White Paper: Bridging the gap between surveillance data and antimicrobial stewardship in the animal sector-practical guidance from the JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks

Whi e Pape : B idging he gap be ween su eillance da a and an imic obial s ewa dship in he animal sec o —p ac ical guidance om he JPIAMR ARCH and COMBACTE-MAGNET EPI-Ne ne wo ks Monica Comp i 1 †, Rodolphe Made 2 *†, Elena Mazzolini 3 †, Giulia de Angelis 4,5 , Nico T. Mu e s 6 , Ni hya Babu Rajend an 7,8 , Liliana Galia 1 , E elina Tacconelli 1,7,8 and Remco Sch ij e 9 on behal o he ARCH wo king g oup‡ 1 In ec ious Diseases Sec ion, Depa men o Diagnos ics and Public Heal h, Uni e si y o Ve ona, Ve ona, I aly; 2 Uni e si y o Lyon, F ench Agency o Food, En i onmen al and Occupa ional Heal h and Sa e y (ANSES), Labo a o y o Lyon, An imic obial Resis ance and Bac e ial Vi ulence Uni , Lyon, F ance; 3 Depa men o Epidemiology, Is i u o Zoop o ila ico Spe imen ale delle Venezie, Legna o, Padua, I aly; 4 Dipa imen o di Scienze Bio ecnologiche di base, Cliniche In ensi ologiche e Pe iope a o ie, Uni e si a` Ca olica del Sac o Cuo e, Rome, I aly; 5 Dipa imen o di Scienze di Labo a o io e In e i ologiche, Fondazione Policlinico Uni e si a io A. Gemelli IRCCS, Rome, I aly; 6 Ins i u e o Hygiene and Public Heal h, Bonn Uni e si y Hospi al, Bonn, Ge many; 7 In ec ious Diseases, Depa men o In e nal Medicine I, Tu¨bingen Uni e si y Hospi al, Tu¨bingen, Ge many; 8 Ge man Cen e o In ec ion Resea ch (DZIF), Clinical Resea ch Uni o heal hca e associa ed in ec ions, Tu¨bingen, Ge many; 9 Ve E ecT, Bil ho en, The Ne he lands *Co esponding au ho . E-mail: odolphe.made @anses. †Equally con ibu ing i s au ho s. ‡Membe s a e lis ed in he Acknowledgemen s sec ion. Backg ound: The JPIAMR ARCH and COMBACTE-MAGNET EPI-Ne ne wo ks ha e joined e o s o o mula e a se o a ge ac ions o link he su eillance o an imic obial usage (AMU) and an imic obial esis ance (AMR) wi h an imic obial s ewa dship (AMS) ac i i ies in ou di e en se ings. This Whi e Pape ocuses on he e e ina y se ing and emb aces he One Heal h app oach. Me hods: A e iew o he li e a u e was ca ied ou add essing esea ch ques ions in h ee a eas: AMS leade ship and accoun abili y; AMU su eillance and AMS; and AMR su eillance and AMS. Consensus on a ge ac ions was eached h ough a RAND-modi ied Delphi p ocess in ol ing o e 40 expe s in in ec ious diseases, clinical mic o- biology, AMS, e e ina y medicine and public heal h, om 18 coun ies. Resul s/discussion: Fo y-six a ge ac ions we e de eloped and quali ied as essen ial o desi able. Essen ial ac ions included he se up o AMS eams in all e e ina y se ings, building go e nmen -suppo ed AMS p o- g ammes and ollowing speci ic equi emen s on he p oduc ion, collec ion and communica ion o AMU and AMR da a. Ac i i ies o AMS eams should be ailo ed o he local si ua ion and capaci ies, and be linked o local o na ional su eillance sys ems and in ec ion con ol p og ammes. Se e al esea ch p io i ies we e also iden i- ied, such as he need o de elop mo e clinical b eakpoin s in e e ina y medicine. Conclusions: This Whi e Pape o e s a p ac ical ool o e e ina y p ac i ione s and policy make s o imp o e AMS in he One Heal h app oach, hanks o su eillance da a gene a ed in he e e ina y se ing. This wo k may also be use ul o medical doc o s wishing o be e unde s and he speci ici ies o he e e ina y se ing and a- cili a e c oss-sec o al collabo a ions. In oduc ion Ve e ina y and human medicine sha e he esponsibili y o p e- se ing he e icacy o an ibio ics and p e en ing he sp ead o an imic obial esis ance (AMR). To a la ge ex en , he an imic obial d ugs (o classes) ha a e used in animals a e he same as hose in human se ings 1–3 and esis an bac e ia can be ans e ed be ween animals, he en i onmen and humans h ough di e en ou es o ansmission. 1–4 This ende s AMR a One Heal h issue equi ing mul i-sec o al collabo a ions. 4–6 To p e en he sp ead o AMR, an imic obial s ewa dship (AMS) should be de eloped collec i ely in all se ings whe e an imic o- bials a e used as ‘a cohe en se o ac ions which p omo e using V CThe Au ho (s) 2020. Published by Ox o d Uni e si y P ess on behal o he B i ish Socie y o An imic obial Chemo he apy. This is an Open Access a icle dis ibu ed unde he e ms o he C ea i e Commons A ibu ion Non-Comme cial License (h p://c ea i ecom mons.o g/licenses/by-nc/4.0/), which pe mi s non-comme cial e-use, dis ibu ion, and ep oduc ion in any medium, p o ided he o iginal wo k is p ope ly ci ed. Fo comme cial e-use, please con ac [email p o ec ed] ii52 J An imic ob Chemo he 2020; 75 Suppl 2: ii52–ii66 doi:10.1093/jac/dkaa429 Downloaded om h ps://academic.oup.com/jac/a icle/75/Supplemen _2/ii52/6024992 by Uni e sidad de Se illa use on 19 July 2023 an imic obials esponsibly’. 7 Indeed, AMS in e en ions in one se - ing can ha e a posi i e impac in ano he , 5 and his is pa icula ly he case o he animal sec o , whe e in e en ions a e commonly ca ied ou wi h a public heal h pe spec i e. 1,8,9 Howe e , he speci ici ies o each se ing should always be ca e ully aken in o accoun when de ising an AMS p og amme. 10–14 The e e ina y sec o is highly he e ogeneous. Ve e ina ians can wo k as independen p i a e p ac i ione s (ac ing alone) o be o ganized in e e ina y clinics o hospi als wi h mul iple s a , ha can be owned by indi iduals o by na ional o mul ina ional e e - ina y heal hca e en e p ises. Ve e ina ians deal wi h di e en ani- mal species ha include companion animals, ood-p oducing animals and, al hough less commonly, wild animals. Ve e ina ians can p esc ibe and dispense an imic obials o a ious pu poses, i.e. ea men , me aphylaxis (adminis a ion o a d ug o a g oup o clinically heal hy animals in con ac wi h diseased animals), 15 p e en ion and g ow h p omo ion (whe e allowed) o indi idual animals o g oups o animals. 15–17 Access o an imic obials also di e s g ea ly be ween coun ies 18–20 and is some imes eadily a ailable wi hou any p esc ip ion o a me s o pe owne s, 21–23 leading o u he di icul ies in con olling an imic obial usage (AMU). Moni o ing AMU is impo an o quan i a i ely assess he pe - o mance o a Na ional Ac ion Plan (NAP) in educing he o e all use o an imic obials, o a ge in e en ions in animal species o p e en using unjus i ied amoun s o an imic obials and o check ha he e e ina y use o an imic obials c i ically impo an o human heal h is minimized. 24–26 When ca ied ou a he le el o p esc ip ion, i can become a benchma king ool whe e p esc ibe s, selle s o a me s can compa e hei an imic obial usage agains a egional a e age o a pa icula ood-p oduc ion sec o . 27–30 Al hough such sys ems may equi e speci ic legisla ion, hey can be use ul o educe AMU, especially when linked wi h incen i es o lowe usage o a ge ed in e en ions o high an imic obial use s. 31 I is no ewo hy ha NAPs on AMR, al hough ecom- mended by he Wo ld Heal h O ganiza ion (WHO) and WHO Membe S a es, a e no legally binding. This limi s he powe o NAPs as a go e nance ool. 32 In addi ion, i is key o moni o AMR in animal bac e ial pa ho- gens 33–35 o help e e ina ians and a me s use an imic obials mo e p uden ly, ollow AMR ends and ad ise ac ion a na ional o mo e local le els. Mo eo e , showing AMS eams and o he ac o s in animal heal h ha hei e o s succeed no only in dec easing AMU bu also AMR is necessa y o main ain hei commi men . In he One Heal h app oach i is also pa amoun o moni o AMR in zoono ic and commensal bac e ia 36,37 om heal hy animals o as- sess he isk o ansmission o humans h ough he ood chain (o by di ec con ac ), as his can lead o be e isk managemen in e en ions. 38 O no e, commensal bac e ia a e a use ul indica o o he compa ison o AMR a es o e ime and be ween di e en animal species, coun ies o a ms. Despi e a gene al call o de elop moni o ing sys ems ha a e able o p o ide ele an , accu a e and comple e da a o d i e AMS p og ammes in all se ings, including he animal sec o , many gaps s ill emain, along wi h many ha moniza ion challenges. Fo example, only agmen a y da a on AMU and AMR a e a ailable o companion and aqua ic animals. 39–42 Rega ding AMR da a, mos o he a ailable in o ma ion comes om heal hy e es ial ood-p oducing animals and ela i ely ew mul i-annual p og ammes a e in place o he moni o ing o AMR in animal pa hogens. 43–45 The complexi y o he e e ina y se ing (including i s in e - connec ions wi h he human sec o , he a ying pu poses o su eillance sys ems 26,46,47 and he non-homogeneous a ailabili y o su eillance da a and esou ces a ound he wo ld 48,49 ) make many ac i i ies di icul o s anda dize. Thus, p ac ical de ails a e no a ailable o many AMS ac i i ies, and indica ions on how su eillance da a should in e wine wi h AMS in e en ions a e lacking. The JPIAMR ARCH 50 and COMBACTE-MAGNET EPI-Ne 51 ne - wo ks ha e come oge he o he sha ed goal o implemen ing a amewo k o ac ions o acili a e an ibio ic policy in e en ions and os e use o su eillance da a on AMR and consump ion and implemen a ion o AMS ac i i ies inhuman and animal heal h. In his ega d, he ARCH and COMBACTE-MAGNET EPI-Ne in e na ional expe panel is ocusing on ou se ings: hospi al, ou pa ien , long- e m ca e acili y, and e e ina y. The e o s in- ol e h ee a eas: (i) AMS leade ship and accoun abili y; (ii) AMU and AMS; and (iii) AMR and AMS, all conside ing he easibili y o he ac ions and he One Heal h app oach. This Whi e Pape ocuses on he e e ina y sec o and a ge s e e ina ians, policymake s and o he ac o s in animal and human heal h who a e in ol ed in AMS ac i i ies. The p oposed guidance is in ended as a p ac ical ool ega ding he p oduc ion and use o AMU and AMR da a o plan and implemen AMS p og ammes in line wi h he One Heal h app oach and applicable in di e en e e ina y con ex s, including esou ce-limi ed coun ies. Dissemina ion o he in ended audience will be ensu edby he ne - wo ks in ol ed in he JPIAMR ARCH p ojec as lis ed in Table 1o he i s pape in his se ies. 52 Checklis o ma s o he a ge ac ions a e downloadable om he ARCH websi e. 50 These check- lis s can be used by heal h p o essionals and policymake s o es ablish and/o moni o s ewa dship ac i i ies. Me hods Adop ing a One Heal h app oach, he p esen p ojec was planned o de- elop expe consensus conside ing he li e a u e and guidance on AMS and su eillance. A i s d a o a ge s and a RAND-modi ied Delphi p o- cess we e used o alida ion o a ge s (p o ocol on ARCH websi e). 50 The p ocess in ol ed de elopmen o key esea ch ques ions a ising om a sys ema ic e iew on su eillance epo ing o AMR ha was p e iously de eloped (EPI-Ne COACH p ojec ) 53 and adap ed o a e e - ina y se ing (Table 1); a na a i e e iew o he a ailable e idence was pe o med, and a i s d a o a ge s was p o ided o he expe s in a web-based su ey. Ag eemen was exp essed on a nine-poin Like scale. A 2 day ace- o- ace mee ing ook place a he end o Oc obe 2019. A li e a u e sea ch o ele an publica ions in English, published in he las 10 yea s, was ca ied ou using MEDLINE (Na ional Lib a y o Medicine, Be hesda, MD, USA) using a combina ion o he ollowing e ms: an imic obial*, consump ion, animal*, e e ina y, an imic obial d ug esis ance, su eillance. Mo e de ails a e a ailable in he i s pape in his se ies. 52 Du ing he mee ing, he expe s we e p esen ed wi h a summa y o he a ailable e idence and he esul s o he online su ey. The en i e se o a ge s was e iewed and discussed. Following he mee ing, a co e eam (M.C., E.M., R.M., R.S.) o he e e ina y wo king g oup pe o med a u he e ision and ine- uning o he lis o a ge s, which was hen app o ed by he en i e panel in an addi ional consul a ion. To co e all di e en e e in- a y ea u es and ela ed in e connec ions wi h human heal h, di e en An imic obial su eillance and s ewa dship in he animal sec o JAC ii53 Downloaded om h ps://academic.oup.com/jac/a icle/75/Supplemen _2/ii52/6024992 by Uni e sidad de Se illa use on 19 July 2023 se ings ( a ms, e e ina y clinics, e c.) and animal popula ions (companion and ood-p oducing animals, including aqua ic animals) we e conside ed. Recommenda ions, s a e o he a , and o iginal app oaches we e e alua ed by ocusing on easibili y and adap abili y o di e en economic and e e ina y con ex s o compile a lis o ‘essen ial’ and ‘desi able’ a ge s. Ta ge s we e ecognized as ‘essen ial’ when widely p ac icable i no al eady b oadly accomplished, and ‘desi able’ in he case o limi ed easibili y o ha ing a esou ce-in ensi e na u e. Topics o which mo e e idence was equi ed in o de o d aw up ecommenda ions we e added as p io i y opics o u he esea ch. O e 40 expe s om 18 coun ies and ep esen ing 30 ne wo ks de el- oped he p o ocol, con ibu ed o eaching a consensus and app o ed he inal lis o indica ions (see i s pape in his se ies). 52 Resul s A o al o 49 guidance documen s (23 in e na ional and 26 na ion- al documen s) and 45 a icles including sys ema ic e iews, s ud- ies and expe opinions we e included o he ull e idence app aisal. 1,3,4,8–17,19,20,22,24,27,28,31,33,34,36–38,40,41,46–48,54–117 In e - na ional and na ional guidelines, p ac ical guides o ools, su eillance epo s and sys ema ic e iews p o ided mos o he e idence. The majo i y o he documen s (71/94, 76%) we e om high-income coun ies (Eu ope, No h Ame ica, Aus alia and New Zealand). Fo wo esea ch ques ions (‘Should he epo se speci ic h esholds o es ablishing empi ical he apy and su gical p ophy- laxis?’ and ‘Which c i e ia should be used o d i e selec i e epo - ing o an ibiog ams?’), he in o ma ion did no allow d a ing o speci ic a ge s, and hus hese opics we e add essed as u u e esea ch a eas. An ini ial se o 65 a ge s was de eloped based on e ie ed documen s and assessed by eigh expe s in he ield o human and e e ina y medicine h ough he online su ey. Consensus was eached on 54 a ge s, and addi ional commen s we e p o- ided o mos o hem. Ele en a ge s, whe e he ag eemen was no eached a e i s consul a ion, we e discussed in he mee ing. Main opics o discussion e ol ed a ound: (i) he o ganiza ion o AMS conside ing pa icipan s and oles o he AMS eam and ins i u ional suppo ; (ii) bac e ial species o moni o conside ing human and animal heal h; and (iii) how o deal wi h he lack o clinical b eakpoin s o implemen AMS ac i i ies. Nine a ge s we e dele ed du ing he mee ing. All o he a ge s we e econside ed and p oposed o eph asing (some we e me ged o spli ) o addi ional e alua ion ollowing he sugges ions o he panel. A e he mee ing, a lis o 46 e ised a ge s (25 essen ial and 21 desi able) was d a ed by he co e g oup and app o ed by he en i e expe panel. Tables2–4, espec i ely, lis he ecommended a ge s o AMS leade ship and accoun abili y, AMU and AMS, and AMR and AMS. Tables 5–8 e e o he s a emen s o Tables 2–4. Discussion In e es ingly, AMS leade ship and accoun abili y in he animal sec- o was one o he main opics o discussion du ing he mee ing. This may e eal ha mo e e o s ha e been made o de elop AMR and AMU su eillance sys ems in compa ison wi h e o s o s uc- u ing and guiding AMS ac i i ies in e e ina y p ac ices. Al hough p elimina y ag eemen was eached o all p oposed a ge s bu one wi hin he online su ey, commen s and sugges ions we e p o ided du ing he consul a ions ha equi ed u he e alua ion. This is likely due o he b oad he e ogenei y o he e e ina y sec o conside ing animal species, animal popula ions ( ood-p oducing animals including aquacul u e and companion animals) and he a ious con ex s whe e animal heal hca e is p o ided ( a ms, small e e ina y clinics, la ge hospi als, e c.). The expe g oup is awa e ha he desi able composi ion o he AMS eam desc ibed is o en no easible, bu he ac ion poin aims o de ine he bes op ions when es ablishing an AMS eam. Ve y o en, he eam may be composed o only a a me and his/he e e ina ian, wo king oge he o a ionalize AMU. Howe e , o la ge clinics and a ming indus ies ha ha e hei own pha ma- cies and labo a o ies, he composi ion o he AMS eam could come close o wha is ecommended. 10,12,54,99,100 Deba es also a ose ega ding he ole o animal owne s. Al hough pe owne s a e esponsible o he adminis a iono an i- mic obial ea men s o hei animals, i is no ealis ic o include hem in AMS eams. On he o he hand, a me s (and also b eede s o ho ses o companion animals), who a e p o essional animal keepe s, do bea esponsibili y o he p uden use o an ibio - ics 11,55,56 and ha e a majo ole o play in AMS. 4,19,90 S ill, pe own- e s should be a ge ed by educa ional ac i i ies o os e he Table 1. Key ques ions o he e e ina y se ing 1. Leade ship commi men , accoun abili y and an imic obial s ewa d- ship eam - Pa icipan s in he an imic obial s ewa dship eam - Ta ge s o an imic obial s ewa dship (e.g. is an imic obial s ewa dship a ge ed o diseased animals?) - Ins i u ional suppo o o ganiza ion and managemen o an imic obial s ewa dship p og ammes: legal amewo k - Ins i u ional suppo o o ganiza ion and managemen o an imic obial s ewa dship p og ammes: s a ing pe sonnel 2. An imic obial usage and an imic obial s ewa dship - Which an ibio ics should be moni o ed? - Which me ics should be employed o moni o ing an imic obial usage? - Should he su eillance speci y he pu pose o an imic obial usage? - Which c i e ia o epo ing and ime in e al should be used? - Who should be he end use o he epo ? - Should a es ic i e policy be adop ed? - Should a anking o an ibio ic use be adop ed? 3. An imic obial esis ance and an imic obial s ewa dship - Which c i e ia a e needed o a ge esis an pa hogens? - How should esis ance be moni o ed? - Which p e alence da a and selec i e moni o ing sc eening should be conside ed? - Which c i e ia o epo ing and ime in e al should be used? - Which c i e ia should be applied o s a i y he esul s? - Who should be he end use o he epo ? - Should he epo se speci ic h esholds o es ablishing empi ical he apy and su gical p ophylaxis? - Which c i e ia should be used o d i e selec i e epo ing o an ibiog ams? Comp i e al. ii54 Downloaded om h ps://academic.oup.com/jac/a icle/75/Supplemen _2/ii52/6024992 by Uni e sidad de Se illa use on 19 July 2023 app op ia e use o an imic obials, along wi h e e ina ians, a me s and o he ac o s in animal heal h. 13,58,101,118 AMS should be implemen ed om he local o he global le el, spanning human heal h, animal heal h and he en i on- men . 2,12,58,119 The e o e, e en in he e e ina y se ing, AMS should be de ised and suppo ed a a highe le el, especially by go e nmen s and indus y 57,59,60,110 in he o m o NAPs and good p ac ice cha e s. These should ecommend measu es o educe AMR and p o ide guidance o AMS eams in he ield. Se ing a ge s o educ ion, 61,62 as well as es ic ing AMU in ani- mals, 9,41,63,104 has been shown o be e y e ec i e in se e al coun- ies. 120 To os e AMS, go e nmen s should suppo AMU and AMR moni o ing sys ems. 39,58,59,113 Mo e b oadly, ins i u ional suppo is c ucial in e ms o communica ion and p og ess epo ing, and o ensu e anspa ency o in o ma ion on bo h AMU and AMR. The e mus also be suppo o any olun a y app oaches, p o ided hey a e in line wi h go e nmen policy. 60 Fo example, indus y ini ia i es o es ic he use o some an imic obial classes ha e been shown o be e icien a educing esis ance a es 120,121 and should be encou aged. The de elopmen o quali y policies in e e ina y clinics wi h a dedica ed componen on AMS ac i i ies should also be p omo ed. The design o AMU o AMR moni o ing sys ems should depend on hei objec i es, exis ing con ex s and capaci ies, and be consis en wi h na ional guidelines, i any. 14,48 Howe e , exis ing policies on access and use o an imic obials may di e subs an ial- ly among coun ies. 19,21,22,42,56 A e e ina y p esc ip ion may o may no be compulso y, impai ing he a ailabili y o he d-le el benchma king. Addi ionally, he lack o na ional legisla ions/ egu- la ions s ill pe mi s some coun ies o use an imic obials as g ow h p omo e s, 17,18,122 al hough his p ac ice is s ongly discou aged by in e na ional o ganiza ions, including he WHO, 1 he Wo ld O ganisa ion o Animal Heal h (OIE), 123 and Eu opean legisla- ion. 15 To help in hei design, ankings o an imic obials om in e - na ional o ganiza ions can be used (WHO, OIE, EMA), in pa icula ca ego iza ions ha conside he isk ha animal usage o an imi- c obials may pose o public heal h in he One Heal h app oach. 9 The consensus be ween expe s ega ding AMU s a emen s was easily achie ed, likely due o he nume ous e o s ha ha e al eady been es ablished in his ield, namely in he amewo k o he Eu opean Su eillance o Ve e ina y An imic obial Consump ion (ESVAC). I usage o all an imic obials canno be moni o ed, as would be desi able, 64 a ge ing speci ic animal species and an imic obial classes is p e e ed. A majo issue is ha AMU da a can be collec ed in di e en ways. 26,28,40,92 When possible, p esc ip ions and, e en be e , animal adminis a ion da a should be collec ed om e e ina ians and a me s as hese p o ide he mos accu a e da a on AMU (when p ope ly eco ded) and allow benchma king. 27,36,62,112 I his is no possible, sales da a may be collec ed om pha maceu ical companies. 26,65,66 Table 2. Leade ship commi men , accoun abili y and an imic obial s ewa dship eam An imic obial s ewa dship p og amme and eam 1.1. Essen ial An imic obial s ewa dship p og ammes should be in place in e e y se ing whe e an imic obials a e used o ea ood-p oducing o companion ani- mals, wi h a ge s and in e en ions ailo ed o he local si ua ion and linked o local and na ional su eillance sys ems and in ec ion con ol p og ammes. 1.2. Essen ial An imic obial s ewa dship p og ammes should be de ined, planned, implemen ed and e alua ed by a dedica ed and compe en eam. This eam should be ailo ed, depending on he animal species and p oduc ion ype, o he local con ex and a ailabili y o esou ces and pe sonnel. 1.3. Desi able The eam should include a e e ina ian compe en in an imic obial s ewa dship and ep esen a i es o all p o essionals in ol ed in animal ca e (pa a- e e ina ians, e e ina y nu ses, a me s, e e ina y pha macis s, mic obiologis s om diagnos ic labo a o ies, e c.) in a collabo a i e ap- p oach, unde he leade ship o he e e ina ian. This eam should seek p o essional ad ice om addi ional expe s when needed o adequa ely ul il hei an imic obial s ewa dship ac i i ies. Ins i u ional suppo o o ganiza ion and managemen o an imic obial s ewa dship p og ammes 1.4. Essen ial An imic obial s ewa dship p og ammes should be suppo ed a he go e nmen al le el h ough amewo ks such as he Na ional Ac ion Plan in line wi h ele an in e na ional s anda ds. The Na ional Ac ion Plan should include egula o y decisions o es ic he usage o an imic obials in ood- p oducing and companion animals, se speci ic educ ion a ge s o an imic obial usage and es ablish moni o ing sys ems o an imic obial usage and an imic obial esis ance. 1.5. Desi able Su eillance da a on an imic obial usage and an imic obial esis ance should be made eely a ailable o local an imic obial s ewa dship eams, as well as o all o he p o essionals wo king in animal, human o en i onmen al heal h. 1.6. Desi able Volun a y app oaches o imp o e an imic obial s ewa dship and su eillance in he animal sec o should be encou aged, e.g. when he a ming in- dus y adop s i s own measu es o inc ease biosecu i y, in ec ion con ol and educe an imic obial usage. An imic obial su eillance and s ewa dship in he animal sec o JAC ii55 Downloaded om h ps://academic.oup.com/jac/a icle/75/Supplemen _2/ii52/6024992 by Uni e sidad de Se illa use on 19 July 2023 Table 3. An imic obial usage and an imic obial s ewa dship Which ypes o an imic obial usage, animal species and an imic obials should be moni o ed? 2.1. Essen ial An imic obial usage should be moni o ed wha e e he pu pose o an imic obial adminis a ion. This includes g ow h p omo ion, a p ac ice ha should be discou aged. 2.2. Essen ial An imic obial usage should be moni o ed in ood-p oducing (including aqua ic) and companion animals. 2.3. Desi able An imic obial usage should be moni o ed o all animals o which an imic obials a e au ho ized in a coun y. 2.4. Essen ial I na ional moni o ing o an imic obial usage including all an imic obials is no easible, a isk-based app oach should be p omo ed o a ge moni o ing o he mos ele an an ibio ics o animal and/o human heal h and only wi hin he mos impo an animal species in a coun y o egion. 2.5. Essen ial The choice o an imic obials o be moni o ed should be guided by he Wo ld Heal h O ganiza ion (WHO) anking o c i ically impo an an imic obials, by he Wo ld O ganisa ion o Animal Heal h (OIE) lis o an imic obial agen s o e e ina y impo ance and by speci ic ankings o isk o public heal h om an imic obial e- sis ance due o he use o an imic obials in e e ina y medicine (example in Table 5). Which me ics should be employed? 2.6. Essen ial An imic obial usage should be moni o ed a leas a he coun y le el, o all o selec ed combina ions o animal species and an imic obials. 2.7. Desi able An imic obial usage should be moni o ed a he le el o each p esc ip ion, sale o animal adminis a ion, such as e e ina y clinics, pha macies and a ms, o all o selec ed combina ions o animal species and an imic obials. 2.8. Essen ial Sales da a a e he minimum ha should be p o ided o all o selec ed combina ions o animal species and an imic obials, in kilog ams o ac i e ing edien o all animals and in millig ams pe popula ion co ec ion uni (PCU) o ood-p oducing animals. 2.9. Desi able When da a a e a ailable on p esc ip ions, sales and animal adminis a ion, he amoun o o e all usage should be s anda dized acco ding o animal p oduc ion and an imic obial daily doses o an imic obial ea men cou se. Which da a and s a i ica ion c i e ia should be adop ed? 2.10. Desi able Addi ional da a should be collec ed as pa o an an imic obial usage moni o ing such as age, p oduc ion ype, ou e o adminis a ion o ea men ype ( he apy, me aphylaxis, p ophylaxis o g ow h p omo ion). The da a analysis should be s a i ied acco ding o hese addi ional da a. Which c i e ia o ime in e al and epo ing should be used? 2.11. Essen ial An imic obial usage da a should be epo ed annually. 2.12. Essen ial Su eillance da a on an imic obial usage should be epo ed a he na ional le el. 2.13. Desi able Su eillance da a on an imic obial usage should be epo ed a he local le el. 2.14. Essen ial All me hods used o p o ide an imic obial usage da a should be clea ly desc ibed. 2.15. Desi able An imic obial usage and an imic obial esis ance da a in he animal sec o should be analysed, in e p e ed and epo ed in he same epo . In he One Heal h ap- p oach, his epo should also include da a on an imic obial usage and an imic obial esis ance om he human sec o . 2.16. Desi able The epo should include an English e sion o os e easie sha ing o in o ma ion be ween coun ies. Who should be he end use o he epo ? 2.17. Essen ial The end use s o epo s on an imic obial usage should be an imic obial s ewa dship eams and all o he s akeholde s in animal, human and en i onmen al heal h a he local, ins i u ional o indus y le el. 2.18. Desi able The epo should be eely a ailable online o anyone and include a summa y ha is unde s andable o he gene al public. Comp i e al. ii56 Downloaded om h ps://academic.oup.com/jac/a icle/75/Supplemen _2/ii52/6024992 by Uni e sidad de Se illa use on 19 July 2023 Table 4. An imic obial esis ance and an imic obial s ewa dship Which animal species and esis an bac e ia should be a ge ed? 3.1. Essen ial An imic obial esis ance should be moni o ed in ood-p oducing (including aqua ic) and companion animals. 3.2. Essen ial The a ge esis an bac e ia should be animal pa hogens, bu also zoono ic pa hogens and commensals in he One Heal h app oach. 3.3. Essen ial OIE c i e ia should be ollowed o he choice o animal pa hogenic bac e ia o moni o (Table 6). Examples om OIE in e es ial ood-p oducing ani- mals a e p o ided in Table 7. 3.4. Desi able In companion animals, a ge pa hogenic bac e ia may include me hicillin- esis an S aphylococcus au eus (MRSA) and me hicillin- esis an S aphylococcus pseudin e medius om skin samples and Esche ichia coli om u ine samples, conside ing hei impo ance o animal heal h and he zoono ic po en ial o MRSA. 3.5. Essen ial Selec ion c i e ia o he oodbo ne zoono ic and commensal bac e ia o include in an an imic obial esis ance in eg a ed su eillance p og amme should depend on public heal h p io i ies, an imic obial use p ac ices and he es ima es o he bu den o oodbo ne illnesses, as s a ed by WHO (Table 8). 3.6. Essen ial The choice o an imic obials o moni o should be guided by he WHO anking o c i ically impo an an imic obials, by he OIE lis o an imic obial agen s o e e ina y impo ance and by speci ic ankings o isk o public heal h om an imic obial esis ance due o he use o an imic obials in e e ina y medicine (example in Table 5). How should esis ance be moni o ed? 3.7. Essen ial Fo animal pa hogenic bac e ia, samples should o igina e om diseased o dead animals. 3.8. Essen ial Fo indica o and zoono ic bac e ia om ood-p oducing animals, samples should be aken om heal hy animals o de ined age. 3.9. Essen ial S anda dized and in e na ionally ecognized an imic obial suscep ibili y es ing me hods should be used. 3.10. Desi able To suppo ield an imic obial s ewa dship eams and p o ide ecommenda ions o an imic obial he apy in e e ina y se ings, clinical b eakpoin s should be used o in e p e an imic obial suscep ibili y es ing esul s. I no a ailable, epidemiological cu -o alues may be used. When he ob- jec i e is o de ec dec eased suscep ibili y (i.e. o display a mic obiological esis ance), epidemiological cu -o s should be used. 3.11. Desi able Quan i a i e da a (MICs o inhibi ion zone diame e s) should be collec ed a he han in e p e ed da a (suscep ible/in e media e/ esis ance o wild ype/non-wild ype). 3.12. Desi able Speci ic moni o ing schemes may be pe o med in heal hy animals and ood he eo using selec i e media, e.g. o de ec he p esence ESBL/AmpC, ca bapenemase-p oducing, colis in- esis an En e obac e ales, MRSA o ancomycin- esis an en e ococci o assess public heal h isk. 3.13. Desi able Resis ance mechanisms should be cha ac e ized a he molecula le el, e.g. using he polyme ase chain eac ion, sequencing o whole-genome sequencing o colis in- esis an ESBL/AmpC- and ca bapenemase-p oducing En e obac e ales. Which da a and s a i ica ion c i e ia should be adop ed? 3.14. Desi able Addi ional da a should be collec ed as pa o an imic obial esis ance moni o ing, such as age, p oduc ion ype and specimen, and i he an imic o- bial suscep ibili y es ing was eques ed due o a p e ious an imic obial ea men ailu e. The analysis should be s a i ied acco ding o hese add- i ional da a. Con inued An imic obial su eillance and s ewa dship in he animal sec o JAC ii57 Downloaded om h ps://academic.oup.com/jac/a icle/75/Supplemen _2/ii52/6024992 by Uni e sidad de Se illa use on 19 July 2023 Howe e , such da a ha e a numbe o limi a ions, such as lack o in o ma ion on he animal species, ca ego ies (adul e sus young animal) o be ea ed and scope o ea men s. Rega ding he moni o ing o AMR, he online su ey highligh ed se e al a eas o only pa ial ag eemen , such as he bac e ia o be moni o ed. This is likely due o he complexi y o AMR moni o ing in he animal sec o , as bo h animal and public heal h need o be conside ed. The di e ences in design possibili ies o AMU also apply o he moni o ing o AMR, 34,35,46,67,124 especially since i should be done o animal bac e ial pa hogens o help in he de el- opmen o empi ical he apy ecommenda ions in he e e ina y se ing, 10,34,47,49 and o zoono ic and commensal bac e ia in he One Heal h app oach. 35,36,55,68,97 This leads o e y di e en sampling schemes: passi e moni o ing in diseased animals o animal pa hogens and ac i e moni o ing in heal hy animals o commensal and zoono ic bac e ia. Moni o ing sys ems may ely on pheno ypic iden i ica ion o esis ance,bu molecula iden i ica- ion o AMR de e minan s b ings mo e accu a e insigh s in o he epidemiology o esis ance genes, 36,48,58,69 especially be ween he animal and human sec o s, and can gene a e be e isk- managemen measu es. A speci ic challenge ha applies o he ansla ion o AMR su - eillance da a in o AMS ac ions is he lack o clinical b eakpoin s o in e p e an imic obial suscep ibili y es ing (AST) esul s o many combina ions o animal species, bac e ial species and clinical o m. The la ge majo i y o exis ing b eakpoin s we e p oduced by he CLSI. 125 In 2019, he Ve e ina y Commi ee on An imic obial Suscep ibili y Tes ing (Ve CAST) o he EUCAST p oposed i s i s clinical b eakpoin s. 126 Howe e , de eloping clinical b eakpoin s is a long and di icul p ocess, and i is unlikely ha many o he miss- ing ones will be de e mined in he sho e m. When no b eakpoin is a ailable, epidemiological cu -o s (ECOFFs) can be used as an al e na i e. 36,108,114 Howe e , ECOFFs de ec dec eased suscep i- bili ies and, as such, a e no p ope indica o s o clinical esis - ance. 46,115 When using ECOFFs ins ead o clinical b eakpoin s, esis ance a es can be o e es ima ed, so one should be cau ious when p o iding ea men ecommenda ions based on hem. 46 Indeed, using ECOFFs mus no lead o w ongly ecommending he p esc ip ion o c i ically impo an an imic obials when olde d ugs emain clinically e icien . Because in e p e a i e c i e ia, ei he clinical b eakpoin s o ECOFFs, can change o e ime, i is impo an o collec and epo on quan i a i e da a (inhibi ion diame e s o MICs) o enable he ecalcula ion o esis ance a es in his o ical da a and s ill be able o analyse ends. 33,36,46,69,115 To ensu e ha AMR and AMU moni o ing sys ems se e AMS in he One Heal h app oach, i is key o epo da a join ly wi h hose o AMU and AMR in o he sec o s, especially he human one. 36,48,60 This p e en s he p o ision o a agmen ed pic u e o he AMR si u- a ion and acili a es a ecip ocal unde s anding be ween ac o s ha need o collabo a e o imp o e AMS. Howe e , c oss-sec o al da a analysis o AMU and AMR da a is complex and equi es p uden in e p e a ion. This is why expe s should always seek o summa ize he esul s in a o ma ha is unde s andable by all s akeholde s in animal, public and en i onmen al heal h, as well as by he gene al public. 48 Table 4. Con inued Which c i e ia o ime in e al and epo ing should be used? 3.15. Essen ial The ime in e al o epo ing esis ance da a should be annual, bu eme ging esis ances should be epo ed in as imely a ashion as possible. 3.16. Essen ial Su eillance da a on an imic obial esis ance should be epo ed a he na ional le el. 3.17. Desi able Su eillance da a on an imic obial esis ance should be epo ed a he local le el. 3.18. Essen ial All s anda ds and guidance documen s used o bac e ial isola ion, bac e ial iden i ica ion and an imic obial suscep ibili y es ing should be clea ly desc ibed. 3.19. Desi able An imic obial usage and an imic obial esis ance da a in he animal sec o should be analysed, in e p e ed and epo ed in he same epo . In he One Heal h app oach, his epo should also include da a on an imic obial usage and an imic obial esis ance om he human sec o . 3.20. Desi able The epo should include an English e sion o os e easie sha ing o in o ma ion be ween coun ies. Who should be he end use s o he epo ? 3.21. Essen ial The end use s o epo s on an imic obial esis ance should be an imic obial s ewa dship eams and all o he s akeholde s in animal, human and en- i onmen al heal h a he local, ins i u ional o indus y le el. 3.22. Desi able The epo should be eely a ailable online o anyone and include a summa y ha is unde s andable o he gene al public. Comp i e al. ii58 Downloaded om h ps://academic.oup.com/jac/a icle/75/Supplemen _2/ii52/6024992 by Uni e sidad de Se illa use on 19 July 2023 Fu he opics we e explo ed and add essed as esea ch a eas du ing consul a ions. Al hough planning dedica ed ime and allo- ca ing speci ic measu es o AMS eams a e essen ial o AMS ac i - i ies, de ailed in o ma ion on he minimum equi emen s o pe sonnel acco ding o he asks o AMS p og ammes a e lacking in he li e a u e. Addi ionally, he lack o clinical b eakpoin s o many an imic obials o many animal species emains an impo - an limi a ion o he in e p e a ion o AST and o guide p uden use o an imic obials. This ep esen s he main issue ha mus be add essed o imp o e AMS ac i i ies. Due o he lack o a ailable documen s e ie ed o wo key ques ions and ollowing he nu- me ous discussions among he panel, addi ional opics we e con- side ed as impo an u u e esea ch a eas ha should be in es iga ed and could complemen he cu en checklis . The main esea ch p io i ies a e summa ized in Table9. To ou knowledge, his is he i s ime ha a consensus om an in e na ional g oup o e e ina y and medical expe s has been eached in he e e ina y se ing ega ding AMS leade ship and ac- coun abili y, as well as on he AMU and AMR in o ma ion ha moni- o ing sys ems should p o ide in he animal sec o o suppo AMS Table 5. Ca ego iza ion o an imic obials conside ing he isk o public heal h om hei usage in e e ina y medicine due o an imic obial esis ance, by he An imic obial Ad ice Ad Hoc Expe G oup (AMEG) om he Eu opean Medicines Agency (EMA) 9 Ca ego y Lis o d ugs Ca ego y A ‘A oid’ •Aminopenicillins •Ca bapenems •O he cephalospo ins (o he han 1s , 2nd, 3 d and 4 h gene a ion) and penems (ATC code J01DI), including combina ions o 3 d-gene a ion cephalospo ins wi h b-lac amase inhibi o s •Glycopep ides •Glycylcyclines •Ke olides •Lipopep ides •Monobac ams •Oxazolidinones •Penicillins (ca boxypenicillins and u eidopenicillins, including combina ions wi h b-lac amase inhibi o s) •Phosphonic acid de i a i es •Pseudomonic acid •Ri amycins (excep i aximin) •Rimino enazines •S ep og amins •Sul ones •D ugs used solely o ea ube culosis o o he mycobac e ial diseases •Subs ances newly au ho ized in human medicine ollowing publica ion o he AMEG ca ego iza ion Ca ego y B ‘Res ic ’ •3 d- and 4 h-gene a ion cephalospo ins, excep combina ions wi h b-lac amase inhibi o s •Polymyxins •Quinolones ( luo oquinolones and o he quinolones) Ca ego y C ‘Cau ion’ •Aminoglycosides (excep spec inomycin) •Aminopenicillins in combina ion wi h b-lac amase inhibi o s •Amphenicols •1s - and 2nd-gene a ion cephalospo ins and cephamycins •Mac olides (no including ke olides) •Lincosamides •Pleu omu ilins •Ri amycins ( i aximin only) Ca ego y D ‘P uden ’ •Aminopenicillins wi hou b-lac amase inhibi o s •Cyclic polypep ides •Ni o u an de i a i es •Ni oimidazoles •Penicillins (an is aphylococcal penicillins and na u al penicillins) •Aminoglycosides (spec inomycin only) •S e oid an ibac e ials •Sulphonamides, dihyd o ola e educ ase inhibi o s and combina ions •Te acyclines An imic obial su eillance and s ewa dship in he animal sec o JAC ii59 Downloaded om h ps://academic.oup.com/jac/a icle/75/Supplemen _2/ii52/6024992 by Uni e sidad de Se illa use on 19 July 2023 ac i i ies in he One Heal h app oach. The ini ial s ep o he li e a u e e iew was use ul in guiding g oup discussions and inding ag ee- men . Howe e , he subjec i e na u e o he expe s’ opinions and he small numbe o pa icipan s emain limi a ions o he app oach. A majo s eng h o his documen is ha i p o ides p ac ical andconcise indica ions o AMS eams in he ield, bu also o ins i- u ions wishing o suppo AMS om a highe le el, especially when i ela es o he p oduc ion o AMR and AMU da a ha a e ele an o p esc ibe s, selle s and use s o an imic obials in ani- mals. These indica ions a e also use ul o medical doc o s wishing o be e unde s and he speci ici ies o he e e ina y sec o in e ms o su eillance and AMS, especially as some ac i i ies a e designed wi h a public heal h pe spec i e. This wo k also enabled he iden i ica ion o se e al impo an u u e esea ch a eas o a- cili a e he de elopmen o AMS p og ammes and he ansla ion o AMR su eillance da a in o p uden use o an imic obials in he e e ina y se ing. Howe e , due o he di e si y and complexi y o he e e ina y sec o , along wi h he ac ha di e se economic con ex s we e conside ed, many a ge s o he checklis a e a he gene ic and need o be adap ed o each speci ic con ex . In his scena io, he indica ions gi en he ein ep esen a i s s ep o be - e s uc u e AMS ac i i ies in he animal sec o . Conclusions A lis o essen ial and desi able a ge s was p oduced ollowing de- elopmen o consensus be ween expe s om bo h medical and Table 6. OIE c i e ia o be conside ed in he choice o animal bac e ial pa hogens o inclusion in an AMR moni o ing p og amme a •Impac on animal heal h and wel a e •Implica ion o an imic obial esis ance o he animal bac e ial pa hogen on he apeu ic op ions in e e ina y p ac ice •Impac on ood secu i y and on p oduc ion (economic impo ance o associa ed diseases) •Bac e ial diseases esponsible o he majo i y o e e ina y an imic obial usage (s a i ied by usage o di e en classes o hei impo ance) •Exis ence o alida ed suscep ibili y es ing me hodologies o he bac e ial pa hogen •Exis ence o quali y assu ance p og ammes o o he pa hogen- educ ion op ions ha a e non-an imic obial, such as accines and Good Ag icul u al P ac ices a Adap ed om Table 2o e e ence 33. Table 7. OIE example o bac e ial pa hogens in e es ial ood-p oducing animals o include in an AMR moni o ing p og amme a Species Respi a o y pa hogens En e ic pa hogens O he pa hogens Ca le Pas eu ella mul ocida, Mannheimia haemoly ica Esche ichia coli, Salmonella spp. Udde pa hogens b , such as S aphylococcus au eus, S ep ococcus spp. Pigs Ac inobacillus pleu opneumoniae Esche ichia coli, Salmonella spp. S ep ococcus suis Poul y – Salmonella spp. Esche ichia coli a Adap ed om in o ma ion in e e ence 33. b Re e s o pa hogens causing mas i is (mamma y gland in ec ion). Table 8. Foodbo ne and indica o bac e ia o include in an AMR moni o ing p og amme •In e es ial ood-p oducing animals, zoono ic bac e ia ypically include Salmonella spp. and Campylobac e spp. om caecal samples •In e es ial ood-p oducing animals, indica o bac e ia (animal commensal bac e ia as po en ial ese oi o d ug esis ance genes) ypically in- clude Esche ichia coli and en e ococci om caecal samples •O he bac e ia (e.g. me hicillin- esis an S aphylococcus au eus, Clos idioides spp. and Lis e ia monocy ogenes om e es ial ood-p oducing ani- mals o Vib io pa ahaemoly icus and Salmonella spp. om aquacul u e p oduc ion) may be included acco ding o he epidemiology o oodbo ne diseases in he a ea Comp i e al. ii60 Downloaded om h ps://academic.oup.com/jac/a icle/75/Supplemen _2/ii52/6024992 by Uni e sidad de Se illa use on 19 July 2023