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How to Impact antibiotic prescribing? van Buul, L.W.

2015

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van Buul, L. W. (2015). How to Impact antibiotic prescribing? A contribution to antibiotic stewardship in long-term

care.

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Abstract

Introduction: The common occurrence of infectious diseases in nursing homes and

residential care facilities may result in substantial antibiotic use, and consequently antibiotic resistance. Focusing on these settings, this article aims to provide a comprehensive overview of the literature available on antibiotic use, antibiotic resistance,andstrategiestoreduceantibioticresistance. Methods:Relevantliteraturewasidentifiedbyconductingasystematicsearchinthe MEDLINEandEMBASEdatabases.Additionalarticleswereidentifiedbyreviewingthe referencelistsofincludedarticles,bysearchingGoogleScholar,andbysearchingWeb sitesofrelevantorganizations. Results:Atotalof156articleswereincludedinthereview.Antibioticuseinlongterm

care facilities is common; reportedannual prevalencerates range from 47% to 79%. Partoftheprescribedantibioticsispotentiallyinappropriate.

The occurrence of antibiotic resistance is substantial in the longterm care setting. Riskfactorsfortheacquisitionofresistantpathogensincludepriorantibioticuse,the presence of invasive devices, such as urinary catheters and feeding tubes, lower functionalstatus,andavarietyofotherresidentandfacilityrelatedfactors.Infection with antibioticresistant pathogens is associated with increased morbidity, mortality, andhealthcarecosts.

Two general strategies to reduce antibiotic resistance in longterm care facilities are theimplementationofinfectioncontrolmeasuresandantibioticstewardship.

Conclusion: The findings of this review call for the conduction of research and the

Introduction

Elderly people living in nursing homes and residential care facilities are at increased risk of acquiring infectious diseases. This is because of several agerelated factors, such as pathologic alterations to the immune system, functional disability, the presence of chronic diseases, and the use of invasive devices, such as urinary cathetersandfeedingtubes.13Inaddition,severalfacilityrelatedfactorsincreasethe risk of spread of infectious diseases, such as residents living in close proximity and participating in social activities, and serial close contactof dependent residentswith staff and medical equipment.1,3 Because of the presence of these biological and environmental factors, infectious diseases commonly occur in nursing homes and residential care facilities. An incidence rate ranging from 3 to 7 infections per 1000 residentcare days has been reported.46 In addition, a pointprevalence rate that varies between 6.7% and 7.6% was found for infections in nursing home residents.7 Whereas some studies report urinary tract infection (UTI) as the most common infectious disease in nursing homes and residential care facilities,5,79 other studies report respiratory tract infection (RTI) as the most common infection.4,1012 Skin and soft tissue infections (SSTIs) also represent a frequently reported type of infection.4,8,11



Thecommonoccurrenceofinfectiousdiseasesinnursinghomesandresidentialcare facilities may result in substantial use of antibiotics in these settings, which in turn may enhance the development of antibiotic resistance. Over the past few decades, several studies have been published with regard to antibiotic use and resistance in these facilities. In addition, strategies have been proposed to reduce antibiotic resistance. This article aimed to integrate this information by providing a comprehensiveoverviewoftheliteratureonantibioticuse,antibioticresistance,and strategiestoreduceantibioticresistance,therebyfocusingonlongtermcarefacilities (nursing homes, where the main focus in on providing nursing care, and residential carefacilities/assistedlivingfacilities,wherethemainfocusisonprovidinga“home” forresidents).Basedonthisliteratureoverview,weformulateimplicationsforfuture researchandpolicydevelopment.



Methods

Relevantliterature was identifiedbyconductingasystematicsearchin theMEDLINE and EMBASE databases. We used the following key words for the search in the MEDLINE database: “residential facilities [MeSH Terms] AND (antibacterial agents [MeSH Terms] OR drug resistance, microbial [MeSH terms]).” For the search in the EMBASE database, the following key words were used: “(’nursing home’/exp OR ’residential home’/exp) AND (’antibiotic agent’/exp OR ’antibiotic resistance’/exp).” Only publications in English, focused on humans, and listed in the database before May5,2011,wereconsidered.



Evaluatingthearticlesresultingfromthesystematicsearch,2researchers(L.v.B.and J.v.d.S.) identified 3 “areas of interest”: antibiotic use, antibiotic resistance, and strategies to reduce antibiotic resistance. The same researchers developed general and “area of interest” specific inclusion and exclusion criteria, based on a set of articlestheyconsideredhighlyrelevant(Box1).Thearticlesresultingfromthesearch in the MEDLINE database were independently screened for inclusion by both researchers. In case of discrepancy in the judgment for relevance, the article was discusseduntilconsensuswasreached.Next,thearticlesresultingfromthesearchin theEMBASEdatabasewerescreenedforrelevancebythefirstresearcher(L.v.B.);the second researcher (J.v.d.S.) screened a random sample of 10% and all articles that wereincludedbythefirstresearcher.



Weadditionallyincludedarticlesbyreviewingthereferencelistsofincludedarticles, by hand searching Google Scholar, and by searching Web sites of relevant organizations (eg, the European Centre for Disease Prevention and Control, the American Medical Directors Association, the Society for Healthcare Epidemiology of America,theAssociationforProfessionalsinInfectionControlandEpidemiology,and theWorldHealthOrganization).



Results

Figure 1 shows the flow diagram of the literature search. Of 978 articles retrieved with the systematic search in MEDLINE and EMBASE and of 18 articles identified otherwise(ie,byreviewingthereferencelistsofincludedarticles,byhandsearching Google Scholar, and by searching Web sites of relevant organizations), 159 met the inclusioncriteriafor1ormorearea(s)ofinterest(Box1).Mostofthese159articles was allocated to the area of interest “antibiotic resistance” (n = 103). Fewer articles dealtwith“antibioticuse”(n=44)or“strategiestoreduceantibioticresistance”(n= 16).Threearticlesthatmettheinclusioncriteriawerenotcitedbecauseofdifficulties interpretingresultsowingtoaninadequatedescriptionofmethods.Mostofthe156 includedarticleswereoriginalarticles(n=107).Othertypesofarticleswerereviews (n=30),letters(n=10),reports(n=3),editorials(n=3),andguidelines(n=3). 

 Figure1.Flowdiagramoftheliteraturesearch.



Antibioticuseinnursinghomesandresidentialcarefacilities

Incidence/prevalenceofantibioticuse

Table 1 presents an overview of 26 studies that investigated the incidence and/or prevalence of antibiotic use among residents in longterm care settings (inclusion criteria: Box 1). Of these, 22 were identified with the systematic search and 4 were identifiedotherwise.





Factorsassociatedwithantibioticuse

Weidentifiedfactorsassociatedwithantibioticuseinlongtermcarefacilitiesonthe resident level, facility level, and geographical level. On the resident level, the use of invasive devices, such as urinary catheters or feeding tubes, was significantly associated with antibiotic use.13,35 Furthermore, higher rates of antibiotic use were found in residents with higher probabilities of nursing home discharge and in residents receiving extensive medical or rehabilitation services.13 A factor on the facilitylevelisthefacilitytype:Moroetal28reportedahigherprevalenceofantibiotic use in residents of nursing homes (13.1%) than in residents of residential care facilities(4.9%)inItaly.Inaddition,Loebetal35foundhigherratesofantibioticusein facilitieswithmorehealthcareaidesper100residents.Thisfindingmaybeexplained byconfounding,asfacilitieswithmorehealthcareaidesmayaccommodateresidents whorequiremorecare.Onthegeographicallevel,antibioticusehasbeenreportedto differ withinandbetweencountries.Blixetal29reportedlarge variationinantibiotic use among 133 nursing homes in Norway: from 4 to 44 defined daily doses per 100 beddays.Substantialvariationinincidenceofantibioticusewasalsofoundbetween longterm care facilities in the United States (8.014.8 antibiotic courses per 1000 residentcaredayspermonth).37Withregardtodifferencesinantibioticusebetween countries, Loeb et al35 reported that nursing homes in the United States prescribed significantly more antibiotics than Canadian nursing homes. Furthermore, The European Centre for Disease Prevention and Control funded 2 related projects (the European Surveillance of Antimicrobial Consumption [ESAC] project and the HealthcareAssociated Infections in Longterm care Facilities [HALT] project) that reported substantial variation in antibiotic use among European nursing homes. Althoughtheirresultsarederivedfromahighnumberofnursinghomes(304and117 respectively) in a high number of countries (19 and 13 respectively), drawing conclusionswascomplicatedbythefactthatadisproportionatenumberofcaseswas provided by nursing homes in only 3 countries (ie, Belgium, Italy, and Northern Ireland).38,39However,weightedanalyses(inthiscasebyrandomlyselecting5nursing homes per country) resulted in similar conclusions: there was large variation in antibiotic prescription rates among European countries, ranging from 1.4% in GermanyandLatviato19.4%inNorthernIrelandinApril2009andfrom1.2%inLatvia to13.4%inFinlandinNovember2009.27



Appropriatenessofantibioticuse

dosage,ortreatmentduration,hasbeeninvestigatedinseveralstudies,therebyusing various criteria. Zimmer et al25 reviewed the use of antibiotics in more than 2000 nursinghomepatientsandjudgedevidencetostartantibiotictreatmentasadequate in 62% of cases. This judgment was based on criteria for appropriateness that had been developed by an expert panel. In another study, only 49% of 120 antibiotic prescriptions were considered appropriate. The primary reason for rating a prescriptionasnotappropriateinthisstudywasthatamoreeffectiveantibioticagent was recommended by infectious disease specialists and a hospital pharmacist (ie, in 71% of the cases).30 The same percentage of appropriate antibiotic prescriptions (49%)wasfoundbyLoebetal,14withtheleastappropriateprescriptionsinUTI(28%) and more appropriate prescriptions in RTI (58%) and SSTI (65%). In the latter study, appropriatenessofantibioticprescribingwasjudgedbasedonfulfillmentofdiagnostic criteriaderivedfromdefinitionsofinfectionsinlongtermcarefacilities,asdeveloped by McGeer et al.43 Clinical situations in which antibiotics are often prescribed inappropriatelyareviralrespiratoryinfectionsandasymptomaticbacteriuria,whereas antibiotic treatment for these conditions is not recommended.40 Warren et al17 reported that of more than 2000 antibiotic prescriptions in nursing home residents, 13% were for viral respiratory infection and 9% for asymptomatic bacteriuria. The same percentage of inappropriate prescriptions for asymptomatic bacteriuria was foundinanotherstudy.19



Aspecificdomaininthedeterminationofappropriatenessofantibioticprescribingis the use of antibiotics at the end of life. As early as 1979, it was observed that antibiotics were withheld in nursing home residents with endstage disease who developed fever (ie, a proxy for an infectious disease).44 There is an ongoing debate abouttheappropriatenessofantibioticprescribinginpatientsattheendoflifewho developRTIs,astheeffectonneitherlifeprolongationnordiscomfortreliefisclear.45 48   Adverseeffects

Even when antibiotics are prescribed appropriately, they pose a risk in terms of adverseeffects.Thisriskhasbeenreportedtobeelevatedintheelderly.49,50Asolder personsoftenusemultipledrugs,adverseeffectsowingtodruginteractionscanbean issue.Inaddition,elderlyaremoresusceptibletoadversedrugreactionsasaresultof decreasedkidneyandliverfunctionandthepresenceofmultimorbidity.Furthermore, elderly who are being treated or have recently been treated with antibiotics are at increased risk of Clostridium difficileassociated diarrhea.9,45,49 Nevertheless, the greatest concern in terms of adverse consequences of antibiotic use is the development of antibiotic resistance, which potentially causes both an individual burdenandathreatforpublichealth.9,45,49,51

  

Antibioticresistanceinnursinghomesandresidentialcarefacilities

Incidenceandprevalenceofantibioticresistance

Weidentified60studiesin14countriesthatinvestigatedtheincidenceorprevalence of antibioticresistant pathogens in longterm care facilities.18,22,52109 We found that colonizationorinfectionofresidentshasbeenstudiedmostcommonlyformethicillin resistant Staphylococcus aureus (MRSA), multidrug resistant gramnegative bacteria (MDRGN), and vancomycinresistant Enterococci (VRE). Trick et al103 reported colonization with at least 1 of these resistant pathogens in 43% of the persons residinginalongtermcarefacility(n=117)intheUnitedStates.Otherstudiesfrom the United States reported MRSA colonization prevalence rates ranging from 8% to 82% between 1991 and 2000, and from 11% to 59% between 2001 and 2011.18,53,54,61,73,75,76,78,81,83,86,89,91,93,98,99,102WithregardtoMDRGNandVRE,prevalence rates ranging from 23% to 51%63,86,91,96 and from 1% to 19%60,86,91 were reported, respectively. O’Fallon et al87 found that 31% of longterm care facility residents (n = 135) were colonized by at least 1 multidrugresistant gramnegative organism at baselineofacohortstudy.Theyalsofoundthat39%oftheresidentsacquiredatleast 1oftheseorganismsduringthestudyperiodof1year,manyofwhom(62%)hadnot beencolonizedatbaseline.



European studies have also addressed antibiotic resistance. The highest prevalence rateofMRSAcolonization(38%)hasbeenreportedamongresidents(n=109)oflong term care facilities in France,62 and prevalence rates varying between 17% and 22% werefoundinnursinghomeresidents(159<n<3037)intheUnitedKingdom.52,65,97A lowerMRSAcolonizationprevalenceratehasbeenreportedinItaly(8%and19%,n= 551 and n = 88 respectively),22,82 Slovenia (9% and 12%, n = 107 and n = 127 respectively),56,106 Ireland (9% and 10%, n = 743 and n = 754 respectively),88 and Belgium(5%,n=2857andn=2908).69,100Prevalenceratesweresubstantiallylowerin studies from the Northern European countries Germany (1.1%, n = 3236),105 Finland (0.9%,n=213),71andtheNetherlands(0.2%0.8%,204<n<89,573[thesamplesize of 89,573 is based on the number of isolates analyzed by laboratories; the other reported sample sizes are based on the number of residents]).59,66,67,101,107 ColonizationwithresistantpathogensotherthanMRSAduringresidencyinlongterm care facilities has been reported in France (an increase in extendedspectrum  lactamaseproducing pathogens in the period 19962006),84 Ireland (prevalence of multidrugresistantEscherichiacoli:40.5%oftheresidents[n=294]),95andGermany (prevalenceofVRE:4.3%oftheresidents[n=188]).110



Riskfactorsforcolonizationorinfectionwithantibioticresistantorganisms

Table2presentsanoverviewofresidentandfacilityrelatedcharacteristicsthatwere identified as significant risk factors for colonization or infection with antibiotic resistant organisms in 2 or more articles. At the resident level, prior antibiotic treatmentwasmostfrequentlyreportedasariskfactorforcolonizationorinfection

Table2.Riskfactors*forbecomingcolonizedorinfectedwithantibioticresistantorganismsinlongtermcarefacilities.  No.ofarticlesinwhichreported,bytypeofanalysis(+references) Riskfactor No.of articlesin which reported

Bivariable† Multivariable† Review

Residentfactors Priorantibiotictreatment 35 1318,21,70,96,103,105,116122 1262,80,86,87,100,109,123128 102,41,42,113,115,129133 Presenceofinvasivedevices(eg, urinarycatheter,feeding tube) 29 7102,103,111,118,119,121,134 962,94,96,100,105,125,127,128,135 132,41,42,113,115,129133,136138 Lowerfunctionalstatus 26 853,68,77,96,102,109,111,139 786,103,105,111,121,125,140 112,41,113,115,129,130,132,133,136138 Priorhospitalization 18 1018,65,68,70,94,117,120122,141 3100,105,123 541,115,131,133,138 Presenceofdecubitusulcers 15 5102,105,111,117,142 586,100,120,126,134 541,113,115,132,138 Presenceofwounds 14 553,62,70,102,142 1105 82,41,113,129,131,132,136,137 Priorcolonizationbyantibiotic resistantorganisms‡ 10 318,103,118 396,134,143 42,41,113,129 Urinaryincontinence 7 287,139 1134 441,113,115,138 Presenceofcomorbidities Diabetesmellitusand/or peripheralvasculardisease ‘Underlyingillness’ Renaldisease/insufficiency Comorbiditiesingeneral Priorpneumonia Inflammatoryboweldisease  7  4 3 3 3 2 2102,120_   218,102 1134 1102 1102 194_        42,41,113,115_  441,42,130,138 1113 241,129 241,113 1113 Malesex 5 1142 394,120,134 1113 Fecalincontinence 4 1139 186 2115,138 Higherintensityofnursingcare 4  1109 341,129,133 Lengthofstayinthefacility ‘longer’ 4y 14y <6mo ‘shorter’whencomparing interquartileranges  3 1 1 2 2      2105,120 2103,141   186 1100    341,42,113     Higherage 3 1120  2113,115 Lowercognitivestatus 2  1120 1130 Facilityfactors Lackofinfectioncontrolpolicy 5   542,113,115,138,144 Higherpatienttostaffratio 5   542,113,115,138,144_ Frequentstaffturnover 4   4113,115,138,144 Staffingbynonprofessional personnel 4   4113,115,138,144 Facilitysize Large Medium  4 1    1105  441,113,115,133  Highernumberofresidentsper bedroom 3  1100 242,113 Morefrequentresidentto residentcontact 2   2138,144 Limitedfacilitiesforhandwashing 2   242,113 * Includedinthisoverviewareriskfactorsthatwerereportedtobesignificantinarticlesthatinvestigatedtheriskfactorbybivariable(column3)or multivariableanalysis(column4),andbysystematicandnonsystematicreviewarticles(column5). † Riskfactorsthatwereidentifiedinastudybybothbivariableandmultivariableanalysisarelistedonlyinthecolumn“multivariable”. ‡ Eithercolonization/infectionwithanantibioticresistantorganismisariskfactorfor(another)infectionorcolonizationwithoneantibioticresistant organismisariskfactorforcolonizationwithanotherantibioticresistantorganism.  withantibioticresistantorganisms,followedbythepresenceofinvasivedevices,such asurinarycathetersorfeedingtubes.Anotherfrequentlyreportedriskfactorislower functional status, which may be explained by the fact that residents with a lower functionalstatushavemorefrequentcontactwithhealthcareworkersandtherefore moreopportunitiesforacquisitionofantibioticresistantorganisms.86,103,105Otherrisk factors that are related to the physical status of residents include the presence of decubitus ulcers, the presence of wounds, urinary incontinence, the presence of comorbidities, and fecal incontinence. In addition, several articles report prior

hospitalization as a risk factor, which suggests that the hospital is a source of antibioticresistant organisms. Nevertheless, Hsu111 did not find an association between prior hospitalization and MRSA carriage in nursing home residents and argued that nursing homes serve as reservoirs of antibioticresistant pathogens as well.Thiswassupportedbyotherauthors,whoidentifiednursinghomestayasarisk factor for colonization with MRSA at hospital admission.112114 Both “longer” and “shorter” length of stay in longterm care facilities have been associated with increased risk of colonization or infection with antibioticresistant organisms. Prolongeddurationofstayinthefacilitymayincreasethelikelihoodofacquisitionof antibioticresistant organisms from other colonized residents or health care workers.86 With regard to the risk factor “shorter length of stay in the facility,” von Baumetal105arguethatthisassociationmaybeconfoundedbypriorhospitalization of residents admitted to a longterm care facility. Other reported risk factors on the resident level include prior colonization by antibioticresistant organisms, male sex, higherintensityofnursingcare,higherage,andlowercognitivestatus.



Alackofinfectioncontrolpolicyisthemostfrequentlyreportedfacilityrelatedfactor that is associated with an increased risk of becoming colonized or infected with antibioticresistantorganisms.Thisincludesalackofhygienicmeasures,suchashand washing,theuseofgloves,coughetiquette,andbarrierprecautions.115Otherfactors onthefacilitylevelincludeanumberoffactorsrelatedtostaffing(ie,higherpatient tostaffratio,frequentstaffturnover,andstaffingbynonprofessionalpersonnel),an increased number of residents per bedroom, increased residenttoresident contact, increasedfacilitysize,andlimitedfacilitiesforhandwashing.



Consequencesofinfectionwithantibioticresistantorganisms

different therapeutic approaches in this population, such as less frequent hospital referral and withholding of treatment in residents with severe dementia. Another consequence reported on the resident level involves quality of life. Loeb et al148 investigatedthequalityoflifeofasmallnumberofresidents(n=14)colonizedwith multiresistant organisms and found a trend toward more depressive symptoms, dysfunctional behavior, dependency in activities of daily living, and lower health related quality of life. This trend toward worse quality of life may be related to isolation precautions, which may impede opportunities for residents to socialize or participateingroupactivities.113,148



Strategiestoreduceantibioticresistanceinlongtermcaresettings

Implementationofinfectioncontrolmeasures

Infection control refers to measures directed at preventing or decreasing the emergence and spread of infectious diseases. This results in a lower incidence of infectiousdiseasesandantibioticuse,andinturntoareducedemergenceandspread ofantibioticresistantorganisms.Examplesofinfectioncontrolmeasuresinthelong term care facility include hand washing, the use of gloves, disinfection of surfaces, coughetiquette,appropriateventilation,immunizationofresidents,andminimaluse of invasive devices, such as urinary catheters and feeding tubes.1,21,113,131,149151 Furthermore, important components of infection control programs include the assignment of a welltrained infection control practitioner to head the program, the assignment of an infection control committee, the dissemination of an infection controlplan,staffeducation,ensuring sufficientadministrative andfinancialsupport to undertake core infection control functions, and the surveillance of antibiotic resistantorganismsandantibioticuse.149152Theimplementationofinfectioncontrol programs,however,canbechallenginginlongtermcaresettings.Lackofpersonnel, high workload, insufficient training, and a lack of resources are examples of factors thatcanimpairtheimplementationofinfectioncontrolmeasures.1,6,103,113,153155 

Improvingtherationaluseofantibiotics(antibioticstewardship)

Warnings not to abuse antibiotics date back to Alexander Fleming in the 1940s.158 Morerecently,severalinitiativeshavebeentakeninpromotingrationalantibioticuse in longterm care settings. In 2000, Nicolle et al9 published a guideline with recommendations on antibiotic prescribing for RTI, UTI, SSTI, diarrhea, and fever of unknownorigin.Inanotherguideline,publishedbyLoebetal,40minimumcriteriafor the initiation of antibiotics in longterm care facilities were formulated. Both guidelines represent highly cited works. In addition to adherence to guidelines on antibiotic prescribing, other elements of antibiotic stewardship programs include physicianeducationonantibioticprescribing,providingfeedbackonprescriptions(eg, antibiotic use review by a pharmacist), monitoring appropriateness of antibiotic prescribing, providing resources for obtaining cultures for diagnosis, using restricted formularies, using antibiotic order forms, and limiting the use of broadspectrum antibiotics.9,25,131,152,159 The involvement of nursing staff is considered important for the success of antibiotic stewardship programs, as the information on which physiciansbasetreatmentdecisionsisoftenderivedfromnursingassessments.132,154 At the physician level, factors that need to be addressed in the successful implementation of antibiotic stewardship programs include knowledge and preferences regarding antibiotic use, and perceived expectations of the patient and thefamilyofthepatientwithregardtoantibiotictreatment.160



In the European setting, the availability of antibiotic stewardship resources was investigatedbytheESACprojectgroup.Datawereobtainedfrom260nursinghomes in 17 countries. A finding that suggests room for improvement is that no specific guidelinesforrationaluseofantibioticsinthelongtermcaresettingwereavailablein 50%ofthenursinghomes.Furthermore,arestrictedantibioticformularywasusedin only 16.2% of the facilities and the same percentage of facilities did not provide regulartrainingofphysiciansonappropriateantibioticprescribing.38



Discussion

Remarkably,fewerthan0.3%oftheMEDLINEandEMBASEpublicationsonantibiotic use and antibiotic resistance focus on longterm care facilities. Research on these topicsmayberelativelyunderdevelopedinthelongtermcaresetting,comparedwith other health care settings, such as the hospital and primary care. Of the articles identifiedforthelongtermcaresetting,morewereallocatedtotheareaofinterest “antibioticresistance”(103/159)thantotheareaofinterest“antibioticuse”(44/159), which indicates that relatively more research focuses on the former topic. A broad interest in antibiotic resistance concurs with the World Health Organization’s theme of World Health Day 2011, during which the agency called on governments to undertake action with regard to the resistance problem in all health care settings undertheslogan“noactiontodaymeansnocuretomorrow.”161



The ESAC project reported large variation among countries in antibiotic use for nursing home residents. The highest prevalence rates were found for northern Europeancountries(ie,NorthernIrelandandFinland).27Thisisaremarkablefinding, as in primary care settings, southern European countries account for the highest antibioticuse.162



Interestingly, some authors report that only 49% to 62% of the antibiotics in long term care facilities are prescribed appropriately14,25,30; however, these studies based their findings on different criteria for judging appropriateness of antibiotic prescribing. The lack of a universally accepted definition for diagnosing infectious diseasesandsubsequentappropriateprescribingofantibiotics,163incombinationwith the small number of studies conducted, complicates drawing conclusions on the appropriatenessofantibioticprescribinginlongtermcarefacilities.



In addition to prior antibiotic treatment and presence of invasive devices, such as urinary catheters and feeding tubes, lower functional status is one of the most frequently reported risk factors for becoming colonized or infected with antibiotic resistant organisms in longterm care facilities. Some of the authors who identified this association by multivariable analysis suggest that this may be because residents with lower functional status have more frequent contact with health care workers.86,103,105 Another explanation, which we did not encounter in the retrieved literature,maybethatresidentswithlowerfunctionalstatusaremorevulnerablefor theacquisitionofinfectionsbecauseofamorecompromisedimmunesystem.



Thehospitaliscommonlyregardedasasourceofantibioticresistantpathogensfrom which transmission to other healthcare setting occurs. Nonetheless, some studies retrievedwiththeliteraturesearchsuggestedthatlongtermcarefacilitiesmayserve asreservoirsforantibioticresistantpathogensaswell.112114Thesestudiesfocusedon the epidemiology of transmission (eg, by determining prior nursing home stay in colonizedpatientsadmittedtothehospital),andcouldnotdrawfirmconclusionswith regardtothetransmissionofresistantstrainsfromonehealthcarefacilitytoanother.

Studiesfocusingonmolecularepidemiology,whichwerenotaddressedinthisreview, are better suitable to elucidate the role of the nursing home in the transmission of antibioticresistant pathogens. For example, a Dutch study on the distribution of MRSA isolates between 1998 and 2005 indicated nursing homes as a potential intermediateforMRSAtransmissionfromthecommunitytothehospital.164



This review addressed antibiotic use and antibiotic resistance as separate issues, because the studies on antibiotic use differ from those on antibiotic resistance in termsofstudysettinganddesign.Comparingthesestudiesacrosscountriesprovides inconsistent evidence for an association between antibiotic use and antibiotic resistance. For example, Germany, a country with a low antibiotic use point prevalence (1.4%),27 is reported to have a low prevalence of MRSA resistance when compared with other European countries (1.1%).105 In Italy, with a moderate antibiotic use pointprevalence (8.4%),28 resistance rates were alsomoderate (8% to 19%).22,82 By contrast, in Northern Ireland (19.4%) and Finland (13.4%),27 antibiotic usepointprevalencewasreportedtobeamongthehighestinEurope,butreported MRSA prevalence was moderate to low in these countries (9%10% and 0.9%, respectively).71,88Thisinconsistentevidenceforanassociationbetweenantibioticuse andresistanceonthecountrylevelmaybeexplainedbyantibioticresistancenotonly being associated with antibiotic use, but also with the extent to which infection controlactivitiesareimplementedinlongtermcarefacilities.



Many articles that we retrieved through the literature search focused on specific interventions to reduce antibiotic resistance, such as hand washing and implementation of guidelines. Such articles were not included this review, as we aimed to provide a general overview of strategies to reduce antibiotic resistance rather than an overview of effectiveness of specific interventions. This explains the relativelylownumberofarticlesallocatedtotheareaofinterest“strategiestoreduce antibiotic resistance” (16/159); clearly, a higher numberof articleswould have been allocatedtothisareaofinterestifspecificinterventionswouldhavebeenincluded. 

We also did not include articles that addressed antibiotic use and resistance in subgroups of longterm care facility residents (eg, residents with pneumonia or residentswithinvasivedevices,suchasurinarycathetersandfeedingtubes).Instead, aratherbroadfocusonthegenerallongtermcarefacilitypopulationwaschosento ensureacomprehensivesituationanalysiswithoutelaborationonsubgroupdetails. 

missed. We are, however, confident that the most relevant literature is included in thisreview,asmanyarticlesidentifiedwiththesearchstrategywereencounteredin the reference lists of other identified articles. Furthermore, additional relevant articles were included by reviewing the reference lists of included articles, by hand searchingGoogleScholar,andbysearchingWebsitesofrelevantorganizations.



The relatively low percentage of publications on antibiotic use and resistance that focus on longterm care facilities indicates a need for more research specific to this setting. In addition, further research is required to elucidate the extent of the problem of inappropriate antibiotic prescribing. Although it may promote comparability of results if future studies used a universal definition for appropriateness of antibiotic prescribing, it is questionable whether this is feasible. Differentcountriesusedifferentguidelinesfordiagnosisandtreatmentof infectious diseases in longterm care residents, which may call for definitions tailored to the specific situation in these countries. Other areas for future research include further elucidation of the role of nursing homes as a possible source of antibioticresistant pathogens, investigation of the association between lower functional status and becoming colonized or infected with antibioticresistant organisms, and possible associations between antibiotic use rates and antibiotic resistance rates within countries,alsoaddressingthedegreetowhichresistanceisavoidable.



Theseriousconsequencesofantibioticresistanceinlongtermcarefacilitiesprovidea rationalefortheconductionofresearchandthedevelopmentofpoliciesdirectedat reducing antibiotic resistance in these facilities. These should focus on both the implementationofinfectioncontrolmeasuresandantibioticstewardship.Withregard to infection control measures, training of health care personnel is crucial to implement hygiene practice. To establish a sustainable training program, facilities should allocate adequate resources. The assignment of an infection control committee or an infection control practitioner may facilitate the development and sustainabilityofsuchaprogram.Withregardtoantibioticstewardship,itisimportant that physicians are well educated on the diagnosis and treatment of infectious diseases in residents, and that this education is based on relevant guidelines. Other measures to facilitate appropriate antibiotic prescribing include monitoring of antibiotic use, encouraging physicians and pharmacists to develop and regularly review formularies, and promoting specimen culturing in residents with suspected infection. It is important to realize that, although infection control measures and antibioticstewardshipaddressdifferentaspectsoftheantibioticresistanceproblem, theyarecloselyinterrelated.Forexample,theeffectofrationalantibioticprescribing by physicians is abolished if no attention is paid to infection control measures by nursingstaff.Therefore,strategiestocombatantibioticresistancearemorelikelyto besuccessfuliftheyaremultifaceted.Hence,theyrequireclosecollaborationamong alldisciplinesinvolved.



Differencesbetweentypesoflongtermcarefacilitiesshouldbetakenintoaccountin researchandpolicydevelopmenttoreduceantibioticresistance.Whereasresidential care facilities or assisted living facilities generally have a main focus on providing a “home” for their residents, the focus of nursing homes is on providing nursing care. Consequently,thewayinwhichmedicalcareisorganizedoftendiffersbetweenthese types of facilities. For example, in US nursing homes, medical care may include provisionofantibioticsandintravenousfluids,whereassuchservicesarenotdirectly available in assisted living environments.165 This difference in antibiotic availability may explain the finding of Moro et al28 that the prevalence of antibiotic use was higherinnursinghomesthaninresidentialcarefacilities.



The organization of medical care in longterm care facilities also differs among countries, because of distinct health care systems. This may result in international variation in antibiotic use, antibiotic resistance, and opportunities to implement infection control and antibiotic stewardship measures. As a consequence, extrapolation of research and policy to other countries or other longterm care settings is frequently complicated. Therefore, research on the impact of different types of longterm care facilities and different health care systems on antibiotic use and resistance is needed (eg, collaborative crossnational studies), to explain differences in antibiotic use and resistance between countries and health care settings.



Despite the potential limitations, we believe that this review clearly points out that antibiotic use and antibiotic resistance in the longterm care setting is common and that it causes substantial burden to individuals, longterm care facilities, and public health. This calls for the conduction of research and the development of policies directed at reducing the antibiotic resistance and subsequent burden for longterm carefacilitiesandtheirresidents.

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