Antibiotics and antiseptics for pressure ulcers

83 Pages·2016·0.92 MB·English

CochraneDatabaseofSystematicReviews
Antibiotics and antiseptics for pressure ulcers (Review)
NormanG,DumvilleJC,MooreZEH,TannerJ,ChristieJ,GotoS
NormanG,DumvilleJC,MooreZEH,TannerJ,ChristieJ,GotoS.
Antibioticsandantisepticsforpressureulcers.
CochraneDatabaseofSystematicReviews2016,Issue4.Art.No.:CD011586.
DOI:10.1002/14651858.CD011586.pub2.
www.cochranelibrary.com
Antibioticsandantisepticsforpressureulcers(Review)
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAINLANGUAGESUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Figure1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Figure2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Figure3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
AUTHORS’CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
CHARACTERISTICSOFSTUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
DATAANDANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Analysis1.1.Comparison1Povidoneiodineversushydrocolloid(granuflex),Outcome1Completewoundhealing. . 59
Analysis2.1.Comparison2Povidoneiodineversushydrogel,Outcome1Completewoundhealing. . . . . . . 59
Analysis3.1.Comparison3Povidoneiodineversussaline,Outcome1Infection(eradication). . . . . . . . . 60
Analysis4.1.Comparison4Povidoneiodineversusprotease-modulatingmatrixtreatment,Outcome1Completewound
healing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
Analysis5.1.Comparison5Cadexomeriodineversusstandardcare,Outcome1Completewoundhealing. . . . . 61
Analysis5.2.Comparison5Cadexomeriodineversusstandardcare,Outcome2Adverseevents. . . . . . . . 61
Analysis5.3.Comparison5Cadexomeriodineversusstandardcare,Outcome3Reductioninwoundarea. . . . . 62
Analysis5.4.Comparison5Cadexomeriodineversusstandardcare,Outcome4Pain. . . . . . . . . . . . 62
Analysis6.1.Comparison6Pineresinsalveversushydrocolloid,Outcome1Completewoundhealing. . . . . . 63
Analysis6.2.Comparison6Pineresinsalveversushydrocolloid,Outcome2Infection. . . . . . . . . . . . 63
Analysis7.1.Comparison7Iodinesugarversuslysozyme,Outcome1Completewoundhealing. . . . . . . . 64
Analysis7.2.Comparison7Iodinesugarversuslysozyme,Outcome2Adverseevents. . . . . . . . . . . . 64
Analysis7.3.Comparison7Iodinesugarversuslysozyme,Outcome3Seriousadverseevents. . . . . . . . . 65
Analysis7.4.Comparison7Iodinesugarversuslysozyme,Outcome4Reductioninwoundareabyatleast25%. . . 65
Analysis7.5.Comparison7Iodinesugarversuslysozyme,Outcome5Improvementinwoundinfectionstatus(tohighest
level). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
Analysis8.1.Comparison8Iodinesugarversusgentianviolet,Outcome1Changeinwoundarea. . . . . . . . 66
Analysis8.2.Comparison8Iodinesugarversusgentianviolet,Outcome2Changeinresistance(eradicationofMRSA). 67
Analysis9.1.Comparison9Polyhexanidedressingversuspolyhexanideswabs,Outcome1Changeinresistance(eradication
ofMRSA). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
Analysis9.2.Comparison9Polyhexanidedressingversuspolyhexanideswabs,Outcome2Pain. . . . . . . . 68
Analysis10.1.Comparison10Povidoneiodineversussilversulfadiazine,Outcome1Infection(eradication). . . . 68
Analysis13.1.Comparison13Honeyversusethoxy-diaminoacridineplusnitrofurazone,Outcome1Completewound
healing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Analysis14.1.Comparison14Silversulfadiazineversussaline,Outcome1Infection(eradication). . . . . . . . 69
ADDITIONALTABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
CONTRIBUTIONSOFAUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
DECLARATIONSOFINTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
SOURCESOFSUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
DIFFERENCESBETWEENPROTOCOLANDREVIEW . . . . . . . . . . . . . . . . . . . . . 81
Antibioticsandantisepticsforpressureulcers(Review) i
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
[InterventionReview]
Antibiotics and antiseptics for pressure ulcers
GillNorman1,JoCDumville1,ZenaEHMoore2,JudithTanner3,JaniceChristie1,SaoriGoto4
1SchoolofNursing,MidwiferyandSocialWork,UniversityofManchester,Manchester,UK.2SchoolofNursing&Midwifery,Royal
CollegeofSurgeonsinIreland,Dublin,Ireland.3SchoolofHealthSciences,UniversityofNottingham,Nottingham,UK.4Department
ofSurgery,KyotoUniversityHospital,Kyoto,Japan
Contactaddress:GillNorman,SchoolofNursing,MidwiferyandSocialWork,UniversityofManchester,JeanMcFarlaneBuilding,
OxfordRoad,Manchester,M139PL,[email protected].
Editorialgroup:CochraneWoundsGroup.
Publicationstatusanddate:New,publishedinIssue4,2016.
Reviewcontentassessedasup-to-date: 17September2015.
Citation: NormanG,DumvilleJC,MooreZEH,TannerJ,ChristieJ,GotoS.Antibioticsandantisepticsforpressureulcers.Cochrane
DatabaseofSystematicReviews2016,Issue4.Art.No.:CD011586.DOI:10.1002/14651858.CD011586.pub2.
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
ABSTRACT
Background
Pressureulcers,alsoknownasbedsores,decubitusulcersandpressureinjuries,arelocalisedareasofinjurytotheskinortheunderlying
tissue,orboth.Arangeoftreatmentswithantimicrobialproperties,includingimpregnateddressings,arewidelyusedinthetreatment
ofpressureulcers.Aclearandcurrentoverviewisrequiredtofacilitatedecisionmakingregardinguseofantisepticorantibiotictherapies
inthetreatmentofpressureulcers.ThisreviewisoneofasuiteofCochranereviewsinvestigatingtheuseofantisepticsandantibiotics
indifferenttypesofwounds. Italsoformspartofasuiteofreviewsinvestigating theuseofdifferenttypesofdressingsandtopical
treatmentsinthetreatmentofpressureulcers.
Objectives
Toassesstheeffectsofsystemicandtopicalantibiotics,andtopicalantisepticsonthehealingofinfectedanduninfectedpressureulcers
beingtreatedinanyclinicalsetting.
Searchmethods
InOctober2015wesearched:theCochraneWoundsSpecialisedRegister,theCochraneCentralRegisterofControlledTrials(CEN-
TRAL)(TheCochraneLibrary),OvidMEDLINE,OvidMEDLINE(In-Process&OtherNon-IndexedCitations),OvidEMBASE,
andEBSCOCINAHLPlus.Wealsosearchedthreeclinicaltrialsregistriesandthereferencesofincludedstudiesandrelevantsystematic
reviews.Therewerenorestrictionsbasedonlanguageordateofpublicationorstudysetting.
Selectioncriteria
RandomisedcontrolledtrialswhichenrolledadultswithpressureulcersofstageIIorabovewereincludedinthereview.
Datacollectionandanalysis
Tworeviewauthorsindependentlyperformedstudyselection,riskofbiasassessmentanddataextraction.
Antibioticsandantisepticsforpressureulcers(Review) 1
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Mainresults
Weincluded12trials(576participants);11hadtwoarmsandonehadthreearms.Allassessedtopicalagents,nonelookedatsystemic
antibiotics.Theincludedtrialsassessedthefollowingantimicrobialagents:povidoneiodine,cadexomeriodine,gentianviolet,lysozyme,
silver dressings, honey, pine resin, polyhexanide, silver sulfadiazine, and nitrofurazone with ethoxy-diaminoacridine. Comparators
includedarangeofotherdressingsandointmentswithoutantimicrobialpropertiesandalternativeantimicrobials.Eachcomparison
hadonlyonetrial,participantnumberswerelowandfollow-uptimesshort.Theevidencevariedfrommoderatetoverylowquality.
Sixtrialsreportedtheprimaryoutcomeofwoundhealing.Allexceptonecomparedanantisepticwithanon-antimicrobialcomparator.
Therewassomemoderateandlowqualityevidencethatfewerulcersmayhealintheshorttermwhentreatedwithpovidoneiodine
comparedwithnon-antimicrobialalternatives(protease-modulatingdressings(riskratio(RR)0.78,95%confidenceinterval(CI)0.62
to0.98)andhydrogel(RR0.64,95%CI0.43to0.97));andnocleardifferencebetweenpovidoneiodineandathirdnon-antimicrobial
treatment(hydrocolloid)(lowqualityevidence).Pineresinsalvemayhealmorepressureulcersthanhydrocolloid(RR2.83,95%CI
1.14to7.05)(lowqualityevidence).Thereisnocleardifferencebetweencadexomeriodineandstandardcare,andbetweenhoneya
combinedantisepticandantibiotictreatment(verylowqualityevidence).
Sixtrialsreportedadverseevents(primarysafetyoutcome).Fourreportednoadverseevents;therewasverylowqualityevidencefrom
oneshowingnoclearevidenceofadifferencebetweencadexomeriodineandstandardcare;inonetrialitwasnotclearwhetherdata
wereappropriatelyreported.
Therewaslimitedreportingofsecondaryoutcomes.Thefivetrialsthatreportedchangeinwoundsizeasacontinuousoutcomedidnot
reportanyclearevidencefavouringanyparticularantiseptic/anti-microbialtreatments.Forbacterialresistance,onetrialfoundsome
evidenceofmoreMRSAeradicationinparticipantswithulcertreatedwithapolyhexanidedressingcomparedwithapolyhexanide
swab(RR1.48,95%CI1.02to2.13);patientsinthedressinggroupalsoreportedlesspain(MD−2.03,95%CI−2.66to−1.40).
Therewasno clearevidence of adifferencebetweeninterventions ininfectionresolution inthreeothercomparisons. Evidence for
secondaryoutcomesvariedfrommoderatetoverylowquality;wherenoGRADEassessmentwaspossibleweidentifiedsubstantial
limitationswhichanassessmentwouldhavetakenintoaccount.
Authors’conclusions
The relative effects of systemic and topical antimicrobial treatments on pressure ulcers are not clear. Where differences in wound
healingwerefound,thesesometimesfavouredthecomparatortreatmentwithoutantimicrobialproperties.Thetrialsaresmall,clinically
heterogenous,generallyofshortduration,andathighorunclearriskofbias.Thequalityoftheevidencerangesfrommoderatetovery
low;evidenceonallcomparisonswassubjecttosomelimitations.
PLAIN LANGUAGE SUMMARY
Antibioticsandantisepticsforpressureulcers
Whatarepressureulcersandwhoisatrisk?
Pressureulcers,alsoknownasbedsores,decubitusulcersandpressureinjuries,arewoundsinvolvingtheskinandoftenthetissuethat
liesunderneath.Pressureulcerscanbepainful,maybecomeinfected,andaffectpeople’squalityoflife.Peopleatriskofdeveloping
pressureulcersincludethosewithspinalcordinjuries,andthosewhoareimmobileorhavelimitedmobility,suchaselderlypeopleand
peoplewhoareill.
Whyuseantisepticsandantibioticstotreatpressureulcers?
Wherepressureulcersareinfected,antibiotics orantisepticsareusedtokillorslowthegrowthofthemicro-organisms causing the
infectionandmaypreventaninfectionfromgettingworseorspreading.Thismayalsohelptheulcertoheal.Whereulcersarenot
infectedtheyusuallystillhavepopulationsofmicro-organismspresent.Itisthoughtthattheymayhealbetterifthesearereducedby
antimicrobialagents.However,therelationshipbetweeninfectionandmicro-organismpopulationsinwoundsandwoundhealingis
notveryclear.
Whatwefound
InOctober2015wesearchedforasmanystudiesaswecouldfindthatwererandomisedcontrolledtrialsandcomparedtheuseof
anantibiotic orantiseptic withothertreatmentsforpressure ulcers.Wefound12trialsinvolving atotalof576 participants. Most
Antibioticsandantisepticsforpressureulcers(Review) 2
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
study participants were older people in hospital. Most ulcers were not infected at the start of the trials. The different treatments
assessedincludedpovidoneiodine,cadexomeriodine,gentianviolet,lysozyme,silverdressings,honey,pineresin,silversulfadiazine,
polyhexanideandacombinationofnitrofurazoneandethoxy-diaminoacridine.Silversulfadiazineandnitrofurazonearetopical(locally
acting)antibioticswhiletheothertreatmentsareantiseptics.Notrialslookedatsystemic(actingacrossthewholebody)antibiotics.
Thetreatmentswerecomparedwith eachotherortotreatmentswithout antimicrobial qualities. Mostevidence onwound healing
camefromtrialscomparingantisepticstotreatmentswithoutantimicrobialqualities.
Therewasnoconsistentevidenceofabenefittousinganyparticularantimicrobialtreatmentforpressureulcers.However,therewas
somelimitedevidencethatmoreulcershealedwhentreatedwithsometypesofalternativedressingswithoutantimicrobialproperties
thanwhentreatedwithpovidoneiodine.Allthestudieshadlownumbersofparticipants,andinsomecasesthesenumberswerevery
small.Manystudiesdidnotreportimportantinformationabouthowtheywerecarriedoutsoitwasdifficulttotellwhethertheresults
presentedwerelikelytobetrue.More,betterquality,researchisneededtodeterminetheeffectsofantimicrobialtreatmentsonpressure
ulcers.
BACKGROUND Childrenwithpressureulcersarerecognisedasadiscretepopula-
tionthatincludesbothneonatesandolderchildrenwitharangeof
conditionsandriskfactors(EPUAP-NPUAP-PPPIA2014;NICE
2014);theyarecaredforinspecialistpaediatricfacilities,and,ac-
Descriptionofthecondition cordingly,areoutsidethescopeofthisreview.
Pressure ulcers, also known as bedsores, decubitus ulcers, pres-
sure injuries or pressure sores are defined as “a localized injury
Classificationofpressureulcers
totheskinand/or underlyingtissueusuallyoverabony promi-
nence, as a result of pressure, or pressure in combination with One of the most widely recognised ways of classifying pressure
shear”(EPUAP-NPUAP-PPPIA2014).Pressureulcersareatype ulcersaccordingtoseverityisthatoftheNationalPressureUlcer
ofcomplexwoundthathealsbysecondaryintention(throughthe AdvisoryPanel(NPUAP).Theirinternationalclassificationrecog-
growthofnewtissue). nises four categories, or stages, of pressure ulcers and two cate-
Prolongedexposureofanareaofthebodytopressureorcompres- goriesofunclassifiablepressureinjuriesinwhichwounddepthor
sion candamage cells,interruptthelocal blood circulation (i.e. extent,orboth,cannotbeaccuratelydetermined:suchulcersare
reduce perfusion), andtrigger acascade of biochemical changes generallysevereandwouldbegroupedclinicallywithcategory3
thatmayleadtotissuedamage andulceration(Gebhardt2002; or 4ulcers(EPUAP-NPUAP-PPPIA 2014).Thedefinitions for
Loerakker 2010).Immobility canalsoleadtoincreaseddamage thecategoriesofseverityforulcersareasfollows:
fromshearandfriction,forexample,whenpeoplearepulledinto Category/Stage 1: non-blanchable erythema: “Intact skin with
positioninchairsandbeds. non-blanchable redness of a localised area usually over a bony
Peopleatparticularriskofpressureulcersarethosewhocannot prominence.Darklypigmentedskinmaynothavevisibleblanch-
reposition themselves when they are seated in a chair or lying ing;itscolourmaydifferfromthesurroundingarea.Theareamay
in bed. This includes those with limited activity and mobility bepainful,firm,soft,warmerorcoolerascomparedtoadjacent
orreducedbodilysensation, suchaselderlypeople,peoplewith tissue.Category/StageImaybedifficulttodetectinindividuals
spinalcordinjuries(Gefen2014),andthosewithacuteorchronic withdarkskintones.Mayindicate’atrisk’individuals(aheralding
healthconditions(Allman1997;Bergstrom1998;Berlowitz1990; signofrisk).”
Brandeis1994).Arecentsystematicreview,Coleman2013,iden- Category2:partialthicknesstissueloss:“Partialthicknesslossof
tifiedthekeyriskfactorsforpressureulcersas:limitationsofmo- dermispresentingasashallowopenulcerwitharedpinkwound
bilityoractivity;reducedperfusion(includingadiagnosisofdi- bed,withoutslough.Mayalsopresentasanintactoropen/rup-
abetes); and the presence of a stage 1 pressure ulcer (see classi- turedserum-filledor sero-sanguinous filledblister.Presentsas a
fication below). A recent cohort study found that predictors of shiny or dry shallowulcer without slough or bruising (bruising
poorhealingincludedtheseverityoftheulcerandthepresenceof indicatessuspecteddeeptissueinjury).Thiscategory/stageshould
peripheralarterialdisease(poorcirculation/perfusionofthelimb; notbeusedtodescribeskintears,tapeburns,perinealdermatitis,
McGinnis2014). macerationorexcoriation.“
Antibioticsandantisepticsforpressureulcers(Review) 3
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Category3:fullthicknesstissueloss:”Fullthicknesstissueloss. munity and acute settings - although data collection is not yet
Subcutaneousfatmaybevisiblebutbone,tendonormuscleare universal -aspartoftheNationalHealthService(NHS)Safety
not exposed. Slough may be present but does not obscure the Thermometerinitiative(Power2012).InApril2014,prevalence
depthoftissueloss.Mayincludeunderminingandtunnelling.The inNHSpatientswas4.6%(NHS2014).Thesedatarepresentpa-
depthofaCategory/StageIIIpressureulcervariesbyanatomical tientscaredforacrossarangeofsettingsincludingacutehospital
location. The bridge of thenose, ear, occiput and malleolusdo wards,communityandresidentialcareandathome.Mostpatients
not have subcutaneous tissue and Category/Stage III ulcerscan hadcategory2ulcers(3.0%),with1.1%havingcategory 3and
beshallow.Incontrast,areasofsignificantadipositycandevelop 0.6%havingcategory4ulcers(category1ulcerswerenotincluded
extremelydeepCategory/Stage IIIpressure ulcers.Bone/tendon inthereporting).Thepointprevalenceofpressureulcerationin
isnotvisibleordirectlypalpable.“ thetotaladultpopulation(ratherthanthosecurrentlyreceiving
Category 4:fullthicknesstissue losswith exposedmuscle,ten- medicaltreatment)wasrecentlyestimatedusingacross-sectional
donorbone:”Fullthicknesstissuelosswithexposedbone,ten- surveyundertakeninLeeds,intheUK.Thetotaladultpopulation
donormuscle.Sloughorescharmaybepresentinsomepartsof was751,485,andthepointprevalence(includingstageIulcers)
thewoundbed.Oftenincludesunderminingandtunnelling.The was0.31per1000(Hall2014).Pressureulcerprevalenceestimates
depthofaCategory/StageIVpressureulcervariesbyanatomical specificallyforcommunitysettingshavereportedratesof0.77per
location. The bridge of thenose, ear, occiput and malleolusdo 1000adultsinaUKurbanarea(Stevenson2013).
nothavesubcutaneoustissueandtheseulcerscanbeshallow.Cat- Worldwidefiguresshowarangeofprevalenceforpressureulcers.
egory/StageIVulcerscanextendintomuscleand/orsupporting DatafromtheUSAshowedthatincidenceoffacility-acquired(i.e.
structures(e.g.,fascia,tendonorjointcapsule)makingosteomyeli- hospital-acquired)ulcersrangedfrom9.2%(generalcardiaccare)
tispossible.Exposedbone/muscleisvisibleordirectlypalpable.“ to 10.3% (surgical intensive care unit) of which 3.3% were se-
The two additional categories of unclassifiable wounds that are vere(category3/4/unclassifiable;VanGilder2009).Australianes-
alsorecognisedare: timatesofpressureulcerprevalenceinacutecarerangefrom4.5%
Unstageable/unclassified: full thickness skin or tissue loss- to 27% (Prentice 2001), while in Japan prevalence across 5000
depthunknown:”Fullthicknesstissuelossinwhichactualdepth hospitalswasreportedasbeing4.26%(Sanada2008).Lowerfig-
oftheulceriscompletelyobscured byslough(yellow,tan,gray, ures (1.8%) were noted in a cross-sectional descriptive study of
greenorbrown)and/oreschar(tan,brownorblack)inthewound pressure ulcer prevalenceinateachinghospital inChina (Zhao
bed.Furtherdescription:Untilenoughsloughand/orescharare 2010),thoughdatafromasurveyofhospitalpatientsacrosssev-
removedtoexposethebaseofthewound,thetruedepthcannot eral European countries found an overall prevalence of 10.5%
bedetermined;butitwillbeeitheraCategory/StageIIIorIV.Sta- (Vanderwee 2007). A review of pressure ulcer prevalence across
ble(dry,adherent,intactwithouterythemaorfluctuance)eschar Scandinavia,IcelandandIreland,foundthatthemeanprevalence
ontheheelsservesas“thebody’snatural(biological)cover”and inNorwaywas17%(range4.8%to29%),16%inIreland(range
shouldnotberemoved.“ 4% to 37%), 15% in Denmark (range 2.2% to 35.5%), 25%
Suspecteddeeptissueinjury-depthunknown:”Purpleorma- inSweden(range0.04%to42.7%),and8.9%inIceland(single
roonlocalizedareaofdiscolouredintactskinorblood-filledblis- study,norangeavailable)(Moore2013a).
ter due to damage of underlying soft tissue from pressure and/ Theprevalenceinhigh-riskpopulationgroupsmaybeverymuch
orshear.Furtherdescription:Theareamaybeprecededbytissue higher:asurveyofpeoplewithaspinalcordinjuryfoundapoint
thatispainful,firm,mushy,boggy,warmerorcoolerascompared prevalenceof23%;furthermore,thelifetimeriskinthisgroupis
to adjacent tissue. Deep tissue injury may be difficult to detect estimatedtobe70%(Raghaven2003).
inindividualswithdarkskintones.Evolutionmayincludeathin
blisteroveradarkwoundbed.Thewoundmayfurtherevolveand
becomecoveredbythineschar.Evolutionmayberapidexposing Costofpressureulcers
additionallayersoftissueevenwithtreatment.“
ThecostoftreatingpressureulcersintheUKhasbeenestimated
torangefromGBP1214foracategory1ulcertoGBP14,108
for acategory 4 ulcer (Dealey2012). These cost estimates may
Prevalence
beconservativeduetotheomissionofnegativepressurewound
Pressure ulcers are one of the most common types of complex therapy from costings, which were updated from a point prior
wound.Prevalencereferstothenumberofpeoplewithapressure to the widespread use of this therapy; they also do not include
ulceratapointintime,orduringaspecifictimeperiod(Bonita precautionsrequiredfordealingwithantibiotic-resistantinfection.
2006).Prevalenceestimatesdifferaccordingtothepopulationas- Themaindriveroftheseincreasedcostsisnotulcercategoryper
sessed,theassessmentmethodsusedandthecategoryorcategories sebuttheincreasedrateofcomplicationsinhighercategoryulcers
ofulcersthatareincludedintheestimates. andthesubsequentincreaseintimetohealing.IntheUK,forthe
IntheUK,nationalpressureulcerdataarecollectedacrosscom- year2000, thetotalcostfortreatingpressureulcerslaybetween
Antibioticsandantisepticsforpressureulcers(Review) 4
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
GBP1.4billionandGBP2.1billion(Bennett2004). 1.7specieswhenitwasnot(Sapico1986).Amorerecentprospec-
Pressureulcersincreaselengthofhospitalstayandassociatedhos- tivecohortstudyfollowed145patientswithcategory2orhigher
pitalcosts(Allman1999).FiguresfromtheUSAsuggestthat’pres- pressureulcers:77%ofthesepeoplehadpressureulcerscontaining
sure ulcer’ was noted as a diagnosis for half a million hospital Staphylococcusaureus,Gram-negativebacilliorboth(Braga2013).
staysin2006;foradults,thetotalhospitalcostforthesestayswas The document ’Wound Infection in Clinical Practice - An Inter-
USD11billion(Russo2008).Currentdataoncostsfromother nationalConsensus’definesascenarioleadingtowoundinfection
healthcaresystemsarehardtoidentify,butcoststotheAustralian where”bacteriamultiply,healingisdisruptedandwoundtissues
healthcaresystemfortreatingpressureulcerationhavebeenesti- aredamaged(localinfection)“(WUWHS2008).Thedocument
matedatAUD285millionannually(Graves2005).Thereisalsoa alsonotesthat”Bacteriamayproduceproblemsnearby(spreading
substantialsocietalnon-healthservicecostinprolongedsickleave infection)orcausesystemicillness(systemicinfection)“.Indeed,
(absenceduetobeingunwell)forpeoplewhoareinemployment woundinfectionhasbeenconceptualisedasbeingatoneendofa
whentheydevelopapressureulcer(Gorecki2009). continuumofinfection(Kingsley2004).
Kingsleydefinedacontinuumofinfectionthatbeginswithsterility
(abriefperiod,possiblyfollowingsurgery)andprogressesthrough
Impactofpressureulcersonpeople contamination(presenceofmicrobesbutlittleactivegrowthand
noclinicalproblems),tocolonisation(thenormalstatusquowith
Theimpactofpressureulcersonaffectedindividuals islarge.A
woundflorabeingmanagedbythehostimmunesystemandno
systematicreviewfoundthatpressureulcershadanimpactacross
damagetowoundtissues),culminatingincriticalcolonisationand
physical, social and psychological domains as a resultof one or
theninfection(Kingsley2004).
more of the following distressing symptoms: pain, exudate and
Inaddition,Kingsleydefinedcriticalcolonisationasapointbe-
odour, increased care burden, prolonged rehabilitation, require-
tweencolonisation and infection where the’healthy’balance of
ment for bed-rest, and hospitalisation (Gorecki 2009). The ad-
woundfloraisnolongermaintainedbythehost,andthebacterial
justedhealth-relatedqualityoflifeofpeoplewithpressureulcers
loadorspeciespresentinthewound,orboth,shiftawayfroma
hasbeenshowntobelowerthanthatforcomparable individu-
so-calledsafe level(Kingsley 2004).Othershaveconceptualised
alswithoutpressureulcers(Essex2009).Pressureulcersmayalso
criticalcolonisation asinvasion ofthewound surfacebymicro-
becomeinfected,andthiscangiverisetoserioussystemic(whole
organisms(AWMA2011;Edwards2004).
body)infections.
Theclassicclinicalsignsofinfectionincludelocalisedpain,heat,
redness, swelling and purulence (pus). The concept of critical
Woundinfection colonisation lacks clear diagnostic criteria; it is generally noted
asbeing associated with delayedhealingintheabsence of overt
Complexwounds suchaspressureulcersofferanidealenviron-
signsofwoundinfection(Carville2008;Cutting2004),possibly
mentfor microbial colonisation: thisisespeciallytruefor those
withothersymptomssuchasincreasedexudate(thoughlessthan
pressureulcersthatmaybeparticularlyexposedtobacterialcon-
ininfection)andhypergranulation/friable tissue (Cutting2004;
tamination from faecal material (Bowler 2001). However, most
Gardner2001),althoughassociatedevidenceislimited.
woundswillcontainsomemicro-organismsandthiswillnotnec-
Wehavebeenunabletoidentifyrecentorlarge-scaledataonthe
essarilyleadtoadverseevents(WUWHS2008).
ratesofclinicalinfectionofpressureulcers;earlystudiesofsmall
Thereareseveralrecogniseddefinitionsforwoundinfection(e.g.
numbersofpatientsproducedanestimateof1.4casesofinfection
CDC 2008; WUWHS 2008). Recently there has been a move
per1000patientdayswithanulcer(Nicolle1994),whileapoint
awayfromtheviewthatdensityofbacteriaisthekeyfactor(i.e.
prevalence study found that 6% of all nursing home residents
thatabacterialloadgreaterthan1x105g−1isapredictorofin-
participating received treatment for an infected pressure ulcer (
fection)towardstheviewthatinfectionwithenough-orspecific
Garibaldi1981).
types of - pathogenic micro-organisms, or both (Bowler 2003;
Althoughthereisawidespreadviewamongstthosewithclinical
Davies 2007; Madsen 1996; Trengove 1996), and the possible
expertiseinthefieldthathealingofpressureulcersislikelytobe
productionofbiofilms(Percival2004;Wolcott2008),maylead
retardedbycriticalcolonisationortopical/localinfection,theem-
tonegativeoutcomesandpotentiallydelayhealing.However,the
piricalevidencetosupportthisisextremelylimited(Howell-Jones
impactofmicrobial colonisation onwoundhealingisnotinde-
2005). Indeed, theAustralian Wound Management Association
pendent of thehost response; the ability of the host to provide
statesthat”Thetrueextentofbacterialimpairmentofwoundheal-
anadequateimmuneresponseislikelytobeascriticalindeter-
ingisunknown“ (AWMA 2011).Inparticularthereisadearth
miningwhetherawoundhealsasthespecificsoftheflorainthe
ofclinicalstudiestodemonstratealinkbetweeninfectionresolu-
wound.Regardingwoundflora,investigationintothemicrobiol-
tionorreductionofthemicrobiologicalloadandwoundhealing;
ogyofpressureulcershasbeenlimited-onestudyofthebacteria
todate, randomised evidence hasnot supportedalinkbetween
presentin25pressureulcersofdifferentcategoriesfoundamean
reduction in bacterial load and faster healing in pressure ulcers
numberof5.8specieswhennecrotictissuewaspresent,butonly
Antibioticsandantisepticsforpressureulcers(Review) 5
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
(Jull2013;O’Meara2001;Storm-Versloot2010).Thismaystem Antibiotics are substances that destroy or inhibit the growth of
inpartfromthedifficultyofculturingmicro-organismsfromthe micro-organisms (Macpherson 2004). Systemicantibiotic treat-
biofilms present in pressure ulcers (Smith 2010), meaning that mentsincludegroupsofdrugsthatsharesimilarmodesofaction
microbiologicalloadisnotaccuratelyrepresentedinsamples. such as penicillins, cephalosporins, aminoglycosides, macrolides
Thereisalimitedandconflictingevidencebasefortherelation- andquinolones. Otherantibiotics thatdonotbelong toone of
shipbetweenbacterialload,ordiversityorstructure,andwound thesemaingroupsincludeclindamycin,metronidazole,trimetho-
healinginothertypesofchronicwoundssuchasvenouslegand primandco-trimazole(BNF2013).
diabeticfootulcers(Davies2007;Halbert1992;Hansson1995; Topicalantimicrobialagentsthatareapplieddirectlytotheulcer
Madsen1996;Moore2010;Sotto2012).Theapplicabilityofthis includebothantibiotics andantiseptics.Antisepticsarethought
evidencetopressureulcersisuncertain,asthereareknownmicro- to prevent the growth of pathogenic micro-organisms without
biologicaldifferencesbetweenthewoundtypes.Inparticularthe damaginglivingtissue(Macpherson2004).Topicalapplications
proportion of anaerobic bacteria (thought tobe correlatedwith broadlyfallintolotionsusedforwoundirrigationorcleaningwith
non-healing) andmycobacteria appearstobe higherinpressure abriefcontacttime(unlessusedasapack/soakplacedintooronto
ulcersthaninvenouslegulcers(Dowd2008).Thereareknown thewound),orboth,andproductsthatareinprolongedcontact
differencesinthemicrobiologyofpressureulcersatdifferentstages withthewoundsuchascreams,ointmentsandimpregnateddress-
ofhealing,butnodemonstrationthatthesedifferencesareimpli- ings (BNF 2013). Agents used primarily for wound irrigation/
catedinthehealingprocess(Sapico1986). cleaningarecommonlybasedonpovidone-iodine,chlorhexidine
and peroxide agents. Less commonly used agents include tradi-
tionalproductssuchasgentianvioletandhypochlorites.Creams
andointmentsforlongercontactincludefusidicacid,mupirocin,
Descriptionoftheintervention neomycinsulphateandiodine(oftenascadexomeriodine;BNF
2013).
Standardcareforadultswith pressureulcersincludestheuseof
The British National Formulary (BNF) categorises antimicro-
pressure redistribution devices such as high-specification foam
bialdressingsunderhoney-based,iodine-based, silver-basedand
mattresses or cushions, or both (McInnes 2011); debridement
’other’, which includes dressings impregnated with agents such
where appropriate and non-gauze dressings (BNF 2013), with
aschlorhexidineorperoxides.Recommendationsaboutdressing
foam, hydrocolloid or alginate bases (NICE 2014). Othergen-
typesforwoundsthoughttobeinfectedarebasedprimarilyonthe
eralstrategiesincludetheprovisionofpatienteducation,manage-
levelofwoundexudate,asthisdeterminesthedressingsubstrate,
ment of pain, optimising circulation/perfusion, optimising nu-
aswellastheantimicrobialagent(BNF2013).
trition and, where appropriate, performing surgical wound clo-
Despiteguidance fromNICEthereisahighuseofsilverdress-
sure(AWMA2011;EPUAP-NPUAP-PPPIA2014).Treatmentof
ings(11%)comparedwithotherantimicrobialdressings(2%for
clinicalinfectionisalsoakeystrategyasitisthoughtthatalocally
nextmostcommonlyprescribedantimicrobialdressing)(MeReC
infectedwoundmightshowretardedhealingandmaygiveriseto
2010).Highprescriptioncostsmeanthatsilverdressingsaccount
asystemicinfection.
foradisproportionateamount(22%)oftheannualNHSexpen-
Routineuseofantibioticsandantisepticsisnotcurrentlyrecom-
diture on dressings (MeReC2010). Itseemspossible thatsome
mendedforthetreatmentofuninfectedpressureulcersinadults,
ofthesedressingsarebeingusedprophylactically(i.e.toprevent
andsystemicantibioticsarerecommendedonlywhenthereisclin-
infectioninwoundsthatarenotclinicallyinfected).Thereisalsoa
icalevidenceofsystemicsepsis(seriousinfection),spreadingcel-
highlevelofuseofbothsystemicantibioticsandtopicalagentsin
lulitis(deepskininfection)orunderlyingosteomyelitis(bonein-
patientswithchronicwounds.Generalpracticemorbiditydatafor
fection;NICE2014).Antibioticuseshouldberestrictedtocases
Walesfrom2000showedthattwiceasmanypatientswithchronic
ofclearclinicalneedinthetreatmentofpressureulcers,aswithall
woundswereprescribedsystemicantibioticsinthepreviousyear
conditions.Internationally,antibiotic-resistantbacteriaandmul-
compared with matched controls, with a mean number of pre-
tidrug-resistantbacteriaareincreasingasaclinicalproblem;these
scriptionsperyearof2.3(range0to22)comparedwith0.6(range
bacteria have been found in isolates from a substantial propor-
0to14)forcontrolpatients.Thesamedatashowedhighlevels
tionofpatientswithpressureulcers,evenincommunitysettings
ofprescriptionfortopicalagentssuchassilversulfadiazine(185
(Cataldo2011;Ellis2003;Heym2004).Inappropriateuseofan-
timesper1000patientsperyear)andmetronidazole(223times
tibioticsisnotrestrictedtothosegivensystemically;topicalantibi-
per 1000 patients per year) in this group (Howell-Jones 2006).
oticsarealsonotrecommendedforuseonnon-infectedwounds
Againitappearspossiblethatsomeprescriptionsmaybeforthe
(NICE2014).
treatmentofwoundsthatarenotclinicallyinfected.
Therearetwomainapproacheswhenanantimicrobialinterven-
tionisconsideredclinicallyappropriate:anantibioticmaybead-
ministeredsystemically(orally,intravenouslyorintramuscularly),
Howtheinterventionmightwork
oratopicalantibioticorantisepticmaybeapplied(NICE2014).
Antibioticsandantisepticsforpressureulcers(Review) 6
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Therationalefortreatingclinicallyinfectedwoundswithantimi- antimicrobialagentinsteadofstandardcare,andwhetherdifferent
crobialandantisepticagentsistokillorslowthegrowth ofthe anti-microbialpreparationshavedifferentimpactsonhealing.
pathogenic micro-organisms, thus preventing an infection from
worseningandspreading(Kingsley2004).Improvedhealingmay
be a secondary benefit, although evidence of an association be-
tweenwoundhealingandinfectionislimited(seeDescriptionof
theintervention;Jull2013;O’Meara2001;Storm-Versloot2010). OBJECTIVES
Thereisawidelyheldviewthatwoundsthatdonotshowclear
signsofclinicalinfection,buthavecharacteristicssuchasretarded Toassesstheeffectsofsystemicandtopicalantibiotics,andtopi-
healing,mayalsobenefitfromareductioninbacterialload.Again, calantisepticsonthehealingofinfectedanduninfectedpressure
evidence for this is limited (see Description of the condition; ulcersbeingtreatedinanyclinicalsetting.
AWMA2011,Howell-Jones2005).
NormallyantibioticsworkbyinhibitingDNAorproteinsynthe-
sis,orbydisruptingbacterialcellwalls.Antisepticscanbebacte-
METHODS
riocidal(inthattheykillmicro-organisms) ortheycanworkby
slowingthegrowthoforganisms(bacteriostatic).Antisepticscan
haveawidespectrumofactionthatisnotrestrictedtobacteria,
andoftenworkbydamagingthesurfaceofmicrobes(Macpherson
Criteriaforconsideringstudiesforthisreview
2004).
Whyitisimportanttodothisreview
Typesofstudies
Whethersystemicortopicalantimicrobialsortopicalantiseptics Elements of this Methods section are based on the standard
canpromotehealinginpressureulcersremainsuncertain.Anear- CochraneWoundsProtocolTemplate.
liersystematicreview ofantimicrobial agentsusedforthetreat- Weincludedpublishedandunpublishedrandomisedcontrolled
ment of all types of chronic wounds was not able to generate trials(RCTs),includingclusterRCTs,irrespectiveoflanguageof
definitiveconclusionsabouttheuseofsystemicortopicalagentsin report.Weincludedcross-overtrialsonlyiftheyreportedoutcome
pressureulcersbecauseofmethodologicalproblemsintheprimary dataattheendofthefirsttreatmentperiod,priortocross-over.
literature(O’Meara2001).Sincethefirstreviewwaspublished, Quasi-randomisedstudieswereexcluded.WeincludedRCTsre-
asubstantialnumberofadditionalrelevanttrialshavebeenpub- portedonlyasabstractsonlywhenavailabledataweresufficientfor
lishedthatrelatetopressureulcers;theseincludetrialsofsilver- reasonabledataextractioneitherfromtheabstractitselforfrom
orhoney-basedtopicalpreparations.Thisreviewisoneofanum- thestudyauthors.
berofCochrane reviews investigating theuseofantibiotics and
antisepticsinthetreatmentofdifferenttypesofcomplexwounds,
eachof which updateselementsof theoriginal O’Mearareview
Typesofparticipants
(O’Meara2001).WhiletherewillbesomeoverlapwithCochrane
reviewsofindividualantimicrobialagentsinwounds(Jull2013; Weincludedstudiesthatrecruitedadultsdiagnosedwithapres-
Storm-Versloot2010),andwithreviewsofdifferenttypesofdress- sureulcerofcategory2orabove(i.e.worse)managedinanycare
ings(Dumville2015a;Dumville2015b;Moore2013b),thisre- setting.Weexcludedparticipantswithcategory1ulcers.Weac-
viewwillprovideasinglesynthesisoftherandomisedevidencere- ceptedstudyauthors’definitionsofwhattheyclassedasacategory
latingtoallsystemicandtopicalantimicrobialsforpressureulcers. 2orabovepressureulcerunlessitwasclearthatwoundswithun-
Twonotablesystematicreviewsofarangeoftreatmentsforpres- brokenskinwereincluded.Thisincludedacceptingauthors’deci-
sureulcershaveincludedsometypesofantimicrobialtreatments sionsthatawoundwasapressureulcerratherthan,forexample,
in wider assessments of dressings or topical treatments (Reddy an incontinence relatedsore/wound. Studies thatrecruited par-
2008;Smith2013).Acomprehensivereviewofallantisepticand ticipantswithcategory2orabovepressureulcersalongsidepeo-
antibiotictreatmentofpressureulcersis,however,lacking. plewith othertypesofwounds wereincludediftheproportion
Thereisawiderangeofoptionsavailabletohealthprofessionals ofparticipantswithpressureulcersofcategory2orabovewasat
whoareconsideringusingantimicrobialtherapyforpressureul- least75%.Wedidnotrestrictthereviewtotrialsthatrecruited
cers,eitherasatreatmentfororprophylaxisagainstclinicalinfec- only participants with colonised, criticallycolonised or infected
tion. Evidence-based decision-making on theimpact of antimi- wounds atbaseline, but whereinformation about wound status
crobial agents on healing of pressure ulcers can be challenging. isreporteditwasrecorded.Unstageableulcerswereincludedand
Keyproblemsincludedecisionsaboutwhetherorwhentousean recordedassuch.
Antibioticsandantisepticsforpressureulcers(Review) 7
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Typesofinterventions Primaryoutcomes
Theprimaryinterventionsofinterestweretopicalantisepticagents The primary effectiveness outcome for this review was wound
orantibacterial(antibiotic)agentsdeliveredeithersystemicallyor healing.Trialistsusedarangeofdifferentmethodsofmeasuring
topically.WeincludedanyRCTinwhichtheuseofatopicalor andreportingthisoutcome.RCTsthatreportedoneormoreof
systemicantibioticoratopicalantisepticwasthekeysystematic thefollowing wereconsidered toprovide themostrelevantand
differencebetweentreatmentgroups.Systemicantibioticsmaybe rigorousmeasuresofwoundhealing.
administeredorallyor byotherroutes(e.g.intravenously, intra- • Timetocompletewoundhealing(correctlyanalysedusing
muscularly).Bothinterventionandcontrolregimenscouldcon- survival,time-to-eventapproaches).Ideallytheoutcomewillbe
sistofantibioticsorantisepticsadministeredsinglyorincombina- adjusted(bystudyauthors)forappropriatecovariatese.g.
tion;controlregimensmightalsoincludeplacebo,anotherther- baselineulcerarea/duration.
apy,standardcareornotreatment.Studiesthatevaluatedco-inter- • Proportionofwoundscompletelyhealedduringfollow-up
ventions(e.g.pressure-relievingdevices)wereincluded,provided (frequencyofcompletehealing).
thatthesetreatmentsweredeliveredinastandardisedwayacross
Weused, andreported,authors’ definitions ofcompletewound
thetrialarms.Wedecidedtoincludestudieswheredressingsas
healing.Wereportedoutcomemeasuresatthelatesttimepoint
wellasantisepticorantibiotictreatmentdifferedbetweengroups
available(assumedtobelengthoffollow-up,ifnotspecified)and
forthisreview.
thetimepointspecifiedinthemethodsasbeingofprimaryinterest
Weexcludedevaluationsofantibiotics/antisepticsusedtoprepare
(ifthiswasdifferentfromlatesttimepointavailable).
forthesurgicaltreatmentofulcers(i.e.thesurgicalclosureofulcers
Where both the outcomes above were reported we planned to
orskingrafting),andphysicalandbiologicaltherapiessometimes
presentalldata for reference,butto focuson reporting timeto
purportedtohaveincidentalantimicrobialpropertiessuchasheat
healing.Whentimewasanalysedasacontinuousmeasure,butit
therapyandlarvaltherapy.
wasunclearwhetherallwoundshealed,wedocumentedtheuse
Weanticipatedthatinterventionswouldconsistofantisepticand
oftheoutcomeinthestudy,butdidnotextract,summariseoruse
antibiotic agents, which might include (but not be limited to)
thedatainameta-analysis.
thefollowingtopicalagentsthatmaybeavailableintheformof
Theprimary safetyoutcome forthereviewwas allreportedad-
creams,sprays,ointment,orimpregnatedintodifferenttypesof
verseevents.Reporteddatawereextractedonallseriousandnon-
dressings:chlorhexidine;povidone-iodine;hydrogenperoxideand
serious adverse eventswhen aclearmethodology for the collec-
potassium permanganate; benzoyl peroxide; hypochlorites (e.g.
tionofadverseeventdatawasprovided.Thismethodology had
Eusol);gentianviolet;mupirocinandfusidicacid;neomycinsul-
tomakeitclearwhethereventswerereportedattheparticipant
phate;peroxides;iodine,silverandhoney.
levelorwhethermultipleevents/personwerereported,inwhich
Systemic antibiotics might include penicillins, cephalosporins,
caseappropriateadjustmentsneededtobemadefordatacluster-
aminoglycosides, macrolides and quinolones, clindamycin,
ing.Individualtypesofadverseeventsotherthanpainorinfection
metronidazole,trimethoprimandco-trimazole.
werenotextracted(seeSecondaryoutcomes).
Typesofoutcomemeasures Secondaryoutcomes
Welistprimaryandsecondaryoutcomemeasuresbelow.Ifatrial Thefollowingsecondaryoutcomeswereincluded.
wasotherwiseeligible(correctstudydesign,populationandinter- • Change(andrateofchange)inwoundsize,with
vention/comparator)butdidnotreportarelevantlistedoutcome, adjustmentforbaselinesize(weattemptedtocontactstudy
thenwe contacted thestudy authors where possible inorder to authorstorequestadjustedmeanswhennotpresented).When
establishwhethertheoutcomewasmeasuredbutnotreported. changeorrateofchangeinwoundsizewasreportedwithout
Wereportoutcomemeasuresatthelatesttimepointavailablefora adjustmentforbaselinesize,useoftheoutcomeinthestudywas
study(assumedtobelengthoffollow-upifnotspecified)andthe documented,butdatawerenotextracted,summarisedorusedin
timepointspecifiedinthemethodsasbeingofprimaryinterest(if anymeta-analysis.
thisisdifferentfromlatesttimepointavailable).Foralloutcomes • Changesininfectionstatus;signsorsymptomsofclinical
weclassed(andcategorised)outcomesfrom: infection(weusedstudyauthors’definitionsofclinical
• onetoeightweeksasshort-term; infection).Wedidnotincludedataonbacterialload,diversityor
• betweeneightand26weeksasmedium-term;and thepresenceofindividualspecies,whereitwasnotclearhowthe
• over26weeksaslong-term. outcomerelatedtoinfection.
• Changesinbacterial(antibiotic)resistance.
Reviewauthorsusedtheirjudgementbasedonconsideration of • Health-relatedqualityoflife:qualityoflifewasincluded
heterogeneitytodeterminewhetherstatisticalpoolingwithinthese whenitwasreportedusingavalidatedscalesuchastheSF-36
timecategorieswasappropriate. (Ware1992)orEQ-5D(EuroQoLGroup1990)oravalidated
Antibioticsandantisepticsforpressureulcers(Review) 8
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.