Antibiotic prophylaxis for preventing burn wound infection

177 Pages·2013·1.3 MB·English

Antibiotic prophylaxis for preventing burn wound infection
(Review)
Barajas-Nava LA, López-Alcalde J, Roqué i Figuls M, SolàI, BonfillCosp X
ThisisareprintofaCochranereview,preparedandmaintainedbyTheCochraneCollaborationandpublishedinTheCochraneLibrary
2013,Issue6
http://www.thecochranelibrary.com
Antibioticprophylaxisforpreventingburnwoundinfection(Review)
Copyright©2013TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAINLANGUAGESUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Figure1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Figure2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Figure3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
AUTHORS’CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
CHARACTERISTICSOFSTUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
DATAANDANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
Analysis1.1.Comparison1Topicalantibioticprophylaxis,Outcome1Burnwoundinfection. . . . . . . . . 120
Analysis1.2.Comparison1Topicalantibioticprophylaxis,Outcome2Infectionsintheburnedpeople(sepsis). . . 122
Analysis1.3.Comparison1Topicalantibioticprophylaxis,Outcome3Infectionsinburnedpeople(bacteraemia). . 123
Analysis1.4.Comparison1Topicalantibioticprophylaxis,Outcome4Infectionsinburnedpeople(pneumonia). . 124
Analysis1.5.Comparison 1Topical antibiotic prophylaxis,Outcome5Infections inburnedpeople(urinary tract
infection). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
Analysis1.6.Comparison1Topicalantibioticprophylaxis,Outcome6Adverseevents. . . . . . . . . . . . 125
Analysis1.7.Comparison1Topicalantibioticprophylaxis,Outcome7Infection-relatedmortality. . . . . . . 126
Analysis1.8.Comparison1Topicalantibioticprophylaxis,Outcome8Antibioticresistance(MRSA). . . . . . 127
Analysis1.9.Comparison1Topicalantibioticprophylaxis,Outcome9All-causemortality. . . . . . . . . . 128
Analysis1.10.Comparison1Topicalantibioticprophylaxis,Outcome10Lengthofhospitalstay(LOS). . . . . 129
Analysis2.1.Comparison2Systemicantibioticprophylaxis(general),Outcome1Burnwoundinfection. . . . . 130
Analysis2.2.Comparison2Systemicantibioticprophylaxis(general),Outcome2Infectionsinburnedpeople(sepsis). 131
Analysis 2.3. Comparison 2 Systemicantibiotic prophylaxis (general), Outcome 3 Infections in burned people
(bacteraemia). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
Analysis 2.4. Comparison 2 Systemicantibiotic prophylaxis (general), Outcome 4 Infections in burned people
(pneumonia). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
Analysis2.5.Comparison2Systemicantibioticprophylaxis(general),Outcome5Infectionsinburnedpeople(urinary
tractinfection). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
Analysis2.6.Comparison2Systemicantibioticprophylaxis(general),Outcome6Infection-relatedmortality. . . . 133
Analysis2.7.Comparison2Systemicantibioticprophylaxis(general),Outcome7Antibioticresistance(MRSA). . . 133
Analysis2.8.Comparison2Systemicantibioticprophylaxis(general),Outcome8All-causemortality. . . . . . 134
Analysis2.9.Comparison2Systemicantibioticprophylaxis(general),Outcome9Lengthofhospitalstay(LOS). . . 134
Analysis3.1.Comparison3Systemicantibioticprophylaxis(perioperative),Outcome1Burnwoundinfection. . . 135
Analysis3.2.Comparison3Systemicantibioticprophylaxis(perioperative),Outcome2Infectionsinburnedpeople
(bacteraemia). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
Analysis3.3.Comparison3Systemicantibioticprophylaxis(perioperative),Outcome3Infectionsinburnedpeople
(pneumonia). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
Analysis3.4.Comparison3Systemicantibioticprophylaxis(perioperative),Outcome4Infectionsinburnedpeople
(urinarytractinfection). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
Analysis3.5.Comparison3Systemicantibioticprophylaxis(perioperative),Outcome5Adverseevents. . . . . . 138
Analysis3.6.Comparison3Systemicantibioticprophylaxis(perioperative),Outcome6All-causemortality. . . . 138
Analysis3.7.Comparison3Systemicantibioticprophylaxis(perioperative),Outcome7Lengthofhospitalstay(LOS). 139
Analysis4.1.Comparison4Non-absorbable antibioticprophylaxis(selectivedecontaminationofthedigestivetract),
Outcome1Burnwoundinfection. . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Antibioticprophylaxisforpreventingburnwoundinfection(Review) i
Copyright©2013TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Analysis4.2.Comparison4Non-absorbable antibioticprophylaxis(selectivedecontaminationofthedigestivetract),
Outcome2Infectionsinburnedpeople(sepsis). . . . . . . . . . . . . . . . . . . . . . . 140
Analysis4.3.Comparison4Non-absorbable antibioticprophylaxis(selectivedecontaminationofthedigestivetract),
Outcome3Infectionsinburnedpeople(bacteraemia). . . . . . . . . . . . . . . . . . . . . 140
Analysis4.4.Comparison4Non-absorbable antibioticprophylaxis(selectivedecontaminationofthedigestivetract),
Outcome4Infectionsinburnedpeople(pneumonia). . . . . . . . . . . . . . . . . . . . . 141
Analysis4.5.Comparison4Non-absorbable antibioticprophylaxis(selectivedecontaminationofthedigestivetract),
Outcome5Infectionsinburnedpeople(urinarytractinfection). . . . . . . . . . . . . . . . . 141
Analysis4.6.Comparison4Non-absorbable antibioticprophylaxis(selectivedecontaminationofthedigestivetract),
Outcome6Adverseevents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
Analysis4.7.Comparison4Non-absorbable antibioticprophylaxis(selectivedecontaminationofthedigestivetract),
Outcome7Antibioticresistance(MRSA). . . . . . . . . . . . . . . . . . . . . . . . . 142
Analysis4.8.Comparison4Non-absorbable antibioticprophylaxis(selectivedecontaminationofthedigestivetract),
Outcome8All-causemortality. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
Analysis4.9.Comparison4Non-absorbable antibioticprophylaxis(selectivedecontaminationofthedigestivetract),
Outcome9Lengthofhospitalstay(LOS). . . . . . . . . . . . . . . . . . . . . . . . . 144
Analysis5.1.Comparison5Localantibioticprophylaxis(airway),Outcome1Infectionsinburnedpeople(sepsis). . 144
Analysis5.2.Comparison5Localantibioticprophylaxis(airway),Outcome2All-causemortality. . . . . . . . 145
Analysis6.1.Comparison6Antibioticprophylaxisvscontrol/placebo,Outcome1Burnwoundinfection. . . . . 146
Analysis6.2.Comparison6Antibioticprophylaxisvscontrol/placebo,Outcome2Infectionsinburnedpeople(sepsis). 147
Analysis 6.3. Comparison 6 Antibiotic prophylaxisvs control/placebo, Outcome 3 Infections in burned people
(bacteraemia). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148
Analysis 6.4. Comparison 6 Antibiotic prophylaxisvs control/placebo, Outcome 4 Infections in burned people
(pneumonia). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
Analysis6.5.Comparison6Antibioticprophylaxisvscontrol/placebo,Outcome5Infectionsinburnedpeople(urinary
tractinfection). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150
Analysis6.6.Comparison6Antibioticprophylaxisvscontrol/placebo,Outcome6Infection-relatedmortality. . . . 151
Analysis6.7.Comparison6Antibioticprophylaxisvscontrol/placebo,Outcome7Adverseevents. . . . . . . . 152
Analysis6.8.Comparison6Antibioticprophylaxisvscontrol/placebo,Outcome8Antibioticresistance(MRSA). . 153
Analysis6.9.Comparison6Antibioticprophylaxisvscontrol/placebo,Outcome9All-causemortality. . . . . . 154
Analysis6.10.Comparison6Antibioticprophylaxisvscontrol/placebo,Outcome10Lengthofhospitalstay(LOS). 155
ADDITIONALTABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
CONTRIBUTIONSOFAUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172
DECLARATIONSOFINTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
SOURCESOFSUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
DIFFERENCESBETWEENPROTOCOLANDREVIEW . . . . . . . . . . . . . . . . . . . . . 173
NOTES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174
Antibioticprophylaxisforpreventingburnwoundinfection(Review) ii
Copyright©2013TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
[InterventionReview]
Antibiotic prophylaxis for preventing burn wound infection
LeticiaABarajas-Nava1,JesúsLópez-Alcalde2,MartaRoquéiFiguls3,IvanSolà3,XavierBonfillCosp4
1IberoamericanCochraneCentre,InstituteofBiomedicalResearch(IIBSantPau),Barcelona,Spain.2HealthTechnologyAssessment
Unit,LaínEntralgoAgency(CochraneCollaboratingCentre),Madrid,Spain.3IberoamericanCochraneCentre,InstituteofBiomedical
Research (IIB Sant Pau), CIBER Epidemiología y Salud Pública (CIBERESP), Spain, Barcelona, Spain. 4Iberoamerican Cochrane
Centre, Institute of Biomedical Research(IIB Sant Pau), CIBER Epidemiología y SaludPública (CIBERESP), Spain -Universitat
AutònomadeBarcelona,Barcelona,Spain
Contactaddress:LeticiaABarajas-Nava,IberoamericanCochraneCentre,InstituteofBiomedicalResearch(IIBSantPau),C/Sant
AntoniMaClaret171,CasadeConvalescència,Barcelona,Barcelona,08041,[email protected].
Editorialgroup:CochraneWoundsGroup.
Publicationstatusanddate:New,publishedinIssue6,2013.
Reviewcontentassessedasup-to-date: 31January2013.
Citation:Barajas-NavaLA,López-AlcaldeJ,RoquéiFigulsM,SolàI,BonfillCospX.Antibioticprophylaxisforpreventingburnwound
infection.CochraneDatabaseofSystematicReviews2013,Issue6.Art.No.:CD008738.DOI:10.1002/14651858.CD008738.pub2.
Copyright©2013TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
ABSTRACT
Background
Infectionofburnwoundsisaseriousproblembecauseitcandelayhealing,increasescarringandinvasiveinfectionmayresultinthe
deathofthepatient.Antibiotic prophylaxisisoneof severalinterventions thatmaypreventburn wound infectionandprotectthe
burnedpatientfrominvasiveinfections.
Objectives
Toassesstheeffectsofantibioticprophylaxisonratesofburnwoundinfection.
Searchmethods
InJanuary2013wesearchedtheWoundsGroupSpecialisedRegister;TheCochraneCentralRegisterofControlledTrials(CENTRAL);
OvidMEDLINE;OvidMEDLINE-In-Process&OtherNon-IndexedCitations(2013); OvidEMBASE;EBSCOCINAHLand
referencelistsofrelevantarticles.Therewerenorestrictionswithrespecttolanguage,dateofpublicationorstudysetting.
Selectioncriteria
Allrandomised controlledtrials(RCTs) thatevaluatedtheefficacy andsafety of antibiotic prophylaxisfor theprevention of BWI.
Quasi-randomisedstudieswereexcluded.
Datacollectionandanalysis
Tworeviewauthorsindependentlyselectedstudies,assessedtheriskofbias, andextractedrelevantdata.Riskratio(RR)andmean
difference(MD)wereestimatedfordichotomousdataandcontinuousdata,respectively.WhensufficientnumbersofcomparableRCTs
wereavailable,trialswerepooledinameta-analysistoestimatethecombinedeffect.
Antibioticprophylaxisforpreventingburnwoundinfection(Review) 1
Copyright©2013TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Mainresults
Thisreviewincludes36RCTs(2117participants);twentysix(72%)evaluatedtopicalantibiotics,sevenevaluatedsystemicantibiotics
(fouroftheseadministeredtheantibioticperioperativelyandthreeadministereduponhospitaladmissionorduringroutinetreatment),
twoevaluatedprophylaxiswithnonabsorbableantibiotics,andoneevaluatedlocalantibioticsadministeredviatheairway.
The11trials(645participants)thatevaluatedtopicalprophylaxiswithsilversulfadiazinewerepooledinametaanalysis.Therewas
astatisticallysignificantincreaseinburnwoundinfectionassociatedwithsilversulfadiazinecomparedwithdressings/skinsubstitute
(OR=1.87;95%CI:1.09to3.19,I2=0%).Thesetrialswereathigh,orunclear,riskofbias.Silversulfadiazinewasalsoassociated
withsignificantlylongerlengthofhospitalstaycomparedwithdressings/skinsubstitute(MD=2.11days;95%CI:1.93to2.28).
Systemicantibioticprophylaxisinnon-surgicalpatientswasevaluatedinthreetrials(119participants)andtherewasnoevidenceof
aneffectonratesofburnwoundinfection.Systemicantibiotics(trimethoprim-sulfamethoxazole)wereassociatedwithasignificant
reductioninpneumonia(onlyonetrial,40participants)(RR=0.18;95%CI:0.05to0.72)butnotsepsis(twotrials59participants)
(RR=0.43;95%CI:0.12to1.61).
Perioperativesystemicantibioticprophylaxishadnoeffectonanyoftheoutcomesofthisreview.
Selectivedecontaminationofthedigestivetractwithnon-absorbableantibioticshadnosignificanteffectonratesofalltypesofinfection
(2trials,140participants).Moreover,therewasastatisticallysignificantincreaseinratesofMRSAassociatedwithuseofnon-absorbable
antibioticspluscefotaximecomparedwithplacebo(RR=2.22;95%CI:1.21to4.07).
Therewasnoevidenceofadifferenceinmortalityorratesofsepsiswithlocalairwayantibioticprophylaxiscomparedwithplacebo
(onlyonetrial,30participants).
Authors’conclusions
Theconclusionsweareabletodrawregardingtheeffectsofprophylacticantibioticsinpeoplewithburnsarelimitedbythevolumeand
qualityoftheexistingresearch(largelysmallnumbersofsmallstudiesatunclearorhighriskofbiasforeachcomparison).Thelargest
volumeofevidencesuggeststhattopicalsilversulfadiazineisassociatedwithasignificantincreaseinratesofburnwoundinfectionand
increasedlengthofhospitalstaycomparedwithdressingsorskinsubstitutes;thisevidenceisatunclearorhighriskofbias.Currently
theeffectsof otherformsof antibiotic prophylaxison burn wound infection are unclear. Onesmallstudy reportedareduction in
incidenceofpneumoniaassociatedwithaspecificsystematicantibioticregimen.
PLAIN LANGUAGE SUMMARY
Antibioticstopreventburnwoundsbecominginfected
Burninjuriesareaseriousproblem.Theyareassociatedwithasignificantincidenceofdeathanddisability,multiplesurgicalprocedures,
prolongedhospitalisation,andhighcostsofhealthcare.
Variousantibioticsareusedwiththeaimofreducingtheriskofinfectioninburnpatientsbeforeitoccurs.Someantibioticsareused
locallyontheskin(topicaltreatments),othersaretakenorally,orbyinjection,andaffectthewholebody(systemictreatments).Itis
notclearifprophylacticantibioticsarebeneficial.
Thirtysixstudiesinvolving2117participantsareincludedinthisreview.Thestudiescomparedpeoplewithburnswhoweregiven
antibioticswithpeoplealsowithburnswhoreceivedeitheraninactivetreatment(placebo),notreatment,wounddressings,oranother
topicalpreparationorantibiotic.Twenty-sixtrials(72%)evaluatedtopicalantibioticsandsmallernumbersevaluatedantibioticsgiven
orally,intravenouslyorviatheairway.Moststudiesweresmallandofpoorquality.
Therewas some evidence thataparticularantibiotic (silversulfadiazine) applieddirectlytotheburn actuallyincreases theratesof
infectionbybetween8%and80%.Otherwisetherewasnotenoughresearchevidenceabouttheeffectsofantibioticstoenablereliable
conclusionstobedrawn.
Antibioticprophylaxisforpreventingburnwoundinfection(Review) 2
Copyright©2013TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
BACKGROUND (eschar))replacestheskinand,eventually,willbecolonisedwith
micro-organisms (De Macedo 2005; Erol2004;Sharma2007).
Theproliferationofmicro-organismsintheburnwoundmaybe
followedbytissueinvasion,givingrisetoburnwoundinfection
Descriptionofthecondition (BWI)andinvasive(systemic)infections.Commoninvasiveinfec-
tionsinpeoplewithburnsincludepulmonaryinfections,urinary
The International Society for Burn Injuries defines a burn as an
tractinfection,bacteraemiaandsepsis(Ansermino2004;Church
injurytotheskinorotherorganictissuecausedbythermaltrauma
2006;Pruitt1998).Burninjuryalsohasasevereimpactonthe
(Latarjet1995).Askinburnisthedestructionofsome,orall,of
host’simmune system,resulting ina generalimpairment of the
thedifferentlayersofcellsintheskinbyahotliquid(scald),ahot
hostdefences(Munster1984;Sharma2007).
solid(contactburn),oraflame(flameburn).Skininjuriesdueto
Decidingwhetheraburnwoundisinfectedcanbedifficult.Firstly,
ultravioletradiation,radioactivity,electricityorchemicals,aswell
theinflammation resultingfromtheinjurycanmimicthatseen
as respiratory damage resulting fromsmoke inhalation, are also
withinfection.Secondly,theinterpretationofsurfaceculturesis
consideredtobeburns(Latarjet1995;Peden2002;Peden2008;
oftendifficultduetotheextensiveandrapidmicrobialcolonisa-
WHO2006).
tionofthewound(Ansermino2004),withmicro-organismscom-
Burninjuriesareamajorsourceofmorbidityandmortality;they
ingfromthepersonsskinorfromexternalsources(Church2006;
representapublichealthproblemandasignificantburdentothe
Erol2004;Wurtz1995).
healthcaresystem(Church2006;WHO2006).Everyyear,more
Thenatureandextentoftheburnwound,togetherwiththetype
than300,000peopleworldwidediefromfire-relatedburns,most
andamountofcolonisingmicro-organismscaninfluencetherisk
of them(i.e. 90%) occurring in low and middle-income coun-
of invasive infection. The spectrumof infective agents thatcan
tries (Mock 2008; Peden 2002). However, burns also represent
bepresentintheburnwoundsvaries.Nowadays,Gram-positive
oneof themaincausesofinjury-relateddeathinsomehigh-in-
bacteriasuchasStaphylococcusaureus,andGram-negativebacteria
comecountries,suchas theUSAandcertainEuropeancountries
such as Pseudomona aeruginosa are the predominant pathogens.
(Church2006;Hyder2009;Mathers2003;Miniño2006;WHO
Nonetheless,othermicro-organisms,suchasfungi,rickettsiasand
2006).Millionsofburnvictimssufferpermanentdisability and
viruses, can also be implicated (Church 2006; Mayhall 2003;
disfigurement,whichisoftenstigmatising;itisestimatedthat10
Polavarapu 2008; Sharma 2007). It should also be noted that
milliondisability-adjustedlifeyearsarelosteachyearataworld-
multidrug-resistantmicro-organisms,suchasmethicillin-resistant
widelevelthroughburninjury(Hyder2009;Mock2008;Peden
Staphylococcusaureus(MRSA),arepathogensfrequentlyidentified
2008).Burnscreateaheavyeconomicburdenforhealthservices.
in burns (Church 2006; DeSanti 2005; Mayhall 2003; Sharma
Treatmentcostsdependuponthetypeandseverityoftheburn,as
2007).
wellasassociatedcostssuchashospitalisation,theneedforlong-
Burn wound infection (BWI)is a serious problem: itcan delay
termrehabilitation,thelossofschooling/absencefromwork,fu-
woundhealing,canincreasethescarringandcanfavourtheprolif-
ture unemployment, and social rejection. In spite of this, there
erationofmicro-organismsthatmayresultininvasiveinfections
areactuallyveryfewstudiesthatprovideevidenceoftheoverall
(Church2006;Edwards2004;Singer2002).Nowadays,afterthe
impactandcostofburns(Mock2008;Peden2008).
initialresuscitationofburnvictims,upto75%ofalldeathsarea
Infections are considered to be one of the most important and
consequenceofinfection,ratherthansuddencellularfluidimbal-
potentially serious complications in peoplewith burns (Church
ance(osmoticshock)anddecreasedvolumeofbloodplasma(hy-
2006;Murray2008).AreportbytheNationalBurnRepository
povolaemia)(Ansermino2004;Bang2002;Church2006;Sharma
oftheUnitedStatesmentionsthatina10-yearperiodtherewere
2007;Sheridan2005).
19,655casesofcomplicationsinpeoplewithburns;31%ofthese
werepulmonarycomplications,17%wererelatedtothewound
infectionandcellulitis,and15%wereduetosepticaemiaandother
infectious complications (Latenser 2007; Murray 2008). These
Descriptionoftheintervention
dataaresupportedbysimilarreportscarriedoutinothercountries
(Alp2012;SEMPSPH2008;Soares2006). Preventionofinfectionofburnwoundsrequiresateamapproach,
Infectionsgenerallyariseintheacuteperiodaftertheburninjury andshouldbeanearlyfocusofthecareofburnedpatients,with
(Church2006;Sheridan2005).Burnwoundsarehighlysuscepti- particularconsideration giventoinfection-control practicesand
bletoinfectionduetothelossofskinintegrityandthereduction long-termrehabilitativecare(Murray2008).
ofimmunitymediatedbythecells.Oncethephysicalbarrierofthe Avarietyofinterventionsexistsforpreventinginfectionsinburn
skinhasbeencompromised,thereispotentialfortheinvasionof wounds:namely,earlyremovaloffull-thicknessburnedtissue(de-
microbesintothebody(Murray2008;Sharma2007).Anareaof bridement);earlydefinitivewoundclosure;strictenforcementof
deadtissue,withfewornobloodvessels(avascularnecrotictissue infection-controlprocedures(handwashing,useofpersonalpro-
Antibioticprophylaxisforpreventingburnwoundinfection(Review) 3
Copyright©2013TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
tectiveequipment,i.e.gown,gloves,andmasks);andtheuseof Theuseofantibioticshasbeenconsideredusefulintreatmentof
antimicrobialprophylaxis(Church2006;DeSanti2005;Murray infections in burn victims (Polavarapu 2008). In some centres,
2008;Weber2002;Weber2004).Thereisawidevarietyoftopi- patientswithevidenceofapositivemicrobiologicalculturefrom
calantimicrobialagentsavailableforuseasprophylaxisforBWI, a burn site were given systemic antibiotic prophylaxis in an at-
suchassilvernitrateandsilversulphadiazine (Ansermino2004; tempttopreventwoundinfectionandsepsis(Atoyebi1992;Haq
Church2006).Moreover,topicalantimicrobialshavebeenused 1990;Lee2009;Onuba1987),thoughthisisnowcontroversial
together with systemic (whole body) antibiotics to prevent and (Ansermino2004).Thereisthoughttobeapaucityofhighqual-
treatinfection.Arangeofantibiotics, androutesofadministra- ityresearchevidencetodeterminetheeffectivenessandcost-effi-
tionhavebeenevaluatedforthepreventionofsystemicinfection ciencyofantibioticprophylaxisforpreventingBWI(Avni2010;
in people with burn wounds. For example, oral trimethoprim- Lee2009;Ugburo2004).Moreover,theuseofprophylactican-
sulphamethoxazoleprophylaxisandintravenouscephalothinpro- tibiotics may not be safe: it may increase the risk of diarrhoea
phylaxis(Alexander1982;Kimura1998). duetoovergrowthoftoxigenicstrainsofClostridiumdifficileand
To address complications of smoke inhalation, local antibiotic othersecondaryinfections,allergicreactionstothedrugorbone
prophylaxis administered via the airway has been tested by us- marrowsuppression(Alexander2009;Church2006;Ergün2004;
ingaerosolizedantibiotics(Levine1978).Themostrecentclinical Still2002).Finally,itmayalsopromotetheemergenceofresis-
practiceguidelines,however,donotrecommendtheroutinead- tant strains of micro-organisms, making thetreatment of infec-
ministrationofprophylacticantibioticsinburnedpersons.Antibi- tionsevenmoredifficult(Altoparlak2004;Church2006;Murphy
oticsare recommendedonly forpatients withknown infections 2003).
(Alsbjörn 2007; Brychta 2011; Hospenthal 2011; NSW Severe Thereisconsiderabledebateconcerningtheuseofantibioticpro-
BurnInjuryService2008).Beforethewideadoptionofearlyexci- phylaxisforthepreventionoftheBWIandthereforeaCochrane
sionandclosureofdeepwounds,infectionwasafrequentoccur- systematicreviewoftheavailableevidenceiswarranted.
renceintheburnwound(Sheridan2005).Nowadays,however,
theearlyexcisionofescharandavascularisedtissuesimprovesthe
perfusion of the burned tissues, and allows systemic antibiotics
toreachadequatetherapeuticlevelsintheburnwound(Church OBJECTIVES
2006;Kumar2006;Mayhall2003).Despitethefactthatsystemic
infection,suchassepsis,isnowlessfrequent,infectioninpeople To assess the effects of antibiotic prophylaxis on rates of burn
withburnscontinuestobeaseriousthreat(Church2006;Kumar woundinfection.
2006;Sheridan2005).
Thisreviewwillfocusontheeffectsofantibioticprophylaxis(oral
(PO),parenteral(entrytobodynotviagastrointestinal tract)or METHODS
topicalantimicrobials)forpreventingburnwoundinfections.
Criteriaforconsideringstudiesforthisreview
Howtheinterventionmightwork
Improvementsinrecoveryforseriouslyburnedpeoplehavebeen
Typesofstudies
attributedtomedicaladvancesinwoundcareandinfectioncontrol
practices(Church2006;DeSanti2005). Randomisedcontrolledtrials(RCTs),publishedorunpublished,
Theefficacyofcommonly-usedantimicrobialagentsinburnsunits with allocation to interventions atthe individual level(patient-
isdynamicduetotheability ofmicro-organisms todevelopre- RCT)oratthegrouplevel(cluster-RCT),testingtheefficacyand
sistance quickly (Church 2006; Mayhall 2003). The antibiotic safetyofantibioticprophylaxisforthepreventionofburnwound
regimenofchoiceisdeterminedbythepathogenknown,orsus- infections.Quasi-randomisedstudieswereexcluded.
pected,tocausetheinfection(Church2006).Theuseofanef-
fective antimicrobial agent, however, could reduce substantially
Typesofparticipants
themicrobialloadintheopensurfaceoftheburnwound,and,
therefore,reducetheriskofinfection.Bearingtheaboveinmind, Peopleofanyageorgender,withanytypeofburninjurytothe
antibiotic prophylaxismightbeausefulwayofprotectingburn epidermis,dermis,subcutaneous tissues, vessels,nerve,tendons,
victimsagainstwound,andinvasive,infections. orbone;butnotresidualburnwounds(thesetypeofwoundsmay
havehadpreviousinfectionsortreatments)admittedtoanyunit
inthehospitalsetting,ortreatedinanoutpatientsetting.
We included studies regardless of the severity of the burn (de-
Whyitisimportanttodothisreview
terminedbyeitherclinicalevaluationorobjectiveassessment,or
Antibioticprophylaxisforpreventingburnwoundinfection(Review) 4
Copyright©2013TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
both)orthetypeofburninjury(e.g.chemical,scald,orflame). • Outcome2:Invasiveinfections,suchaspneumonia,
Wedidnotexcludestudiesdependingonthepresenceofinhala- urinarytractinfections(UTI),bacteraemiaorbloodinfections
tioninjuryorco-morbidity. (sepsis),orcentralvenouscatheter-associatedbloodstream
Weexcludedstudiesthatcontainedmixedpopulation,i.e.people infections.Weadmittedanymeasureforquantifyinginfections,
with already infected wounds in addition to those without an suchasincidencerateorincidencedensityrate.
infection(unlessthedatawerepresentedseparately). • Outcome3:Infection-relatedmortality:i.e.mortalitydue
toinfectionofburnwounds,sepsis,oranotherinfective
complication.
Typesofinterventions • Outcome4:Adverseevents:thoseconsideredbythestudy
Prophylaxiswasdefinedastheadministrationofantibioticstopa- investigatorstoberelatedtoantibioticprophylaxis,suchas
tientswithoutadocumentedinfection,regardlessofthesignsof toxicity,allergies,antibiotic-associateddiarrhoeaduetothe
systemicinflammation, withtheaimofpreventingburnwound overgrowthoftoxigenicstrainsofClostridiumdifficile,etc.
infectionandinvasiveinfection.Studiesofthetreatmentofresid-
ualburnwoundswasnotincludedsincetheobjectiveofthisre-
viewistoassesstheeffectoffirstintentionprophylaxis. Secondaryoutcomes
Weincludedanyofthefollowingantibioticprophylaxis: • Outcome5:Objectivemeasuresofwoundhealingrate:
• Systemicantibioticsgivenorallyorparenterally suchastimetocompletehealing;proportionofwounds
(intravenouslyorviaintramuscularinjection). completelyhealedwithinatrialperiod;proportionof
• Selectiveintestinaldecontaminationwithantibiotics(non- participantswithcompletelyhealedwounds;orproportionof
absorbableantibiotictherapy). woundspartlyhealedinaspecifiedtimeperiod.
• Topicalantibiotics,suchastopicalantimicrobialdressings • Outcome6:Antibioticresistance:definedastheclinical
orointments(Merriam-Webster2012). infectionorcolonisationcausedbybacteriaresistanttooneor
• Localairwayprophylaxis,suchasaerosolisedantibiotics. moreantibiotics(seeDifferencesbetweenprotocolandreview).
• Outcome7:All-causemortality:wetriedtoanalysethis
Eligiblecomparisonswereplacebo,notreatment,usualcareoran
outcomeaccordingtothelongestcommontimepointof
alternative intervention. Alternative interventions could include
assessmentamongtheincludedstudies.
nonpharmacologicalmeasuressuchasisolation oftheburnpa-
• Outcome8:Lengthofhospitalstay(LOS).
tient,surgicalexcision;orpharmacologicalmeasures,suchasan-
otherantibioticregimen.Trialscomparingdifferentantibioticsor Studieswereeligibleforinclusioneveniftheyonlyreportedsec-
differentantibioticdosages,routesofadministration, timingsor ondaryoutcomes,astheseoutcomesarerelevanttopatients.
durationofadministrationwereeligibleforinclusion.Antibiotic
prophylaxiscouldbegivenatanymomentafteradmission(’gen-
eralprophylaxis’)orcouldbespecificallygivenbeforesurgicalpro- Searchmethodsforidentificationofstudies
cedures(’perioperativeprophylaxis’).Wedidnothaveaminimum
durationoftheinterventionoroffollow-upasinclusioncriteria.
Weexcludedstudiesevaluatingantibiotic-impregnatedcatheters; Electronicsearches
ointments or dressings that contained antimicrobials (iodine,
InJanuary2013wesearchedthefollowingelectronicdatabasesto
chlorhexidine);andantifungals,sincetheyarenotconsideredto
findreportsofrelevantRCTs:
beantibiotictherapies.Dressingsforsuperficialpartial-thickness
• TheCochraneWoundsGroupSpecialisedRegister
burnsareevaluatedinanotherCochranereview(Wasiak2008),
(searched25January2013);
theprincipalobjectiveofwhichwasnottheevaluationofantibi-
• TheCochraneCentralRegisterofControlledTrials
oticprophylaxis.
(CENTRAL)-(TheCochraneLibrary2012,Issue12);
• OvidMEDLINE-1950toJanuaryWeek32013;
Typesofoutcomemeasures • OvidMEDLINE-In-Process&OtherNon-Indexed
Citations,January23,2013;
• OvidEMBASE-1980to2013Week03;
• EBSCOCINAHL-1982to25January2013.
Primaryoutcomes
• Outcome1:Burnwoundinfection:studiesreportingan WesearchedtheCochraneCentralRegisterofControlledTrials
objectivemeasureofburnwoundinfection.Diagnosisshould (CENTRAL)usingthefollowingexplodedMeSHheadingsand
relyonclinicalexamination(burnwoundappearance)and keywords:
culturedata,ifpossible,however,burnwoundinfections #1MeSHdescriptorBurnsexplodealltrees
diagnosedonlybyclinicalexaminationwerealsoeligible. #2(burnorburnsorburnedorscald*):ti,ab,kw
Antibioticprophylaxisforpreventingburnwoundinfection(Review) 5
Copyright©2013TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
#3(thermalNEXTinjur*):ti,ab,kw Thetable of excludedstudiesprovides detailsof allstudies that
#4(#1OR#2OR#3) appeared initially to meet our inclusion criteria, but which on
#5MeSHdescriptorAnti-BacterialAgentsexplodealltrees closerexaminationdidnot,withthereasonsfortheirexclusions.
#6MeSHdescriptorAnti-InfectiveAgents,Localexplodealltrees Anydisagreementswereresolvedthroughdiscussion bythetwo
#7 (antibiotic* or amoxicillin or ampicillin* or bacitracin or review authors. Disagreements thatcould not easily be resolved
cephalothin or cefazolin or cefotaxime or cefoperazone or cef- werereferredtoathirdreviewauthor(JL).
tazidimeorceftriaxoneorcefuroximeorchloramphenicolorci-
profloxacinorclarithromycinorclindamycinorcloxacillinorcol-
istin or colymycin or erythromycinor flucloxacillin or furazoli- Dataextractionandmanagement
doneor“fusidicacid”orgentamicinor gramicidinorimipenem
Datafromthestudieswereextractedindependentlybytworeview
or“mafenideacetate” ormupirocinornatamycinorneomycinor
authors(LBandCJ)usingstandardisedforms.Detailsofincluded
nitrofurazoneoroxacillinorpenicillinorpiperacillinorpolymyxin
trialswereextractedandsummarisedusingadataextractionsheet.
or rifam* or “silver nitrate” or “silver sulfadiazine” or “sulfac-
Datafromtrialspublishedinduplicatewereincludedonlyonce,
etamide sodium” or tobramycin or amphotericin or tazocin or
but maximal data extracted. All discrepancies were resolved by
teicoplaninortetracylcinor(trimethopri*NEXTsulfamethoxa-
consensusamongthereviewauthors.Wheninformationwithin
zole)orvancomycin):ti,ab,kw
trialreportswasnotclear,weattemptedtocontactauthorsofthe
#8(#5OR#6OR#7)
trialreportstorequestfurtherdetails.
#9(#4AND#8)
Weextractedthefollowingdata:
ThesearchstrategiesforOvidMEDLINE,OvidEMBASEand
• Characteristicsofthetrial:studydesign,setting/location,
EBSCOCINAHLcanbefoundinAppendix1.TheOvidMED-
country,periodofstudy,methodofrandomisation,allocation
LINE search was combined with the Cochrane Highly Sensi-
concealment,blinding,unitofrandomisation,unitofanalysis,
tive Search Strategy for identifying randomised trials in MED-
samplesizecalculation,useofIntention-to-treatanalysis.
LINE:sensitivity-andprecision-maximizing version(2008revi-
• Participants:number,randomised,excluded(post-
sion)(Lefebvre2011).TheEMBASEandCINAHLsearcheswere
randomisation),reasonsforexclusion,participantsassessed,
combinedwiththetrialfiltersdevelopedbytheScottishIntercol-
withdrawals,reasonsforwithdrawals,age,gender,inclusion
legiateGuidelinesNetwork(SIGN2011).Therewerenorestric-
criteria,exclusioncriteria,burnedsurface(%oftotalbody
tionswithrespecttolanguage,dateofpublicationorstudysetting.
surfacearea),full-thicknessburns,inhalationinjury,timepost-
Wesearchedinthefollowingtrialsregistersusingthekeywords:
burn,burntype,thestateofthewoundsatbaseline,co-
prophylaxis,antibiotic,andburn:
morbidities.
• InternationalStandardRandomizedControlledTrial
• Typeofintervention:interventiongroup:antibiotic,dose,
NumberRegister(http://www.controlled-trials.com/isrctn/)(last
route,frequency,durationoftreatment,co-interventions.
searchedMay2012);
Controlgroup:descriptionoftheinterventionapplied(ifany).
• USNationalInstitutesofHealthtrialregistry(http://
• Outcomedata.
www.clinicaltrials.gov)(lastsearchedMay2012).
• Sourceoffunding,conflictsofinterest.
DatawereenteredintoReviewManagerbyonereviewauthor(LB)
Searchingotherresources (RevMan2011),anddoublecheckedbyasecondreviewauthor
Wesearchedthereferencelistsofallidentifiedstudiestofindany (JL).
furtherrelevanttrials.
Assessmentofriskofbiasinincludedstudies
Datacollectionandanalysis Tworeviewauthors(LBandCJ)independentlyassessedtherisk
of bias ofeachincluded study using thecriteriaoutlinedin the
tool designed by the Cochrane Collaboration (Higgins 2011a)
(seeDifferencesbetweenprotocolandreview).Weconsideredthe
Selectionofstudies
followingdomains:
Tworeviewauthors(LBandCJ)independentlyassessedalltitles 1. Randomsequencegeneration(selectionbias).
and abstracts of studies identified by thesearch strategy against 2. Allocationconcealment(selectionbias).
theeligibilitycriteriaintermsoftheirrelevanceanddesign.The 3. Blindingforparticipantsandpersonnel(performancebias).
fulltextversionsofallpotentiallyeligiblestudieswereretrieved, 4. Blindingofoutcomeassessment(detectionbias).
andthetworeviewauthorsindependentlyassessedtheeligibility 5. Incompleteoutcomedata(attritionbias).
ofeachstudyagainsttheinclusioncriteria. 6. Selectiveoutcomereporting(reportingbias).
Antibioticprophylaxisforpreventingburnwoundinfection(Review) 6
Copyright©2013TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
7. Othersourcesofbias(consideredincombination,thatis,if comes).Welabelledeachcriterionasbeingat’low’,’high’or’un-
atleastoneoftheseothersourcesofbiasisconsideredtobe clear’riskofbias.SeeAppendix2fordetailsofcriteriaonwhich
’high’,thisdomainwillbejudgedas’high’): thejudgementswerebased.Wetriedtoobtainthisinformation
i) forcluster-randomisedtrials,weassessedthese fromthetrialreports,but,whentherewasnotenoughinforma-
additionalsourcesofbias:recruitmentbias;baselineimbalance tiontomakeajudgement,wewrotetothetrialauthorsforclar-
eitheracrossclustersorpatients;lossofclustersandincorrect ification.Disagreementswereresolvedbydiscussionandconsen-
analysis(Higgins2011b,Section16.3.2); sus.Weincludedtwofiguresinthereview:a’Riskofbiasgraph
ii) forthetrialswheretheunitofrandomisationwasthe figure’(Figure1)anda‘Riskofbiassummaryfigure’(Figure2).
patient,wealsoassessedwhetherthereweresimilarbaseline Weassessedtheoverallriskofbiasforeachoutcome(orclassof
characteristicsbetweenthestudygroups; similar outcomes) within eachstudy. Each outcome (or class of
iii) foralltheincludedstudieswealsoassessedwhether outcomes)wasdefinedashavinga‘lowriskofbias’onlyifitwas
therewerebaselineimbalancesinfactorsthatarestronglyrelated atlowriskof biasfor allthedomains; at‘highriskofbias’ if it
tooutcomemeasures,whethertheanalysisoftime-to-eventdata demonstratedhighriskofbiasforoneormoreofthedomains;
wasadequate,whetherthestudywasstoppedearlyduetosome orat‘unclearriskofbias’ifitdemonstratedunclearriskofbias
data-dependentprocess,andwhethertherewasanydeclared foratleastonedomainwithoutanyoftheotherdomainsbeing
financialsupport. describedas‘highriskofbias’.
We made assessments for each main outcome (or class of out-
Figure1. Riskofbiasgraph:reviewauthors’judgementsabouteachriskofbiasitempresentedas
percentagesacrossallincludedstudies.
Antibioticprophylaxisforpreventingburnwoundinfection(Review) 7
Copyright©2013TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.