Changes in antimicrobial susceptibility of commonly clinically significant isolates before and after the interventions on surgical prophylactic antibiotics (SPAs) in Shanghai

h ttp : / / w w w . b j m i c r o b i o l . c o m . b r /

Clinical

Microbiology

Changes

in

antimicrobial

susceptibility

of

commonly

clinically

significant

isolates

before

and

after

the

interventions

on

surgical

prophylactic

antibiotics

(SPAs)

in

Shanghai

Su

Wang

_,

_Li-Zhong

_Han

_,

_Yu-Xing

_Ni

_,

_Yi-Bo

_Zhang

_,

_Qun

_Wang

_,

_Da-Ke

_Shi

_,

Wen-Hui

Li

_,

_Yi-Chen

_Wang

_,

_Chen-Rong

_Mi

a_{ShanghaiJiaoTongUniversitySchoolofMedicine,RuijinHospital,DepartmentofClinicalMicrobiology,Shanghai,China} b_{ShanghaiJiaoTongUniversitySchoolofMedicine,RuijinHospital,DepartmentofHospitalInfectionControl,Shanghai,China}

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received11May2017

Accepted1December2017

Availableonline12February2018 AssociateEditor:AfonsoBarth

Keywords:

Surgicalprophylacticantibiotics Intervention

Resistance

Nosocomialinfection

a

b

s

t

r

a

c

t

Surveillancesandinterventionsonantibioticsusehavebeensuggestedtoimprove

seri-ousdrug-resistanceworldwide.Since2007,ourhospitalhaveproposedmanymeasures

forregulatingsurgicalprophylacticantibiotics(carbapenems,thirdgen.cephalosporins,

vancomycin, etc.) prescribing practices, like formulary restriction or replacement for

surgical prophylactic antibiotics and timely feedback. To assess the impacts on

drug-resistance after interventions, we enrolled infected patients in 2006 (pre-intervention

period)and2014(post-interventionperiod)inatertiaryhospitalinShanghai.Proportions

oftargetedpathogenswereanalyzed:methicillin-resistantStaphylococcusaureus(MRSA),

vancomycin-resistant Enterococcus spp. (VRE), imipenem-resistant Escherichia coli (IREC), imipenem-resistantKlebsiellapneumoniae(IRKP),imipenem-resistantAcinetobacterbaumannii

(IRAB)andimipenem-resistantPseudomonasaeruginosa(IRPA)isolates.Ratesofthemwere

estimatedandcomparedbetweenSurgicalDepartment,ICUandInternalDepartment

dur-ingtwoperiods.ThetotalproportionsoftargetedisolatesinSurgicalDepartment(62.44%, 2006;64.09%,2014)weremorethanthoseinICU(46.13%,2006;50.99%,2014)andinInternal

Department(44.54%,2006;51.20%,2014).OnlyMRSAhasdecreasedsignificantly(80.48%,

2006;55.97%,2014)(p<0.0001).ThepercentagesofVREandIRECin3departmentswereall <15%,andtheslightestchangewerealsobothobservedinSurgicalDepartment(VRE:0.76%, 2006;2.03%,2014)(IREC:2.69%,2006;2.63%,2014).Theinterventionsonsurgical prophylac-ticantibioticscanbeeffectiveforimprovingresistance;antimicrobialstewardshipmustbe combinedwithinfectioncontrolpractices.

©2018SociedadeBrasileiradeMicrobiologia.PublishedbyElsevierEditoraLtda.Thisis anopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/

licenses/by-nc-nd/4.0/).

∗ _{Correspondingauthorat:DepartmentofHospitalInfection-Control,RuijinHospital,ShanghaiJiaoTongUniversitySchoolofMedicine,}

No.197RuijinERRoad,Shanghai,China.

∗∗ _{Correspondingauthorat:DepartmentofClinicalMicrobiology,RuijinHospital,ShanghaiJiaoTongUniversitySchoolofMedicine,No.}

197RuijinERRoad,Shanghai,China.

E-mails:hanlizhong1107@163.com(L.Han),miro924@163.com(C.Mi).

https://doi.org/10.1016/j.bjm.2017.12.004

1517-8382/©2018SociedadeBrasileiradeMicrobiologia.PublishedbyElsevierEditoraLtda.ThisisanopenaccessarticleundertheCC BY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

Sinceturnofthe21stcentury,theemergenceoforganisms

withincreased resistanceto available antibioticshas been

continuouslyconcerned bythepublic.1–4 _{Simultaneously,it}

has become a global threat to human health, provoking

adverse outcomes, high care costs and prolonged

hospi-tal stays.5 _{The unrestrained use of antibiotics has been}

implicatedasasignificantreservoir ofthegreatly changed

resistance.1,6 _{Thusoptimizinguseofantibioticshasbecome}

oneofthemostessentialpartstocontainresistance.6,7_Astudy

inFrancehasshowedsuccessfulcontrolon

fluoroquinolone-resistant Pseudomonas aeruginosa and methicillin-resistant

Staphylococcus aureus (MRSA) by fluoroquinolone

prescrip-tion restriction.8 _{Similarly, another multifaceted proactive}

intervention program including antimicrobial stewardship

hasalso minimizedthe nosocomialtransmission and

out-breaks of vancomycin-resistant Enterococcus spp. (VRE) in

HongKong.9_{What’sbetter,reportsfromtheUSandKoreahave}

demonstratedthatthemonitoringonantibiotics(surgical

pro-phylactic antibiotics(SPAs)) could reduce the antimicrobial

useandlengthofhospitalstay,improvetheclinicaland

finan-cialoutcomesandevenslowdownthepreviouslyincreasing

antimicrobialresistanceratesofsomepathogens.5,10,11

Astudy onceperformedinChinacollecting230,800

pre-scriptions between 2007 and 2009 has revealed excessive

overprescribing, including twice as many prescriptions as

recommendedbytheWHO.12 _{Herein,ahospital-wide}

inter-ventionprojectwaslaunchedinourhospitaltoimprovethe

quality of SPAs in 2007, and the backend alerts of

Hospi-talInformationSystem(HIS)and arestrictionsystemwere

introducedoneyearlater.13,14_{Allmeasuresintendedto}

mini-mizetheunnecessaryusageofantibioticsbytimelyfeedback

andprospectiveaudit.Althoughtheyhavebeenconfirmedto

enhancetheappropriatenessofantibioticuseandimprovethe

qualityoftreatment,13_{theeffectsonchangesinantimicrobial}

resistancewarrantedfurtherresearches.Thusweconducted

the study to compare the antimicrobial resistant rates of

sixmajornosocomialpathogensbetweenthepre-and

post-interventionperiods.Toourknowledge,moststudiestodate

focusedmoreontherapidgrowthofdrug-resistantbacteria

duetotheantibioticsabuseinChinaorthedecreasesofdrug

consumptionduetoantimicrobialstewardship.15–18_Whether

theinterventionsonSPAswereeffectivetoantimicrobial

resis-tance,however,hasnotbeendocumentedwellinShanghai,

eveninChina.

Materials

and

methods

Setting

Ruijin Hospital is a tertiary university-affiliated hospital,

locatedinShanghai,alargemetropolitanregioninChinaof

over24millioninhabitants.Itisageneral1800-bedhospital

integratedwithemergency,intensivecareunit(ICU),surgery

andotherdepartments,servingapproximately115,000patient

visits per year. In addition to native residents, patients

fromotherprovincesinChinaalsocomeforbettermedical

treatment.

ThestudywasapprovedbyRuijinHospitalEthics

Commit-tee(ShanghaiJiaoTongUniversitySchoolofMedicine),andthe

ReviewBoardexemptedrequestforinformedconsentbecause

nopatient-leveldatawereobtained.

Interventions

Theinterventionmeasureswere describedbefore.14 _Briefly,

medical records of the patients prescribed SPAs (with

emphasis on carbapenems, third gen. cephalosporins and

vancomycin) were selective examined,forexample,timing

ofantibioticadministration,appropriatenessoftheregimen

anddurationofSPAs.Moreover,thebackendalertsofHISand

arestrictionsystemweredesignedtomonitorand improve

theuseofSPAsinlinewiththeinclusionofassessingtheuse

ofSPAs.Ratiosofadherencetotherecommendationswere

measuredregularlyandtimelyfeedbackwasgiventosurgical

staffs.Thesurgeonswereprovidedwithsystematicallectures

ontherationaluseofSPAs,whichmayfacilitatethe

propaga-tion.

Isolates

Weperformed aninterruptedtime seriesstudy ofpatients

with infections in 2006 (pre-intervention period) and 2014

(post-interventionperiod).Caseswereidentifiedfromthe

lab-oratorydatabaseoftheDepartmentofClinicalMicrobiology.

Only the first isolatefrom the same species wasreviewed

andrecordedperpatientamongthetwoperiods.Toevaluate

the effect of interventions in SPAs on antimicrobial

resis-tance, pathogens belonging to six major species or genus

wereenrolledincurrentstudyreferringtotheprimer

stud-iesasfollowing1,3_{:S.aureus,Enterococcusspp.,Escherichiacoli,}

Klebsiella pneumoniae,Acinetobacter baumanniiand P.

aerugin-osa. Antimicrobialsusceptibilitydata,includingMRSA,VRE,

imipenem-resistantE.coli(IREC),imipenem-resistantK.

pneu-moniae (IRKP), imipenem-resistant A. baumannii (IRAB) and

imipenem-resistantP.aeruginosa(IRPA)werecollected.Species

wereidentifiedbystandardbiochemicalmethodsortheVITEK

2 compact system (bioMérieux, Marcyl’Étoile, France). The

antimicrobialsusceptibilitiesofclinical isolateswere

deter-minedbythediskdiffusionmethodaccordingtotheClinical

andLaboratoryStandardsInstitute(CLSI)criteriaortheVITEK

2compactsystem(bioMérieux,Marcyl’Étoile,France)

follow-ing the specifications, and results were interpreted using

theCLSIcriteria.19_{Variationsinthesusceptibilityphenotype}

abovewereestimatedfrompre-andpost-interventionperiods

amongdifferentdepartments(ICU,InternalDepartmentand

SurgicalDepartment).

Statisticalanalysis

Values were presentedas apercentage ofthe group.

Pear-son’s chi square test was used for testing the differences

ofproportionsandresistantratesbetweentwogroupswith

Fisher’sexacttestasappropriate.Atwo-tailedpvalueof<0.05

wasregarded asstatisticallysignificant.Allstatistical

anal-ysiswasperformedbySAS8.2(SASInstituteInc.,Cary,NC,

100.00

A

B

Antibiotic use density (per patient-da

ys) 0.00 0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 Type II operation Type I operation Apr-2 005 Apr-2 006 Apr-2 007 Apr-2 009 Apr-2 010 Apr-2 012 Apr-2 013 Apr-2 014 Apr-2 011 Apr-2 008 Oct-200 5 Oct-200 6 Oct-200 7 Oct-200 8 Oct-201 0 Oct-201 1 Oct-201 2 Oct-201 3 Oct-201 4 Oct-200 9 Apr-2 005 Apr-2 006 Apr-2 007 Apr-2 009 Apr-2 010 Apr-2 012 Apr-2 013 Apr-2 014 Apr-2 011 Apr-2 008 Oct-200 5 Oct-200 6 Oct-200 7 Oct-200 8 Oct-201 0 Oct-201 1 Oct-201 2 Oct-201 3 Oct-201 4 Oct-200 9

Fig.1–ChangingtrendsofSPAsuseamongSurgicalDepartmentfrom2005to2014.(A)TheratesofqualifiedSPAs prescriptionsintotal,(B)theantibioticusedensityintypeIandIIoperation.

Results

Totalcharacteristic

TheseculartrendofthequalifiedSPAsuseintotalafter

inter-ventionsin2007wasonasharpincreaseandtheratebecame

stableat85%since2013(Fig.1A).Theantibioticusedensityin

typeIandIIoperationbothshoweddownwardtrends,andthe

slopechangeintypeIoperationwasmorepositive(Fig.1B).

Besides,thedescendingcurveshavebeengradualsince2014,

thiswasalsowhy2014asapost-interventionperiodinour

study.

Thetotalnumbersofclinical isolateswere 3774in2006

and5127in2014.Theproportionsoftargetedisolatesamong

all reported isolates were shown in Table 1. The isolates

enrolledaccountedfor51.27%(2006)and55.14%(2014)ofall

reportedisolates.Theproportionoftargetedisolatesin

Sur-gicalDepartment(62.36%in2006;64.09%in2014)wasmore

than thatinICU(46.13%in2006;50.99%in2014)and

Inter-nalDepartment(44.54%in2006;51.20%in2014)(Table1).A

sharpdecreasewasonlyfoundintheproportionofS.aureus

amongall3departments(Total:11.02%in2006;6.20%in2014)

(p≤0.0001).

Changesofresistantratesinsurgicaldepartment

Only the percentageofMRSA isolateshas dropped

signifi-cantlyaftertheinterventions(80.48%in2006;55.97%in2014)

(p<0.0001).Incontrast,VRE(0.76%in2006;2.03%in2014),IRKP

(2.91%in2006;13.11%in2014),IRAB(28.21%in2006;69.64%

in2014)andIRPA(46.53%in2006;54.73%in2014)rosewithin

post-interventionperiod.Notably,theslightchangesofVRE,

IRECandIRPAhavenotbeenregardedassignificant(p>0.05).

Table1–Proportionsoftargetedpathogensbelongingto6speciesorgenusamongdifferentdepartments.

T ICU Internal Surgical

2006(%) 2014(%) p 2006(%) 2014(%) p 2006(%) 2014(%) p 2006(%) 2014(%) p S.aureus 416(11.02) 318(6.20) <0.0001 54(7.74) 54(3.81) 0.0001111(6.48) 105(4.95) 0.0412251(18.42) 159(10.00) <0.0001 Enterococcusspp. 321(8.51) 582(11.35) <0.000151(7.31) 216(15.25) <0.0001139(8.11) 218(10.28) 0.0219131(9.61) 148(9.31) 0.7790 E.coli 407(10.78) 489(9.54) 0.053432(4.58) 55(3.88) 0.4459189(11.03) 244(11.50) 0.6471186(13.65) 190(11.95) 0.1679 K.pneumoniae 281(7.45) 596(11.62) <0.000156(8.02) 130(9.18) 0.3768122(7.12) 260(12.26) <0.0001103(7.56) 206(12.96) <0.0001 A.baumanii 239(6.33) 478(9.32) <0.000165(9.31) 185(13.06) 0.012096(5.60) 125(5.89) 0.702478(5.72) 168(10.57) <0.0001 P.aeruginosa 271(7.18) 364(7.10) 0.883364(9.17) 82(5.79) 0.0040106(6.19) 134(6.32) 0.8690101(7.41) 148(9.31) 0.0642 Total 1935(51.27)2827(55.14) 0.0003322(46.13)722(50.99) 0.0357763(44.54)1086(51.20) <0.0001850(62.36)1019(64.09) 0.3321 T,thetotalnumberoftargetedisolatesin2006and2014.

Total,thetotalnumberoftargetedisolatesin2006and2014. %,thepercentageoftargetedisolatesinallreportedisolates.

Table2–RatesofMRSA,VRE,IREC,IRKP,IRABandIRPA in2006and2014amongSurgicalDepartment.

2006 2014 Trend p R T % R T % S.aureus 202 251 80.48%89 159 55.97%↓ <0.0001 Enterococcusspp. 1 131 0.76% 3 148 2.03%↑ 0.7028 E.coli 5 186 2.69% 5 190 2.63%↓ 1.0000 K.pneumoniae 3 103 2.91%27 206 13.11%↑ 0.0043 A.baumanii 22 78 28.21%117 168 69.64%↑ <0.0001 P.aeruginosa 47 101 46.53% 81 148 54.73%↑ 0.2039 R,thenumberofantibiotic-resistantisolates(MRSA,VRE,IREC, IRKP,IRABandIRPA).

T,thetotalnumberofclinicalisolates.

Trend,thetrendoftheresistantratesin2014comparedtothatin 2006.

Changesofresistantratesindifferentdepartments

ThepercentagesofMRSAinSurgicalDepartment(80.48%in 2006;55.97%in2014)stayedbetweenthoseinICU(90.74%in 2006;78.85%in2014)andInternalDepartment(58.56%in2006; 44.23%in2014) but with the greatestdecreasing tendency. ThepercentagesofVREandIRECin3departmentswereall below15%,andthenarrowestmarginswereobservedbothin SurgicalDepartment(Fig.2).Asubstantialclimbinthe

inci-denceofIRABhasbeenobservedwithsimilarrangesinall

3departments.Separately,theminimumincreasedrangesof

IRKP(0.82%in2006;6.15%in2014)andIRPA(46.88%in2006;

51.22%in2014)wereinInternalDepartmentandICU

respec-tively(Fig.2).

Discussion

Itisnotoriousthat extensive use ofantibioticscan

poten-tiateantibioticresistance,whichwillbedifficultandcostly

to control.4 _{And evidently, the control of antibiotic use}

deserves tobe undertaken.Reports formseveral countries

haveclaimedthataweb-basedauditandfeedback

interven-tioncanincreaseadherencetoempiricalantibioticprescribing

guidelines.20–23_{Betterthanthat,since2000whenaUSstudy}

foundthatantibiotic-utilizationinterventionsmaybe

partic-ularlyimportantforcontrolofmultidrug-resistant(MDR)K.

pneumonia,24_{therehavebeenworldwidereportsonthe}

reduc-tionofresistanceratesinmajorpathogensduetoantibiotic

interventions.5,11,25,26_{Chinamanufacturedandconsumedthe}

largestquantityofantibioticsbycountryaccordingtoasurvey

in2007.18_{Sincethesameyear,manymeasuresfor}

regulat-ing SPAs prescribing practices have been proposed in our

hospital, suchas continuing educationalsessions forSPAs

prescribing, signature of liability forms, formulary

restric-tionorreplacementandtimelyfeedback.13,14_{Thepreliminary}

studyhavedemonstratedthattheinterventionshadresulted

in the increased rates of qualified SPAs prescriptions and

thedecreaseddurationofSPAs.13_{Ofinterest,thesefindings}

were inaccordance withthose ofBantaretal.,26_but

oppo-sitetothoseofGyssensetal.,27_{whoreporteda25%growthin}

antibioticuseaftersimilarintervention.Consideringwealso

notedunstableutilizationlevelsofSPAsonthebaselinephase

(Fig. 1), this is notsurprising. Therefore, the currentstudy

aimedtoassesstheimpactsofinterventionsonantimicrobial

susceptibilitybetweenpre-andpost-interventionperiods.

Inthis study,thehighestproportionoftargetedisolates

belongingto6species/genuswasfoundinSurgical

Depart-ment(Table1),whichsupportedthenecessityofinterventions

onSPAsinourhospital.MonitoringofSPAsandtimely

feed-backwerewidelyappliedstrategiestoimproveprofessional

prescriptionpractice.Amulticenterprojecttoprevent

surgi-calsiteinfectionsalsopresentedimprovementinantibiotic

use intheUS.28 _{Inaddition,the interventionson}

prescrip-tionhavebeenprovedtoaccountforadiminishingtendency

ofantibioticsuse,5,26_{thenforthereductionofantimicrobial}

resistance.8,29_{SoimprovingtheappropriatenessofSPAsuse}

maybecomeagoodstartforpreventionandmanagementof

infections.

Themostimportantresultsofthestudyweretheeffectsof

theinterventionsonantimicrobialresistance.Fig.2revealed

thesametrendbutdifferentvolatilityofantimicrobial

resis-tantratestothetargetedpathogensindifferentdepartments

between the 2 periods. Onlythe great decreasing ratio of

MRSAwasobservedinSurgicalDepartmentafterthe

inter-ventions performed (Table 2, Fig. 2). Successful controlsof

MRSAbyprescriptionrestrictionthroughHIShavealsobeen

reportedpreviously.1,8 Someotherinfection controlpolicies

might have contributed to the inverse, such as

promot-ing alcohol-based hand hygiene to all conscious patients

Fig.2–RatesofMRSA,VRE,IREC,IRKP,IRABandIRPAamong3departmentsin2006and2014.‘Internal’meansInternal Department;‘Surgical’meansSurgicalDepartment;‘Total’meansthetotalratesofMRSA,VRE,IREC,IRKP,IRABandIRPAin 3departments.

to be useful in preventing nosocomial outbreaks due to

epidemiologicallyimportantMDRorganismsorvirusesin

clin-icalsettings.9,25,31,32 _{Incontrast to these positiveshifts for}

MRSA,theresistancechangesamongstEnterococcusspp.and

Gram-negativebacilli seemed tobe forthe worse(Table2,

Fig. 2). Compared with those in Internal Department and

ICU, the proportions of VRE and IREC in Surgical

Depart-ment fluctuated minimally and insignificantly, which can

demonstratetheeffectivenessofinterventionsonSPAs(Fig.2,

Table 2). What’s more, the different volatilities between

different departments’ added evidence to the importance

ofinterventionsonantibiotics forcontrollingantimicrobial

resistance.

Theincreasedprevalenceofcarbapenem-resistant

Gram-negativebacilliisolates(i.e.K.pneumoniae,A.baumaniiandP. aeruginosa)havebeenwidelydocumentedduetothereliance

on carbapenemsto treatthese pathogens.33–35 _{As toIRAB,}

themarkedrisehasbeenobservedwithsimilarrangesin3

departments(Fig.2).Unexpectedly,theminimumincreased

rangesofIRKPandIRPAwereinInternalDepartmentandICU

respectively,andtheproportionsofIRPAandIRABin

Surgi-calDepartmentin2014werefarhigherthanthatinCHINET

surveillancesystem.3_{Theseseemedwecouldnotassertthat}

thereduceduseofSPAscouldbringaboutthepositive

volatili-tiesinantimicrobialresistanceespeciallyofnon-fermentative

Gram-negative bacilli. Actually, the dramatically growing

emergenceofcarbapenem-resistantK.pneumoniaisolateshas

beendeemedabigconcernoverthepastdecade,mostlydueto

thediversityofemergingcarbapenemasetypes.1,34_P.

aerugin-osaandA.baumannii,thetwomostfrequentnon-fermenters

causingnosocomialinfectionsandoutbreaks,werenotorious

forthemultiplemechanismsofantimicrobialresistanceand

couldsurviveunderawiderangeofenvironmentalconditions

andpersistsforprolongedperiodsonsurfaces,whichmade

theclonaldisseminationofclinicalMDRstrains.4,36_Therefore,

prudentuseofantibioticsisnottheonlystrategyforfighting

antibioticresistance.Itstillrequiresacombinationofgood

infectioncontrolpractices,likehandhygiene,environmental

disinfection,andthescreeningofespeciallynon-fermenters

infectedpatientsinorder toachieve acomprehensive

con-trolofresistance.Friedrichevenfoundacorrelationbetween

useofsingleantibioticsandchangesintheresistanceprofiles

ofsomeGram-negative aerobesbyusing dataanalysis(i.e.

simplelinearregression).37 _{Onelastthing,clinicaland}

eco-nomicalcostswerestillquestionableandwarrantedfurther

follow-up.

Therearestillsomelimitationsinourstudy:first,the

con-trolofconfounderslikepatientcharacteristicsandeffectsof

otherinfectioncontrolstrategiesandhadbeenprecluded.

Sec-ond,wedidnotcomparethepatient-leveloutcomesbetween

the2periods.However,itprovidesthestepstoneforthefuture

expandedresearchassociatedwithmulticenterandfurther

antibioticsprescribingsurveillancetocontrolpossible

resis-tance.

Conclusions

OurstudyindicatedthattheinterventionsonSPAsandtimely

feedback could leadto promptand positive effects on the

amountofantibioticprescribed,andcouldbeusefuloptionsto

improveantimicrobialresistanceofsomepathogens(MRSA,

VRE,IREC,etc.).Inadditiontoadministrationofappropriate

antimicrobialagents,strictinfectioncontroleffortsarealso

essential,likehandhygiene,environmentaldisinfection,and

thescreeningofespeciallynon-fermentersinfectedpatients.

Theperiodicsurveillanceofdrugresistanceiscrucialnotjust

for epidemiological purposes but also for establishing and

improving guidelinesforthe antimicrobialstewardshipand

Funding

Thiswork was supported by the National Natural Science

FoundationofChina(grantno.81472010)andtheShanghai

Three-Year Plan of the Key Subjects Construction in

Pub-licHealth-InfectiousDiseasesandPathogenicMicroorganism

(grantno.15GWZK0102).

Conflicts

of

interest

Theauthorshavedeclaredthatnocompetinginterestsexist.

Acknowledgments

WewouldliketothankShu-ZhenXiaoandFei-FeiGuforthe

preparationofthesusceptibilitydata,andtheDepartmentof

ClinicalMicrobiologyatRuijinHospitalforexcellent

labora-toryprovisionandtechnicalassistance.

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