Antimicrobialresistantbacteria:whatdoesthatmean,andhowdoesitaffectme?
CarlesVilalta
KeyPoints
•Thetermresistantbacteriacanhavedifferentimplications dependingonthecontextofthedefinition
•Recommendeddrugbreakpointsarespecificforeachpairbuganddrug(andprobablyanimalspecific) andshouldnotbe
extrapolated
•Antimicrobialresistance isubiquitousbutmisuseofintimicrobialsexertsaselectivepressureonresistantbacteriaandincreases
theriskofcollateralgenetransmission
ͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲͲ
Occasionally,andwithmorefrequency,weseeandhearaboutdeathsrelatedtomultidrugresistantbugs,commonlycalledsuperbugsbythemedia.Thisscenarioand
itsimplicationshasincreasedsociety’sawarenessabouttheuseofantimicrobials,bothinhumansandanimals,andtheirpotentialroleinselectingresistantbacteria.
Thehighertheuseofantimicrobials,thehighertheriskofselectingresistantbugs.Butdoweknowwhatitmeanswhenwehear thetermresistantineitherafarm
context,orinlabresults?Actually,thebasicdefinitionisverystraightforward.Aresistantbacteriumistheonethatcanresistanditisnotaffectedbyanantimicrobial.
However,behindthatdefinitionaretwodifferentapproachesthatareworthknowing.
Thefirstwayofdefiningbacteriaasresistantisfromthepharmacologicalapproach.Youmightrecognizethatthisapproachwas usedwhentheresultfromthelabor
thedatayouarelookingathasthecategoriesofSusceptible(S),Intermediate(I)orResistant(R)oragivenminimuminhibitoryconcentration(MIC).TheMICisthe
minimumamountofdrugneededtoinhibitthegrowthofbacteriaonaPetridishorinatube.Itwillbeexpressedasmg/mlorμg/μl.ThehighertheMICthemore
resistantthebacteriacanbe.Thatmeanswhentreatingasickanimalwewouldneedmoreantimicrobialtoreachthesitewherethebacteriaare.Sometimesthat
difficultycanbeovercomebyincreasingthedose,treatingmorefrequently,orprolongingthetreatment.Thatwouldworkuntilwereachthepointwherethedose
wouldbetoohigh,causingtheliverandkidneysoftheanimaltobeunabletogetridofmoreofthecompound.Thedrugthen startstoaccumulateinthebody,
intoxicatingoreventuallykillingtheanimal.TohelpveterinarianschoosetherighttreatmentsomeorganizationsdividedtheMICdistributionintothreebreakpoints
basedonthelikelihoodofsuccessofthetreatment,oraccordingtoachievableconcentrationsofthatspecificantimicrobial in thesiteofaction.Thus,S,I,andRmean
high,medium,orlowlikelihoodofsuccessinthetreatmentofthatantimicrobialintheregistereddoseagainstthatspecificpathogen.Tofacilitatethediagnosticjob,
somelabsusewhatiscalledinfusiondisks,disksembeddedwithacertainconcentrationofdrugandplacedontoacultureof thespecificmicrobeofinterest.With
thoseplateswecantestdifferentdrugsandinfertheirlikelihoodoftreatmentsuccess,usingtheradiusoftheinhibitionzones.Finally,thebreakpointsarespecificto
theparticulardrugandmicrobecombinationstested,andshouldnotbeusedtoinferbreakpointsforothercombinations.
Thesecondmethodisfromthebacteriapointofview(microbiological
approach)andusesabreakpointorcutͲoffvaluethatseparatesthe
MICdistributionofthebacteriathatdonotexpresscertainresistant
genes(wildtype)versusthedistributionofthemicrobesthatexpress
thosemechanisms.Basically,herewewillcallbacteriaresistantifthey
haveresistantgenes,creatingthepotentialtobeantimicrobially
resistant.Toestablishthatseparationweneedtocategorizethe
bacteriaaccordingtotheresistantgenesthattheymaypossessandlink
thattotheMICofeachspecificstrainagainstthatspecificcompound.
Animportantcomplicationindetermininggenebasedresistanceisthe
potentialforthetransferofaresistancegenebetweenbacteriaor
bacteriafamilies(Figure1).Thesetransfersmakeithardertousean
antimicrobialonanybacteriainpossessionofthoseresistantgenes.
Acquisitionofresistanceagainstacertaintypeofdrugcancausethe
bacteriatoalsoberesistanttoanothercompound.Thisiswhatiscalled
crossͲresistance.
Eventhoughtheterm“resistant”isunderstoodasamicrobebeing
resistantagainstanantimicrobial,wecanseethathowthelabelwas
reached,affectsitsmeaning.Insomecases,bacteriahavethegenetic
potentialtoavoidthechemicalcompoundandinsomeothercasesnot
enoughdrugwillreachtheinfectionsitetoreducethebacteriatoa
levelthattheimmunesystemcantakecareof.Themoreinformation
wehaveabouttheunderlyingcauseofresistance,thebetter.
Mistreatmentsandundertreatmentscanshiftbacterialselection
towardsaresistantstrainofthebacteria.
Figure1(Right): Pathwaysofresistantgenesspread.Source:CenterforDiseaseControland
Prevention
OriginallypublishedintheNationalHogFarmer
http://www.nationalhogfarmer.com/animalͲhealth/antimicrobialͲresistantͲbacteriaͲwhatͲ
doesͲmeanͲandͲhowͲdoesͲitͲaffectͲme?NL=NHFͲ001&Issue=NHFͲ001_20170509_NHFͲ
001_384&sfvc4enews=42&cl=article_1_b&utm_rid=CPG02000000738166&utm_campaig
n=16830&utm_medium=email&elq2=7e427f837ad7428fb2e0af6482655bfd
Ifyouarefurtherinterestedinthistopicyoumightbeinterestedinthe
shortvideomadebytheHarvardmedicalschooltitled‘TheEvolutionof
Bacteriaona“MegaͲPlate”PetriDish’thatshowsbacteriaovercoming
a1000Ͳfolditsspecifickillingconcentration.
https://www.youtube.com/watch?v=plVk4NVIUh8
5/12/2017