Risk factors for laboratory-confirmed bloodstream infection in neonates undergoing surgical procedures

(1)

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

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

Original

article

Risk

factors

for

laboratory-conﬁrmed

bloodstream

infection

in

neonates

undergoing

surgical

procedures

Roberta

Maia

de

Castro

Romanelli

a,b,c,∗

_,

_Lêni

_Márcia

_Anchieta

a,b

_,

Elaine

Alvarenga

de

Almeida

Carvalho

a

_,

_Lorena

_Ferreira

_da

_Glória

_e

_Silva

d

_,

Rafael

Viana

Pessoa

Nunes

e

_,

_Paulo

_Henrique

_Mourão

c

_,

_Wanessa

_Trindade

_Clemente

c,f

_,

Maria

Cândida

Ferrarez

Bouzada

a,b

a_Department_of_Pediatrics,_Faculdade_de_Medicina,_Universidade_Federal_de_Minas_Gerais_(UFMG),_Belo_Horizonte,_MG,_Brazil b_Neonatal_Unit_for_Progressive_Care,_Hospital_das_Clínicas,_Universidade_Federal_de_Minas_Gerais_(UFMG),_Belo_Horizonte,_MG,_Brazil c_Hospital_Infection_Control_Committee,_Hospital_das_Clínicas,_Universidade_Federal_de_Minas_Gerais_(UFMG),_Brazil

d_Pediatrics_Infectious_Diseases,_Hospital_Infantil_João_Paulo_II,_Fundac¸ão_Hospitalar_do_Estado_de_Minas_Gerais,_Belo_Horizonte,_MG,

Brazil

e_Faculdade_de_Medicina,_Universidade_Federal_de_Minas_Gerais_(UFMG),_Belo_Horizonte,_MG,_Brazil

f_Department_of_{Complementary}_{Propedeutics,}_Faculdade_de_Medicina,_Universidade_Federal_de_Minas_Gerais_(UFMG),_Belo_Horizonte,

MG,Brazil

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received23September2013

Accepted18December2013

Availableonline29March2014

Keywords:

Newbornintensivecareunits

Infectioncontrol

Surgery Sepsis

a

b

s

t

r

a

c

t

Background:HealthcareAssociatedInfectionsconstituteanimportantproblemin

Neona-talUnitsandinvasivedevicesarefrequentlyinvolved.However,studiesonriskfactorsof

newbornswhoundergosurgicalproceduresarescarce.

Objective:Toidentifyriskfactorsforlaboratory-conﬁrmedbloodstreaminfectioninneonates

undergoingsurgicalprocedures.

Methods:Thiscase–controlstudywasconductedfromJanuary2008toMay2011,inareferral

center.Caseswereof21newbornswhounderwentsurgeryandpresentedtheﬁrstepisode

oflaboratory-conﬁrmedbloodstreaminfection.Controlwas42newbornswhounderwent

surgicalprocedureswithoutnotiﬁcationoflaboratory-conﬁrmedbloodstreaminfectionin

thestudyperiod.InformationwasobtainedfromthedatabaseoftheHospitalInfection

Con-trolCommitteeNotiﬁcationofinfectionsandrelatedclinicaldataofpatientsthatroutinely

collectedbytrainedprofessionalsandfollowtherecommendationsofAgênciaNacionalde

VigilânciaSanitáriaandanalyzedwithStatisticalPackageforSocialSciences.

Results:Duringthestudyperiod,1141patientswereadmittedtoNeonatalUnitand582

Healthcare AssociatedInfections were reported (incidence-density of 25.75 Healthcare

AssociatedInfections/patient-days).Inthe comparativeanalysis,a higherproportionof

laboratory-conﬁrmedbloodstreaminfectionwasobservedinpreterminfantsundergoing

surgery(p=0.03) anduse ofnon-invasiveventilationwasa protective factor(p=0.048).

Statisticallysigniﬁcantdifferencewasalsoobservedformechanicalventilationduration

∗ _{Corresponding}_author_at:_Av_Alfredo_Balena_190,₁◦_andar,_Ala_Oeste,_Comissão_de_Controle_de_Infecc¸ão_Hospitalar_(CCIH),_30130-100,

SantaEﬁgênia,BeloHorizonte,MG,Brazil.

E-mailaddresses:rmcromanelli@ig.com.br,rmcromanelli@unifenas.br(R.M.d.C.Romanelli).

http://dx.doi.org/10.1016/j.bjid.2013.12.003

(2)

(p=0.004),durationofnon-invasiveventilation(p=0.04),andparenteralnutritionduration

(p=0.003).Inmultivariateanalysisdurationofparenteralnutritionremainedsigniﬁcantly

associatedwithlaboratory-conﬁrmedbloodstreaminfection(p=0.041).

Conclusions:Shorteningtimeonparenteralnutritionwheneverpossibleandpreferencefor

non-invasive ventilation in neonates undergoing surgery shouldbe considered in the

assistanceofthesepatients,withthegoalofreducingHealthcareAssociatedInfections,

especiallylaboratory-conﬁrmedbloodstreaminfection.

Introduction

HealthcareAssociatedInfections(HAI)constitutean

impor-tant problem in neonatal units and are associated to

highermorbidity,mortalityanddurationofhospitalizationof

newborns.1–3

Ratesofinfectionreportedininternationalstudiesrange

from0.1%innewbornsattermto20%inprematureinfants,

andareinverselyrelatedtobirthweight.4,5 _In_Brazil,_higher

rates are observed – they can reach 69.3% – and

infec-tionaffectsmainlyinfantsweighinglessthan1000g.6–8 _The

incidence density (ID) also varies with birth weight, from

approximately12%per1000patient-daysinnewborns

weigh-ingmorethan2500g,to51.9%per1000patient-daysinthose

withlessthan1000g.7–9

Thereareseveralriskfactorsassociatedwithnosocomial

infectionsinneonatalunits,suchasprematurity,

mechani-calventilation(MV)andcentralvenouscatheter(CVC),length

of stay in the unit, as well as parenteral nutrition (PN),

antibiotics, and malformations.2,6,10,11 _Surgical _procedures

determinesurveillanceofwoundinfectionandsurveillance

recommendationstoinvestigatethisevent.12–14_But_risk

fac-torsforlaboratory-conﬁrmedbloodstreaminfection(LCBI)in

surgicalneonatesarescarcenationallyandinternationally.In

apreviousstudyatthesame NeonatalUnit forProgressive

Care(NUPC)wherethisstudywasconducted,surgery,MV,and

CVCwereidentiﬁedasindependentriskfactorsforLCBI.15

TheaimofthisstudywastoidentifyriskfactorsforLCBI

inneonatesundergoingsurgicalproceduresataNUPCina

referralhospital.

Patients

and

methods

TheNUPCatHospitaldas Clínicas ofUniversidade Federal

deMinasGeraisisatertiaryreferralcenterforassistanceof

patientswithdiverseclinicalconditions,includinghigh-risk

newborns.Thiscase–controlstudywasconductedfrom

Jan-uary2008toMay2011.

Casedeﬁnition

Newborns(NB)whounderwentsurgeryandpresentedtheﬁrst

episodeofLCBI,deﬁnedbythereportingcriteriaofinfection

ininfantsunderoneyear–accordingtotheNationalAgency

forSanitarySurveillance(AgênciaNacionaldeVigilância

San-itária–ANVISA),12_–_after_the_procedure,_were_the_subject_of

thisstudy.OnlytheﬁrstepisodeofLCBIwasconsidered;

there-fore,patientswereincludedonlyonce.

Criteriafornotiﬁcationofinfectionattributedto

commen-sal microorganisms (e.g. coagulase-negative Staphylococcus)

were notincluded, duetothenecessityofisolationintwo

samplesofbloodcultureassociatedwithclinicalsigns.12,13

Controldeﬁnition

Controlswerenewbornswhounderwentsurgicalprocedures

withoutanysignsorsymptomsofsepsisoranynotiﬁcation

ofLCBI inthepost-operative period.Two controlspercase

matchedforweightwereselected.

Datacollection

Theinformationwasobtainedfromthedatabaseofthe

Hos-pitalInfectionControlCommittee(HICC)andpatientrecords.

Variablesincludedwere:typeofsurgery,birthweightdivided

byage,prematurity(gestationalagelessthan37weeks),

pres-enceofmalformations,useofinvasivedevices(CVCandMV),

useofnon-invasiveventilation(NIV),useofcontinuous

posi-tiveairwaypressure(CPAP),chestdrain,useofPN,andprior

antibioticuse(ATM).Inaddition,surgicalfastingandfasting

duration,mortality,time(indays)withCVC,MV,NIVinCPAP,

chesttube,PN,ATMandnumberofATMregimenswerealso

evaluated.

Statisticalanalysis

The softwareused foranalysis wasthe Statistical Package

forSocial Sciences (SPSS),version 13.0. Thedistributionof

patients by birth weight (used for matching) and type of

surgerywasconsideredonlyinthedescriptiveanalysis.For

thecomparativeanalysisbetweengroups(casevs.control),

2 _test _was _used_for _categorical_variables. _For _quantitative

variables,Student’s ttest orMann–Whitney testwas used,

according to analysisof variance testevaluated by Levine.

Statistical signiﬁcance was considered at 5%. Multivariate

analysiswasperformedbybinarylogisticregression,

consid-eringthedependentvariabletheoccurrenceofLCBI,andas

predictors the risk factors signiﬁcantly (p<0.05) associated

with LCBIin univariateanalysis. Individualcontributionof

eachriskfactorwastested(Waldchi-square),thereby

elim-inatingtheoverlapbetweenthepredictors.Thisstudyispart

ofthe activitiesofSurveillance and ControlofInfectionin

Neonatology,anditwasapprovedbytheInstitutionalReview

(3)

Table1–Distributionofnewbornsaccordingtoweight rangeandincidencedensityofhealthcareassociated infections(HAI),NeonatalUnitforProgressiveCare, HC/UFMG,January2008toApril2011.

Birthweight Patients atrisk

HAI Patient-day IDofHAIa

Until750g 22 45 1113 40.4 751–1000g 69 95 3575 26.6 1001–1500g 165 115 4951 23.2 1501–2500g 466 197 7636 25.8 >2500g 439 130 5323 24.4 Total 1161 582 22,598 25.8

a _ID_of_HAI_–_incidence_density_of_healthcare_associated_infections.

Table2–Birthweightdistributionofnewbornswho underwentsurgicalprocedures,NeonatalUnitfor ProgressiveCare,HC/UFMG,January2008–April2011.

Birthweight Cases Controls Total

n(%) n(%) n(%) Until750g 2(9.52) 1(2.38) 3(4.76) 751–1000g 4(19.05) 10(23.81) 14(22.22) 1001–1500g 3(14.29) 6(14.28) 9(14.29) 1501–2500g 9(42.85) 17(40.48) 26(41.27) >2500g 3(14.29) 8(19.05) 11(17.46) Total 21(100) 42(100) 63(100)

Results

Duringthestudyperiod,1141patientswereadmittedtoNUPC, with22,598patient-days.Atotalof582HAIwerereportedwith anIDof25.75/1000patient-days.From theseinfections,126 wereLCBIwithIDHAIof5.58/1000patient-days(Table1).

Amonghigh-riskpatientsadmittedintheperiod,we

iden-tiﬁed21casesofsurgicalpatientswithnotiﬁcationofLCBI,

whowerematchedto42neonatesundergoingsurgical

proce-dures,butwithoutLCBI.Birthweightdistributionofcasesand

controlsisshowninTable2,withhigherfrequencyofpatients

intheweightrange1501–2500g(41.27%),followedbypatients

weighingbetween751and1000g(22.22%).

Preterm infants undergoing surgery had 3.75 greater

chanceofLCBIthantermbabies.Althoughstatisticalanalisis

presentedp=0,048forNIV,itwasnotsigniﬁcantconsidering

that95%CIincluded1(Table3).Forcontinuousvariables,

sta-tisticallysigniﬁcantdifferencewasobservedforMVduration

(greaterincases),durationofNIV(greaterincontrols),andPN

duration(greaterincases)(Table4).

Variablesincludedinthe multivariatelogisticregression

model were prematurity (yes or no), duration of MV, NIV,

andPN(numberofdays).Themodelincreasedthepredictive

valueof66.7–84.1%,correctlyidentifying13 ofthe21 cases

ofLCBI(61.9%) and40 of42 controls(95.2%).LengthofPN

wastheonlyriskfactorthatremainedindependently

asso-ciatedwithLCBI(p=0.041).EachdayonPNincreasedby9%

(95%CIOR:1.00–1.17)the probabilityofLCBI.Althoughnot

statisticallysigniﬁcant,durationofNIVtendedtobea

pro-tectivefactor(p=0.071),aseachdayonNIVwasassociated

withadecreaseintheprobabilityofLCBIby29%(95%CIOR:

0.49–1.03).Prematurity and timeon MVwere not

indepen-dently associatedwithLCBI inthe ﬁnalmodel(p=0.29 and

p=0.22,respectively)(Table5).

Discussion

Inneonatesundergoingsurgery,prematurity,durationofMV

andPNusewereidentiﬁedasriskfactorsforprogressionto

LCBI, but onlyduration of PN use has remained

indepen-dentlyassociated(p=0.041)inthemultivariateanalysis.Many

reportsininternational10,16–18_and_national2,6_literature_deﬁne

thesevariablesaspredictorsofsepsis.However,noneofthe

studiesweredesignedtoassessriskfactorsforLCBIin

new-bornswhounderwentsurgicalprocedures.

Inapreviousstudy15_surgical_procedure_itself_was_found_to

beanindependentriskfactorforLCBIinnewborns.Mokaddas

et al.19 _evaluated_patients _with_suspected_sepsis_in_a

Pedi-atricSurgicalUnitand2.3%ofthemhadLCBI.Ofallsurgical

pediatricpatients,82%hadcongenitalabnormalitiesand87%

requiredsurgicalinterventions.Bhattacharyyaetal.20

identi-ﬁeda6.2%rateofinfectionreportedamongsurgicalpatients

evaluated, although the authors have not included

infec-tionsotherthanLCBI.Higherprevalenceofinfectioninthese

childrenwasassociatedtonutritionalstatus(p<0.0001)and

several surgicalinterventions(p<0.0001).Besides,the

stud-ieswereconductedinthePediatricIntensiveCareUnitand

wasnotrestrictedtonewborns.Nonetheless,neonateswere

atincreasedriskofsepsiswhencomparedtootherchildren

(4.2%<0.05).

Itshouldbeconsideredthatpatientswhoundergosurgical

proceduresarevulnerabletocomplications(suchas

extuba-tionfailureanddietintolerance)andtheyneedprolongedPN,

asidentiﬁedinthepresentstudyasriskfactorforLCBI.They

alsohavelongerlengthofstayintheNeonatalIntensiveCare

Unitwithfrequentuseinvasivedevices,suchasMV,

associ-atedwithLCBIinunivariateanalysis.

Zakariyaetal.21_studied_only_infants_who_developed_LCBI

andalsoidentiﬁedMVasariskfactorinthelogistic

regres-sionmodelwithanOR=3.59(CI95%=1.16–11.07).However,

theauthorsincludedallneonates,notonlythoseundergoing

surgery.

AstudybySuetal.18_included_only_neonates_and_identiﬁed

ahigherproportionofnosocomialinfectioninpatients

under-going surgicalprocedures(13%comparedto6.9%; p<0001).

Inmultivariateanalysis,MVandPNremainedindependently

associatedwithinfection,increasingtheriskby21%and30%,

respectively.

Another study in the same city conducted in a private

NeonatalIntensiveCareUnit,2_which_included_not_only

new-borns undergoing surgery, alsodemonstrated that invasive

deviceswereassociatedwithHAIinthispopulation.In

multi-variateanalysis,theuseandlengthofMVwasalsoassociated

withBSInotassociatedwithCVC.Otherriskfactorsforsepsis

innewbornsdescribedintheliterature–suchasprematurity,

congenitalanomalies,lengthofantibiotictherapy,anduseof

CVC2,10,17,18_did_not_turn_out_to_be_associated_with_LCBI_in_this

study,although prematuritywassigniﬁcantlyassociatedin

univariateanalysisandpreterminfantspresented3.75greater

(4)

Table3–Associationofriskfactorswithlaboratoryconﬁrmedbloodstreaminfectioninneonatesundergoingsurgery. NeonatalUnitforProgressiveCare.HC/UFMG.January2008–April2011.

Laboratoryconﬁrmedbloodstreaminfection Univariateanalysis

Cases Controls p OR 95%CI n=21 n=42 Sex Malen(%) 13(61.91) 18(42.86) 0.15a _– _– Femalen(%) 8(38.09) 24(57.14) Prematurity Non(%) 4(19.05) 20(47.62) 0.032a _3.86 _1.1–13.4 Yesn(%) 17(80.95) 22(52.38) Malformation Non(%) 1(4.76) 6(14.29) 0.41a _– _– Yesn(%) 20(95.24) 36(85.71) CVC Non(%) 0 2(4.76) 0.55a _– _– Yesn(%) 21(100) 40(95.24) MV Non(%) 0 5(11.90) 0.16a Yesn(%) 21(100) 37(88.10) NIV Non(%) 20(95.24) 31(73.81) 0.048a _0.14 _0.017–1.18 Yesn(%) 1(4.76) 11(26.19) CPAP Non(%) 12(57.14) 23(54.76) 0.86a _– _– Yesn(%) 9(42.86) 19(45.24) Chestdrain Non(%) 17(80.95) 36(85.71) 0.72a _– _– Yesn(%) 4(19.05) 6(14.29) Parenteralnutrition Non(%) 1(4.76) 7(16.67) 0.25a _– _– Yesn(%) 20(95.24) 35(83.33) PreviousATM Non(%) 0 1(2.38) 1.00a _– _– Yesn(%) 21(100) 41(97.62) Surgicalfasting Non(%) 1(4.76) 1(2.38) 0.99a _– _– Yesn(%) 20(95.24) 41(97.62) Death Non(%) 14(66.67) 35(83.33) 0.20a _– _– Yesn(%) 7(33.33) 7(16.67)

OR,oddsratio;CI,conﬁdenceinterval;CVC,centralvenouscatheter;MV,mechanicalventilation;NIV,noninvasiveventilation;CPAP,continuous positiveairwaypressure;ATM,antimicrobials;SD,standarddeviation.

a 2_.

prematurityisdirectlyrelatedtohigherratesofsepsis,but

moststudiesfocusonbirthweight,whichisinversely

asso-ciatedtoinfection.1,2,10,18_LCBI_rates_of_50%_were_observed_in

newbornsunder750g,4_as_well_as_ID_of₃₇_per₁₀₀₀

patient-days.15

Stoll et al.22 _studied _extreme_preterm _infants_according

to gestational age and also found high mortalityin these

patients, inaddition torates ofinfection of33–38%. Auriti

etal.23_also_identiﬁed_different_risk_factors_for_newborns

clas-siﬁedasverylowbirthweight(VLBW),consideringcumulative

probabilityofhavinginfectionmoreprevalentinthisgroup.

Riskfactorsincludedgestationalage<28weeksandCPAPuse.

Invasiveprocedureswereassociatedwithhigherriskastheir

durationincreased,withthehighestriskassociatedwithMV

for sevendays or more (RR:3.82; 95% CI 2.83–5.17). These

authorsalsoreportedasriskfactorsforinfectiontheuseofPN

(OR:8.1;95%CI3.2–20.5)andmalformations(OR:2.1;95%CI

1.5–3.5),especiallyforheaviernewborns,whichisconfounded

bytheneedforsurgicalprocedures.

In the present study infection was notassociated with

CPAP.However,theuseofNIVmighthavebeenaprotective

factorforLCBI(1casecomparedto11controls),reducingthe

chance ofLCBI by86%. AlthoughOR was0.14, the 95% CI

(5)

Table4–Continuousvariablesassociatedwithlaboratoryconﬁrmedbloodstreaminfectioninneonatesundergoing surgery.NeonatalUnitforProgressiveCare.HC/UFMG.January2008–April2011.

DurationofCVC(days) Mean(SD) 30.67(16.58) 22.29(18.82) 0.09a DurationofMV(days) Median(range) 18.0(28.5) 7.0(16.25) 0.004b

DurationofNIV(days) Median(range)

0.0(0.00) 0.0(2.25) 0.040b

DurationofCPAP(days) Médian(SD)

2.24(4.49) 3.10(5.13) 0.52a

DurationofChestDrain Median(range)

0.00(0.00) 0.0(0.00) 0.51b

DurationofPN Median(range)

17.0(21.00) 11.0(11.5) 0.003b

Durationoffasting(days) Median(range)

3.80(5.82) 4.4(5.49) 0.36b

SchemesofATM Median(SD)

1.71(1.45) 1.48(1.37) 0.52a

CVC,centralvenouscatheter;MV,mechanicalventilation;NIV,noninvasiveventilation;CPAP,continuouspositiveairwaypressure;ATM, antimicrobials;SD,standarddeviation.

a _T_test. b _{Mann–Whitney.}

Table5–Logisticregressionmodelforpredictinglaboratory-conﬁrmedbloodstreaminfectioninneonatesundergoing surgicalprocedures.NeonatalUnitforProgressiveCare.HC/UFMG.January2008–April2011.

Predictor B Wald p OR(95%CI)

Prematurity 0.793 1.140 0.286 2.21(0.52–9.47)

DaysofMV 0.029 1.498 0.221 1.03(0.98–1.08)

DaysofNIV −0.344 3.252 0.071 0.71(0.49–1.03)

DaysofPN 0.081 4.193 0.041 1.09(1.00–1.17)

B,slopefromlogisticregressionequation;Wald,Waldchi-square;OR,oddsratiopredictedbythemodel;CI,conﬁdenceinterval;MV,mechanical ventilation;NIV,non-invasiveventilation;PN,parenteralnutrition.

workofbreathinginnewbornsundergoingNIV,comparedto thosewhousedContinuousPositivePressureAirway,without presenting complications, suchas necrotizing enterocolitis and gastrointestinalperforations. However,it wasnot con-sideredforriskfactoranalysis.24–26 Itshouldbepointedout

thatNVIisalessinvasiveventilatorysupport,thusreducing

severalrisksofMV.

There are signiﬁcant variations in predictors of HAI

among neonatal Intensive Care Units, predominating

sep-sis.Ratesofinfectioninnewbornsvarybetween4.7%16_and

69.3%.1–10,21,27–30_Despite_most_of_the_referred_studies_having

notusedindexbypatient-days,theirresultsareinlinewith

theoveralldensityofinfectionsfoundinthisstudy–25.75per

1000patient-days.However,whenconsideringonlyLCBI,the

IDwas5.58/1000patient-days,whichmayraisetheissueof

notiﬁcationforclinicallysuspectedsepsis,whichisnolonger

recommendedbytheNHSNcriteria.13

The limitation of this study was the small number of

patients and the difﬁculty of matching newbornswho did

notundergosurgicalprocedures:hospitalizationandweight

rangewerenotconsidered,onlypatientsundergoingsurgery

withoutLCBIduringthestudyperiod.However,therearefew

studiesintheliteraturethatwerecarriedoninneonatalunits

withpatientsundergoingsurgicalproceduresandtheydidnot

includeonlypatientswithLCBIascase.

Duetothelackofspeciﬁcsignsandsymptomsof

neona-tal sepsis, so that other diagnoses could be ruled out, we

have chosentoincludeonlyneonateswithLCBI,

consider-ing that adequate blood cultures are not always obtained,

owingtotechnicaldifﬁcultiesofcollectingsamplesininfants.

Theexclusionofpatientswithsepsiscausedbycommensal

microorganismscancreateaselectionbias,underestimating

thenumberofcases,sincemoststudies6–9 _report_coagulase

negativeStaphylococcusasthemainagentofneonatalsepsis.

However,thegoalofthisstudywastoincreasethespeciﬁcity

ofdiagnosisandavoidinclusionofcasesdiagnosedbyonly

onebloodcultureoftheseagents.

Whenpossible,shorteningthetimeonparenteralnutrition

withprogressionofenteraldietandpreferencefor

noninva-siveventilationinneonatesundergoingsurgeryadmittedto

theIntensiveCareUnitshouldbeconsideredinthecareof

thesepatients,withthegoalofreducingHAI,especiallyLCBI.

Conﬂicts

of

interest

Theauthorsdeclarenoconﬂictsofinterest.

r

e

f

e

r

e

n

c

e

s

1.OgunlesiTA,OgunfoworaOB,OsinupebiO,OlanrewajuDM. ChangingtrendsinnewbornsepsisinSagamu,Nigeria:

(6)

bacterialaetiology,riskfactorsandantibioticsusceptibility.J PaediatrChildHealth.2011;47:5–11.

2. CoutoRC,PedrosaTM,TofaniCdeP,PedrosoER.Riskfactors fornosocomialinfectioninaneonatalintensivecareunit. InfectControlHospEpidemiol.2006;27:571–5.

3. Sadowska-KrawczenkoI,JankowskaA,KurylakA.

Healthcare-associatedinfectionsinaneonatalintensivecare unit.ArchMedSci.2012;8:854–8.

4. KaufmanD,FairchildKD.Clinicalmicrobiologyofbacterial andfungalsepsisinvery-low-birth-weightinfants.Clin MicrobiolRev.2004;17:638–80.

5. SrivastavaS,ShettyN.Healthcare-associatedinfectionsin neonatalunits:lessonsfromcontrastingworlds.JHosp Infect.2007;65:e292–396.

6. BritoDVD,BritoCS,ResendeDS,MoreiradoÓJ,AbdallahVO, GontijoFilhoPP.NosocomialinfectionsinBrazilianneonatal intensivecareunit:a4-yearsurveillancestudy.RevSocBras MedTrop.2010;43:633–7.

7. CoutoRC,CarvalhoEAA,PedrosaTMG,PedrosoER,NetoMC, BiscioneFM.A10-yearprospectivesurveillanceof

nosocomialinfectionsinneonatalintensivecareunits.AmJ InfectControl.2007;35:183–9.

8. Pessoa-SilvaCL,RichtmannR,CalilR,etal.

Healthcare-associatedinfectionsamongneonatesinBrazil. InfectControlHospEpidemiol.2004;25:772–7.

9. KawagoeJY,SegreCAM,PereiraCR,CardosoMFS,SilvaCV, FukushimaJT.Riskfactorsfornosocomialinfectionsin criticallyillnewborns:a5-yearprospectivecohortstudy.AmJ InfectControl.2001;29:109–14.

10.AzizK,McMillanDD,AndrewsW,etal.Variationsinratesof nosocomialinfectionamongCanadianneonatalintensive careunitsmaybepractice-related.BMCPediatr.2005;5:22.

11.KamathS,MallayaS,ShenoyS.Nosocomialinfectionsin neonatalintensivecareunits:proﬁle,riskfactorassessment andantibiogram.IndianJPediatr.2010;77:37–9.

12.Brasil,MinistériodaSaúdeAgênciaNacionaldeVigilância

Sanitária,Neonatologia.Critériosnacionaisdeinfecc¸ões

relacionadasàassistênciaàsaúde.Brasília:Ministérioda

Saúde;2010,2aversão.Disponívelem:http://www.anvisa.gov.

br/servicosaude/manuais/manualdeﬁnicaocriterios nacionaisinfec%E7%F5esrelacionadasassistenciasaude neonatologia.pdf[accessed30.01.11].

13.CenterforDiseasesControlandPrevention(CDC)CDC/NHSN

SurveillanceDeﬁnitionofHealthcare-AssociatedInfection

andCriteriaforSpeciﬁcTypesofInfectionsintheAcuteCare

Setting;2013.Disponívelem:http://www.cdc.gov/nhsn/

PDFs/pscManual/PSC-Manual-portfolio.pdf[accessed 03.08.13].

14.MuYiEdwardsJR,HoranTC,Berrios-TorresSI,FridkinSK. Improvingrisk-adjustedmeasuresofsurgicalsiteinfection forthenationalhealthcaresafetynetwork.InfectControl HospEpidemiol.2011;32:970–86.

15.RomanelliRMC,AnchietaLM,MourãoMV,etal.Pediatria (Santiago).2013;89:189–96.

16.MoroML,DeToniA,StolﬁI,CarrieriMP,BragaM,ZuninC. Riskfactorsfornosocomialsepsisinnewbornintensiveand intermediatecareunits.EurJPediatr.1996;155:315–22.

17.BalkhyHH,El-SaedA,KhawajahM,DichineeR,MemishZA. Neonatalratesandriskfactorsofdevice-associated bloodstreaminfectioninatertiarycarecenterinSaudi Arabia.AmJInfectControl.2010;38:159–61.

18.SuBH,HseiehHY,ChiuHY,LinHC.Nosocomialinfectionina neonatalintensivecareunit:aprospectivestudyinTaiwan. AmJInfectControl.2007;35:190–5.

19.MokaddasEM,ShettySA,AbdullahAA,RotimiVO.A4-year prospectivestudyofsepticemiainpediatricsurgicalpatients atatertiarycareteachinghospitalinKuwait.JPediatrSurg. 2011;46:679–84.

20.BhattacharyyaN,KosloskeAM,MacarthurC.Nosocomial infectioninpediatricsurgicalpatients:astudyof608infants andchildren.JPediatrSurg.1993;28:338–44.

21.ZakariyaBP,RiskFactors.Predictorsofmortalityinculture provenneonatalsepsis.IndianJPediatr.2012;79:358–61.

22.StollBJ,HansenNL,BellEF,etal.Neonataloutcomesof extremelypreterminfantsfromtheNICHDneonatalresearch network.Pediatrics.2010;126:443–56.

23.AuritiC,RonchettiMP,PezzottiP,etal.Determinantsof nosocomialinfectionin6neonatalintensivecareunits:an Italianmulticenterprospectivecohortstudy.InfectControl HospEpidemiol.2010;31:926–33.

24.AliN,ClaureN,AlegriaX,D’UgardC,OrganeroR,BancalariE. Effectsofnon-invasivepressuresupportventilation(NI-PSV) onventilationandrespiratoryeffortinverylowbirthweight infants.PediatrPulmonol.2007;42:704–10.

25.DumpaV,KatzK,NorthrupV,B.HandariV.SNIPPVvsNIPPV: doessynchronizationmatter?JPerinatol.2012;32:

438–42.

26.BhandariV.Nasalintermittentpositivepressureventilation inthenewborn:reviewofliteratureandevidence-based guidelines.JPerinatol.2010;30:505–12.

27.BallotDE,NanaT,SriruttanC,CooperPA.Bacterial

bloodstreaminfectionsinneonatesinadevelopingcountry. Internationalscholarlyresearchnetwork.ISRNPediatr. 2012:1–6[ArticleID508512].

28.CimiottiJP,HaasJ,SaimanL,LarsonEL.Impactofstafﬁngon bloodstreaminfectionsintheneonatalintensivecareunit. ArchPediatrAdolescMed.2006;160:832–6.

29.YogarajJS,ElwardAM,FraserVJ.Rate,riskfactors,and outcomesofnosocomialprimarybloodstreaminfectionin pediatricintensivecareunitpatients.Pediatrics.

2002;110:481–5.

30.DonovanEF,SparlingK,LakeMR,etal.Theinvestmentcase forpreventingNICU-associatedinfections.AmJPerinatol. 2013;30:179–84.