Rev. Bras. Hematol. Hemoter. vol.37 número6

rev bras hematol hemoter. 2015;37(6):371–372

w w w . r b h h . o r g

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

Scientific

Comment

Clostridium

difficile

infection

is

a

frequent

but

well-controlled

event

after

hematopoietic

cell

transplantation

夽

Paolo

Fabrizio

Caimi

a_{CaseWesternReserveUniversity,Cleveland,UnitedStates}

b_{CaseComprehensiveCancerCenter,Cleveland,UnitedStates}

Clostridiumdifficileinfection(CDI)isthemostcommoncause

ofnosocomialdiarrheaandrepresentsafrequentand

impor-tantsourceofgastrointestinalmorbidityafterhematopoietic

stemcelltransplantation(HSCT).PatientsundergoingHSCT

haveseveralriskfactorsforthedevelopmentofCDI,including

multiplepriorhospitalizations,frequentuseofwidespectrum

antibiotics,disease-andtreatment-related

immunosuppres-sionandmucosalbarrierdisruptionsecondarytoconditioning

regimens,particularlywhentheyaremyeloablativeorinclude

total body irradiation. Consequently, patients undergoing

HSCThaveanincidenceofCDIthatishigherthanthegeneral

hospitalizedpopulation;itisashighas15–30%afterallogeneic

HSCT.1

ThemajorityofreportsofCDIinHSCTpatientsoriginate

fromtransplantcenterslocatedindevelopedcountries.The

manuscriptbyPilcanteet al.2_{isthefirstreportofthe}

inci-dence,riskfactorsandoutcomesofCDIinpatientsundergoing

HSCTinanacademicmedicalcenterinChile.

Theresultspresentedare compatiblewithotherreports,

confirmingthe global importanceofCDI inHSCTpatients.

When compared to previous reports, the incidence ofCDI

observed inthis study appears to bein the lower portion

of the reported spectrum, possibly as a result of multiple

factors, including antibiotic use patterns, cultural dietary

habits, and possibly the degree of C. difficile colonization

affectingthegeneralhospitalizedpatientpopulationofChile.

RecentreportsbyKinnebrew3 _{and Bruminhent}4 _showhigh

ratesofcolonizationbyC.difficileatthetime ofadmission

DOIoforiginalarticle:http://dx.doi.org/10.1016/j.bjhh.2015.07.010.

夽

SeepaperbyPilcanteetal.onpages388–94.

Correspondingauthorat:11000EuclidAvenue,MailStopB700,44122,Cleveland,OH,UnitedStates.

E-mailaddress:paolo.caimi@case.edu

fortheHSCTprocedureintwoUS centers.Developmentof

CDI was preceded by colonization, with rare cases of CDI

developing in patients without previous colonization. It is

possiblethatlowercolonizationratesatadmissionwerethe

main determinantfor alower incidence ofCDI in Chilean

patients undergoing HSCT. As in other publications, the

majorityofCDIcasesoccurredearlyinthetransplantperiod,

with40%ofcasesoccurringwithinthefirstsevendays.

How-ever,themediantimetoCDIwaslongerthanotherstudies,

suggesting that late infections had a larger effect in this

cohort.Again, priorhospitalizations,antibioticuse patterns

andtherateofcolonizationmayhavehadanimpactonthese

results.

WhilepreviousstudieshaveobservedanassociationofCDI

withthedevelopmentofacuteGVHD(aGVHD),andincreased

riskofgastrointestinalaGVHD,5_{thisfindinghasnotbeen}

con-sistent. Ithasbeen postulated that CDImay represent the

initialinsult that stimulatesthe immune responseagainst

thegastrointestinaltract.However,thehigherrateofaGVHD

couldhaveoccurredduetoincreasedtestinginpatientswith

CDIaspartoftheclinicalevaluationofdiarrheainthe

post-transplant setting.Moreover, patients with aGVHD require

frequenthospitalizationsandhaveincreasedriskofinfectious

complicationsandantibioticuse.Inarecentstudy,Guddati

etal.reportedthatpatientswithGVHDhadahigherrateof

C.difficilecolonizationinpost-engraftmenthospitalizations,6

likelyasaresultoftheincreasedneedformedical

interven-tionsandinpatientcare.

http://dx.doi.org/10.1016/j.bjhh.2015.09.001

1516-8484/©2015Associac¸ãoBrasileiradeHematologia,HemoterapiaeTerapiaCelular.PublishedbyElsevierEditoraLtda.Allrights

372

TheassociationobservedbetweenCDIandlongertimeto

neutrophilengraftmentinallogeneic HSCTobservedinthe

studybyPilcanteetal.needstobeinterpretedwithcaution.2

Onepreviousstudyidentifiedtheuseofumbilicalcordblood

graftsasariskfactorforCDI,likelyasaresultoftheirslower

engraftment.7_{However,thepresenceofacorrelationbetween}

CDIanddelayedengraftmentisnotsufficienttoestablisha

causalrelationship.Thereversecausationcouldbepossible

(delayedengraftmentcausingincreaseinCDI)orbothCDIand

slowerengraftmentcouldbetheresultofotherriskfactors(i.e.

intensity of conditioning chemotherapy, myelosuppressive

antibiotics,priorbonemarrowdamageor

immunosuppres-sion,etc.).Subsequent studiesshouldfocus onthe specific

sequence ofevents and the presenceor other clinical and

laboratoryriskfactorsfordelayedengraftment.

Diarrheal illness is a common event in the post HSCT

period,and CDIshould beconsideredhigh inthe

differen-tialdiagnosis.WhileearlierliteraturesuggestedthatCDIin

HSCTrecipientswas moresevereand was associatedwith

increasednon-relapse mortality,8 _{recentretrospective}

anal-yses suggest that the majorityof casesofCDI are mild to

moderateandrespondwelltoantibiotictherapy.5,9_The

out-comesreportedbyPilcanteetal.confirmthatmostpatients

experience milddiarrhealillness that respondstoa single

course of antibiotics.2 _{Moreover, transplant outcomes and}

overallsurvivaldonotappeartobeaffectedbytheincidenceof

CDI.TheseandotherresultssuggestthatwhileCDIiscommon

afterHSCT,itisrarelyalife-threateningevent.Overthelast

decade,heightenedawareness,improvedtestingmethodsand

earlytreatmentofCDIinHSCTrecipientshavecontributedto

areductionintheseverityofthediarrhealillnessassociated

erebylimitingitsimpactonpost-transplantoutcomes.

Conflicts

of

interest

Theauthordeclaresnoconflictsofinterest.

r

e

f

e

r

e

n

c

e

s

1.ZacharioudakisIM,ZiakasPD,MylonakisE.Clostridiumdifficile

infectioninthehematopoieticunit:ameta-analysisof

publishedstudies.BiolBloodMarrowTransplant. 2014;20(10):1650–4.

2.PilcanteJE,RojasP,AjenjoM,SarmientoM,OcqueteauM,Ernst D,etal.Clostridiumdifficileinfectioninpatientsundergoing hematopoieticcelltransplantation.Resultsfromthe transplantationgroupattheHospitalClínicoPontificia UniversidadCatólica,Santiago,Chile.RevBrasHematol Hemoter.2015;37(6):388–94.

3.KinnebrewMA,LeeYJ,JenqRR,LipumaL,LittmannER, GobourneA,etal.EarlyClostridiumdifficileinfectionduring allogeneichematopoieticstemcelltransplantation.PLOSONE. 2014;9(3):e90158.

4.BruminhentJ,WangZX,HuC,WagnerJ,SundayR,BobikB, etal.Clostridiumdifficilecolonizationanddiseaseinpatients undergoinghematopoieticstemcelltransplantation.Biol BloodMarrowTransplant.2014;20(9):1329–34.

5.AlonsoCD,DufresneSF,HannaDB,LabbéAC,TreadwaySB, NeofytosD,etal.Clostridiumdifficileinfectionafteradult autologousstemcelltransplantation:amulticenterstudyof epidemiologyandriskfactors.BiolBloodMarrowTransplant. 2013;19(10):1502–8.

6.GuddatiAK,KumarG,AhmedS,AliM,KumarN,HariP,etal. IncidenceandoutcomesofClostridiumdifficile-associated diseaseinhematopoieticcelltransplantrecipients.IntJ Hematol.2014;99(6):758–65.

7.WillemsL,PorcherR,LafaurieM,CasinI,RobinM,XhaardA, etal.Clostridiumdifficileinfectionafterallogeneic

hematopoieticstemcelltransplantation:incidence,risk factors,andoutcome.BiolBloodMarrowTransplant. 2012;18(8):1295–301.

8.ChakrabartiS,LeesA,JonesSG,MilliganDW.Clostridiumdifficile

infectioninallogeneicstemcelltransplantrecipientsis associatedwithseveregraft-versus-hostdiseaseand non-relapsemortality.BoneMarrowTransplant. 2000;26(8):871–6.

9.JainT,CroswellC,Urday-CornejoV,AwaliR,CutrightJ,

SalimniaH,etal.Clostridiumdifficilecolonizationin

hematopoieticstemcelltransplantrecipients:aprospective

studyoftheepidemiologyandoutcomesinvolvingtoxigenic

andnontoxigenicstrains.BiolBloodMarrowTransplant.2015,