antibiotic resistance in foodborne pathogens · antibiotic resistance in foodborne pathogens page 2...

ANTIBIOTIC RESISTANCE IN FOODBORNE PATHOGENS

MAY 2013

ACSPIWhitePaperbyCarolineSmithDeWaal,J.D.,andSusanVaughnGrooters,M.P.H.


AntibioticResistanceinFoodborneOutbreaks,2013,wasresearchedandwrittenbyCarolineSmithDeWaalandSusanVaughnGrooters.WegratefullyacknowledgetheassistanceofMarcusGlassman,AngelaKraszewski,CindyRoberts,andMichaelF.Jacobsoninpreparingthisreport.Wealsowouldliketoacknowledgethoseworkinginstateandfederalpublichealthagencieswhoprovidedinformationandinspirationforthisreport.

CenterforScienceinthePublicInterest(CSPI)isanon‐profitorganizationbasedinWashington,DC.Since1971,CSPIhasbeenworkingtoimprovethepublic’shealth,largelythroughitsworkonnutritionandfood‐safetyissues.CSPIissupportedprimarilybythe900,000subscriberstoitsNutritionActionHealthletterandbyfoundationgrants.

CenterforScienceinthePublicInterest

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Copyright©2013byCenterforScienceinthePublicInterest;May2013


TableofContents

ExecutiveSummary______________________________________________________________________________________1

Introduction ______________________________________________________________________________________________2

Findings___________________________________________________________________________________________________3

Background_______________________________________________________________________________________________7

AntimicrobialDrugSalesandDistributionData____________________________________________________ 11

References______________________________________________________________________________________________ 12

Appendix‐FoodborneOutbreakLineListing_______________________________________________________ 14


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ExecutiveSummary

Theillnesses,hospitalizations,anddeathsreportedaspartofthiswhitepaperarethosefromantibioticresistantfoodbornepathogens.Overall,thoseoutbreaksrevealthatantibioticresistantfoodbornepathogenscan,anddo,contaminateourfoodsupply.Theresultingillnessesbecomedifficulttotreatastheantibioticsneededtotreatthemaremorelimited.

Thisreportdetailsantibiotic‐resistantfoodborneoutbreaksfrom1973to2011.Intotal,55outbreakswereidentified.Fooditemsmostlikelyassociatedwithantibioticresistantpathogensincludeddairyproducts,groundbeef,andpoultry.Thesethreefoodcategorieswereimplicatedinmorethanhalfofreportedoutbreaks(31of55).Salmonellaspp.wasthemostcommoncauseofantibiotic‐resistantoutbreaksidentified(48of55).Pathogensexhibitingmulti‐drugresistancetofiveormoreantibioticswereidentifiedinmorethanhalfoftheoutbreaks(31of55,56%).

Managingantibioticresistance,withavoluntaryapproach

InAprilof2012,theFDAissuedaplantoaddressantimicrobialresistanceinthefoodsupply,withthereleaseofguidanceforindustry:TheJudiciousUseofMedicallyImportantAntimicrobialDrugsinFood‐ProducingAnimals(GFI209).TheFDA’sstrategyistolimituseofantimicrobialsinfood‐producinganimalsthatarealsoimportantinhumanhealth,andultimatelytocurbthedevelopmentofantimicrobialresistance.Usingavoluntaryapproach,theguidanceencouragesdrugcompaniestochangethelabelingofmedicallyimportantantimicrobialsinfood‐producinganimalstopreventtheiruseinanimalsforgrowthpromotionorincreasedfeedefficiency.ThisvoluntaryapproachisflawedinlightofFDA’spublichealthmission.Legislationsuchas“ThePreservationofAntibioticsfortheMedicalTreatmentAct”wouldprovideclearerstandardstolimittheuseofeightclassesofantibiotics,deemedcriticallyimportantforuseinhumanmedicine,thatarealsousedinanimalagriculture.ThisActprovidesamorerigorousmeasuretoaddresstheproblemofantibioticresistancebyspecificallyaddressingusesofantibioticsinanimalagriculturethatarecriticaltotreatmentofhumandisease.

APublicHealthCrisis

“[T]hereisclearevidenceofadversehumanhealthconsequencesduetoresistantorganismsresultingfromnon‐humanusageofantimicrobials.Theseconsequencesincludeinfectionsthatwouldnothaveotherwiseoccurred,increasedfrequencyoftreatmentfailures(insomecasesdeath)andincreasedseverityofinfections,asdocumentedforinstancebyfluoroquinoloneresistanthumanSalmonellainfections.”

— WorldHealthOrganization,2003


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Introduction

Thisreportillustratesthelinkbetweenfoods,mostlyofanimalorigin,andoutbreaksofantibiotic‐resistantpathogensinhumans.Outbreakscausedbyantibiotic‐resistantbacteriaarenotanemergingproblem,butanestablishedproblemthatneedsmoreroutinescrutiny‐andprevention‐bypublichealthofficials.Informationonoutbreaksoffoodborneillnessduetoantibiotic‐resistantbacteriaislimited.SalmonellaandE.coliarenotroutinelytestedforantibioticresistanceand,evenwhentestsareperformed,resultsarenotrequiredtobereportedtotheCentersforDiseaseControlandPrevention(CDC).TheCenterforScienceinthePublicInterest(CSPI)inthiswhitepaperdescribesatotalof55foodborneoutbreaksbetween1973and2011thatwerecausedbybacteriaresistanttoatleastoneantibiotic.

TheNationalAntimicrobialResistanceMonitoringSystem(NARMS)collectsdataonpatternsofresistanceinpathogens,butthosedataarenotlinkedtoactualoutbreaks.Also,CDCdoesnottrackandpublishinformationaboutoutbreaksorsporadicillnessescausedbyresistantbacteria,asitdoesforpathogensinitsFoodNetsystem.Thus,intheabsenceofotherdata,CSPIhasdevelopedadatabaseofoutbreaksduetoantibiotic‐resistantbacteriainthefoodchaintoinformhealthofficialsandthepublicandtoencouragecarefultrackingofthoseoutbreaksinthefuture.Catalogingfoodborneillnessoutbreaksassociatedwithantibiotic‐resistantpathogensisacriticalstepinunderstandingthelinkbetweenadministeringantibioticstofarmanimalsandhumanillnessand,ultimately,preventingtheproblem.

Limitinguseinanimalstopreservecephalosporineffectivenessinhumans

Twopopulationsthataremostatriskoffoodborneillnessarechildrenandimmune‐compromisedindividuals.Ceftriaxoneorcefotaximearethird‐generationcephalosporinsandareoftenthetreatmentofchoiceforseverelycomplicatedpediatricsalmonellosis.Concernsaboutthepervasivenessofplasmidsthatconferresistancetofirst‐,second‐,andthird‐generationcephalosporinsledFDAinJanuary2012toannouncethatitwouldbantheextra‐labeluseofcertaincephalosporinantibioticsinmajorspeciesoffood‐producinganimals.ThatbantookeffectonApril5,2012.


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Findings

Whileantibiotic‐resistantoutbreakshavebeencataloguedsincethe1970s,themajorityhave(34,58%)occurredsince2000.Dairyproductsaccountedforaquarteroftheoutbreaks(14outbreaks,25%).Contaminatedgroundbeefwasalsoacommoncause(10outbreaks,18%).Contaminatedpoultryproductscausedsevenoutbreaks,produceitemscausedfour,andseafoodaccountedfortwo.Oneoutbreakeachwaslinkedtoporkandeggs.Multi‐ingredientfoodscausedthreeoutbreaks,andnospecificfoodvehiclewasdeterminedforthirteenoftheoutbreaks,thoughcharacteristicsoftheoutbreaksindicatedthattheywerefoodrelated(Figure1).

The55reportedoutbreakssickened20,601individuals,ofwhom3,166requiredhospitalizationand27died.Two‐thirds(67%)ofthedeathswereduetoahugemilk‐associatedoutbreakin1985thatkilled18andsickened16,659people.Thatoutbreakwasalsoresponsiblefor88%(2,777)ofallreportedhospitalizations.

14

10

7

42

1 1

13

3

0

5

10

15

20

#ofOutbreaks

Figure1.OutbreaksbyFoodCategoryN=55


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ThemostcommoncauseofoutbreakswasSalmonellaspp.,identifiedin48ofthe55outbreaks(seeFigure2).SalmonellaTyphimuriumwasthemostfrequentlyidentifiedserotype,associatedwith19outbreaks(35%oftotaloutbreaks).S.Typhimurium‐associatedoutbreakscaused17,979illnessesandincludedthelargemilk‐associatedoutbreakin1985.ThesecondmostfrequentlyidentifiedserotypewasSalmonellaNewport,implicatedin15outbreakswith872linkedcases.AdditionalSalmonellaserotypeswereimplicatedinsixteenoutbreaks,andtwooutbreakswerecausedbymultipleSalmonellaserotypes.Ofthosesixteen,SalmonellaHeidelbergaccountedforfouroutbreaks,andSalmonellaHadarwasimplicatedintwooutbreaks.Byetiology,themediannumberofoutbreaksis10.

Amongotherresistantpathogensthatcausedoutbreaks,enterotoxigenicEscherichiacoli(ETEC)causedfiveoutbreaks,with446illnesses.CampylobacterjejuniandStaphylococcusaureuswereeachimplicatedinoneoutbreak.

Drug‐resistancepatternsshowthatthemajorityofoutbreaks(39of55,70%)wereresistanttoatleastoneantibiotic,streptomycin(Figure3).StreptomycinisanaminoglycosideclassifiedbytheWorldHealthOrganization(WHO)as“criticallyimportant”andbytheFoodandDrugAdministration(FDA)(GuidanceforIndustry152)as“highlyimportant”fortreatmentinhumanmedicine.(Seepage11forfurther

19

16 15

5

1 1

0

5

10

15

20

S.Typhimurium* OtherSalmonella*

S.Newport* E.coliETEC Campylobacter S.aureus

#ofOutbreaks

Figure2.OutbreaksbyEtiologyN=55

*MultipleSalmonella serotypesimplicatedintwooutbreaks


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discussionoftheWHOandFDAcategories.)Resistancetotetracycline,acommonlyusedantibioticinfoodanimalproduction,deemedtobehighlyimportantinhumanmedicinebytheFDAandtheWHO,wasdetectedin47of55outbreaks(85%).Cephalosporinantibiotic‐resistanceoccurredin28outbreaks,andresistancetocephamycin,anantibioticsimilartocephalosporin,occurredin15outbreaks.

Thirty‐one(56%)outbreaksinvolvedapathogenwithmulti‐drugresistancetofiveormoreantibiotics(Figure4).Eitherreportingofantibiotic‐resistantoutbreaksisimproving,ortherecouldbeanappreciableincreaseinoutbreaksresultingfromresistantbacteria,astwo‐thirdsofthoseoutbreaksoccurredinthelasttwodecades.Anoutbreakassociatedwitheggsin1973hadanunknownantibiotic‐resistanceprofile,asdidtwooutbreaksfromrawmilk,onein1979,andtheotherin1980.Thus,thetotalnumberofoutbreakswithresistanceprofilesis52,not55.

3936

19

2 1 3 14

10

47

25

15 15 17

5 3 1

1410

4

05101520253035404550

#ofOutbreaks

Figure3.DrugResistanceProfilesbyWHOcategories(55Outbreaks)

CriticallyImportant HighlyImportant NotclassifiedonWHO'slist


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Meatandpoultryproductswereidentifiedin18outbreaks:10ingroundbeef,7inpoultry,and1inpork.GroundbeefcontaminatedwithSalmonellaNewportcausedsevenoutbreaks,andtheotherthreewereSalmonellaTyphimurium‐associated.SixofthepoultryoutbreakswerelinkedtoSalmonellaspp.contamination,andonewasassociatedwithE.coliO27:H7.Meatandpoultryoutbreakscaused1,639casesofillness,with191hospitalizations,andeightdeaths.

Therewere14outbreaksassociatedwithdairy:8wereassociatedwithmilkproducts,and6wereassociatedwithcheeses.In11ofthe14outbreaks(79%),theimplicatedfooditemwasdescribedasbeingraw/unpasteurizedmilkorcheese.Pasteurizedmilkcausedthreeoutbreaks,includingthelargeoutbreakin1985.Allofthedairy‐associatedoutbreaksidentifiedSalmonellaspp.astheetiologicagent–tenassociatedwithS.Typhimurium,threewithS.Newport(includingonealsolinkedtoS.Meleagridis),andonewithS.Dublin.Overall,dairyoutbreakswereresponsiblefor17,257illnesses,2,871hospitalizations,and19deaths.

6

4

65

10

6

15

0

5

10

15

20

One Two Three Four Five Six Seven+

#ofOutbreaks

#ofIneffectiveDrugs

Figure4.IndividualDrugResistancesperOutbreakN=52


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Background

Thediscoveryofantibacterialagentsinthefirsthalfofthe20thcenturyradicallychangedtheoutcomeofcommonhumandiseases.Manyillnessesthatweredeadlybeforeantibioticsbecameavailablearenowreadilytreatable.Theabilityofbacteriatoevolvemechanismstoresistattackbyantimicrobials1wasrecognizedsoonafterthewidespreaddeploymentofthefirstantibiotics.

Resistanceisaninevitableconsequenceofantibioticuse;themorethatantibioticsareused,themorebacteriawilldevelopresistance.Inrecentyears,scientistshavebeguntounderstandatthemolecularlevelthesophisticatedmechanismsthatenablebacteriatofendofforneutralizeantibiotics.Antibioticresistanceisrecognizedasagrowingproblemthatposesamajorthreattothecontinuedeffectivenessofantibioticsusedtotreathumanandveterinaryillnesses.Furtherexacerbatingtheproblem,pharmaceuticalcompaniesaredevelopingfewernewantibioticstoreplacethosethatarenolongereffective(Silbergeldetal.,2008).

Numerousstudieshavedocumenteddirecttransferenceofantibiotic‐resistantbacteriafromanimalstohumans.Researchershavefoundthatwhenantibioticswereadministeredtoanimalstotreatinfections,theprevalenceofantibiotic‐resistantE.coliandCampylobacterbacteriaalsoincreasedinhumans(Levyet.al,1976;Smithet.al,1999).Otherstudieshaveconfirmedthatantibiotic‐resistantCampylobacter,SalmonellaTyphimuriumDT104,andSalmonellaNewporthavemovedfromanimalstohumansthroughfoodsofanimalorigin(Smithetal.,1999;Ribotetal.,2002).Reflectingthefactthatbacteriacandevelopresistancetonumerousantibioticsatthesametime,onegroupofrelatedantibiotic‐resistantSalmonellaNewportstrainsisresistanttomostavailableantimicrobialagentsapprovedforthetreatmentofsalmonellosis,particularlyinchildren(Guptaetal.,2003).

Thehumanhealthconsequencesofresistantpathogensincludemoreseriousinfectionsandincreasedfrequencyoftreatmentfailures.Patientsmayexperienceprolonged

1Theterm“antimicrobial”isabroadtermreferringtosubstancesthatactagainstavarietyofmicroorganisms,includingbacteria,viruses,parasites,andfungi.Theterm“antibiotic”isanarrowertermreferringtosubstancesusedtotreatbacterialinfections.Classically,antibioticswereproducedbyamicroorganism,butnowbothmanufacturedandnaturally‐occurringsubstancesthatkillbacteriaarecalledantibiotics.Mostoftheconcernwithantimicrobialuseinagricultureiswithbacterialresistance,so“antibiotic”isusedinthisreport.


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durationofillness,increasedfrequencyofbloodstreaminfections,greaterlikelihoodofhospitalization,andincreasedmortality(Anguloetal.,2004).

Health‐care costs increasewith longer hospital stays and the need formore expensiveantibioticstofightresistantpathogens.Theantibioticsusedtotreatresistantpathogenscanbemoretoxic,withmoreserioussideeffectsinthepatients.

Thereportedoutbreaksdocumenttheproblemofantibiotic‐resistantfoodbornepathogens,butanyrisk‐managementstrategyiscomplicatedbythedivisionofauthorityamongseveralfederalagenciesandthediversestakeholders,particularlythedrugmanufacturersandcattle,hog,andpoultryindustries.Themainobstacleforresearchersworkingtoidentifysolutionstoantimicrobialresistanceisalackofdata–especiallydataondruguse.Morerobustdataisneededonthetypesandquantitiesofantibioticssoldforuseinfood‐producinganimals,thespeciesinwhichtheyareused,whentheyareadministered,thepurposeoftheiruse(diseasetreatment,diseaseprevention,orgrowthpromotion),andthemethodusedtoadministerthem.Denmark,forexample,collectsdataonantibioticusefromdrugcompanies,veterinarypharmacies,feedmills,privatecompanies,andveterinarians.Reportingincludesspecies‐specificdrugadministrationdata,theageatwhichanimalsaregivendrugs,thediseasesbeingtreated,anddosage.SuchdatahaveallowedDanishresearcherstodeterminehowchangesintheuseofantibioticsinanimalsaffecttheemergenceofantibiotic‐resistantbacteria(DANMAP,2011).InformationlikethoseisnotcollectedintheUnitedSates.

Manyoftheantibioticsusedforfood‐producinganimalsarethesame,orbelongtothesameclasses,asthoseusedinhumanmedicine.Resistancetooneantibioticinaclassoftenresultsinresistancetoalldrugsinthatclass,furthercompoundingtheproblem.Inaddition,thegenesthatcanrenderonebacteriumresistantcanevenbesharedbydifferentspeciesthroughhorizontalgenetransfer.Widespreaduseofantibioticsinagricultureincreasesthelikelihoodthattheywillbecomeineffectiveagainsthumanillnesses.

TheWHOhasdevelopedcriteriaforrankingantimicrobialsaccordingtotheirimportanceinhumanmedicine.TherankingsareregularlyreviewedbyWHO’sAdvisoryGrouponIntegratedSurveillanceofAntimicrobialResistance(AGISAR).Thisrankingofdifferentdrugsfromahumanhealthperspectivewasdevisedforusebygovernmentsandother


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stakeholderswhentheydeveloprisk‐managementstrategiesconcerningtheuseofantimicrobialsinfoodanimals.

TheWHOdividesantimicrobialsintothreecategoriesbasedontheiroverallimportancetohumanhealth:criticallyimportant,highlyimportant,andimportant(WHO,2011).WHOranksantimicrobialagentsascriticallyimportantwhen:

1) Theyarethesoleoroneoffewoptionsfortreatmentofhumaninfections,and2) Theyareusedtotreatdiseasescausedbyorganismsthatmaybetransmittedvia

non‐humansourcesororganismsthatmayacquireresistancegenesfromnon‐humansources.

Antimicrobialsthatmeetjustoneofthosecriteriaarerankedashighlyimportant,whileantimicrobialsthatmeetneithercriterionarerankedasimportant.

In2003,theFDAalsorankedantimicrobialdrugsaccordingtotheirimportanceinhumanmedicine(FDA,2003).TheFDArankingsaredividedinto“criticallyimportant”,“highlyimportant”and“important”.However,theFDAfocusedonantibioticsusedtotreatfoodborneillnessinhumans,ratherthanonthebroaderspectrumofhumandisease.Forexample,FDAranksfourth‐generationcephalosporins,whichareanimportanttreatmentforpneumoniaandoneofthefewtherapiesforcancerpatientswithcomplicationsfromchemotherapy,ashighlyimportant,whileWHOranksthemascriticallyimportant(FDA2003,WHO2011).

Antibioticsareusedinfood‐producinganimalstotreatorpreventillnesses,forexample,duringtheweaningperiodofyounganimals.Theymayalsobeusedforlongperiodsatlowlevelstopromotegrowth,increasefeedefficiency,orcompensateforunsanitarygrowingconditionsonconcentratedanimalfeedingoperations(CAFOs).Increasedfeedefficiencymeansanimalsrequirelessfeedperpoundofweightgain,whichtranslatesintolowercostsforproducers.Manyanimalproducersbelievetheuseofantibioticsforgrowthpromotionalsopreventsdisease(GAO,2011).

Intheindustrialmodelofanimalhusbandry,largenumbersofpigs,chickens,orcattleareraisedinconfinedareas.Intheporkandchickenindustries,large‐scaleconcentratedhousingsystemsreducecostsforlabor,feed,andhousing.However,theincreasedstressofcrowdingandunsanitaryconditionsmakesanimalsmoresusceptibletothespreadof


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infectiousdiseases.Manyproducerscommonlyadministeranantibiotictoanentireflockorherdviafeedorwater,butthatgivesthemlesscontroloverthedosageconsumedbyindividualanimals.Thenontherapeutic2useofantibiotics,sometimesadministeredthroughoutananimal’slife,isamongthepracticesofgreatestconcernforthedevelopmentofantibioticresistance.

Beginningin2008,antibioticdrugmanufacturerswererequiredtoreportannuallytotheFDAtheamountofdrugstheysoldordistributedforuseinfood‐producinganimals(FDA,2010a,FDA,2011a,FDA,2013).Threeyearsofdatashowthattheaggregatequantityofantibioticsbeingsoldforuseinfood‐producinganimalspeciesincreasedfrom28.81to29.86millionpoundsfrom2009to2011.Combinedtotalsofdrugdistributioninhumanmedicinedatachangedlittleoverthattimeperiodfromapproximately7.31to7.25millionpounds.ThedatareportedtoFDAisnotbrokendownbyspecies,routeofadministration,orpurposeofuse.Thus,antibioticssoldforuseinfoodanimalsconstituteabout80%ofallantibioticsdistributedintheUnitedStates.Ofthoseantibioticssoldin2011(excludingnotindependentlyreportedor“other”antibioticsandIonophores),approximatelythreequartersusedinanimalagricultureareidenticalorsimilartothoseusedinhumanmedicine(Table1).

2Nontherapeuticreferstousewhenanimalsaretreatedintheabsenceofbacterialdiseaseorexposuretodisease.


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Theuseofcriticallyimportantantimicrobials,suchasaminoglycosides,cephalosporins,andmacrolides,appearstohavedecreasedfrom2009to2011basedondistributionandsalesdata(bothanimalandhuman).Ontheotherhand,theuseinanimalsofpenicillins,aclassthatincludescriticallyimportantantibiotics,appearstohaveincreasedfrom2009to2011.Therewasalsoasignificantincreaseinsalesanddistributionofthehighlyimportantclassofantibiotics,tetracyclines,infood‐producinganimals.

Table 1. Antimicrobial Drugs Approved for Domestic Use in Humans and Food-Producing Animals*. Sales and Distribution Data Reported to FDA by Drug Class.

2009 Animal Annual Totals (LBS)

2010 Animal Annual Totals (LBS)

2011 Animal Annual Totals(LBS) WHO Status

Aminoglycosides 748,862 442,675 473,762 Critically / highly

Cephalosporins 91,113 54,207 58,667 Critically / highly

Ionophores 8,246,671 8,424,167 9,090,230 Not ranked

Lincosamides 255,377 340,952 419,101 Important

Macrolides 1,900,352 1,219,661 1,284,933 Critically

Penicillins 1,345,953 1,920,112 1,940,427 Critically / highly

Sulfas 1,141,715 1,116,020 817,959 Highly

Tetracyclines 10,167,481 12,328,521 12,439,744 Highly

Other (Not Indepen- dently Reported (NIR))** 4,910,501 3,345,398 3,330,241

Total 28,808,024 29,191,712 29,855,066

2009 Human Annual Total (LBS)

2010 Human Annual Total (LBS)

2011 Human Annual Total (LBS) WHO Status

Aminoglycosides 20,682 15,413 14,297 Critically / highly

Cephalosporins 1,101,465 1,107,957 1,095,499 Critically / highly

Ionophores 0 0 0 Not ranked

Lincosamides 153,744 152,637 157,531 Important

Macrolides 388,626 362,239 361,620 Critically

Penicillins 3,217,027 3,174,502 3,219,677 Critically / highly

Sulfas 1,039,352 1,057,081 1,061,887 Highly

Tetracyclines 289,108 284,800 250,957 Highly

Other (Not Indepen-dently Reported (NIR))** 1,102,567 1,074,121 1,089,921

Total 7,312,570 7,228,750 7,251,390

* For all classes except aminoglycosides and ionophores, data includes antimicrobial drug products which are approved and labeled for use in both food- and non-food- producing animals.

** NIR is used for antimicrobial classes with fewer than three sponsors actively marketing products. This category includes fluoroquinolones and streptogramins. *** Human drug use data is based on data from the IMS Health, IMS National Sales Perspectives.


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References

AnguloF.J.,Nargund,V.N.,andChiller,T.C.2004.EvidenceofanAssociationBetweenUseofAnti‐microbialAgentsinFoodAnimalsandAnti‐microbialResistanceAmongBacteriaIsolatedfromHumansandtheHumanHealthConsequencesofSuchResistance.J.Vet.Med.BInfect.Dis.Vet.PublicHealth,51,374‐379.

CentersforDiseaseControlandPrevention.About Antimicrobial Resistance: A Brief Overview . RetrievedJuly22,2010fromCDCwebsiteathttp://cdc.gov/drugresistance/about.html

TheDanishIntegratedAntimicrobialResistanceMonitoringandResearchProgramme.DANMAP2011‐Useofantimicrobialagentsandoccurrenceofantimicrobialresistanceinbacteriafromfoodanimals,foodandhumansinDenmark.AvailablefromtheDANMAPwebsite:http://www.danmap.org/Downloads/~/media/Projekt%20sites/Danmap/DANMAP%20reports/Danmap_2011.ashx

FoodandDrugAdministration(FDA).2011.2010SummaryReportonAntimicrobialsSoldorDistributedforUseinFood‐ProducingAnimals.AvailablefromtheFDAwebsiteathttp://www.fda.gov/downloads/ForIndustry/UserFees/AnimalDrugUserFeeActADUFA/UCM277657.pdf

FoodandDrugAdministration(FDA).2011.NationalAntimicrobialResistanceMonitoringSystem–EntericBacteria(NARMS):2009ExecutiveReport.AvailablefromtheFDAwebsiteathttp://www.fda.gov/downloads/AnimalVeterinary/SafetyHealth/AntimicrobialResistance/NationalAntimicrobialResistanceMonitoringSystem/UCM268954.pdfhttp://www.fda.gov/downloads/AnimalVeterinary/SafetyHealth/AntimicrobialResistance/NationalAntimicrobialResistanceMonitoringSystem/UCM268954.pdf

FoodandDrugAdministration(FDA).2013.2011SummaryReportonAntimicrobialsSoldorDistributedforUseinFood‐ProducingAnimals.RetrievedfromU.S.DepartmentofHealthandHumanServices,FoodandDrugAdministrationwebsite:http://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm338178.htm

FoodandDrugAdministration(FDA).2010.2009SummaryReportonAntimicrobialsSoldorDistributedforUseinFood‐ProducingAnimals.AvailablefromtheFDAwebsiteathttp://www.fda.gov/downloads/ForIndustry/UserFees/AnimalDrugUserFeeActADUFA/UCM231851.pdf

FoodandDrugAdministration(FDA).2010,June.TheJudiciousUseofMedicallyImportantAntimicrobialDrugsinFood‐ProducingAnimals.(DraftGuidance#209).AvailablefromtheFDAwebsiteathttp://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM216936.pdf

FoodandDrugAdministration(FDA).2010.EstimatesofAntibacterialDrugSalesinHumanMedicine.AvailablefromtheFDAwebsiteathttp://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm261160.htm


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FoodandDrugAdministration(FDA).2003.GuidanceforIndustry#152.EvaluatingtheSafetyofAntimicrobialNewAnimalDrugswithRegardtoTheirMicrobiologicalEffectsonBacteriaofHumanHealthConcern.AvailablefromtheFDAwebsiteathttp://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM052519.pdf

Gupta,A.,Fontana,J.,Crowe,C.,Bolstorff,B.,Stout,A.,VanDuyne,S.,Hoekstra,M.P.,Whichard,J.M.,Barrett,T.J.,andAngulo,F.J.2003.EmergenceofMultidrug‐ResistantSalmonellaentericaSerotypeNewportInfections.JournalofInfectiousDiseases,188,1707‐1716

Levy,S.B.,FitzGerald,G.B.,andMacone,A.B.1976.ChangesinIntestinalFloraofFarmPersonnelafterIntroductionofaTetracycline‐SupplementedFeedonaFarm.NewEnglandJournalofMedicine,295,583‐588.

Ribot,E.M.,Wierzba,R.K.,Angulo,F.J.,andBarrett,T.J.2002.SalmonellaentericaserotypeTyphimuriumDT104IsolatedfromHumans,UnitedStates,1985,1990,and1995.EmergingInfectiousDiseases,8(4),387‐391.

Silbergeld,E.K.,Price,L.,andGraham,J.2008.AntimicrobialResistanceandHumanHealth.RetrievedfromPewCommissiononIndustrialFarmAnimalProductionwebsite:http://www.pewtrusts.org/uploadedFiles/wwwpewtrustsorg/Reports/Industrial_Agriculture/PCIFAP_AntbioRprtv.pdf

Smith,K.E.,Besser,J.M.,Hedberg,C.W.,Leano,F.T.,BenderJ.B.,Wicklund,J.H.,Johnson,B.P.,Moore,K.A.,andOsterholm,M.T.1999.Quinolone‐resistantCampylobacterjejuniinfectionsinMinnesota,1992‐1998.NewEnglandJournalofMedicine,340.

U.S.GovernmentAccountabilityOffice(GAO).2011.AgenciesHaveMadeLimitedProgressAddressingAntibioticUseinAnimals.GAO‐11‐801.AvailablefromtheGAOwebsiteathttp://gao.gov/assets/330/323090.pdf

U.S.GovernmentAccountabilityOffice(GAO).2004.FederalAgenciesNeedtoBetterFocusEffortstoAddressRisktoHumansfromAntibioticUseinAnimals.GAO‐04‐490.AvailablefromtheGAOwebsiteathttp://www.gao.gov/new.items/d04490.pdf

WorldHealthOrganization(WHO).2011.WHOAdvisoryGrouponIntegratedSurveillanceofAntimicrobialResistance(AGISAR).CriticallyImportantAntimicrobialsforHumanMedicine,3rdRevision.AvailablefromtheWHOwebsiteat:http://apps.who.int/iris/bitstream/10665/77376/1/9789241504485_eng.pdf

WorldHealthOrganization(WHO).RegionalOfficeforEurope.2011.TacklingantibioticresistancefromafoodsafetyperspectiveinEurope.AvailablefromtheWHOwebsiteathttp://www.euro.who.int/__data/assets/pdf_file/0005/136454/e94889.pdf

WorldHealthOrganization(WHO).2009.Reportofthe1stMeetingoftheWHOAdvisoryGrouponIntegratedSurveillanceofAntimicrobialResistance.AvailablefromtheWHOwebsiteathttp://apps.who.int/medicinedocs/index/assoc/s16735e/s16735e.pdf

WorldHealthOrganization(WHO).2003.JointFAO/OIE/WHOExpertWorkshoponnon‐HumanAntimicrobialUsageandAntimicrobialResistance:Scientificassessment.AvailablefromtheWHOwebsiteathttp://www.who.int/foodsafety/publications/micro/en/amr.pdf

Appendix. Antibiotic-Resistant Foodborne Outbreaks

Year Location Bacteria Food/Source Cases Hosp Death Resistances Drug Family WHO Status

1973 ME S. Typhimurium Eggs 32 NR NR unknown

streptomycin aminoglycosides critically important

sulfamethoxazole sulfonamides highly important

tetracycline tetracycline highly important

1977 KY S. Typhimurium Raw milk 3 NR NR ampicillin penicillin critically important

carbenicillin penicillin critically important

kanamycin aminoglycosides highly important

penicillin penicillin critically important



1979 CA, OR S. Dublin Raw milk 39 NR NR unknown

1980 MT S. Typhimurium Raw milk NR NR unknown

ampicillin penicillin critically important

chloramphenicol amphenicol highly important



sulfonamide* sulfonamides highly important



carbenicillin penicillin critically important



streptomycin aminoglycosides critically importantampicillin penicillin critically important











1987 GA S. Havana Chicken 73 36 1 tetracycline tetracycline highly important



sulfisoxazole sulfonamides highly important




trimethoprim-sulfamethoxazole

sulfonamides *






amoxicillin/clavulanate penicillin critically important






E. coli O153:H45 (ETEC)

WI

AZ

1994

1997

S. Stanley

S. Typhimurium DT104

NE

WA

1995

1996


Mexican-style soft cheese (queso fresco) (raw milk)

Unknown, chocolate milk suspected

19

19

89

16659Pasteurized milk

Alfalfa sprouts

12

NR27

18

298 2

45 0715

Ground beef 11 1

NRGround beef

Raw milk NR 1

MD, FL, CO

1984 OR S. Typhimurium

S. Typhimurium1983 AZ

1975

1983

S. Newport

182777

S. NewportMN, SD, NE, IA

Salad bar

1985 IL

1985 CA

S. Typhimurium

0

S. Newport Ground beef 22

Unknown, banquet food

NR

5

0

NR

0

NR205

5


























sulfonamides *

ciprofloxacin fluoroquinolone critically important

tetracycline tetracycline highly Important

2000 TN Staphylococcus aureus (MRSA)

Pork, barbeque, vegetable

l d l

3 0 0 methecillin penicillin *








cefoxitin cephamycin highly important

ceftiofur cephalosporin (3G) *

cephalothin cephalosporin (1G) highly important





2001 WI E. coli O169:H41/ST (ETEC)

Quesadilla, fajitas, nacho chips, beans

21 0 0 tetracycline tetracycline highly important

1998

CA

1998 NY S. I 4,[5],12:i- Unknown, dinner reception multiple foods suspected

2000

CT

1997

1997

1997 CA

1997

2001

Campylobacter jejuni

KS

MD

VT

PA, NJ S. Typhimurium Pasteurized milk

128Unknown, gravy, potato, pineapple

93

S. Typhimurium 9

NR

S. Heidelberg

86

79Mexican-style cheese (raw milk)


2Pork

S. Typhimurium var Copenhagen DT104b

13

Mexican-style cheese (raw milk)

31 14 NR

2

706

NR

27 0

1

0

6

31 0

12

0

S. Newport Italian-style soft cheese (raw milk)

NR

Raw milk






ceftiofur cephalosporin *






kanamycin (2/3 resistant)

aminoglycosides highly important

ceftriaxone (2) cephalosporin (3G) critically important




2003 TN E. coli O169:H49 (ETEC)

Catfish, coleslaw

41 2 0 tetracycline tetracycline highly important








nalidixic acid quinolone critically important


sulfisoxazole sulfonamides highly important


sulfonamides *

amoxicillin/clavulanate penicillin critically importantampicillin penicillin critically importantcefoxitin cephamycin highly important


ceftriaxone cephalosporin highly important

















2004 NY S. Istanbul Chicken 42 14 0 tetracycline tetracycline highly important

2005 MN S. Heidelberg Chicken 4 1 0 gentamicin streptomycin sulfonamide*

aminoglycosides aminoglycosides sulfonamides

critically important critically important highly important

9 states

49E. coli O27:H7/ST (ETEC)

Ground beef 56

Chicken lasagna

2002

2002

2003

0

Ground beef 17

0 0

1

011

0

47


E. coli O6:H16 (ETEC)

NV 130Shrimp

OR

S. NewportNY, MI, PA, OH, CT

Sandwich, turkey

2004

100 5 0S. NewportCA

6 0MN

2004

2004 S. Newport Unknown 2 NR

Pasteurized milk

2004 S. Agona 24

IL NR



gentamicin aminoglycosides critically important

nalidixic acid quinolone critically important






















sulfonamides *


2006 AR S. I 4,[5],12:i- Unknown 14 4 0 nalidixic acid quinolone critically important























ceftiofur cephalosporin (3G) *ceftriaxone cephalosporin highly important





Queso fresco, unpasteurized; raw milk

S. Typhimurium PA

2006 CA S. Newport Multiple foods 24

2006 PA S. Schwarzengrund Unknown 6 0 0

S. Typhimurium Root vegetable 3

2005 TN S. Heidelberg Unknown 19

2005 IN, MI, MO, OH

S. Braenderup Tomato 84 8

2005 CO S. Typhimurium S. Newport

Unknown 100

NR

2006 20 2

2006

2005 CO S. Typhimurium Sushi 25 0

1 0

0

0

NR

UT NR NR

2 0

0


























ceftriaxone cephalosporin critically important




























14 states S. Newport Ground beef 4 02009

2009 7 states

IL S. Newport S. Meleagridis

2006 36 0

0

15

TN2006

96


14Ground beef

Mexican-style cheese (cotija), (raw milk)

68

6

S. Newport

Unknown

2007

S. Newport Ground beefCA, AZ, ID, NV

2007 43

9 1 0

IL

Unknown 11

2006 S. Newport Unknown 9 3 0

0 0MN

0

S. Hadar












2011 10 states S. Hadar Ground turkey (Jennie-O ground turkey burgers)

12 3 0 ampicillin amoxicillin/clavulanate cephalothin tetracycline

penicillin penicillin cephalosporin tetracycline

critically important critically important highly important highly important





2011 7 states S. Typhimurium Ground beef 20 8 0 amoxicillin/clavulanateampicillin ceftriaxone cefoxitin kanamycin streptomycin sulfisoxazole tetracycline

penicillin penicillin cephalosporin cephamycin aminoglycosides aminoglycosides sulfonamides tetracycline

critically important critically important critically important highly important highly important critically important highly important highly important

Totals 20601 3166 27

134 states2011 S. Heidelberg Ground turkey (Cargill)

136 37

2 NR NR2009 AZ S. Newport Ground beef

Source: Center for Science in the Public Interest

* Not on WHO's list of antimicrobials used in human medicineNR = Not Reported

antibiotic resistance in foodborne pathogens · antibiotic resistance in foodborne pathogens page 2...

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