ANTIMICROBIAL STEWARDSHIP

ANTIMICROBIAL STEWARDSHIP Australian Pig Veterinarians Annual Conference 11-12 September, 2017 Stephen Page Advanced Veterinary Therapeutics swp@advet.com.au

OUTLINE Importance of AMR Antimicrobial use worldwide Action plans Veterinary antimicrobial stewardship - AMS

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HUMAN PATHOGENS WITH ANTIMICROBIAL RESISTANCE THREATENING PUBLIC HEALTH PRIORITY PATHOGENS WHO 2017 12 threats Critical: Acinetobacter baumannii, carbapenem-resistant Critical: Enterobacteriaceae, carbapenem-resistant, ESBL producing Critical: Pseudomonas aeruginosa, carbapenem-resistant High: Campylobacter spp., fluoroquinolone-resistant High: Enterococcus faecium, vancomycin-resistant High: Helicobacter pylori, clarithromycin-resistant High: Neisseria gonorrhoeae, cephalosporin-resistant High: Salmonellae, fluoroquinolone-resistant High: Staphylococcus aureus, methicillin-resistant, vancomycin-intermediate and resistant Medium: Haemophilus influenzae, ampicillin-resistant Medium: Shigella spp., fluoroquinolone-resistant Medium: Streptococcus pneumoniae, penicillin-non-susceptible 4

There is around a 100-fold variation in the intensity of antibiotic use in livestock between different European countries. Australia 14.8 Scannell, J. W. and A. Bruce (2015). "Antibiotics: expect to use less, more responsibly." Veterinary Record 177(7): 168-170.

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COMPARATIVE GLOBAL ANTIBACTERIAL USE IN LIVESTOCK Rank Country Antibacterial use mg/pcu Reference 1 Norway 3.1 EMA and ESVAC (2016) 2 Iceland 5.2 EMA and ESVAC (2016) 3 Singapore 5.8 AEM 2015 4 Brunei 5.9 AEM 2015 5 Sweden 11.5 EMA and ESVAC (2016) 6 New Zealand 12.0 O Neill 2015 7 AUSTRALIA 14.8 O Neill 2015 8 Finland 22.3 EMA and ESVAC (2016) 9 Slovenia 33.4 EMA and ESVAC (2016) 10 Lithuania 35.5 EMA and ESVAC (2016) 11 Latvia 36.7 EMA and ESVAC (2016) 12 Romania 39.2 EMA and ESVAC (2016) 13 Luxembourg 40.9 EMA and ESVAC (2016) 14 Denmark 44.2 EMA and ESVAC (2016) 15 Ireland 48.0 EMA and ESVAC (2016) 16 Austria 56.3 EMA and ESVAC (2016) 17 Switzerland 56.9 EMA and ESVAC (2016) 18 United Kingdom 62.1 EMA and ESVAC (2016) 19 Slovakia 65.9 EMA and ESVAC (2016) 20 Estonia 68.0 EMA and ESVAC (2016) 21 Netherlands 68.4 EMA and ESVAC (2016) 22 Czech Republic 79.5 EMA and ESVAC (2016) 23 Bulgaria 82.9 EMA and ESVAC (2016) 24 Lao PDR 104.7 AEM 2015 25 France 107.0 EMA and ESVAC (2016) 26 Cambodia 135.9 AEM 2015 27 Malaysia 137.5 AEM 2015 28 Poland 140.8 EMA and ESVAC (2016) 29 Croatia 147.2 EMA and ESVAC (2016) 30 Germany 149.3 EMA and ESVAC (2016) 31 Belgium 158.3 EMA and ESVAC (2016) 32 United States of America 187.5 O Neill 2015 7

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to improve awareness and understanding of antimicrobial resistance through effective communication, education and training; to strengthen the knowledge and evidence base through surveillance and research; to reduce the incidence of infection through effective sanitation, hygiene and infection prevention measures; to optimize the use of antimicrobial medicines in human and animal health; to develop the economic case for sustainable investment that takes account of the needs of all countries and to increase investment in new medicines, diagnostic tools, vaccines and other interventions. 9

NATIONAL STRATEGY OBJECTIVES 1. Increase awareness and understanding of antimicrobial resistance through effective communication, education and training. 2. Implement effective antimicrobial stewardship practices 3. Develop nationally coordinated One Health surveillance of antimicrobial resistance and antimicrobial usage. 4. Improve infection prevention and control measures 5. Agree a national research agenda 6. Strengthen international partnerships and collaboration 7. Establish and support clear governance arrangements to ensure leadership, engagement and accountability for actions to combat antimicrobial resistance.

VETERINARY ANTIMICROBIAL STEWARDSHIP the multifaceted and dynamic approaches required to sustain the clinical efficacy of antimicrobials by optimizing drug use, choice, dosing, duration, and route of administration, while minimizing the emergence of resistance and other adverse effects 12

ANTIMICROBIAL STEWARDSHIP Professional management to reduce resistance selection to preserve the efficacy of antimicrobial agents 5Rs Weese, J. S., S. W. Page and J. F. Prescott (2013). Antimicrobial Stewardship. Antimicrobial Therapy in Veterinary Medicine (Fifth Edition). S. Giguère, J. F. Prescott and P. M. Dowling. Oxford, UK, Wiley-Blackwell: 117-132. 13

ANTIMICROBIAL STEWARDSHIP AMS is about ensuring the Quality Use of antimicrobials, including antibiotics. Good antimicrobial stewardship means using as little as possible, as much as necessary to ensure that high levels of health and welfare are present throughout the entire life of all humans and animals who might require antimicrobials to treat infection. 14

GOOD STEWARDSHIP PRACTICE GSP Is a commitment to a global good Can be individualised to each situation Can commence slowly and build progressively Is not labour or cost intensive 15

REVIEW

REVIEW

REVIEW Burch, D. G. S., et al. (2009). Guidelines for Antimicrobial Use in Swine. Guide to Antimicrobial Use in Animals, Blackwell Publishing, Ltd: 102-125.

EVIEW

EVIEW

REVIEW For 90% TAR [target attainment rates], predicted daily doses at steady-state for bactericidal actions were 1,123 mg/kg (P. multocida) and 43 mg/kg (A. pleuropneumoniae) based on serum MICs. Lower TARs were predicted from broth MIC data; corresponding dose estimates were 95 mg/kg (P. multocida) and 34 mg/kg (A. pleuropneumoniae).

REVIEW MEASUREMENT OF USE - QUALITY APPROPRIATE 1 Optimal Antimicrobial prescription follows a national or endorsed local guideline optimally, including antimicrobial choice, dosage, route and duration, (including for surgical prophylaxis) 2 Adequate Antimicrobial prescription does not optimally follow the national or endorsed local guideline, including antimicrobial choice, dosage, route or duration, however, is a reasonable alternative choice for the likely causative or cultured pathogens; OR for surgical prophylaxis, as above and duration is less than 24 hours INAPPROPRIATE 3 Suboptimal Antimicrobial prescription including antimicrobial choice, dosage, route and duration, is an unreasonable choice for the likely causative or cultured pathogens, including spectrum excessively broad or an unnecessary overlap in spectrum of activity; and/or failure to appropriately de-escalate with microbiological results. 4 Inadequate Antimicrobial prescription including antimicrobial choice, dosage, route or duration is unlikely to treat the likely causative or cultured pathogens; OR an antimicrobial is not indicated for the documented or presumed indication; OR there may be the potential risk of toxicity due to drug interaction; OR for surgical prophylaxis, the duration is greater than 24 hours (except where guidelines endorse this) UNKNOWN 5 Not assessable The indication is not documented and cannot be determined from the clinical case notes; OR the case notes are not comprehensive enough to assess appropriateness; OR the patient is too complex, due to multiple co-morbidities, microbiology results, etc. 24

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1: Primary Prevention: External Biosecurity (bioexclusion) Minimising the introduction of animals Minimising the number of sources of introduced animals Cleaning and disinfection of transport vehicles and containers Isolation of sick animals before introduction Provide clean water, feed, air Housing must exclude pests, control human access, filter exhaust to reduce pathogen load 2: Secondary Prevention: Internal Biosecurity (biocontainment) All-in-all-out production system Hygiene, infection control protocols Housing design ventilation, drainage Litter/bedding materials Early diagnosis of disease Once pathogen present, introduce measures to eliminate or reduce transmission guided by onfarm microbiological risk assessment Reduce stocking density, segregation, sick pens 3: Tertiary Prevention: Individual animal resilience (adaptive capacity to changing environment) Genetic selection Vaccination Management (handling, low stress, enrichment) Nutrition Housing (ventilation, temperature, stocking rate, hygiene 26

REFINEMENT Modify therapeutic objective/plan Take history, examine patient and gather other data as appropriate Make diagnosis Confirm need for antimicrobials Define therapeutic objective(s) Develop therapeutic plan (drug and non-drug measures) Select drug and dosage regimen Prophylactic, Empiric, Directed 5 rights: right drug, right time, right dose, right duration, right route Non-drug measures Supportive, management, nutrition, environment, evidence-based alternatives CONSULT Stewardship 5R cycle and prudent use guidelines Modify Diagnosis Monitor and evaluate Response to treatment Change drug or modify regimen Continue treatment Stop treatment

Core Principles of Judicious Use An analysis of 34 guidelines for prudent use revealed 22 principles that could be assigned to the following 5 categories. 1. Pre-treatment principles 2. Diagnosis 3. Drug selection 4. Drug use 5. Post-treatment guidelines 28

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ANTIBACTERIAL AGENT - 23 CLASS - 13 IMPORTANCE - ASTAG 2016 IMPORTANCE - WHO 2017 Spectinomycin Aminocyclitol med 4 Apramycin Aminoglycoside low 2 Neomycin Aminoglycoside low 2 Trimethoprim S Diaminopyrimidine med 3 Flavophospholipol Glycophospholipid nhu 5 Salinomycin Ionophore nhu 5 Lincomycin Lincosamide med 3 Erythromycin Macrolide low 1 Kitasamycin Macrolide low 1 Tilmicosin Macrolide low 1 Tulathromycin Macrolide low 1 Tylosin Macrolide low 1 Florfenicol Phenicol low 3 Tiamulin Pleuromutilin mhu 4 Olaquindox Quinoxaline nhu 5 Sulfadiazine T+ Sulfonamide low 3 Sulfadimidine T+/- Sulfonamide low 3 Sulfadoxine T+ Sulfonamide low 3 Chlortetracycline Tetracycline low 3 Oxytetracycline Tetracycline low 3 Amoxicillin β lactam penicillin low 2 Penethamate β lactam penicillin low 2 Penicillin (and salts) β lactam penicillin low 2

REPLACEMENT

Good Stewardship Practice GSP Stage 1 in three steps Responsibility senior management appoint a leader of the AMS programme Stocktake on current practices Review of practices against 3R prudent use principles (quantity & quality of use) GSP Stage 2 Develop and implement objectives Review of stage 2: quality of use 32

ANTIMICROBIAL USE QUALITY In order to assess the quality of antimicrobial use it is necessary to have a prescribing guideline which specifically reviews each of the major infectious diseases that require management and provides evidence guided recommendations. Quality of use can be assessed by comparing actual use regimens with those set out in the guideline. ANTIMICROBIAL USE QUANTITY There is no standard measure of the quantity of antimicrobial use. To be able to retrospectively convert records of consumption to standard metrics a table of key data should be prepared and adopted. EDUCATION AND TRAINING There is an industry wide need for ongoing continuing professional development addressing antimicrobial use and antimicrobial resistance and providing updates on important developments both within Australia and globally. AMS PROGRAMME AUDITING There is interest in being able to benchmark performance and this will be aided by the development and implementation of a third party audit programme 33

8 concluding questions What is Appropriate use? Quality use? Best practice? How do we measure it? How important are non-technical drivers of antimicrobial prescribing (ie human factors)? What are the barriers to AMS in your operations? 34

8 concluding questions What are you key sources of information? Literature Infectious diseases / microbiology Education & continuing professional development needs? What is the role of microbiology lab & culture/sensitivity How are the 5Rs already in place What more can be done 35