Complete substitution of the Brazilian endemic clone by other methicillin-resistant Staphylococcus aureus lineages in two public hospitals in Rio de Janeiro, Brazil

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

Complete

substitution

of

the

Brazilian

endemic

clone

by

other

methicillin-resistant

Staphylococcus

aureus

lineages

in

two

public

hospitals

in

Rio

de

Janeiro,

Brazil

Raiane

Cardoso

Chamon

_,

_Sthefanie

_da

_Silva

_Ribeiro

_,

_Thaina

_Miranda

_da

_Costa

_,

Simone

Aranha

Nouér

_,

_Katia

_Regina

_Netto

_dos

_Santos

a_{UniversidadeFederaldoRiodeJaneiro,InstitutodeMicrobiologiaPaulodeGóes,DepartamentodeMicrobiologiaMédica,RiodeJaneiro,}

RJ,Brazil

b_{UniversidadeFederaldoRiodeJaneiro,FaculdadedeMedicina,HospitalUniversitárioClementinoFragaFilho,RiodeJaneiro,RJ,Brazil}

a

r

t

i

c

l

e

i

n

f

o

Received21July2016

Accepted28September2016

Availableonline19November2016

Keywords: Staphylococcusaureus Bloodstreaminfections USA100 Mupirocinresistance

a

b

s

t

r

a

c

t

Staphylococcusaureusisanimportantcauseofbloodstreaminfections.Therefore,themain

purposeofthisworkwastocharacterizeacollectionof139S.aureusisolatesfrom

blood-stream infectionsintwopublichospitalsinrelationtotheirantimicrobialsusceptibility

profile, staphylococcal cassettechromosomemectypes,and clonal relationship.

Methi-cillinresistanceandresistancetoother12agentswereaccessedbythediskdiffusiontest.

Minimuminhibitoryconcentrationtomupirocinwasalsodetermined.TheSCCmectypes

wereaccessedbymultiplexPCR,andtheclonalrelationshipwasdeterminedbypulsed

field gel electrophoresis method and restriction modification system characterization.

Besides,multilocussequencetypingwasperformedforrepresentativemethicillin-resistant

S. aureusisolates.ThemilitaryhospitalshowedadisseminationoftheNewYork/Japan

(USA100/ST5/CC5/SCCmecII)lineageassociatedtomultidrugresistance,includingmupirocin

resistance,andtheteaching hospitalpresentedpolyclonalandnon-multidrug resistant

MRSAisolates.CompletesubstitutionoftheBrazilianendemicclonebyotherlineageswas

foundinbothhospitals.Thesefindingscanhighlightdifferencesinpolicycontroland

pre-ventionofinfectionsusedinthehospitalsandachangeintheepidemiologicalprofileof

MRSAinBrazilianhospitals,withthereplacementofBEC,a previouslywell-established

clone,byotherlineages.

©2016SociedadeBrasileiradeInfectologia.PublishedbyElsevierEditoraLtda.Thisisan

openaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/

by-nc-nd/4.0/).

∗ _{Correspondingauthor.}

E-mailaddress:santoskrn@micro.ufrj.br(K.R.dosSantos).

1 _{Theauthorscontributedequallytothiswork.}

http://dx.doi.org/10.1016/j.bjid.2016.09.015

1413-8670/©2016SociedadeBrasileiradeInfectologia.PublishedbyElsevierEditoraLtda.ThisisanopenaccessarticleundertheCC

Staphylococcus aureus is considered an important cause

of bloodstream infections (BSI), which is associated

with high rates of mortality and morbidity.1 _{Analysis of}

molecularcharacteristicsofS.aureusisolateshaveindicated

avariety ofcirculating lineages insidehospitals,according

tothegeographicarea.InUnitedStates,theNewYork/Japan

clone(USA100/ST5/CC5/SCCmecII)hasbeen replacedbythe

community-acquired MRSA (USA300/ST8/CC8/SCCmecIV)

lineage.1 _{In China, two pandemic hospital-acquired MRSA}

(HA-MRSA) clonesare disseminated,theBrazilian endemic

clone(BEC/ST239/CC8/SCCmecIII)andtheUSA100.2_InBrazil,

theBEClineageremainedprevalentinsidehospitals,3butan

increasingpresenceoftheclonesUSA400(ST1/CC1/SCCmecIV)

and the Pediatric clone (USA800/ST5/CC5/SCCmecIV) have

beenreportedinthelastdecade.3,4 _{Morerecently,SCCmecII}

carrying isolates associated to the CC5 were detected

replacing, almost completely the BEC lineage among BSI

isolatesatahospitallocatedinSãoPaulocity.5

TheimplementationofaHealthCareAssociated

Preven-tionandControlCommittee(HAIPCC)ismandatorybylawin

Brazilianhospitalssince1997.6_{Thesemeasuresapplytothe}

wholehealthcaresystem,suchasthepublicandtheprivate

sector.Publichospitalsareresponsibleforthecareofabout

75%oftheBrazilianpopulation,estimatedin192millionsof

habitants(2012data).However,fundingfortheUnifiedHealth

System(SistemaÚnicodeSaúde–SUS)hasnotbeensufficient

toensureadequatefinancialresourcesforthepublichealth

system,leadingtoinappropriatecontrolofdisseminationof

endemicresistantmicroorganisms.6_{Theaimofthepresent}

studywastocharacterizeS.aureusisolatesfromBSIattwo

publichospitalsastheirantimicrobialresistanceandclonal

disseminationassociatedwithclinicalaspects.

Weevaluated139S.aureusconsecutiveisolatesfromBSI

recoveredina532-bedmilitaryhospital(Hospital1)andina

490-beduniversityteachinghospital(Hospital2),bothlocated

inRiodeJaneirocity,betweenJanuary2008andJune2009.This

studywasapprovedbytheResearchEthicsCommitteeunder

No.159/07.ClinicaldatafrompatientswithS.aureusBSIwere

retrospectivelyabstractedfromthehospitalrecords.S.aureus

isolateswereidentifiedbystandardmethods.BSIswere

clas-sifiedashospital-acquired(HA)orcommunity-acquired(CA)

accordingtotheCentersforDiseaseControl(CDC)criteria.

In order to characterize methicillin resistance,cefoxitin

disk diffusion test was used according to CLSI.7 _Isolates

identifiedasMRSAwerealsosubmittedtoantimicrobial

sus-ceptibilitytestfor12 agentsbythediskdiffusionmethod.7

Minimum inhibitory concentration(MIC) tomupirocin was

determined by Etest® (AB-Biodisk, Solna, Sweden). The

SCCmec types were assessed by multiplex-PCR for MRSA

isolates.8_{Clonalrelationshipwasdeterminedbypulsed-field}

gel electrophoresis(PFGE).9 _{Restrictionmodification system}

characterization(RMtest)10 _{wasusedtoidentifytheclonal}

complexes (CC) of methicillin susceptible S. aureus(MSSA)

isolates.Besides,multilocussequencetyping(MLST)was

per-formedforrepresentativeMRSAisolates.11_{TheFisher’sexact}

test and chi-square testwere used tocompare categorical

data.Significancelevelwasestablishedat5%(p<0.05).

The distribution ofthe 139 S. aureus isolates and their

SCCmectypesandclonalcomplexesineachhospitalisshown

inTable1.Outof75isolatesofHospital1(H1),32(43%)were

characterizedasMRSA,whereasinHospital2(H2)from64

iso-lates13(20%)wereMRSAisolates(p=0.006).WhileatH1the

majorityofMRSAisolatescarriedtheSCCmectypeII(69%),at

H2theSCCmectypeIV(69%)wasthemostprevalent.Overall,

onlyoneisolatefromH2carriedtheSCCmectypeIIIandwas

assignedasST889/CC5.InrelationtotheCCassignment,the

majorityofMRSAandMSSAisolates(83%;62/75)atH1were

relatedtoCC1andCC5.However,therewasapolyclonal

dis-tributionofS.aureusisolatescausingBSI(CCs1,5,8,30,45,

221)atH2regardlessoftheirmethicillinresistance.

Characteristicsof45 MRSAisolatesfromBSIofpatients

from the twohospitalsevaluated are presentedinTable2.

Overall,93%(42isolates),75%(34),and35%(16)oftheMRSA

isolates were resistant to ciprofloxacin, clindamycin, and

mupirocin,respectively.AmongtheMRSAisolatesfromH1,

resistancetothreeormoredrugclasses(multidrugresistance

Table1–Distributionof139methicillin-susceptibleand-resistantStaphylococcusaureusisolates,SCCmectypesand clonalcomplexesfrombloodstreaminfections.

Hospital/methicillin-resistance (numberofisolates)

N(%)ofisolates

SCCmectype Clonalcomplexes

II III IV 1 5 8 30 45 221 ND Hospital1 MRSA(32) 22(69) 0 10(31) 9(28) 23(72) 0 0 0 0 0 MSSA(43) – – – 14(32) 16(37) 1(3) 2(5) 4(9) 0 6(14) Total(75) 23(31) 39(52) 1(1) 2(3) 4(5) 0 6(8) Hospital2 MRSA(13) 2(23) 1a_{(8) 9(69) 3(23) 7(53) 0 1(8) 1(8) 1(8) 0} MSSA(51) – – – 17(33) 6(12) 7(14) 7(14) 4(8) 0 10(19) Total(64) 20(31) 13(20) 7(11) 8(12.5) 5(8) 1(2) 10(15.5) MRSA,methicillin-resistantS.aureus;MSSA,methicillin-susceptibleS.aureus;SCCmec,Staphylococcalcassettechromosomemec;ND,not deter-mined;N,number.

Table2–Generalcharacteristicsof45methicillin-resistantStaphylococcusaureusisolatesfrombloodstreaminfections. Hospital/genotype (noofisolates) Isolate number Isolationdate (mm/dd/yy) Unitor floor Acquisition mode SCCmec type PFGE subtype Clonality ST/CC Antimicrobial resistance profile Hospital1(32)

A(22) 1223a 01/10/2008 11 HA II A1 USA100 5/5 cipclierymuptec 1224a 01/12/2008 ICU HA II A1 USA100 5/5 cipclierymup 1255a 09/02/2008 ICU HA II A1 USA100 5/5 cipclierymup 1258a 09/16/2008 ICU HA II A1 USA100 5/5 cipclierymup 1265a 09/23/2008 9 HA II A1 USA100 5/5 cipclierymup 1266a 09/24/2008 9 HA II A1 USA100 5/5 cipclierymup 1276a 02/12/2008 9 HA II A1 USA100 5/5 cipclierymup 1288a 03/12/2009 ICU HA II A1 USA100 5/5 cipclierymup 1289a 03/13/2009 11 HA II A1 USA100 5/5 cipclierymup 1309a 03/14/2009 ND HA II A1 USA100 5/5 cipclierymupclorif 1290a 03/19/2009 11 HA II A1 USA100 5/5 cipclicloery 1291a 03/31/2009 9 HA II A1 USA100 5/5 cipclierymup 1305a 06/04/2009 11 HA II A1 USA100 5/5 cipclierymupclorif 1308a 06/15/2009 10 HA II A1 USA100 5/5 cipclierymupclorif 1260a 09/17/2008 10 HA II A2 USA100 5/5 cipcliery

1263a 09/22/2008 11 HA II A2 USA100 5/5 cipcliery 1275a 12/02/2008 ICU HA II A2 USA100 5/5 cipcliery 1238a 05/26/2008 8 HA II A3 USA100 5/5 cipclierymup 1240a 05/27/2008 Em HA II A3 USA100 5/5 cipclierymup 1284a 02/02/2009 Em HA II A4 USA100 5/5 cipcliery 1285a 02/16/2009 11 HA II A4 USA100 5/5 cipcliery 1301a 05/27/2009 IU HA II A5 USA100 5/5 cipclicloery

B(9) 1229a 02/09/2008 11 HA IV B1 USA400 1/1 cipcliery

1237a 05/20/2008 11 HA IV B1 USA400 1/1 cipcliery

1307a 06/12/2009 ICU HA IV B1 USA400 1/1 cipclo

1231a 02/13/2008 11 HA IV B2 USA400 1/1 cip

1282a 01/22/2009 ICU HA IV B2 USA400 1/1 cipclo

1268a 09/26/2008 10 HA IV B3 USA400 1/1 cipclierygen

1283a 01/22/2009 ICU HA IV B3 USA400 1/1 cipclo

1295a 05/25/2009 9 HA IV B4 USA400 1/1 –

1302a 05/21/2009 ICU HA IV B5 USA400 1/1 cipclo

F(1) 1306a 06/04/2009 10 HA II F ND 105/5 cipclicloery

Hospital2(13)

A(1) 1087a 01/20/2008 11 HA II A1 USA100 5/5 cipclierymup

B(3) 1094a 01/16/2008 9 CA IV B1 USA400 1/1 cipcliery

1187a 06/12/2008 8 HA IV B1 USA400 1/1 cipclicloery 1100a 01/27/2008 Em CA IV B2 USA400 1/1 cipcliery

C(5) 1214a 06/26/2009 7 HA IV C1 USA800 5/5 –

1318a 08/16/2008 Em HA IV C2 USA800 5/5 cip

1324a 08/08/2008 Em HA IV C3 USA800 5/5 cip

1328a 12/23/2008 Em HA IV C4 USA800 5/5 cipcliery

1326a 12/25/2008 9 HA IV C4 USA800 5/5 –

D(1) 1314a 11/08/2008 7 HA IV D ND 484/30 cipcliery

E(1) 1092a 02/22/2008 9 HA III E ND 889/5 cipcloerygensuttec

G(1) 1212a 06/02/2009 ICU HA II G ND 3050/45 cipcliery

H(1) 1219a 06/06/2009 8 HA II H ND 221/221 cipcliery

ICU,intensivecareunit;Em,emergency;ND,notdetermined;HA,hospitalacquired;CA,communityacquired;SCCmec,Staphylococcal cas-settechromosomemec;PFGE,pulsedfieldgelelectrophoresis;ST,sequencetype;CC,clonalcomplex;cip,ciprofloxacin;cli,clindamycin;ery, erythromycin;mup,mupirocin;tec,teicoplanin;clo,chloramphenicol;rif,rifampin;gen,gentamicin;sut,sulfamethoxazole/trimethoprim.

–MDR)wasverifiedin59.3%(19/32),whileamongtheMRSA isolatesfromH2,MDRwasfoundinonly23%(3/13)(p=0.05). Moreover,97% ofthe MRSA isolates from H1 were related toonlytwodisseminatedlineages,USA100/ST5/CC5/SCCmecII (69%) and USA400/ST1/CC1/SCCmecIV (28%), all of them causing hospital-acquired BSI. Furthermore, 94% (15/16) of mupirocin-resistant isolates were found at H1 and it was associated to the USA100 lineage. Two USA100 isolates

(1238a and 1240a) showed high levels of mupirocin resis-tance (MIC>1024␮g/mL)(datanotshown). Inthis hospital, theprevalentUSA100/ST5/SCCmecIIlineagewasfoundwidely disseminated.AtH2,62%ofMRSAisolatescarriedtheSCCmec IVandwererelatedtoUSA800(38%)orUSA400(23%)lineages. Besides,thepolyclonalpresenceofsporadiclineages(STs484, 889,3050,and221)wasidentifiedinthishospital,theST3050 beingdescribedforthefirsttimeinthisstudy.

Inourstudy,139S. aureusisolatesfrom BSIobtainedat

two different public hospitals in Rio de Janeiro city were

characterized regarding their antimicrobial resistance and

clonalprofile.Weverifiedthatalmost70%oftheBSIisolates

fromthemilitarypublichospital(H1)carriedtheSCCmecIIand

wererelatedtotheUSA100lineage.Allbutoneisolatewere

assignedasUSA400lineage.Thislineageappearstohave

sur-vivalandgrowth advantagesinceithasremainedforyears

asamajorhospital-associatedlineageinUSAandJapan1,12

showingthegoodadaptabilityofsuchclone,evenindifferent

geographicareas.

AtH2, areferenceteaching publichospital,apolyclonal

profile was observed for the MRSA isolates. Interestingly,

wepreviouslyfoundasimilarhigherclonaldiversityamong

MRSAisolatesataprivatehospital.3_{Thesefindingsmaybe}

areflectionoftheoccurrenceoffeweroutbreaksdueto

ade-quateinfectioncontrolmeasuresatthisparticularinstitution,

asfoundinthisteachingpublichospital.Padovezeetal.6

con-ductedacross-sectionalstudyevaluatingacollectionof153

hospitalsfrom fivedifferent Brazilianregions. Theauthors

showedthataminimalstructureisnecessaryforaneffective

preventionofhospitalinfections,speciallythepresenceofan

activeHAIPCC,aswellassterilizationservices,handhygiene

resources,andamicrobiologylaboratory.

Cabocloetal.3_{comparedS.aureusisolatesfromtwohealth}

institutionsinRiodeJaneirobetween2004and2007.Oneof

theseinstitutionswasthesamemilitaryhospital(H1)ofthe

current study.The authors showed adissemination ofthe

USA100, USA400,USA800 andBEClineages atthis military

institution.Moreover,around60%oftheisolateswerefrom

theBEClineage,showingthatatthetimethislineagewasstill

highlypresent.Simultaneously,similarresultswerefoundina

studyconductedataprivatetertiarycarehospitalinSãoPaulo

where40%(13/33)ofMRSAisolatesbelongedtoBECand21%

wererelatedtotheUSA100lineage.13_{AtH2,Cavalcanteetal.}14

showedthattheBEClineagewasresponsibleforaround30%of

allMRSAisolates,between2005and2006.Inthepresentstudy,

carriedoutbetween2008and2009,completeabsenceofthe

BEClineagewasverifiedinbothpublicinstitutionsevaluated,

showingthatcertainglobalMRSAlineagesarereplacingBEC.

Caiaffa-Filhoetal.5_{recentlyevaluatedacollectionof50}

con-secutiveMRSABSIisolatesinaSãoPaulotertiarycareteaching

hospital,betweenOctoberandDecember2010,andfoundthat

asinglePFGEclonerelatedtotheUSA100lineagewas

dissem-inated,almostreplacingtheBECinthatinstitutionduringthe

studyperiod.Thisfindinghighlightsapossiblechangeinthe

epidemiologicalprofileofMRSAinBrazilianhospitals.

MRSAisolatesweremorefrequentlyfoundatH1thanin

theteachinghospital(H2)beingassociatedtoaMDRprofile

and mupirocin resistance.In Brazil, despitethe legislation

mandatingtheimplementationofHAIPCCinthehealth

sys-tem,the lackofqualified professionals,thegrowing health

costs, and limited availability offinancial resources are of

great impact in the infection control.6 _{Therefore, the}

dif-ferencesregardingresistanceratesobservedbetweenMRSA

isolatesfrom the H1 and H2, as well asthe prevalenceof

specificSCCmectypes, maybeareflectionofthe policyfor

controland preventionofinfections and use of

antimicro-bialsinthehospitalsevaluated.Interestingly,theprevalent

USA100clonepresentingMDRprofileisolatedfrom H1had

alreadybeendescribedasaMRSA-daptomycin-resistant

iso-late with vancomycin MIC of 4␮g/mL, also causing BSI,15

confirming the abilityof this lineage to acquireresistance

determinants.Moreover,thislineagewasalsoassociatedwith

mupirocin resistance, a drug used for decolonizing MRSA

nasalcarriage.2_{Althoughonlytwoisolateshaveshowedhigh}

levelsofmupirocinresistance(MIC>1024␮g/mL),both

high-andlow-levelresistancehavebeenassociatedwithS.aureus

decolonization failure.2 _{As showed in a study conducted}

in China,2 _{USA100/ST5 isolates associated with mupirocin}

resistanceleadtopossibleoutbreaks. Thedisseminationof

mupirocin-resistantMRSAisolatesamongH1patientsinour

studyalsohighlightstheimportanceofthejudicioususeof

mupirocinamongthehospitalizedpatients.

MRSA, as well asMSSA isolates, havebeen reported as

importantcausesofnosocomialinfections,suchasBSI.1_The

present study showedthat S. aureusisolates from the CCs

1 and 5, regardless their methicillin-resistancestatus, had

similar clonality at both hospitals. According to Diep and

Otto,16_{theemergenceoftheMRSAlineagesaroundtheworld}

mayberelatedtothesuccessfulconversionofcertainMSSA

isolatesintoMRSAisolatesbytheacquisitionofSCCmec.The

presence ofMSSAand MRSA isolatespresenting the same

CCsand/orSTshavealreadybeenobservedinRiodeJaneiro

hospitals,4_{indicatingtheabilityofcertainlineagestoacquire}

themeccassettethusprovidinganadvantagetotheir

spread-inginhealthinstitutions.

In conclusion, although both institutions evaluated in

the present study are public hospitals, the military

hospi-tal showed dissemination ofthe USA100/ST5/CC5/SCCmecII

lineage associated to multidrug resistance, including to

mupirocin.Ontheotherhand,theteachinghospitalpresented

polyclonalandnon-multidrugresistantMRSAisolates.These

differencesmayreflectthepolicyofcontrolandprevention

ofinfectionsand/oruseofantimicrobialsemployedineach

hospital evaluated. Moreover,complete substitution of the

BEC/ST239/SCCmecIIIbyotherlineageswasfoundinboth

hos-pitals,highlightingachangeintheepidemiologicalprofileof

MRSAinBrazilianhospitals.

Ethics

statement

ThepresentstudywasapprovedbytheResearchEthics

Com-mitteeunderNo.159/07.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

Acknowledgments

Thisstudy wassupportedbygrantsfrom:Fundac¸ãoCarlos

ChagasFilhodeAmparoàPesquisadoEstadodoRiodeJaneiro

(FAPERJ),ConselhoNacionaldeDesenvolvimentoCientíficoe

Tecnológico(CNPq),Coordenac¸ãodeAperfeic¸oamentoPessoal

deNívelSuperior(CAPES),Fundac¸ãoUniversitáriaJosé

We acknowledge the contribution of PhD Rosana

Bar-retoRochaFerreira(InstitutodeMicrobiologiaPaulodeGóes,

UniversidadeFederaldoRiodeJaneiro,RiodeJaneiro)for

pro-vidinglanguagehelpandofthestudentJulianaCuritybade

MelloCamposforthehelpinsomeexperiments.

r

e

f

e

r

e

n

c

e

s

1. RheeY,AroutchevaA,HotaB,etal.Evolvingepidemiologyof

Staphylococcusaureusbacteremia.InfectControlHosp

Epidemiol.2015;36:1417–22.

2. LiuQ,HanL,LiB,etal.VirulencecharacteristicandMLST-agr

geneticbackgroundofhigh-levelmupirocin-resistant,MRSA

isolatesfromShanghaiandWenzhou,China.PLoSONE.

2012;7:e37005.

3. CabocloRM,CavalcanteFS,IorioNL,etal.

Methicillin-resistantStaphylococcusaureusinRiodeJaneiro

hospitals:disseminationoftheUSA400/ST1andUSA800/ST5

SCCmectypeIVandUSA100/ST5SCCmectypeIIlineagesina

publicinstitutionandpolyclonalpresenceinaprivateone.

AmJInfectControl.2013;41:e21–6.

4. SchuenckRP,CavalcanteFS,EmeryE,etal.Staphylococcus

aureusisolatesbelongingtodifferentmultilocussequence

typespresentspecificvirulencegeneprofiles.FEMSImmunol

MedMicrobiol.2012;65:501–4.

5. Caiaffa-FilhoHH,TrindadePA,daCunhaGP,etal.

Methicillin-resistantStaphylococcusaureuscarryingSCCmec

typeIIwasmorefrequentthantheBrazilianendemicclone

asacauseofnosocomialbacteremia.DiagnMicrobiolInfect

Dis.2013;76:518–20.

6. PadovezeMC,FortalezaCM,KifferC,etal.Structurefor

preventionofhealthcare-associatedinfectionsinBrazilian

hospitals:acountrywidestudy.AmJInfectControl.

2016;44:74–9.

7. ClinicalandLaboratoryStandardsInstitute–CLSI.

Performancestandardsforantimicrobialdisksusceptibility

testing.Approvedstandards:M100-S16.Wayne,Pennsylvania,

USA;2015.

8.Milheiric¸oC,OliveiraDC,DeLencastreH.Updatetothe

multiplexPCRstrategyforassignmentformecelementin

Staphylococcusaureus.AntimicrobAgentsChemother. 2007;51:3374–7.

9.VivoniAM,DiepBA,De-Gouveia-MagalhãesAC,etal.Clonal

compositionofStaphylococccusaureusisolatesataBrazilian

universityhospital:identificationofinternationalcirculating

lineages.JClinMicrobiol.2006;44:1686–91.

10.CockfieldJD,PathakS,EdgeworthJD,etal.Rapid

determinationofhospital-acquiredmethicillin-resistant

Staphylococcusaureuslineages.JMedMicrobiol.2007;56: 614–9.

11.EnrightMC,DayNPJ,DaviesCE,etal.Multilocussequence

typingforcharacterizationofmethicillin-resistantand

methicillin-susceptibleclonesofStaphylococcusaureus.JClin

Microbiol.2000;38:1008–15.

12.NakaminamiH,NoguchiN,ItoA,etal.Characterizationof

methicillin-resistantStaphylococcusaureusisolatedfrom

tertiarycarehospitalsinTokyo,Japan.JInfectChemother.

2014;20:512–5.

13.MartinoMDV,CorreaL,PignatariACC,etal.Isolatesof

methicillin-resistantStaphylococcusaureus(MRSA)not

belongingtotheBrazilianepidemicclone.SafHealth.

2015;1:9.

14.CavalcanteFS,SchuenckRP,FerreiraDC,etal.

Methicillin-resistantStaphylococcusaureus:spreadofspecific

lineagesamongpatientsindifferentwardsataBrazilian

teachinghospital.JHospInfect.2014;86:151–4.

15.CavalcanteFS,FerreiraDC,ChamonRC,etal.Daptomycin

andmethicillin-resistantStaphylococcusaureusisolatedfroma

catheter-relatedbloodstreaminfection:acasereport.BMC

ResNotes.2014;25:759.

16.DiepBA,OttoM.Theroleofvirulencedeterminantsin

community-associatedMRSApathogenesis.TrendsMicrobiol.