Article
Reference
Emergence of OXA-48-producing Enterobacteriaceae in Switzerland
POTRON, Anaïs, et al.
POTRON, Anaïs, et al . Emergence of OXA-48-producing Enterobacteriaceae in Switzerland.
International journal of antimicrobial agents , 2012, vol. 40, no. 6, p. 563-4
DOI : 10.1016/j.ijantimicag.2012.07.003 PMID : 23040008
Available at:
http://archive-ouverte.unige.ch/unige:28412
Disclaimer: layout of this document may differ from the published version.
1 / 1
LetterstotheEditor/InternationalJournalofAntimicrobialAgents40 (2012) 562–573 563
Table1
OritavancinMICsversusvancomycinMICsforStaphylococcusaureusandcoagulase-negativestaphylococci(CoNS).
No.ofisolates VANMIC(g/mL) ORIMICrange(g/mL) ORImodalMIC(g/mL) ORIMIC50(g/mL) ORIMIC90(g/mL) Staphylococcusaureus
51 ≤0.25 ≤0.004–0.25 0.03 0.03 0.06
3648 0.5 ≤0.004–0.25 0.03 0.03 0.12
5298 1 ≤0.004–4 0.06 0.06 0.12
78 2 0.03–1 0.25 0.12 0.25
CoNS
15 ≤0.25 ≤0.004–0.06 0.015 0.015 0.06
98 0.5 ≤0.004–0.25 0.015 0.03 0.06
853 1 0.008–1 0.06 0.06 0.5
697 2 0.015–1 0.12 0.12 0.25
1 4 1 N/D N/D N/D
VAN,vancomycin;ORI,oritavancin;MIC,minimuminhibitoryconcentration;MIC50/90,MICsfor50%and90%oftheorganisms,respectively;N/D,notdetermined(as<10 isolates).
Acknowledgments
The authors thank the scientific support personnel at The MedicinesCompany(VilleSaintLaurent,QC,Canada)andEurofins Medinet(Chantilly,VA)fortheircontributionstothisresearch.
Funding:ThisstudywasfundedbyTargantaTherapeutics.
Competinginterests:ThisstudywasfundedbyTargantaThera- peutics,whichisnowawhollyownedsubsidiaryofTheMedicines Company.TheMedicinesCompanyauthorshavenosignificantdec- larationstomakewithrespecttoexternalfunding,ownershipof companystocksorshares,andreimbursementforpreparingthis article.TheMedicinesCompanyauthorswereTargantaTherapeu- ticsemployeesatthetimetheworkwasconducted.
Ethicalapproval:Notrequired.
References
[1]McKayGA, BeaulieuS,Arhin FF, BelleyA, Sarmiento I, ParrJr TR, etal.
Time–killkineticsoforitavancinandcomparatoragentsagainstStaphylococcus aureus,EnterococcusfaecalisandEnterococcusfaecium.JAntimicrobChemother 2009;63:1191–9.
[2]ArhinFF,DraghiDC,PillarCM,ParrJrTR,MoeckG,SahmDF.Comparative invitroactivityprofileoforitavancinagainstrecentGram-positiveclinicaliso- lates.AntimicrobAgentsChemother2009;11:4762–71.
[3] JonesRN,SaderHS,FritscheTR,HoganPA,SheehanDJ.Selectionofasurrogate agent(vancomycinorteicoplanin)forinitialsusceptibilitytestingofdalba- vancin:resultsfromaninternationalantimicrobialsurveillanceprogram.JClin Microbiol2006;44:2622–5.
[4]SliwinskiJ,PrecitM,MercierR-C.RelationshipofinvitroMRSAstraincharacter- isticstotelavancinsusceptibility:amulti-centerevaluation.In:51stInterscience ConferenceonAntimicrobialAgentsandChemotherapy(ICAAC).Washington, DC:ASMPress;2011[AbstractE1333].
[5]ArhinFF,SarmientoI,ParrJrTR,MoeckG.Comparativeinvitroactivityoforita- vancinagainstStaphylococcusaureusstrainsthatareresistant,intermediateor heteroresistanttovancomycin.JAntimicrobChemother2009;64:868–70.
FrancisF.Arhin∗ TheMedicinesCompany,7170FrederickBanting,StLaurent,Quebec H4S2A1,Canada DeborahC.Draghi ChrisM.Pillar1 EurofinsMedinet,14100ParkMeadowDrive,Chantilly,VA20151, USA GregoryMoeck TheMedicinesCompany,7170FrederickBanting,StLaurent,Quebec H4S2A1,Canada DanielF.Sahm EurofinsMedinet,14100ParkMeadowDrive,Chantilly,VA20151, USA
∗Correspondingauthor.Tel.:+15143321008x1700;
fax:+15143326033.
E-mailaddress:francis.arhin@themedco.com(F.F.Arhin)
1Presentaddress:Micromyx,LLC,4717CampusDrive, Kalamazoo,MI49008,USA.
13June2012 doi:10.1016/j.ijantimicag.2012.06.019
EmergenceofOXA-48-producingEnterobacteriaceae inSwitzerland
Sir,
Thecarbapenem-hydrolysing-lactamaseOXA-48isincreas- inglyreportedasasourceofcarbapenemresistanceinEnterobacte- riaceae[1].FirstidentifiedinTurkey,OXA-48-producershavebeen identifiedinmanycountriesoftheMediterraneanarea[1].This resistancedeterminantisatleastendemicinTurkeyandnowin severalNorthAfricancountries[1].Additionalscatteredcasesor relatedoutbreakshavebeenreportedinmanyothercountries[1,2].
TheblaOXA-48genehasbeendetectedinvariousEnterobacteriaceae speciesanditsspreadismainlyassociatedwiththeTn1999-like transposoninsertedintoasingle62-kbIncL/M-typeplasmid[1].
HerewereporttheidentificationofOXA-48-producersinanother Europeancountry.
KlebsiellapneumoniaeAELwasrecoveredinMarch2010from arectalswabofa64-year-oldman.Straincarriagepersisteduntil April2010whenitbecamecomplicatedbyurinarycatheter-related cystitis.EscherichiacoliZANwasrecoveredinFebruary2011from aurinecatheter ofa46-year-oldpatientwithoutcausingactive infection.
Susceptibilitytesting was performedby diskdiffusionassay (Sanofi-DiagnosticPasteur,Marnes-la-Coquette,France),andmin- imuminhibitoryconcentrations(MICs)weredeterminedbyEtest (bioMérieux,LaBalme-les-Grottes,France)andwereinterpreted according to Clinical and Laboratory Standards Institute (CLSI) guidelines[3].Bothisolatesdisplayedanextended-spectrum- lactamase(ESBL)-producingphenotype.KlebsiellapneumoniaeAEL wasresistanttoallpenicillins,extended-spectrumcephalosporins, ertapenem(MIC=6mg/L) andfluoroquinolones.It wassuscepti- ble toimipenem(MIC=0.5mg/L), meropenem(MIC=0.75mg/L) andgentamicin(MIC=0.19mg/L)andofintermediatesusceptibil- itytotigecycline(MIC=2mg/L).EscherichiacoliZANwasresistant to all penicillins, cefotaxime and aztreonam and of intermedi- ate susceptibilityto cefepime, ceftazidime (MIC=1.5mg/L) and tigecycline (MIC=2mg/L). MICs of imipenem, meropenem and ertapenem were, respectively, 0.75, 1.5 and 24mg/L for E. coli ZAN. It was also resistant to trimethoprim/sulfamethoxazole,
564 LetterstotheEditor/InternationalJournalofAntimicrobialAgents40 (2012) 562–573 sulfonamides,tobramycinandgentamicinandwassusceptibleto
amikacin(MIC=1mg/L),chloramphenicol,tetracyclineand fluo- roquinolones.PCRexperimentswithprimersdesignedtodetect AmblerclassA,BandDgenes,followedbysequencing,identified theblaOXA-48 carbapenemasegeneinbothisolates[2].Klebsiella pneumoniaeAELalsopossessedtheESBLblaCTX-M-15genetogether withblaOXA-1andblaSHV-28genes,whereasE.coliZANco-harboured theESBLblaCTX-M-24geneandtheblaTEM-1gene.
ThegeneticenvironmentoftheblaOXA-48genewasdetermined byPCRmappingusingspecificprimersfortheinsertionsequence IS1999,locatedupstreamanddownstreamofthegeneinTn1999 [2].Tn1999wasidentifiedinE.coliZANisolatewhereasTn1999.2, differingfromTn1999bytheinsertion ofan IS1Relement,was identifiedin K.pneumoniaeAEL. In K.pneumoniae AEL,mating- out assays and plasmid DNA analysis performed as described previously [2] allowedidentification of theblaOXA-48 gene in a 62-kbconjugativeplasmidsimilartothatoftheprototypeOXA- 48-positiveK. pneumoniae11978 strainfrom Turkeyand other OXA-48-producersfromothergeographicalorigins[1].Mating-out assaysusingE.coliZAN wereunsuccessful.Tosearchforapos- siblechromosomal locationoftheblaOXA-48gene,thetechnique usingtheendonucleaseI-CeuIwasperformedasdescribedprevi- ously[4]andconfirmedthechromosomallocationoftheblaOXA-48 gene(datanotshown).
Multilocussequencetyping(MLST)performedasdescribedpre- viously [2]showed that K.pneumoniaeAEL belongedtoa new sequence type ST900 (allelic profile 1-6-1-5-4-1-6).Noticeably, ST900isasingle-locusvariantofST101(allelicprofile2-6-1-5-4-1- 6),andOXA-48-producingK.pneumoniaebelongingtoST101have beenreportedinTunisia,SpainandSouthAfrica(personaldata), highlightingthewidedisseminationofthissequence type[2,5].
Escherichiacoli ZANbelongedtoST38,similartootherOXA-48- producingE.coliisolatesreportedinFrancefrompatientscoming fromEgyptandTurkey[1].Interestingly,thoserecentlyidentified isolatesco-producedthesame-lactamasesasE.coliZAN,namely TEM-1andCTX-M-24,suggesting theirclonal spread invarious Europeancountries.
Althoughrecent datasuggest that thecurrent spread ofthe blaOXA-48geneismainlylinkedtothetransferofasingleepidemic IncL/M-type plasmid,K.pneumoniae ST101 and ST395together withE.coliST38maybeconsideredasepidemicstrainsandlikely contributetothespreadofthatresistancedeterminant[1].Interest- ingly,wereporthereforthefirsttimeachromosomalacquisition oftheblaOXA-48gene.Thisreportunderlinesthatimportationof carbapenemase-producersand theirpotentialsubsequentdiffu- sionmayoccurdespitestrictcontrolofantibioticstewardshipand highqualityofhandhygieneasreportedintheUniversityHospital ofGeneva(Geneva,Switzerland).
Acknowledgments
TheauthorsthankplatformGenotypingofPathogensandPublic Health(InstitutPasteur,Paris,France)forcodingMLSTallelesand profilesandmakingthemavailableathttp://www.pasteur.fr/mlst.
Funding: Thisworkwassupportedbyagrant fromtheMin- istère de la Recherche, Université Paris XI (Paris, France) and by INSERM (France). The research leading to these results has alsoreceivedfundingfromtheEuropeanCommunity’s Seventh FrameworkProgrammeFP7/2007-2013undergrantagreementno.
241742(TEMPOtest-QC)andno.282512(R-GNOSIS).
Competinginterests:Nonedeclared.
Ethicalapproval:Notrequired.
References
[1]PoirelL,PotronA,NordmannP.OXA-48-likecarbapenemases:thephantom menace.JAntimicrobChemother2012;67:1597–606.
[2]PotronA,KalpoeJ,PoirelL,NordmannP.Europeandisseminationofasingle OXA-48-producingKlebsiellapneumoniaeclone.ClinMicrobiolInfect2011;17:
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[3]ClinicalandLaboratoryStandardsInstitute.Performancestandardsforantimi- crobialsusceptibilitytesting;twenty-firstinformationalsupplement.Document M100-S21.Wayne,PA:CLSI;2011.
[4]Potron A, Poirel L, Croizé J, Chanteperdrix V, Nordmann P. Genetic and biochemicalcharacterization ofthefirst extended-spectrum CARB-type- lactamase,RTG-4,fromAcinetobacterbaumannii.AntimicrobAgentsChemother 2009;53:3010–16.
[5]LahlaouiH, PoirelL,Barguellil F, MoussaMB,Nordmann P. Carbapenem- hydrolyzingclassD-lactamaseOXA-48inKlebsiellapneumoniaeisolatesfrom Tunisia.EurJClinMicrobiolInfectDis2012;31:937–9.
AnaïsPotron ServicedeBactériologie-Virologie,INSERMU914«Emerging ResistancetoAntibiotics»,HôpitaldeBicêtre,FacultédeMédecineet UniversitéParis-Sud,94275K.-Bicêtre,France JacquesSchrenzel BacteriologyLaboratoryandGenomicResearchLaboratory,Geneva UniversityHospitals,Geneva,Switzerland LaurentPoirel ServicedeBactériologie-Virologie,INSERMU914«Emerging ResistancetoAntibiotics»,HôpitaldeBicêtre,FacultédeMédecineet UniversitéParis-Sud,94275K.-Bicêtre,France GesueleRenzi AbdessalamCherkaoui BacteriologyLaboratoryandGenomicResearchLaboratory,Geneva UniversityHospitals,Geneva,Switzerland PatriceNordmann∗ ServicedeBactériologie-Virologie,INSERMU914«Emerging ResistancetoAntibiotics»,HôpitaldeBicêtre,FacultédeMédecineet UniversitéParis-Sud,94275K.-Bicêtre,France
∗Correspondingauthor.Presentaddress:Servicede Bactériologie-Virologie,HôpitaldeBicêtre,78rueduGénéral Leclerc,94275LeKremlin-Bicêtrecedex,France.
Tel.:+33145213632;fax:+33145216340.
E-mailaddress:nordmann.patrice@bct.aphp.fr(P.Nordmann) 6July2012 doi:10.1016/j.ijantimicag.2012.07.003
Lowprevalenceofvancomycinheteroresistanceamong meticillin-resistantStaphylococcusaureuscausingbacteraemia inHongKong
Sir,
Infectionscausedbymeticillin-resistantStaphylococcusaureus (MRSA) with heterogeneous resistance to vancomycin (hVISA) are more likely to fail treatment with vancomycin, leading to persistentbacteraemia,relapseandtheemergenceofvancomycin- intermediate S. aureus (VISA) [1]. This study investigated 249 consecutivebacteraemiaMRSAisolatesrecoveredfrominpatients treatedinfourhealthcaredistricts(designatedA–D)inHongKong in2009.Thehospitalsinthehealthcaredistrictstogetherserved approximatelyone-halfofthe7millionpopulationinHongKong.
Vancomycinminimalinhibitoryconcentrations(MICs)weredeter- mined by the brothmicrodilution method using an arithmetic dilution(0.094,0.125,0.19,0.25, 0.38,0.5,0.75, 1,1.5,2,3and 4mg/L). Qualitycontrolstrains(includingS.aureusATCC29213 and12in-houseMRSAinternalcontrolstrainswithvancomycin MICsof0.5–4mg/L)wereincludedoneachdayoftesting.Antimi- crobial susceptibilitytestingwasperformedbytheClinical and Laboratory StandardsInstitute(CLSI) diskdiffusionmethod[2].
