Fusarium spp infections in a pediatric burn unit: nine years of experience

braz j infect dis 2 0 1 6;20(4):389–392

w w w . e l s e v i e r . c o m / l o c a t e / b j i d

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

Brief

communication

Fusarium

_spp

_infections

_in

_a

_pediatric

_burn

_unit:

nine

years

of

experience

María

Teresa

Rosanova

,

Martín

Brizuela

,

Mabel

Villasboas

,

Fabian

Guarracino

,

Veronica

Alvarez

_,

_Patricia

_Santos

_,

_Jorge

_{Finquelievich}

a_{HospitaldePediatría“Prof.Dr.JuanP.Garrahan”,DepartamentodeEnfermedadesInfecciosas,BuenosAires,Argentina} b_{HospitaldePediatría“Prof.Dr.JuanP.Garrahan”,UnidaddeCuidadosIntensivosdeQuemados,BuenosAires,Argentina} c_{HospitaldePediatría“Prof.Dr.JuanP.Garrahan”,DepartmentodeMicrobiología,BuenosAires,Argentina}

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Articlehistory:

Received4January2016 Accepted18April2016 Availableonline25May2016

Keywords:

Burn

Fusariumspp Fungalinfections

a

b

s

t

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t

Introduction:Fusariumsppareubiquitousfungirecognizedasopportunisticagentsofhuman infections,andcanproducesevereinfectionsinburnpatients.TheliteratureonFusarium

sppinfectionsinpediatricburnpatientsisscarce.

Objectives: Todescribetheclinicalandepidemiologicalfeaturesaswellasoutcomeof Fusa-riumsppinfectionsinpediatricburnpatients.

Patientsandmethods:Retrospective,descriptivestudyofFusariumsppinfectionsina special-izedintensivecareburnunit.

Results:In15patientsFusariumsppinfectionswerediagnosed.Medianagewas48months. Directfireinjurywasobservedintenpatients.Themedianaffectedburnsurfaceareawas 45%.Twelvepatientshadafullthicknessburn.FourteenpatientshadaGarcesIndex≥3. Fungalinfectiondevelopedatamedianof11daysafterburninjury.Fungiwereisolated fromburnwoundin14patientsandfromtheboneinonepatient.

AmphotericinBwasthedrugofchoicefortreatmentfollowedbyvoriconazole.Median timeoftreatmentcompletionwas23days.Onepatient(7%)diedoffungalinfection-related causes.

Conclusion: In our series Fusarium spp was an uncommon pathogen in severely burnt patients.Theburnwoundwasthemostcommonsiteofinfectionandmortalitywaslow.

©2016ElsevierEditoraLtda.ThisisanopenaccessarticleundertheCCBY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

Infectionisthemostcommonandseverecauseofmorbidity andmortalityinburnpatients.1_{Thelongersurvivalofthis}

populationhasincreasedthefrequencyoffungalinfections.

∗ _{Correspondingauthor.}

E-mailaddress:margris2@yahoo.com.ar(M.T.Rosanova).

Themostcommonlyisolated speciesisCandidasppandin recenttimestherehasbeenanincreaseinfilamentousfungi suchasAspergillusspp,Mucorspp,andFusariumspp.2_Fusarium

spp–afilamentousfungus–isubiquitousintheenvironment andcanbefoundinwaterandinthesoil.3_{Itmainlyproduces}

infections inindividuals withimmunedisorders causedby

http://dx.doi.org/10.1016/j.bjid.2016.04.004

1413-8670/©2016ElsevierEditoraLtda.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/ licenses/by-nc-nd/4.0/).

390

tumors,useofcytostatics,steroids,presenceofdiabetes mel-litus,andHIVinfectionamongothers.Burnpatientsarethe mostcommonlyaffectedimmunocompetenthosts.1,4

CommonlyisolatedFusariumsppareF.solani,F.oxysporum,

F.proliferatum,F.verticilliodes,etc.5

The literature on Fusarium spp infections in pediatric patients with burns is limited. Most publications are case reports of disseminated Fusarium spp infections in cancer patientsorfungalkeratitisinfections.6–8

Theaimofthisstudywastodescribetheepidemiological, clinical,and microbiologicalfeaturesaswell asoutcomeof infectionsduetoFusariumsppinpediatricburnpatients.

Patients

and

methods

Thiswasaretrospective,descriptiveandobservationalstudy ofFusariumsppinfectionsinaspecializedburnintensivecare unitbetweenJanuary2006andMarch2015.

Inclusioncriteria

Allburnpatientswithclinicalandmicrobiologicalevidenceof fungalinfectionbyFusariumsppdocumentedfrom represen-tativesamples,suchasdeepburntissue,and/orblood,and/or othersterilesiteswithpositivecultureswereincluded.

Definition

Clinicalevidencewasdefinedbylocalsignsofinfectionsuch asdrainageofpus,rednessorswellingatthemarginofthe burn, scar separation, localized necrosis, vesicular lesions, and/orpooradherenceofthegraft.

Microbiologicalevidencewas definedbythe isolationof

Fusariumsppindeeptissuesamplesorsterilematerials(blood, purulentmaterials,and/orurine).

Infectiontypes

Infections were defined according to the American Burn Association9_:

TheGarces’Index–anindexofpredictionofseverityand mortalitycalculatedasfollows:40−patientage×1 percent-ageburn(iftypeA),×2(iftypeAB),×3(iftypeB).

• 0–60points:Grade1(slightrisk); • 61–90points:Grade2(moderaterisk); • 91–120points:Grade3(severerisk); • >121points:Grade4(criticalrisk).

Depthofburn

• TypeA:superficialburnwitherythemaandhyperalgesia; • TypeAB:pink-whiteintermediate-colorscar,and

hypoalge-sia;

• TypeBor “fullthickness”:deep, white orblack scarand analgesia.

Microbiology

Inadditiontoregularbacteriologicalstudy,allmaterialswere processedformycologicalstudy.

Table1–Patientscharacteristics.

Variable N(IQR) Percentage

(IQR) Patients 15 100 Age 48m(12–108) Malesex 11 73 Burnsurface 45(30–60) Garcesindex>3 9 60 Fullthickness 12 80 Inhalatoryinjury 11 73 Mechanicalrespiratory assistance 13 87

Centralvenouscatheter 15 100

Vesicalcatheter 15 100

Timebetweeninjury

andinfection 11(4–24) Concomitantinfection withbacteria 13 87 Timeoftreatment 23(17–42) Mortality 1 7 Daysofhospitalization 55(22–60)

Results

Atotalof15 patientswereinfectedbyFusariumsppduring thestudyperiod.Themechanismofburnwasdirectfirein10 patients(66%),hotliquidsinfour(27%),andelectricityinone case(7%);87%(n=13)weremale.Medianagewas48months (IQR12–108months).Themedianbodysurfaceareaburned was45%(IQR30–60%).Eightypercentofpatients(n=12)had deepburns(typeB);60%(n=9)hadaGarces’indexof3,33% (n=5)anindexof4,andtheremaining7%(n=1)anindexof2. Themediantimefromburninjurytoonsetoffungal infec-tionwas11days(IQR4–24days).Allpatientshadcentrallines withamediandwelltimeof20days(IQR12–30).Ofallpatients, 87%(n=13)requiredmechanicalventilationwithamedianof 16days(IQR10–30).Themostcommonsiteofmicrobiological isolationwastheburnwoundin15patients(100%)andbonein onepatient(7%).Inonepatient(7%)Fusariumsppwasisolated frombloodcultures.In87%ofcases(n=13)concomitant bac-terialinfectionswerefound.Empiricalantifungaltreatment wasstartedwithamphotericinBdeoxycholatein14patients (93%)andvoriconazoleinonepatient(7%).Allpatientswere switchedtotreatmentwithvoriconazoleaftermicrobiological isolationofFusariumspp.Medianantifungaltreatmentwas23 days(IQR17–42days).Noadverseeventsrelatedtotheuseof antifungalagentswerereported.Thecombinationofmedical treatment usingamphotericinB,voriconazole, andsurgical removal of infectious foci was effective in all cases. The medianlengthofhospitalstaywas55days(IQR22–60days). Onlyonepatient(7%) died,14daysafteradmissiondueto septicshockrelatedtoFusariumsppinfection(Tables1and2).

Discussion

Infections remain the leading cause of mortality in burn patients.1 _{The use of topical and systemic antimicrobials}

alongwithinfection-controlmeasureshasreducedthe inci-denceofbacterialinfections1_{;however,fungalinfectionshave}

brazj infect dis.2016;20(4):389–392

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Table2–Infectioncharacteristics.

Variable n Percentage

Woundsinfection 15 100

Bloodstream 1 7

Bone 1 7

remainedstableshowinganincidencebetween6and40%in differentseries.1,5,6

Inapreviousstudyconductedatourcenterwereported on 128 infections in 84 patients of which 53 cases (20%) had a documented fungal etiology.4 _{Some risk factors for}

developingfungal infections inburnpatients are extremes of age, large body surface burned (≥40%), inhalation syn-drome,requirementformechanicalventilation,useofbroad spectrumantibiotics, prolonged use ofcentral venous and bladder catheters, presence of diabetes mellitus, and par-enteralnutrition.2,3,10,11

Progressionfrom fungal colonization toinfection ofthe woundisdirectly related tothe body surfacearea burned. Therefore, closemonitoringofpatients withlargesurfaces burned(≥40%)isrecommendedtoestablishearlytherapeutic measures.12

Differentstudiesintheliteraturehavereportedahigher incidenceoffungal infectionsinmoresevereburns.1,3,4,6_In

thisseries, themedianbody surfaceareaburned was45%, reflecting theseverity ofthe study sampleathigh risk for the occurrence of fungal infections inline with published literature.6,10

Candida spp is the most frequently involved species in fungalinfectionsinburns.Inrecenttimestheincidenceof fil-amentousfungisuchasAspergillusspp,andtoalesserextent

Mucorspp and Fusarium spp,has increased.2 _{In aprevious}

studyonfungalinfectionsinourcenterthemostfrequently isolated funguswas Candidaalbicans(3.4%).13 _{In this study}

fungal infectionsoccurred from the secondweekof hospi-talization (median 11 days), coinciding with several other reports.2,3,11

Fusariumcanbeisolatedbytissuebiopsiesthatmayshow thepresenceoffilamentousfungiinandaroundvesselsofthe dermis,thrombosis,andtissuenecrosis.Bloodculturesmay bepositivein50–70%ofcasesinimmunocompromisedhost infections.14,15

The most common site of infection is the burn wound.1,3,4,14_{Inthisstudy100%ofpatientshadinfectionof}

theburn woundand onlyone(7%)had bone involvement. Additionally,fungemiawasdetectedinonlyonepatient(7%). Earlytreatmentoflocalizedformsisessentialtoprevent thespreadofFusariumspp.Mortalityrateshavebeenreduced withearlydebridementofinjuriescombinedwithantifungal treatment.15–17

In our burn unit, amphotericin Bdeoxycholate or lipid formulationsareusedasempiricaltreatmentagainst filamen-tousfungi.WhenFusariumsppisisolatedvoriconazoleisthe drugofchoice.Thetotaldurationoftreatmentvaries accord-ingtotheextensionoftheinfection.Somestudiesreporteda treatmentduration ofatleasttwoweeksafterthelast fun-gal isolationcoincidingwith the managementapproach in ourburnunit.2,11,18_{Mortalityduetofungalinfectionsvaries}

between75and90%andisassociatedwithaburnedsurface

areabetween40%and60%.1,10,19_{Somestudiesfoundno}

differ-enceinmortalityratesaccordingtothefungalagentinvolved. Incontrast,thestudybySchaaletal.20_{foundthatpatients}

withAspergillussppinfectionshada30%mortalitywhereas noneofthoseinfectedwithFusariumsppdied,inlinewiththe lowmortalityratefoundinourstudy.

NirPazetal.3_{reportedan11%mortalityrateinFusarium}

sppinfectionsindifferentinmunocompromisedpatientswith ahigherriskinpatientswithburns.

Inourseries,onepatientdiedofsepticshockdueto infec-tion by Fusarium spp, representing a mortality rate of 7% inthe study period,whichislower than that foundinthe literature.11–20

Conclusions

Fusariumsppwasararelyisolatedpathogeninburnedpatients inourunit.Theburnwoundwasthe mostfrequentsiteof isolation.Mortalitywaslow.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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