AB susceptibility testing in support to responsible AB use in veterinary medicine : current challenges. Pierre WATTIAU

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1 AB susceptibility testing in supprt t respnsible AB use in veterinary medicine : current challenges Pierre WATTIAU Best Practice t reduce Antibitic Resistance BAPCOC Sympsium 18 NOV 2016

2 New Ryal Decree regulating the use f drugs by Vets and Animal wners (MB/BS ) 2

New Ryal Decree regulating the use f drugs by Vets and Animal wners (MB/BS 29-07-2016) DRUG DEPOSIT : Admin.

3 New Ryal Decree regulating the use f drugs by Vets and Animal wners (MB/BS ) DRUG DEPOSIT : Admin. management, Registering, Reprting, Archiving, Transfering DRUG DELIVERY : Registering, Prescriptin t FOOD / NON-FOOD prducing animals SPECIAL MEASURES (nt fr HORSES nr fr INTRA-HUDDER delivery f critical ABs) Use f critical ABs (FQ1,2,3 + CEPH 3,4) is frbidden unless a number f criteria are fulfilled. These critera include - lab islatin f the disease-causing bacterium, - demnstratin f its resistance t 5 nn-critical AB - demnstratin f its susceptibility t 1 critical AB If lab analyses are nt feasible (sampling r culture r susceptibility testing is difficult/impssible), litterature data supprting the sle use f critical ABs must be prvided. 3

New Ryal Decree regulating the use f drugs by Vets and Animal wners (MB/BS 29-07-2016) SPECIAL MEASURES (cntinued) In exceptinal (emergency) cases, a critical AB may be administered t a single

4 New Ryal Decree regulating the use f drugs by Vets and Animal wners (MB/BS ) SPECIAL MEASURES (cntinued) In exceptinal (emergency) cases, a critical AB may be administered t a single animal under the Vet s wn respnsibility : - life-threatening stage f the disease r - risk f irreversible sequelae. Lab analyses remain due and treatment shall be adapted upn results delivery 4

5 Use f critical AB? Very disuasive regulatin Are situatins where critical AB use is permitted realistic? Will ther «critical» r «last-resrt» mlecules later be merged t the list? (Clistine, Pleurmutilins,...)

6 Abut E.cli resistance t 5 nn-critical ABs... EU standard µ-dilutin plate : 2016 MIC data In a panel f 1,073 indicatr E.cli strains islated nn-specifically < pigs, cattle and pultry, 12 (1.1%) d resist t 5 nn-critical ABs and are sensitive t either FQ r CEPHA r bth. In a panel f 483 ESBL-prducing indicatr E.cli strains islated < pigs, cattle and pultry, 34 (7%) d resist t 5 nn-critical ABs frm which just 4 (0.8%) are sensitive t FQ

7 Use f critical AB? Very disuasive regulatin Are situatins where critical AB use is permitted realistic? Will ther «critical» r «last-resrt» mlecules later be merged t the list? (Clistine, Pleurmutilins,...) => Time t Prmte AB Susceptibility Testing (AST) as a supprt t AB treatments?! When is it relevant? What is needed? What is the future?

DISCUSS ISSUES! ADAPT SAMPLING! REFINE / DOCUMENT DIAGNOSTIC! Examples f «BVP / BLP»: - Please cnduct an AST n this swab.

8 Abut the lab islatin f a disease-causing bacterium... FROM THE VETERINARY SIDE : «GVP!» Imprtance f the anamnesis / diagnstic Relevance & Quality f the samples sent t the labratry Relevance f the requested analysis SHARE DOUBTS! DISCUSS ISSUES! ADAPT SAMPLING! REFINE / DOCUMENT DIAGNOSTIC! Examples f «BVP / BLP»: - Please cnduct an AST n this swab... - Pullrse suspected, please cnfirm with the prvided faeces... FROM THE LABORATORY SIDE : «GLP!» Tentative islatin f the disease-causing bacterium Identificatin f the pathgen + cnfirmatin f the pathgenic ptential if unsure Antibitic Suceptibility testing

9 Labratry steps Tentative islatin f the disease-causing bacterium and relevance f subsequent AST Highly specific enrichment / islatin media available (e.g. mbile Salmnellae, sprulating Bacilli / Clstridia...) => islatin mst prbable, AST relevant Semi- r Nn-specific enrichment / islatin media available (Streptccci, Pasteurellae, Salmnella Gallinarum...) => islatin prbable, AST relevant Enrichment / Islatin media available but slw r cumbersme grwth (Mycbacteria, Mycplasmae, Leptspira, Brachyspira...) => islatin hypthetical (expert labs nly), AST nt relevant Bacterium is NOT culturable in free-living frm (Chlamydia, Rickettsia, Cxiella,...) => islatin highly challenging, AST nt relevant

10 Labratry steps Hw t deal with nn-culturable bacteria? Rutine clny identificatin methds nt relevant (MALDI-TOF MS), traditinal AST impssible Mlecular (PCR) testing t rule in / rule ut suspicin (mre expensive) Serlgical testing t rule in / rule ut suspicin (requires additinal bld sampling + sercnversin) => Recmmended (Antibitic?) treatment based n Best Practice, Litterature data, up-t-date Frmularium Awaited new methdlgies fr rutine use in the Veterinary Bacterilgy lab : Whle Genme Sequencing f bacterilgical clnies, Sample / Metagenme / Micrbime Sequencing, AB resistance genes ID r screening (DNA hybridizatin micr-arrays)

11 Labratry issues (1/4) The disease-causing bacterium is present and culturable but... hides within a flra f identical cmmensals (e.g. E.cli) DIAGNOSTIC OF ANIMAL COLIBACILLOSIS evidence fr pathgenicity (E.cli) signatures needed (sertype, virulence factrs,...) Mlecular tests (PCR, hybridizatin µarrays) Analyze bacterial pls Drawbacks : analysis cst, need t analyze > 1 clny, delay

12 Labratry issues (2/4) The disease-causing bacterium is present and culturable but... its presence is nt necessarily a disease signature (pprtunistic) DIAGNOSTIC OF OPPORTUNISTIC INFECTIONS link bacterilgical finding with animal cnditin check fr recrds / symptms f primary infectins Drawbacks : delay, risk f disease misidentificatin

13 Labratry issues (3/4) The disease-causing bacterium is present and culturable but... is mixed with r inhibited by a bunch f ther rganisms («plybacterial») Imprve lab enrichment / (re-)islatin methds if pssible Shtgun identificatin f all clnies (MALDI-TOF) Mlecular detectin f suspected pathgen(s) n pled clnies / unenriched sample Drawbacks : delay, analysis cst

14 Labratry issues (4/4) The disease-causing bacterium is present and culturable but... is present in very lw quantities Optimize lab enrichment / (re-)islatin methds if pssible Mlecular detectin f suspected pathgen(s) n unenriched sample Drawbacks : delay, analysis cst

15 Cnclusins Use f Critical AB in animal prductins strngly discuraged! very strict (unrealistic?) criteria (when AST is feasible) pssibly mre ciritical AB blacklisted in the future Time t prmte systematic lab (AST) supprt t (all) Ab treatments? Critical imprtance f «GVP /GLP»! Bacteria culturability is ne challenging labratry issue True pathgenic nature f a bacterium is anther ne Can mdern technlgies help? Whle Genme sequencing fr in silic AST (expert/ref labs s far) DNA micr-arrays fr rapid screening f AB RES genes Whle sample (micrbime) sequencing fr detecting pathgens and glbal «RESISTOME» Individual resistance prfiling (whenever traditinal r DNA based) still requires strain islatin

16 QUESTIONS? Natinal Reference Labratry fr Antimicrbial Resistance in animals at the Veterinary & Agrchemical Research Institute (CODA-CERVA) Scientists Analysts Bénédicte Callens Debrah Petrne Vicky Jassn Alexandru Radu Cécile Bland Tizian Fancell Jean-Baptiste Hann, Estelle Mérc, Sarah Welby 16

Worldwide initiative to control AMR and role of antimicrobial stewardship

Worldwide initiative to control AMR and role of antimicrobial stewardship GCCMID Dubai, May 2016 Wrldwide initiative t cntrl AMR and rle f antimicrbial stewardship U. Theuretzbacher Center fr Anti-Infective Agents, Vienna, Austria Extensively resistant Gram-negatives Percentage