter the postantibiotic era as safely as possible. Antibiotics were one of the 20th century's greatest achievements, replacing them will be the 21st century's greatest challenge

24 In 1951, the Food and Drug Administration (FDA) approved, for the first time, the use of the antibiotics, penicillin and chlortetracycline, as animal feed additives. Only two years later, another, oxytetracycline, was approved by the FDA for use.

25 It has been estimated in 2015 that animal use accounts for more than half of all anti-microbials produced worldwide.

New Zealand Antibiotic Use Annual use Totals: 53,000kg to 62,000 kg/year (all species). In-feed zinc bacitracin comprised 35-47% of total antibiotic by weight (Poultry).

26 New Zealand Antibiotic Use Annual use Totals: 53,000kg to 62,000 kg/year (all species). In-feed zinc bacitracin comprised 35-47% of total antibiotic by weight (Poultry). Penicillins :15,000-16,000 kg in 2008/09 (Cattle intramammary market). Cephalosporins, 1700kg/yr; Tetracyclines 4-5,000kg/yr Source: NZFSA Antibiotic Sales and Use Overview

27 How does antibiotic use in New Zealand compare with overseas the US and EU? New Zealand has always considered antibiotics as drugs rather than feed additives and has never allowed the level of degree of unrestricted use that was common in the US and Europe. In effect, the ban in Europe, has only raised the bar to an equal footing with New Zealand and the changes made over 10 years ago. New Zealand s regulatory control of antibiotics remains one of the most stringent in the world. Nevertheless, the New Zealand position can be justified because it encourages prudent use without imposing unjustifiably restrictive practices that would jeopardise the health and welfare of the animals.

28 Plan to cover. Other.biotic resistance. What is Antibiotic Resistance?? Veterinary concerns and principles of use Clinical cases Veterinary Guidelines to Prescription

29 Why should we be concerned? The concern is that as a result of improper use, existing antibiotics will become ineffective in treating bacterial infections; and that new antibiotics may not be found in time to prevent a return to the situation where bacterial infections routinely become life-threatening. E.g. Human Tb and Gonorrhoea This was the case up until the discovery of antibiotics in the 20th century.

30 Animal and human health has always been interlinked and bacteria that are resistant to drug therapy can be passed from animals to humans, and vice versa. Therefore veterinarians and human health physicians have an obligation to continue to work together on this key issue.

31 The Netherlands Example In 2011 the Health Council of the Netherlands presented its recommendations on Antibiotics in food animal production and resistant bacteria in humans. These recommendations were entirely adopted by the government and became the cornerstone of the Dutch responsible use policy

32 Of the retail meat samples, 94% contained ESBL-producing isolates of which 39% belonged to E. coli genotypes also present in human samples. These findings are suggestive for transmission of ESBL genes, plasmids and E. coli isolates from poultry to humans, most likely through the food chain. Clin Microbiol Infect 2011; 17:

33 The most relevant recommendations were: ESBLs, not LA-MRSA, constitute the major resistance problem; policy should focus on containment of ESBL-related risks Veterinary use of third and fourth generation cephalosporins in particular should therefore be substantially reduced Systematic use of beta-lactam antibiotics, fluoroquinolones and aminoglycosides in livestock should be banned The veterinary use of colistin (and a number of other antibiotics) should be phased out in order to keep it as a last-resort antibiotic for human health care Off-label use should be limited to exceptional cases, as was originally intended New antibiotics should be reserved for human health care purposes.

34 Transparency and benchmarking of antibiotic use per herd and per veterinarian. Improved herd health, clear responsibilities in herd health management and in prescription/delivery of antibiotics by: mandatory herd health plans; one contracted veterinarian per herd; mandatory periodical veterinary herd inspections; Clear reduction targets for livestock production as a whole: -20% in 2011 and -50% in 2013 with reference to the amount of effective substance sold in (The target was set at -70% in 2015 by government decree in 2012).

35 Sales of veterinary antimicrobials for therapeutic purposes in the Netherlands in tons of active substance

37 Science Making hasty changes without repeatable scientific justification may be difficult to reverse

38 Methicillin-resistant Staphylococcus aureus in dogs and cats: an emerging problem? R. A. Duquette, T. J. Nuttall Journal of Small Animal Practice Volume 45, Issue 12, pages , December 2004 Duquette, R. A. and Nuttall, T. J. (2004), Methicillin-resistant Staphylococcus aureus in dogs and cats: an emerging problem?. Journal of Small Animal Practice, 45: Author Information University of Liverpool Small Animal Teaching Hospital, Faculty of Veterinary Science, Crown Street, Liverpool L7 7EX There is concern over transmission of methicillin-resistant Staphylococcus aureus (MRSA) between animals and humans. The spread of hospital-acquired and community-acquired MRSA is a major challenge in human medicine. MRSA is rarely isolated from animals but methicillin resistance occurs in staphylococci that are more prevalent in animals. MRSA infections in animals are uncommon and most are associated with exposure to medical hospitals, extensive wounds, prolonged hospitalisation and immunosuppression. The risk to human health appears to be small but a survey of methicillin-resistant staphylococci in animals is required. Thorough investigation of possible zoonotic infections to establish linkage is encouraged. Medical and veterinary staff should appreciate that animals can carry MRSA, cooperate in eliminating infections and monitor animals in medical environments. Veterinary clinics should implement guidelines for dealing with MRSA. Responsible antibiotic use should minimise the spread of antibiotic resistance but a UK monitoring scheme is desirable.

40 Every veterinarian must with every clinical case make prudent decisions to ensure antibiotic use is targeted appropriately.

41 P.R.O.T.E.C.T The PROTECT message developed from an initiative of The British Veterinary Association Small Animal Medicine Society to review and promote responsible antibacterial prescribing. BEFORE you give antibacterials, have you thought about..

42 P Practice Policy A practice policy for empirical prescribing (whilst awaiting cultures) can optimize therapy, and minimize inappropriate use of antibacterials.

43 R Reducing prophylaxis Antibacterials are not a substitute for surgical asepsis and the need for prophylactic antibacterial drugs in surgery should be carefully considered. Prophylactic antibacterials are only appropriate in a few medical cases (e.g. immunocompromised patients).

44 O Other Options for Treatment Before prescribing antibacterials consider whether there are other options. Reduce inappropriate antibacterial prescribing due to client pressure, in uncomplicated viral infections avoid with self-limiting disease by providing symptomatic relief (e.g. analgesia, cough suppressants). effective lavage and debridement of infected material can also reduce the need for antibacterials. using topical preparations reduces selection pressure on resistant intestinal flora.

45 T Types of bacteria and drug Before prescribing antibacterials you should consider: Which bacteria are likely to be involved e.g. anaerobic/aerobic, Gram-positive/Gram-negative. The distribution and penetration of the drug. Any potential side effects.

46 E Employing the correct antibacterial Where possible, it is better to use a narrowspectrum than a broad-spectrum antibacterial to limit the effects on commensal bacteria.

47 C Cytology and culture Use cytology and culture to diagnose bacterial infection correctly. Culture is not required in every case but when prolonged courses of antibacterials are likely to be needed, e.g. pyoderma, otitis externa, deep or surgical wounds or following failure of empirical dosing, culture first.

48 T Treating effectively In order to treat effectively it is necessary to: Treat for long enough and at a sufficient dose to kill the bacteria, and then stop. Avoid under-dosing and consider how the drug will penetrate the target area. Repeat culture after long courses of antibacterials.

49 Plan to cover. Other.biotic resistance. What is Antibiotic Resistance?? Veterinary concerns and principles of use Clinical cases Veterinary Guidelines to Prescription

50 Clinical Case Examples

51 DSH, R submandibular swelling and fever.

52 Does this warrant antibiotic treatment? Which antibiotic should I choose?

53 Clinical and in vitro efficacy of amoxicillin against bacteria associated with feline skin wounds and abscesses Can Vet J Jun; 48(6):

54 Results: 41/120 samples yielded only 1 bacterial species (34%). 36/120 produced 2 bacterial species (30%). 27/120 samples grew 3 species (22%) and only 8 yielded >3 (7%).

55 Aerobes and facultative anaerobes: Pasteurella (most commonly) >50% Streptococci Staphylococci Corynebacterium Enterococcus spp. Obligate anaerobes: Prevotella Fusobacterium Porphyromonas Bacteroides

56 Conclusions: Most isolates were sensitive to amoxicillin Only 5/120 cases were not successful after a 7-10 day course of amoxicillin

57 Crossbreed puppy with severe otitis externa

60 Plan to cover. Other.biotic resistance. What is Antibiotic Resistance?? Veterinary concerns and principles of use Clinical cases Veterinary Guidelines to Prescription

61 General guidelines on the use of antibiotics NZVA Policy - Dec 2006 An effective method for the control and treatment of infectious diseases caused by bacteria and certain other micro-organisms.

62 Their use in veterinary practice since the 1950s has assisted in ensuring the health of livestock and companion animals. Antibiotic use has also enabled the production of meat and milk products which are unlikely to present disease problems for the consumer or those concerned with their production. Antibiotic use is also justifiable on animal welfare grounds. In treating animals with antimicrobials, veterinarians should aim to optimise therapeutic efficacy and minimise the potential for development of resistance to antimicrobials.

63 It must be remembered at all times that widespread use of antibiotics is not a substitute for efficient management or good husbandry practice. Treatment of disease is not as effective or as economical as prevention.

Particular care should be taken when prescribing antibiotics which could give rise to cross resistance with drugs used for serious infections in people.

64 Particular care should be taken when prescribing antibiotics which could give rise to cross resistance with drugs used for serious infections in people. These include 3rd and 4th generation cephalosporins and fluoroquinolones. These drugs should be avoided unless there is a good reason to use them rather than another class of antibiotic.

65 How are antibiotics used in animals? Like humans, animals need antibiotics to fight off bacterial infections. At times antibiotics are also used to prevent bacterial infections when there s a likelihood of an infection, in much the same way as they are in humans (e.g. to prevent the spread of bacterial meningitis). The use of antibiotics in cattle and sheep is relatively low because of the pastoral farming systems used in N Z. Use of feed lots in many other countries. Housing in winter - Northern Hemisphere. NZ use tends to be higher in the intensive rearing industries, mainly the pig and poultry industries.

67 The appropriate selection of antibiotics in practice is a critical decision and should be accurate diagnosis; based on: known or predictable sensitivities (sensitivity testing); known pharmacokinetics/tissue distribution to ensure the selected drug reaches the site of infection; known status of immunocompetence. likelihood of compliance with dosing instructions

68 Drug selection While therapy may need to be initiated before the results of diagnostic or sensitivity tests are known, it will need to be reassessed as test results become available. Empirical choices of antibiotic will need to be made:

69 Achieving the goal of reduction in antibiotic use will require a concerted international collaborative effort involving attitudinal and behavioural change across government, research, veterinary and human health professionals, pharmaceutical companies, and a range of associated industries as well as the public. NVZA media release

Antibiotic Resistance

Antibiotic Resistance ACVM information paper Background Within New Zealand and internationally, concerns have been raised about an association between antibiotics used routinely to protect the health of