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Bovine respiratory disease: Efficacy of different prophylactic treatments in veal calves and antimicrobial resistance of isolated Pasteurellaceae

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Bovine respiratory disease: Efficacy of different prophylactic treatments in veal calves and antimicrobial resistance of isolated Pasteurellaceae
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  PreventiveVeterinaryMedicine 103 (2012) 265–273 ContentslistsavailableatSciVerseScienceDirect Preventive   Veterinary   Medicine  journalho   mepage:www.elsevier.com/locate/prevetmed Bovine   respiratory   disease:   Efficacy   of    different   prophylactictreatments   in   veal   calves   and   antimicrobial   resistance   of    isolated Pasteurellaceae M.   Rérat a , ∗ , S.Albini b , 1 , V.    Jaquier b , D.   Hüssy b a  AgroscopeLiebefeld-PosieuxResearchStationALP,P.O.Box64,Tioleyre4,CH-1725Posieux,Switzerland b InstituteofVeterinaryBacteriology,Centrefor     Zoonoses,BacterialAnimalDiseasesandAntimicrobialResistance,VetsuisseFaculty,Universityof    Bern,Postfach8466,3001Bern,Switzerland a   r   ti   c   l   e   i   nf   o Keywords: VealcalvesBovinerespiratorydiseaseAntibioticsusceptibility Pasteurellaceae Minimalinhibitoryconcentration ab   st   ra   ct The   present   study   wasconducted   to   evaluate   the   efficacy   of    twoprophylactic   antibiotictreatmentsagainst   bovine   respiratorydisease   (BRD)invealcalves.In   addition,   the   antibi-otic   susceptibilities   of    isolated   Pasteurellaceae   weretested.Thecalveswere   treated   either   onthe   dayof    arrivalby   a   single   administration   of    tulathromycin(group   A,   n =   20),by   a   peroraladministrationof    chlortetracycline,   sulphadimidine,and   tylosin   (group   B,   n =   20)   for   sevenconsecutivedays,   or   were   not   prophylactically   treated(group   C,   n =   19).Onthe   first   dayof clinically   diagnosedBRD,transtracheal   lavagesampleswere   obtained   priortotherapeutictreatment   andweresubsequently   cultured.   Pasteurellaceae   isolates   were   tested   for   theirsusceptibility   to   12antimicrobial   agentsby   the   determinationof    the   minimal   inhibitoryconcentrations.During   the   first   56dafter   arrival,   differentcalvesingroup   A   andB   sufferedfrom   one   episode   of    clinically   diagnosed   BRDwhilecalvesof    group   Cexperienced   twoepisodes.Theaverage   dailyweight   gainduring   the   sameperiod   wassignificantlyloweringroup   C(0.89   ± 0.04kg/d)than   inthe   two   prophylacticallytreated   groups(1.14   ± 0.05and1.15   ± 0.04   kg/dforgroupA   and   B,   respectively).   Theimproved   performance   of    groupsA   andBincomparison   togroupCcouldbe   related   toalower   incidenceof    respiratorydisorders   during   the   firstdaysafter   arrivalinthe   prophylacticallytreated   animals.   Nodif-ferences   inthe   clinicalefficacy   wereseen   betweenthetwo   tested   prophylactic   treatments.Themostprevalent   bacterial   pathogensisolated( n   =   79)   were   Pasteurella   multocida   (23%of isolated   pathogens),   Mycoplasma   bovis   (18%),   and Mannheimia   varigena   (16%).   For   the   iso-lated   Pasteurellaceae ,ahigh   resistancepattern   wasobservedtotylosin   (83%of    the   tested P.multocida   and   88%   of    the   Mannheimia   spp.   isolates   resistant)   andtilmicosin(56%   of    thetested P.multocida   isolates   non-sensitive). © 2011 Elsevier B.V. All rights reserved. ∗ Correspondingauthor.Tel.:+41264077391;fax:+41264077300. E-mailaddress: michel.rerat@alp.admin.ch(M.   Rérat). 1 Presentaddress:InstituteofVeterinaryBacteriology,Departmentof PoultryandRabbitDiseases,VetsuisseFaculty,Universityof    Zurich,CH-8057   Zurich,Switzerland. 1.Introduction Bovinerespiratorydisease(BRD)isanimportanteco-nomicproblemin   vealproductioninSwitzerlandandotherEuropeancountries.Thisproductionsystemcomprisesthetransportationof    youngcalvesfromtheirbirthfarmstofatteningunitswhereindividualsfromseveraldifferentbreedersaremingled(Ganheimetal.,   2007).Theconfine-mentproceduresduringthetransportandtheminglingof  0167-5877/$–seefrontmatter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.prevetmed.2011.09.003  266  M.Rératetal./    PreventiveVeterinaryMedicine 103 (2012) 265–273 animalsfromdifferentoriginsincreasetheinfectionpres-sure(Ames,1997)andthusincreasetheriskofdeveloping BRD,withamorbiditypeakoccurringwithinthefirst3weeksafterarrivalattheunit(KellyandJanzen,1986). Giventhishighinfectionpressure,vealproducersroutinelytreatcalvesprophylacticallywithantibioticsimmediatelyuponentryintothefatteningunit.InSwitzerland,abouttwothirdsofthetotalantibioticsforveterinaryusearesoldintheformof    pharmaceuticalpremixturesforcalvesandpigs(Swissmedic,2009).Thesepreparationsaremixedintoanimalfeed,milkordrinkingwaterbeforeadministrationandareusedforthepreventionandtreatmentof    infectiousdiseasesoffarmanimalskeptin   denselyhousedgroups.Becauseofthissystematicuseinvealproduction,theroutineadministrationof    in-feedgroupmedicationcanleadtoselectionof    resistantstrainsofthecommensalrespiratorybacterialfloraof    theseanimals(Catryetal.,2005).Twostudieshavebeenpublishedontheantimicro-bialresistancepatternsofrespiratorybacterialpathogensinSwitzerland(Vogeletal.,2001;WettsteinandFrey,2004).InthestudybyVogeletal.(2001),   transtracheallavagesamplesfromlivingcalveswithorwithoutpneumo-niaandfromlungswithor   withoutlesions,collectedafterslaughter,werecultured.Threeof    theoverall7isolated Mannheimiahaemolytica strains(43%)wereresistanttopenicillinandampicillin,butnoneof    theoverall55isolated Pasteurellamultocida strainswereresistant.Furthermore,the P.multocida andthe M.haemolytica strainsshowedhighpercentagesofresistancetostreptomycin(48%and100%),tetracycline(15%and43%),sulphonamides(44%and14%)andtrimethoprim–sulphonamide(11%and0%).Thestudyof    WettsteinandFrey(2004)onrespiratorypathogensisolatedfromdifferentanimalspeciesshowedthat50%of20bovine M.   haemolytica isolatesweremul-tiresistanttotetracycline,ampicillin,andstreptomycin.Becausebacterialpathogenswithresistanceto   antibioticsareofgrowingconcerninthetreatmentofinfectiousdis-easesinhumansandanimalstoday(Swissmedic,2009),newdataareneededto   assesswhethermajorbovineres-piratorybacterialpathogenshaveextendedtheirantibioticresistancepatternssincethelaststudieswereconducted(Vogeletal.,2001;WettsteinandFrey,2004).Inordertoreducetheuseof    antibioticsinthevealproduction,theadministrationof    aninjectableantimicro-bialdrugcouldbeanalternativetotheoralantibiotics.Theobjectiveofthepresentstudywasto   comparetheefficacyofgroupinjectiontherapyatarrivalwithalongactingmacrolidewithstandardprophylacticoralantibi-oticatarrivalandindividualcurativeinjectiontherapyatthetimeofclinicaldiseasewithrespecttogrowthrateandhealthstatus(numberofcases,relapseandnon-responserates).Inaddition,minimalinhibitoryconcentration(MIC)ofcommonantibioticsin Pasteurellaceae wasdetermined. 2.Materialsandmethods  2.1.Studypopulation Sixtycalveswithnegativeantibodytitersforbovineviraldiarrhoeavirus(BVDV)werepurchasedfrom22dairyfarmsanddirectlytransportedtotheresearchstation.The  Table1 Numberofantibiotictreatmentspriortoarrivalatthefatteningunitwithrespecttotheexperimentalgroupsofvealcalves.PrecedingantibiotictreatmentswithStudygroupsof    vealcalves a AB   CPenicillin–streptomycin3   3   3Neomycin–sulphonamide1 1 0Sulphadimidine–trimethoprim2 2 2Enrofloxacin2   1   1Tetracycline1   0   1Tetracycline–spiramycin1   0   1Gentamicin1   1   1Tetracycline–sulphadimidine–tylosin b 2   1   2 a GroupA,B,andC=   groupstreatedprophylacticallybya   singleinjec-tionof    tulathromycin,byaperoraladministrationof    chlortetracycline,sulphadimidine,andtylosin,orwithoutprophylactictreatment,respec-tively. b Treatmentsimilarto   experimentaltreatmentB. criteriaforrecruitingfarmswerethelocation’sproximitywiththeresearchstation(within ≤ 40kmradius)andthepresenceof    a   minimumof    3RedHolsteinbullcalveswitha   bodyweight(BW)between65and80kg.Tenfarmspro-videdjustoneor   twocalves.The60vealcalvesarrivedwithin2datthefatteningunitwithameanageof41 ±   1d.NovaccinationagainstBRDpathogenswas   doneonarrivalinthefatteningunit.Producerswereaskedto   provideinfor-mationregardingantibiotictreatmentspriortothestartof thestudy(Table1).  2.2.Studydesign All   procedures,inaccordancewiththeSwissguide-linesforanimalwelfare,wereapprovedbytheAnimalCareCommitteeoftheCantonFribourg(Switzerland)andweresupervisedbytheSwissFederalVeterinaryOffice.Onecalffromeachfarmwasassignedtooneofthe3experimentalgroups( n =   20pergroup)basedonBW.   Fourtimes,2calveswiththesameoriginwereallocatedintothesameexperimentalgroup(1pairin   groupA,2ingroupB,   and1ingroupC).The3differentexperimentaltreatmentswereeitherasinglesubcutaneousinjectionof 2.5mg   tulathromycin/kgBW(Draxxin10%;Pfizer,Zürich,Switzerland)onthedayof    arrival(groupA),a   peroraldailyadministrationof    18.75mg   chlortetracycline,3mgsul-phadimidine,and30mg   tylosin/kgBW   (CAS45K;Ufamed,Sursee,Switzerland)for7consecutivedays(d1–7;groupB)orno   prophylactictreatment(groupC).Theexperimen-talperiodstarteduponarrivalof    thecalvesatthefatteningunitandlasteduntild56.Thehighvariabilityin   weatherduringtheexperimentalperiod(February–April2007)werepredisposingconditionsforthecalvestodevelopBRD.  2.3.Housingandfeedingfacilities Calveswerehousedin   3groupsof    20calvesin3sepa-ratebarnswithoutexternalyard.Nootherruminantswerepresentinthesamebarnsandnodirectoraerosolcon-tactswereassumedto   bepossiblebetweenthecalvesfromthedifferentgroupsor   withothercalveshousedontheresearchstation.Thecalveswerefeda   100%freshwhole  M.Rératetal./    PreventiveVeterinaryMedicine 103 (2012) 265–273 267 milkrationwithaddedmilkpowder(UFA202PreVitinwith35%skimmilkpowder;UFA,Sursee,Switzerland).Thedietwasfed adlibitum ,identically,forallanimalsandthedrymattercontentvariedfrom120to194g/kgwetweightdependingontheindividualBW.   Theironsupplywasensuredbyaddinga   mineral-andvitamin-richsup-plement(UFAtop-fitPreVitin;UFA;onaverage23.6mgFeperdandpercalf).Calveshadfreeaccesstowaterandhay.  2.4.Casedefinitionandtreatmentprotocol Thehealthstatusofeachcalfwasevaluatedond1afterarrivalatthefatteningunitandthenond7,14,21,28,35,42,49,and56.In   additiontoweeklyclinicalexaminations,the   healthstatusof    calvessuspectedof    beingillwaseval-uated.Theclinicalappearanceof    BRDwasclassifiedinto4grades,accordingtotheseverityof    thedisease(Lekeuxetal.,2002)(Table2).Forobservedgrade2symptoms,the treatmentoffirstchoicewas2intramuscularinjectionsof 20mg   oxytetracycline/kgBW   (Oxytetraseptin;Vetoquinol,Lure,France)everysecondday.Thecriterionforchoosingoxytetracyclineasafirst-linedrugwasthecommonuseofthisantibioticin   largeanimalpracticeforthetreatmentof    BRD.Forobservedgrade3symptoms,anintramuscularinjectionof0.06mgdexamethasone/kgBW(Dexadreson;Veterinaria,Pfäffikon,Switzerland)fora   maximumdura-tionof3dwascombinedwiththetreatmentoutlineaboveforgrade2cases.In   casesof    nonresponsivenesstooxytetracycline(presenceof    respiratorysymptoms,rectaltemperature>40 ◦ Cand/orrespiratoryrate>50/minonthefifthdayoftreatment),thecalveswereadditionallytreatedwith2subcutaneousinjectionsof6mgdanofloxacin/kgBW(Advocid18%;Pfizer,Zürich,Switzerland)everysec-ondday.Thetherapyof    4nonresponders(presenceof respiratorysymptoms,rectaltemperature>40 ◦ Cand/orrespiratoryrate>50/minonthethirddayof    treatment)todanofloxaciningroupCwaschangedto3intramuscularinjectionsof20mgflorfenicol/kgBW(Nuflor;EssexTier-arznei,München,Germany)everysecondday.Duringthetreatment,thehealthstatusofthemorbidcalveswasclini-callyexaminedeveryseconddayandantibiotictreatmentswerecontinueduntilrecoveryfromgeneralsymptoms.Arelapsewas   definedasa   BRDepisoderequiringanantimicrobialtherapyoccurringoneormoredaysaftertheprecedenttreatment.Casesofrelapseweretreatedusingthesameprotocolasforthefirsttreatment.Eachdayof    pro-phylacticortherapeutictreatmentwithanantimicrobialdrugwasconsideredasonedayoftreatment.  2.5.Samplecollection Transtracheallavagesampleswereobtainedonthedayofthefirstepisodeof    clinicallydiagnosedpneumo-niapriortotherapeutictreatmentbya   modifiedtechniquedescribedbyVogeletal.(2001).   Thepunctureregion(linebetweenthemediumandthelowerthirdofthetrachea)wasshearedanddisinfected.Apunctureofthetracheawasperformedwitha   sterileneedle(TSK-Supra,2.00 × 60;Provet,Lyssach,Switzerland)undersubcutaneouslocalanaesthesia(2.5mL    Lidocaine2%;StreuliPharma,Uznach,Switzerland).Acatheter(57cmtrachealsuctiontubewitha   diameterof    1.3mm;   Vygon,Ecouen,France)waspassedovera   distanceof    40–50cmthroughtheneedlein   thetracheaand50mL    of    sodiumchloridesolution(EcoflacNaCl0.9%100mL;   B.Braun,Melsungen,Germany)wasinjected.Thelavagefluidwas   immediatelyaspiratedintothesyringe.If    nofluidcouldbe   aspirated,anadditional50mL    ofsolutionwasinjected.Thecontentsof    thesyringeweretransferredto   asampletubeandstoredbetween2and8 ◦ Cuntilanalysis(withamaximumstoragetimeof 48h).Calveswereweighedatd   0,7,   and56oftheexper-imentalperiod.Theamountof    intakewas   monitoredbyaprogrammableautomatspecificforeachindividualcalf,whichworea   collarwitha   transponder(StandAlone;Förster,Engen,Germany).Hayintakewas   measuredforthewholegroup.  2.6.Bacterialculture Transtracheallavagesampleswerecentrifugedat3000 ×  g  for10min   andthesupernatantwasdiscarded.Thesedimentwasculturedontryptonesoyagarwith5%sheepblood(Oxoid,Basel,Switzerland)andincubatedwitha    -NAD-producing Staphylococcussciuri at37 ◦ Cinanatmosphereof    5%CO 2 ,andonMacConkeyagar(Oxoid)aswellason Pasteurella selectiveagar(Oxoid),incubatedaerobicallyat37 ◦ C.   Allplateswereincubatedfor48handbacterialisolateswereidentifiedbystandardmethods(biochemicaltestsandmoleculartechniques).For   isolationof    Mycoplasma spp.,sampleswereinocu-latedinto Mycoplasma -broth(AxcellBiotechnologiesSA,Lyon,France)complementedwithampicillin(2mg/mL;Sigma-AldrichChemieGmbH,Steinheim,Germany)andincubatedaerobicallyat37 ◦ Cfor3–7dandthensub-culturedonto Mycoplasma -agar(Axcell)withampicillinandreincubatedat37 ◦ Cin   anatmosphereof    5%   CO 2  for5d. Mycoplasma wereidentifiedtospecieslevelbya   PCR specificfor Mycoplasmabovis (Subramaniametal.,1998;Bashiruddinetal.,2005)andby16SrRNAgenesequenceanalysis,asdescribedpreviously(Kuhnertetal.,2002). Allsampleswereadditionallytestedforantibioticresiduesbyfour-platetestusingthemethodrequiredbytheEU(EU,1996).  2.7.Antibioticsusceptibilitytesting  Isolatedstrainsof    Pasteurellaceae ( P.multocida , Mannheimiavarigena and M.haemolytica )weretestedfortheirantimicrobialsusceptibilitytopenicillin,ampi-cillin,gentamicin,chlortetracycline,oxytetracycline,tylosin,tilmicosin,tulathromycin,florfenicol,enrofloxacin,danofloxacin,andtrimethoprim/sulphamethoxazolebydeterminationoftheMICs.MIC   testingwas   performedincation-adjustedMueller–Hintonbrothwithlysedhorseblood(2–5%,v/v)usinga   customSensititreplateBOPO6F(TrekDiagnosticsSystem,EastGrinstead,England)accord-ingtotheguidelinesM31-A3andM45-AoftheClinicalandLaboratoryStandardsInstitute(CLSI,2008,2006).Theplateswereincubatedaerobicallyfor24hat37 ◦ C.  268  M.Rératetal./    PreventiveVeterinaryMedicine 103 (2012) 265–273  Table2 Clinicalclassificationandtherapyofbovinerespiratorydisease(Lekeuxetal.,2002). Grade 1234SubclinicaldiseaseCompensatedclinicaldiseaseNon-compensatedclinicaldiseaseIrreversibleclinicaldiseaseAppetiteNormalDecreasedDecreasedDecreasedBehaviourNormalApathyApathyApathyRespiratoryrate,/min <50 >50 >70 >70Rectaltemperature, ◦ C<40 40–40.5>40.5>40.5RespiratorysymptomsNoneCoughingNasaldischargeDyspnoeaOpenmouthbreathingOrthopneaTreatmentNo   AntibioticsAntibioticsandanti-inflammatorydrugsNo  2.8.Statisticalanalysis Analysisofvariance(ANOVA)wasusedtocomparetheaveragevaluesofcalvesfromeachexperimentalgroup.Dataanalysiswas   implementedusingstandardsoft-ware(NCSS07.1.8;NCSSsoftware,Kaysville,UT,USA).Experimentaltreatmentwasusedasfixedeffectandtheindividualcalveswereusedasrandomeffects.IncludingtheBonferronicorrectionfactorformultiplecomparisonsofthe3groups,valuesof    P  ≤ 0.05wereconsideredstatisti-callysignificant.Averagedailygain(ADG),dailyfeedintake(DFI),meannumberoftreatment,durationoftreatment,levelof relapse,non-responserate,andnumberof    treatmentdaysweresummarizedandanalyzedusingtheone-wayanalysisofvariance.Univariateassociationsbetweentheprecedingvariablesandthetreatmentswereevaluatedusing t  -testsforcontinuousvariablesandtheKruskall–Wallistestfornon-continuousvariables.Dataof    bodyweightandinci-denceofrespiratoryimpairmentwereanalyzedusingtherepeatedmeasuresanalysisof    variance. 3.Results  3.1.Animalsandgrowthperformance OnecalffromgroupCdiedond23afterarrivalfromacutetympanyandwasexcludedfromthetrial.AverageinitialBWwas   similar( P  =0.952)in   thethreegroups(62.6 ±   2.7,62.5 ± 2.2,and63.5 ± 2.4kgforgroupsA,B,andC,respectively).Ond7meanBWwas68.8 ± 2.7,70.7 ±   2.4,and68.2 ±   2.2kgforgroupsA,B,andC,respectively( P    =   0.755)andond56126.9 ±   4.5,127.5 ± 4.4,and114.0 ± 3.9kg   forgroupA,B,andC( P  =0.053).TheADGbetweend0and7was   higher( P  =0.003)ingroupB(1.07 ±   0.08kg/d)thanin   groupC(0.60 ± 0.08kg/d)(groupA:   0.82 ± 0.11kg/d).ThemeanADGduringthewholeexperimentalperiodin   groupsof calvesprophylacticallytreatedwithantibiotics(1.14 ±   0.05and1.15 ± 0.04kg/dforgroupAandB,respectively)washigher( P  <   0.001)thaningroupC(0.89 ± 0.04   kg/d).TheDFIduringtheperiodtheantibioticswerefedingroupB(d1–7)waslower( P  =   0.017)ingroupC(0.61 ± 0.03kgDM/d)thaninthetwogroupsreceivingantibiotics(0.71 ±   0.03,0.71 ± 0.03kg   DM/dforgroupAandB,   respectively).ThemeanDFIduringthewholeexperimentalperiodwas   higher( P  =0.005)ingroupB(1.51 ± 0.06kgDM/d)thaningroupC   (1.20 ±   0.05kg   DM/d)(groupA:1.37 ±   0.06kg   DM/d).  3.2.Healthstatus Duringthefirst13dafterarrival,theincidencerateof respiratorydisorderswashigher( P    =   0.004)in   groupCthaningroupsA   andB(Fig.1).ThemeannumberoftherapeutictreatmentsagainstBRDforthewholeexperimentalperiodwas   higher( P  <   0.001)ingroupC(1.9 ± 0.2   treatmentpercalf)thanin   groupsAandB(0.9 ± 0.2,and0.7   ± 0.2treat-mentpercalfforgroupAandB,respectively;Table3).Takingintoaccounttheprophylactictreatments,averagenumberof    treatmentdayspercalfwasidentical( P  =   0.278)forthethreegroups(15.5 ±   1.7,11.8 ± 1.1,and14.8 ±   2.3forgroupA,B,   andC,   respectively).  3.3.Incidenceofbacterialpathogensandantibiotic susceptibilityoftheisolatedPasteurellaceae Duringthewholeexperimentalperiod,40transtracheallavagesamplesof    calveswithBRDwereobtainedfromthe59originalcalves.Threesamplesshowednobacterialgrowth.Noantibioticresiduesweredetectedinanyofthetranstracheallavagesamplesusingthefourplatetest.Intotal,79strainsof    bacterialpathogenswereisolated:38 Pasteurellaceae ,   30 Mycoplasma spp.(14ofthem M.   bovis ),8 Streptococcus spp.,2  Arcanobacteriumpyogenes andone  Acinetobacterlwoffi .The38 Pasteurellaceae weredetectedin29calves.Inadditiontoone Histophilussomni ,   one Pas-teurella sp.andone P.langaaensis , P.multocida was   detected18times. Mannheimiavarigena wasfound13timesand M.haemolytica only4times. Mannheimia spp.isolateswerealwayspresentconcomitantlywithotherpathogens. P.multocida ,   M.varigena ,   and M.haemolytica weretestedfortheirantibioticsusceptibilitybyMICdetermination.Ofthe13 M.varigena isolates,oneisolatedidnotgrow.Theresult-ingMIC   distributionsarepresentedin   Table4.TheMICsof thequalitycontrolstrains E.coli ATCC25922and S.aureus ATCC29213werewithintheexpectedCLSIqualitycon-trolranges.Limited invitro activityfortheantimicrobialclasses  -lactams(2 P.multocida ,   2 M.haemolytica ,   and1 M.varigena ),tetracyclines(2   P.multocida ,   2 M.haemolyt-ica ,and2 M.   varigena ),andpotentiatedsulphonamides(6  M.Rératetal./    PreventiveVeterinaryMedicine 103 (2012) 265–273 269 Fig.1. Incidenceofrespiratoryimpairment(inpercent)inthe3experimentalgroupsofvealcalvesduringthefirst56   d   afterarrivalatthefatteningunit.GroupA,B,andC=   groupstreatedprophylacticallyby   a   singleinjectionof    tulathromycin,bya   peroraladministrationof    chlortetracycline,sulphadimidine,andtylosin,orwithoutprophylactictreatment,respectively.Valuesaremeans ±   SD;   n =   20,20,and19forgroupA,B,andC,   respectively. P  -valuesforgroup,time,   andtheinteractiongroup × timeeffectsare   <0.001,<0.001,and0.004;respectively.Differencesbetweengroupsinthesameweekwithdifferentlettersaresignificant( P  ≤ 0.017). P  .   multocida ,   and1 M.   varigena )wasobserved.Fifteen P.multocida ,4 M.haemolytica and10 M.   varigena strainswereresistanttotylosin(MIC ≥ 32  g/mL).Tenof    the15 P.mul-tocida strainswereadditionallynon-sensitivetotilmicosin.Alltested Pasteurellaceae isolatesweresensitiveto   gentam-icinandflorfenicol.Theresistanceprofilesperidentifiedspeciesarelistedin   Table5.Intotal,thepercentageof    thetested Pasteurellaceae strainsresistanttooneormoreofthetestedantibioticswas94%(32/34).Multiresistance(resis-tancetomorethan2antibiotics)wasfoundin21%(7/34).Alargevariationinsusceptibilityprofileswasfoundwith11differentresistanceprofiles.One M.varigena isolatewasresistanttoalltestedantibioticswiththeexceptionof    gen-tamicinandflorfenicol.  Table3 Characteristicsofthetherapeutictreatmentsinthe3experimentalgroupsof    vealcalves.Studygroupsof    vealcalves a ABCNumberof    calves202019Numberof    calvestreatedforBRD b 11   1118Total   numberof therapeutictreatments18 c 14 c 37 d Relapserate7/183/1415/37Non-response0/180/144/37Meandurationof therapeutictreatment,d6.7 ± 0.86.9 ± 0.6   8.0 ± 0.9 a GroupA,B,andC=   groupstreatedprophylacticallybya   singleinjec-tionoftulathromycin,by   a   peroraladministrationof    chlortetracycline,sulphadimidine,andtylosin,orwithoutprophylactictreatment,respec-tively. b Equalnumberof    calvessampledby   TTL. c,d ValuesofgroupsA,B,andCwithdifferentsuperscriptsdiffer( P  <   0.001). 4.   Discussion 4.1.Effectofdifferentprophylacticantimicrobialtreatmentsonhealthandgrowthperformance Prophylacticantibioticsmay   be   usedasameansof decreasingacuterespiratorydisordersforseveraldaysafterarrivalat   thefeedlot(Franketal.,   2002)andtoimprovegrowthperformance(DuffandGalyean,2007).Duringthefirst7doftheexperiment(periodof    administra-tionof    theexperimentaltreatmentingroupB),theDFIwashigherin   thetwogroupswithprophylactictreatments,inaccordancewithpriorstudies(Galyeanetal.,   1995)thatshowedanincreaseinfeedintakeduringtheperiodof receivingtheantibiotic.Thiscouldbe   interpretedasaneffectof    theperoralprophylactictreatmentasanantimi-crobialgrowthpromoter,butthetreatmentperinjectionhadthesameeffectaswell.Stantonetal.(2010)foundthatthedairycalvestreatedprophylacticallywithoxytetracy-clineatpostweaningmovementweretwiceaslikelytobetreatedforBRDin   the60dfollowingenrolmentthandairycalvestreatedwithtulathromycin.Inthecurrentstudy,bothprophylacticantibiotictreatmentsdecreasedtheinci-denceof    respiratorydisordersbyhalfandimprovedADGcomparedwithcalvesthatreceivednoantibiotics,aspre-viouslyobservedbyDanielsetal.   (2000).Theexplanationfortheseimprovedperformancesisthefactthathealthyanimalseatmorethandomorbidones.HutchesonandCole(1986)foundthatthemeanfeedintakeofmorbidcalveswas11%lessthanthatof    healthycalvesafter56din   thefeedlot.Thus,theefficacyofaperoraladministra-tionof    antibioticscanbedepreciatedinseverelydiseasedcalves,astheymay   notconsumeenoughof    theantibioticforrecovery(Cole,1996).Thepeakofmorbidityof    BRDingroupCond7–13isinaccordancewiththeresultsof    KellyandJanzen(1986),who   foundthepeakincidenceof    BRDwithinthefirst3weeksafterarrival.Onaverage,eachcalf 
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