On Being the Right Size The Impact of Population Size and Stochastic Effects on the Evolution of Drug Resistance in Hospitals and the Community 英文参考文献.docVIP

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On Being the Right Size The Impact of Population Size and Stochastic Effects on the Evolution of Drug Resistance in Hospitals and the Community 英文参考文献.doc

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On Being the Right Size The Impact of Population Size and Stochastic Effects on the Evolution of Drug Resistance in Hospitals and the Community 英文参考文献

OnBeingtheRightSize:TheImpactofPopulationSize andStochasticEffectsontheEvolutionofDrug ResistanceinHospitalsandtheCommunity RogerD.Kouyos1,2.*,PiaAbelzurWiesch1.,SebastianBonhoeffer1 1InstituteofIntegrativeBiology,ETHZurich,Zurich,Switzerland,2DepartmentofEcologyandEvolutionaryBiology,PrincetonUniversity,Princeton,NewJersey,United StatesofAmerica Abstract The evolution of drug resistant bacteria is a severe public health problem, both in hospitals and in the community. Currently, some countries aim at concentrating highly specialized services in large hospitals in order to improve patient outcomes.Emergentresistantstrainsoftenoriginateinhealthcarefacilities,butitisunknowntowhatextenthospitalsize affectsresistanceevolutionandtheresultingspilloverofhospital-associatedpathogenstothecommunity.Weusedtwo publisheddatasetsfromtheUSandIrelandtoinvestigatetheeffectsofhospitalsizeandcontrolledforseveralconfounders such as antimicrobial usage, sampling frequency, mortality, disinfection and length of stay. The proportion of patients acquiringbothsensitiveandresistantinfectionsinahospitalstronglycorrelatedwithhospitalsize.Moreover,weobserve thesamepatternforboththepercentageofresistantinfectionsandtheincreaseofhospital-acquiredinfectionsovertime. One interpretation of this pattern is that chance effects in small hospitals impede the spread of drug-resistance. To investigatetowhatextentthesizedistributionofhospitalscandirectlyaffecttheprevalenceofantibioticresistance,weuse astochasticepidemiologicalmodeldescribingthespreadofdrugresistanceinahospitalsettingaswellastheinteraction betweenoneorseveralhospitalsandthecommunity.Weshowthatthelevelofdrugresistancetypicallyincreaseswith populationsize:Insmallhospitalschanceeffectscauselargefluctuationsinpathogenpopulationsizeorevenextinctions, both of which impede the acquisition and spread of drug resistance. Finally, we show that indirect transmission via environmentalreservoirscanreducetheeffectofhospitalsizebecausetheslowturnoverint