Antibiotic consumption versus the prevalence of multidrug-resistant Acinetobacter baumannii and Clostridium difficile infections at an ICU from 2014-2015

(1)

ContentslistsavailableatScienceDirect

Journal of Infection and Public Health

jo u r n al ho me p ag e :h t t p : / /w w w . e l s e v i e r . c o m / l o c a t e / j i p h

Antibiotic consumption versus the prevalence of multidrug-resistant Acinetobacter baumannii and Clostridium difﬁcile infections at an ICU from 2014–2015

Grzegorz Ziółkowski

^a

, Iwona Pawłowska

^b

, Lech Krawczyk

^c

, Jadwiga Wojkowska-Mach

^d,∗

aSosnowiecMedicalCollege,Sosnowiec,Poland

bSt.BarbaraSpecializedRegionalHospitalNo.5,DivisionofMicrobiologyandEpidemiology,Sosnowiec,Poland

cMedicalUniversityofSilesia,Katowice,Poland

dJagiellonianUniversityMedicalCollege,ChairofMicrobiology,Krakow,Poland

a r t i c l e i n f o

Articlehistory:

Received28June2017

Receivedinrevisedform12January2018 Accepted21February2018

Keywords:

Acinetobacterbaumannii Hospitalinfections Multidrugresistance Carbapenems Antibioticconsumption Clostridiumdifﬁcile

a b s t r a c t

Background:Acinetobacterbaumanniistrainsarecurrentlythemostcommonlyisolatednon-fermenting rodsatPolishintensivecareunits(ICUs),andtheyarethedominantaetiologicalagentsofpneumonia.This studyaimedtoevaluatetheprevalenceofA.baumanniiisolatedfrompatientswhowerehospitalisedat SosnowiecHospital’sICU.WealsoinvestigatedthedrugsensitivityofA.baumanniiinrelationtoantibiotic consumptionexpressedasthedeﬁneddailydose(DDD)andClostridiumdifﬁcileinfection(CDI).

Methods:Weperformedaretrospective,laboratory-basedstudy,whichcomprisedconsecutive,non- repetitiveA.baumanniiisolatesfrombloodstreaminfectionsandpatientswithpneumoniawhowere hospitalisedfrom2014–2015.

Results:Intheanalysedperiod,187A.baumanniistrainsconstituted13.5%ofallpathogensfromclinical samples.Atotalof76.5%ofthesestrainswereextensivelydrugresistant.ResistanceofA.baumanniito ﬂuoroquinolones,amikacin,andtrimethoprim/sulfamethoxazoleexceeded90%.Atotalof95%ofstrains wereresistanttoimipenemandmeropenem,and100%wereresistanttocephalosporinsandtetracy- clines.Antibioticconsumptionwas191.54DDDfor100patient-days,andthehighestuseofantibiotics involvedampicillinwithsulbactam.ThecumulativeCDIincidenceratewas2.4%.

Conclusions:InourICU,allofthestrainswereextensivelydrugresistantandsensitivetocolistin.Thesig- niﬁcantlyhighconsumptionofcarbapenems,ﬂuoroquinolones,andaminoglycosidesshouldbereduced becausethehighCDIincidenceisprobablyrelatedtoextensiveantibioticconsumption.

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

Abbreviations: ATC, Anatomic-therapeutic-chemical;BAL,Broncho-alveolar lavage;BSI,Bloodstreaminfections;CDI,Clostridiumdifficileinfection;CI,Confidence interval;DDD,Defineddailydose;EARS,AntimicrobialResistanceSurveillance Network;ECDC,EuropeanCentreforDiseasePreventionandControl;EUCAST, EuropeanCommitteeonAntimicrobialSusceptibilityTesting;ICU,Intensivecare unit;KPC,Klebsiellapneumoniaecarbapenemase;MBL,Metallo-␤-lactamases;MDR, Multidrug-resistant;OMP,Outermembraneproteins;OR,Oddsratio;PBP,Penicillin bindingproteins;VAP,Ventilator-associatedpneumonia;XDR,Extensively-drug resistant.

∗ Correspondingauthorat:ChairofMicrobiology,JagiellonianUniversityMedical College,18CzystaStreet,31-121Krakow,Poland.

E-mailaddresses:gziolkowski@wss5.pl(G.Ziółkowski),nc3@wp.pl (I.Pawłowska),lechkraw@onet.pl(L.Krawczyk),mbmach@cyf-kr.edu.pl (J.Wojkowska-Mach).

Introduction

Amonghealthcare-associatedinfections(HAIs)intheintensive careunit(ICU),formsofinfectionsthataredangeroustothelife ofpatientscanbedistinguished,suchaspneumonia,bloodstream infection(BSI),urinarytractinfection,andothers.Theincidenceof HAIsmaybeassociatedwithmanyriskfactors,suchastheuseof invasivediagnosticandtherapeuticprocedures,theenvironment oftreatment(including technologicaladvancement),underlying diseases, and comorbidities, which arethe reasonsfor hospital treatment.Thedifferencesintheincidenceratesuggestdifferences inthecomplexityofHAImonitoringandsurveillancesensitivityin variouscountries,andtheseshouldbemonitoredtosetthecur- rentbenchmarkforthehospitalorunit(e.g.,ICU).Tointroducean internationalbenchmarkonhealthcare-acquiredinfectionsinthe

https://doi.org/10.1016/j.jiph.2018.02.003

1876-0341/©2018TheAuthors.PublishedbyElsevierLimitedonbehalfofKingSaudBinAbdulazizUniversityforHealthSciences.Thisisanopenaccessarticleunderthe CCBY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).

(2)

USA,theresultsofCDC’sNationalHealthcareSafetyNetwork(CDC NHSN)surveillanceshouldbeincluded[1]andtheresultsofdataof lowandmiddleincomecountries,suchasdataofTheInternational NosocomialInfectionControlConsortium(INICC),shouldbecom- mentedon.Unfortunately,althoughdeviceuseinINICCICUswas similartothatreportedfromCDC-NHSNICUs,device-associated HAIinfectionrateswerehigherinINICCICUsthanthosereportedby theCDC-NHSN[2].DataaccordingHAIsincidencefromPolandare alarming.Single-centrestudiesconductedintheICUinWrocław [3]showedthattheincidenceofcatheter-associatedurinarytract infectionwashigherthanthatintheINICCandintheNHSNreport [1,21]andadditionallytheincidenceofventilator-associatedpneumonia(VAP)[4]was10-foldhigherthanthatintheNHSN/CDC report[1].

HAIin ICUshave adverse effects,suchas anextralengthof stayandmortality.DatainPolandshowedthatthelengthofstay ofpatientswithoutHAIswas6.9days,anditwas10.0–15.5days longerforpatientswithHAI[5].HAI-relatedmortality(directly andindirectly)inPolishICUsinmulticentrestudyin2013–14was 10.8%[6]sameasmortalityfoundintheEuropeanCentreforDis- easePreventionandControl(ECDC)reportof2012,wherethemean mortalityaccountedfor15%[7].

Acinetobacterbaumanniistrainsaresomeofthemostimpor- tantopportunisticpathogens,andareresponsibleformostsevere infectionsatICUs.Thesestrainsarecharacterisedbyahighlevel ofresistancetocommonlyusedantibioticsandhaveahighmor- talityrate[8,9].A.baumanniistrainscauseinfections,suchasVAP, surgicalsiteinfections,urinarytractinfections,bacteraemia/sepsis, meningitis, endocarditis,peritonitis,and conjunctival sacinfec- tions[10,11].DatafromPolandshowedthatAcinetobacterspp.are thepredominantmicroorganismsinHAI [5]andpresent aseri- ouschallenge.TheriskfactorsoftheseBSIsmaybeinneoplasms, trauma,surgical procedures, and burns. The sources of bacter- aemiaaremostcommonlyrespiratorytractinfections.Inadults, Acinetobacterspp. may causesurgicalsite infections, leadingto generalisedinfections, suchas sepsis [10]. Antibiotic resistance amongA.baumanniistrainsisrelatedtobeta-lactamaseproduc- tion,penicillin-bindingproteinalterations,permeabilitychanges relatedtooutermembraneproteins,andtoantibioticefﬂux.The genesoftheseenzymesmaybelocatedonplasmids(IMP,VIM enzymes)orchromosomes(OXAenzymes)[10,12].OneAcineto- bacter spp. strain may produce severalbeta-lactamases with a concurrentreduction orchangein outermembraneproteinsor penicillin-bindingproteins.Thisresultsinresistancetomanydrugs fromtheparticularantibioticgroup.Anintensivepharmacologi- caltreatmentofsevereinfectionscausedbyA.baumanniirequires long-termuseofantibioticsandexposespatientstoadverseeffects ofsuchtherapy, suchasanincreasedriskofClostridiumdifﬁcile infection(CDI)[13].

ThisstudyaimedtoevaluatetheprevalenceofA.baumanniiiso- latedfrompatientswhowerehospitalisedatSosnowiecHospital’s ICU.Wealsoinvestigatedthepatients’drugsensitivityinrelationto antibioticconsumptionexpressedasthedeﬁneddailydose(DDD) andCDI.

Materialsandmethods

For the2years of 2014–2015,at theClinical Department of AnaesthesiologyandIntensiveCareof SaintBarbaraSpecialized RegionalHospitalno.5TraumaCentreinSosnowiec,708patients werehospitalised(9688patient-days),withanaverageof13days ofhospitalisation(medianlengthofstay:13;1quartile—13.0;3 quartiles—13.5),andbedoccupancyof0.80.The16-beddepart- mentusedinthisstudyisateachingunitwherecontinuoustraining ofstudentsandresidentsoccurs.

Infections were diagnosed and qualiﬁed according to the ECDCdeﬁnitions.BSIandVAPcaseswereregistered(http://ecdc.

europa.eu/en/publications/Publications/healthcare-associatedinfections-HAI-ICU-protocol.pdf, accessed 23.06.2017). In each case,clinicalsampleswerecollectedformicrobiologicalstudiesto identifytheaetiologicalagentofinfection.BSIwasindicatedbya positivebloodcultureandVAPwasidentiﬁedbybronchoalveolar lavagewith10⁴cfu/ml.Thebacterialstrainswereanalysedatthe DepartmentofMicrobiologyoftheLaboratoryDiagnosticCentre at Saint Barbara Specialized Regional Hospital no.5 — Trauma CentreinSosnowiec.Onlynon-repetitiveisolatesofA.baumannii, excludingstrainsoriginatingfromonepatientorfromthesame infectioncase,wereanalysed.

ThestrainswereidentiﬁedusingBDPhoenixNIDcardsofthe automatedPhoenix100BectonDickinsonDiagnosticSystem(Beck- tonDickinson,Warszawa,Poland)accordingtothemanufacturer’s instructions,withoutmoleculartechniques.

Overall,187strainsofA. baumanniiwereisolated,and these comprised13.54%ofthetotalbacterialisolatesfromclinicalsam- ples among all clinical types of infection in the ICU (Table 1).

Additionally,informationregarding17casesofCDIwasconﬁrmed by a Clostridium difﬁcile A+B cassette test (Stamar, D ˛abrowa- Górnicza,Poland).

Evaluationofdrugsensitivity

SensitivityofA.baumanniitoantimicrobialswasexaminedby theautomatedPhoenix100system.NMIC/ID-204combopanels wereusedtomeasuredrugsensitivity.Thesensitivitytocolistin wasvalidatedwiththeCOLISTINCO256E-test(BioMérieux,Marcy I ´Étoile,France),asperthemanufacturer’sinstructions.Theresults ofdrugsensitivityexaminationswereinterpretedaccordingtothe EuropeanCommitteeonAntimicrobialSusceptibilityTestingcrite- ria[14].

Detectionofthecarbapenemasesmetallo-ˇ-lactamaseand Klebsiellapneumoniaecarbapenemase

Testingfor metallo-␤-lactamase(MBL)wasperformedusing aphenotypicscreeningtestwithEDTA[15].ForphenotypicMBL analyses,BectonDickinsondiscswithimipenem(10␮g)andcef- tazidime(30␮g),andtheMBLinhibitorEDTA(GRASO,Starogard Gda ´nski,Poland)wereused.

For phenotypic screening testsof Klebsiella pneumoniae carbapenemase (KPC), chromogenic media for rapid identification of carbapenem-resistant strains was applied: CHROMagar KPC medium(GRASO,StarogardGda ński,Poland)andmeropenemem discs(10␮g)(BectonDickinson,Sparks,MD,USA)plusboronicacid (GRASO,StarogardGda ński,Poland)[16].

Multidrugresistance

Theresistantandintermediatestrainsweregroupedtogether as drug resistant. Multidrug-resistant strains were deﬁned as not susceptible to one antimicrobial in at least three different antimicrobialclasses.Extensivelydrugresistant(XDR)strainswere deﬁnedassusceptibletonomorethantwoantimicrobialclasses [15,18].

Antibioticconsumption

The aggregatesumof thenumber ofthe deﬁneddaily dose (DDD)accordingtotheATC/DDDsystemoftheWorldHealthOrga- nization(AnatomicalTherapeuticChemical,group“J01”[17]).Only antibioticsfor systemicuseweretakenintoaccount—noanti- fungal(J02),antimycobacterial(J04),orantiviral(J05)drugswere includedintheanalyses.Thedatareferringtousedquantitiesof

(3)

Table1

MicroorganismsisolatedfromclinicalsamplesofICUpatients.

Microorganism Bloodisolates VAPisolates Others Total

N % N % N % N %

Gram-positive 106 60.92 191 28.38 235 44.01 532 38.52

Staphylococcusaureus 8 4.60 55 8.17 18 3.37 81 5.87

Staphylococcuscoagulase-negative 80 45.98 49 7.28 42 7.87 171 12.38

Others 18 10.34 87 12.93 175 32.77 280 20.28

Gram-negative 68 39.08 482 71.62 299 55.99 849 61.48

Acinetobacterbaumannii 17 9.77 130 19.32 40 7.49 187 13.54

Klebsiellaspp. 15 8.62 97 14.41 66 12.36 178 12.89

Escherichiacoli 10 5.75 60 8.92 54 10.11 124 8.98

Pseudomonasaeruginosa 7 4.02 68 10.10 49 9.18 124 8.98

Others 19 10.92 127 18.87 90 16.85 236 17.09

Total 174 673 534 1381

VAP—ventilatorassociatedpneumonia.

Table2

DrugresistanceofAcinetobacterbaumanniistrainsisolatedfromclinicalsamplesofICUpatients.

DrugresistanceofAcinetobacterbaumannii Bloodisolatesn=17 VAPisolatesN=130 Othersn=40 Totaln=187

nR %R nR %R nR %R nR %R

Aminoglycosides

Gentamycin 16 94.12 125 96.15 23 57.50 164 87.70

Tobramycin 11 64.71 117 90.00 38 95.00 166 88.77

Amikacin 14 82.35 124 95.38 40 100.00 178 95.19

Netilmycin 5 29.41 77 59.23 23 57.50 105 56.15

Antipseudomonalcarbapenems

Imipenem 13 76.47 120 92.31 40 100.00 173 92.51

Meropenem 13 76.47 120 92.31 40 100.00 173 92.51

Antipseudomonalﬂuoroquinolones

Ciproﬂoxacin 15 88.24 126 96.92 40 100.00 181 96.79

Levoﬂoxacin 15 88.24 126 96.92 38 95.00 179 95.72

Folatepathwayinhibitors

Trimethoprim/sulfamethoxazole 17 100.00 124 95.38 38 95.00 179 95.72

Polymyxins

Colistin 0 0.00 0 0.00 0 0.00 0 0.00

MDR 4 23.53 5 3.85 1 2.50 10 5.35

XDR 13 76.47 123 94.62 29 72.50 165 88.24

MDRmultidrug-resistantAcinetobacterbaumanniistrains;XDRextensively-drugresistantAcinetobacterbaumanniistrains;VAP—ventilatorassociatedpneumonia.

antibioticsareexpressedintheWHO-recommendeddeﬁneddaily doses(DDDs,accessvalidon27Dec2017:http://www.whocc.no/

atcdddindex/).Theresultsoftheanalysisofusingtheantibiotics areshownusingtheDDD/100patient-daysindex.

Statisticalanalysis

TheprevalenceofA.baumanniiwasdeﬁnedasthenumberofA.

baumanniiisolatesamongallofthebacterialisolatesfromclinical samples.ThecumulativeincidenceofCDIwasdeﬁnedasthenum- berofCDIepisodesdividedbythenumberofpatientsadmittedto thestudiedICU(1/1/2014to12/31/2015).Thedataarepresented asmediansand25th(Q1)and75th(Q3)percentiles.Theoddsratio (OR)and95%conﬁdenceinterval(95%CI)werecalculated.

Ethics

Utilisationofdatacollectedinthisworkforscientiﬁcpurposes wasapprovedbytheBioethicsCommitteeofJagiellonianUniversity MedicalCollege(no.KBET/362/B/2012).Alldataenteredintothe electronicdatabaseandanalysedduringthisstudywerepreviously anonymizedandde-identiﬁed.

Results

WefoundthatthemostcommonisolateswereGram-negative A.baumannii,followedbyKlebsiellaspp.andcoagulase-negative

staphylococci(Table1).A.baumanniiwassigniﬁcantlymorecom- moninVAPcasesthaninBSIcases(19.3%vs.9.8%;OR2.2;95%CI 1.29–3.78)(Table1).

AlloftheA.baumanniistrainsshowed100%sensitivitytocolistin andastrongresistancetootherantibiotics.InVAPcases,thehighest levelofresistancewasobservedamongcephalosporinsandtetra- cyclines(100%),fluoroquinolones(ciprofloxacinandlevofloxacin [96.9%]), aminoglycosides (gentamicin [96.15%]) and amikacin [95.4%]),trimethoprim/sulfamethoxazole(95.4%), andcarbapenems(imipenemandmeropenem[92.3%]).InBSI,thehighestlevel ofresistancewasobservedamongcephalosporinsandtetracyclines (100%),gentamicin(94.1%),fluoroquinolones(ciprofloxacin[88.2%]

andlevoﬂoxacin[88.2%]),andcarbapenems(imipenem[76.47%]

andmeropenem[76.5%]).NoKPCorMBLstrainswereidentiﬁedin thestudyperiod.

XDRphenotypeinfections weredominantinBSI(76.5%) and VAPcases(94.6%).Multidrug-resistantstrainswereisolatedfrom BSIcasesmoreoftenthanfromVAPcases(Table2).

WhenweanalysedantibioticconsumptionattheICUaccord- ing to the ATC codes expressed as DDD/100 patient-days, we observed thehighest usewithinthe penicillingroup(Table3).

Amongthepenicillins,ampicillinwithsulbactamandamoxicillin withclavulanicacidwereusedthemostfrequently.Administra- tionofcarbapenemswasalsohigh,withimipenemusedthemost frequently(Table4).ThecumulativeincidenceofCDIwas2.4%and 10.6/10,000patient-days.

(4)

Table3

UseofantibioticgroupsaccordingtoAnatomic-Therapeutic-Chemical(ATC)codes asper[20].

Antibioticgroups ATCcode DDD DDD/100patient-days

Penicillins J01C 5430 54.7

Carbapenems J01DH 2340 23.6

Sulfonamidesand trimethoprim

J01E 619 6.2

Macrolides, lincosamidesand streptogramins

J01F 1924 19.3

Glycopeptides A07AA

J01XA 1717 17.3

Aminoglycosides J01G 1423 14.3

Cephalosporins J01D 1382 14.0

Otherantimicrobials (metronidazole, colistin,linezolid, rifampicin, nitrofuratoin)

J01X 2156 21.7

Fluoroquinolones J01MA 1413 14.2

Tetracyclines J01A 601 6.0

Total 19005 191.3

ATC—Anatomic-Therapeutic-Chemical;DDD—dailydeﬁneddose.

Discussion

Our study showed a large proportion of Acinetobacter spp.

infectionsamong ICUpatients. Acinetobacterspp.maycomprise 4.1%–19.2%ofallisolatedmicroorganisms[19–21].InVAPcases, accordingtotheECDC,participationofAcinetobacterspp.isgen- erally 4.8%, but may differ between countries (0.7%in Austria and26.2%inRomania)[22].Unfortunately,thereisahighpreva- lence of Acinetobacter spp. infections causing VAP. Similar to multidrugresistanceanalysis,94.6%ofstrainsisolatedfromVAP caseshavebeenclassiﬁedasXDR.AccordingtotheHELICS-ICU report (2004–2005)on BSI, Acinetobacter spp. comprised 2% of infections,andin2012,itwasinvolvedin3.5%ofinfections(0.9%in France,20.2%inRomania)[22].AccordingtotheAmericanSCOPE, thepercentageofthesestrainsinBSIwas1.6%[23].Inourstudy, therateofAcinetobacterspp.infectionwasseveral-foldhigherthan previousstudiesandreached9.77%.Asmanyas76.47%strainshave beenclassiﬁedasXDR.

Over recent years, resistance to A. baumannii hasincreased worldwide,butvariesamongdifferentEuropeancountries,andalso amongdifferentICUs(eveninthesameregion)[24,25].A.bauman- niistrainswiththeXDRphenotypeweredominantinourstudied samples.AnotherPolishstudyconductedin2013showedthatthe percentageofXDRA.baumanniiwas93.9%andwasmostlyfound inBSI[26].

Inourstudy,A.baumanniiwassensitivemostlytocolistin.All of the strains were sensitive, but we found 90% resistance of A.baumanniitoﬂuoroquinolones,amikacin,andtrimethoprimwith sulfamethoxazole,asalsoshownbyGhajavandetal.[12].

The largest hazard for public health is multidrug-resistant strainsinwhichalargeproportionofthemareinsensitivetocar- bapenems(>95%).Resistancetoimipenemandmeropenemismost oftenassociatedwiththepresenceofOXAcarbapenemase[26].One ofthefactorspredisposingtoVAP,causedbymultidrug-resistant Acinetobacterspp.,isprecedingantibiotictherapy,especiallywith thirdgenerationcephalosporinsandcarbapenems[10].Ourstudy showeda highcarbapenemconsumption of2340DDD.Another Polishstudyfrom2003to2005showedthatcarbapenemconsump- tionwas1698.6DDD[20].

Amongtheanalysedstrains, nostrainsproduced carbapenemase(MBLor KPC).EuropeanAntimicrobialResistanceSurveil- lanceNetwork(EARS)datashowedasuddenariseinresistance tocarbapenems, aminoglycosides, and ﬂuoroquinolones among

Table4

DDDforthemostcommonlyusedantibiotics.

Antibioticname ATCcode DDD DDD/100

patient-days Ampicillin+sulbactam J01CR01 2531 25.51 Amoxicillin+clavulanicacid J01CR02 2488 25.08

Vancomycin J01XA01 1717 17.30

Clindamycin J01FF01 1582 15.94

Imipenem+cilastatin J01DH51 1414 14.25

Ciproﬂoxacin J01MA02 1393 14.04

Amikacin J01GB06 988 9.96

Meropenem J01DH02 926 9.33

Colistin J01XB01 757 7.63

Doxycycline J01AA02 601 6.06

ATC—Anatomic-Therapeutic-Chemical;DDD—dailydeﬁneddose.

Acinetobacterspp.throughoutEurope,includingPoland.According totheEuropeanAntimicrobialResistanceSurveillanceNetwork, resistanceto carbapenems of Acinetobacter spp. is dramatically increasing,withan increase inPoland to38.3% in 2012and to 49.7%1yearlater. Resistancetoﬂuoroquinolonesalsoincreased from78.0%in2012to81.4%in2013.Resistancetoaminoglyco- sidesincreasedfrom63.4%in2012to73.8%inthefollowingyear [28].

Thehighlevelofantimicrobialresistanceinthepresentstudyis probablyrelatedtothehighantibioticconsumptioninthestudied ICU.Antibioticadministrationin2012was125DDD/100patient- daysatanICUinEuropeanstudiesand136inPolishstudies[29–31].

InourICU,antibioticconsumptionwas200DDD/100patient-days, whichis50%higherthanthePolishaverage.Ampicillinwithsul- bactamandamoxicillinwithclavulanicwereconsumedthemost frequently.

Anincreasedantibioticusemayleadtoarapidriseinmultidrug resistance, andit alsoexposespatientstoCDI[32–34].Thelat- estdatafromPolandshowedthatnosocomialCDIswereaserious epidemiologicalproblem.TheincidenceratesofCDIoftheentire studiedPolishpopulation,notonlyICUpatients,were6.1and9.6 CDIsper10,000patient-daysin2011and2013,respectively[35].

InanAmericanstudyperformedatanICUfrom1997to1999,the incidenceofCDIwasreportedtobe3.2/1000hospitalisations[36].

OtherICUstudiesfromtheUSAshowedthattheincidenceofCDI rangedfrom0.4to100casesper1000hospitalisations[36,37],and fromSpainitwas3.6/1000hospitalisations[38].Inourstudy,the highincidenceofA.baumanniiintheICUmighthavebeenrelated toselectivepressureofantibiotics.Thispossibilityissupportedby numerousstudiesandameta-analysisbyBauretal.,whoshowed thatimprovingandmeasuringtheappropriateuseofantibiotics (oranantibioticstewardshipprogramme)signiﬁcantlyreducedthe incidenceofCDI[39].Thebeneﬁtsofantibioticstewardshipshould benotonlyareducedincidenceofCDI,butalsoimprovementin theratesofantibioticsusceptibilitytotargetedantibiotics[40].

Conclusions

A.baumanniistrainsarecurrentlythemostcommonlyisolated non-fermentingrodsatPolishICUs,andtheyaredominantaetio- logicalagentsofpneumonia.InourICU,A.baumanniiwassensitive tocolistin. Thisﬁndingsuggests a rationalapproach ofcolistin usefortreatingcarbapenem-resistantA.baumannii.Thehighcon- sumptionofcarbapenems,ﬂuoroquinolones,andaminoglycosides shouldbereduced,whichcouldlowerveryhighCDIincidence.

(5)

Financialsupport

ThisworkhasbeensupportedbyagrantfromtheNationalSci- enceCentre(NoDEC-2012/05/B/NZ7/02880)andunderthegrant fromJagiellonianUniversityMedicalCollegeK/ZDS/007039.

Acknowledgements

The authors thank Mr Maciej Mach for his help in the EnglisheditingandEllenKnapp,PhD,fromEdanzGroup(www.

edanzediting.com/ac)foreditingadraftofthismanuscript.

References

[1]DudeckMA, EdwardsJR,Allen-BridsonK,GrossC, Malpiedi PJ,Peterson KD, etal. National HealthcareSafetyNetwork report,data summaryfor 2013, device-associated module. Am J Infect Control2015;43(3):206–21, http://dx.doi.org/10.1016/j.ajic.2014.11.014.

[2]Rosenthal VD, Al-Abdely HM, El-Kholy AA, AlKhawaja SAA, Leblebi- cioglu H, Mehta Y, et al. International Nosocomial Infection Control Consortium report, data summary of 50 countries for 2010–2015:

device-associated module. Am J Infect Control 2016;44(12):1495–504, http://dx.doi.org/10.1016/j.ajic.2016.08.007.

[3]DuszynskaW,RosenthalVD,SzczesnyA,Wo ´znicaE,UlﬁkK,OstrowskaE,etal.

Urinarytractinfectionsinintensivecareunitpatients–asingle-centre,3-year observationalstudyaccordingtotheINICCproject.AnaesthesiolIntensiveTher 2016;48:1–6.

[4]DuszynskaW,RosenthalVD,DraganB,W ˛egrzynP,MazurA,WojtyraP,etal.

Ventilator-associatedpneumoniamonitoringaccordingtotheINICCprojectat onecentre.AnaesthesiolIntensiveTher2015;47:34–9.

[5]Kubler A,Duszynska W, Rosenthal VD, Fleischer M,Kaiser T,Szewczyk E,et al. Device-associatedinfectionratesandextralength ofstayin an intensive careunitofa universityhospitalinWroclaw,Poland: Interna- tionalNosocomialInfectionControlConsortium’s(INICC)ﬁndings.JCritCare 2012;27(105):e5–10.

[6]WałaszekM,RozanskaA,BulandaM,Wojkowska-MachJ.PolishSocietyof HospitalInfectionsTeam.:Epidemiologyofhealthcare-associatedinfectionsin Polishintensivecare–amulticenterstudybasedonactivesurveillance.Biomed PapMedFacUnivPalacky2018,http://dx.doi.org/10.5507/bp.2018.006.

[7]European Centre for Disease Prevention and Control. Surveillance of healthcare-associatedinfectionsinEurope,2007.Stockholm:ECDC;2012.p.

43–71. http://ecdc.europa.eu/en/publications/Publications/120215SURHAI 2007.pdf[Accessed4October2016].

[8]BoucherH,TalbotGH,BradleyJS,EdwardsJE,GilbertD,RiceLB,etal.Bad bugs,nodrugs:noESKAPE!AnupdatefromtheInfectiousDiseasesSocietyof America.ClinInfectDis2009;48:1–12.

[9]FalagasME,BliziotisIA,SiemposII.AttributablemortalityofA.baumannii infectionsincriticallyillpatients:asystematicreviewofmatchedcohortand case-controlstudies.CritCare2006;10(2).R48.

[10]MaragakisLL,PerlTM.Acinetobacterbaumannii:epidemiology,antimicrobial resistance,andtreatmentoptions.ClinInfectDis2008;46:1254–63.

[11]HoffkenG,NiedermanMS.Nosocomialpenumonia:theimportanceofade- escalatingstrategyforantibiotictreatmentofpenumoniaintheICU.Chest 2002;122:2183–96.

[12]GhajavandH,EsfahaniBN,HavaeiSA,MoghimS,FazeliH.Molecularidentiﬁ- cationofAcinetobacterbaumanniiisolatedfromintensivecareunitsandtheir antimicrobialresistancepatterns.AdvBiomedRes2015;4:110.

[13]GerdingG.GlobalEpidemiologyofClostridiumdifﬁcileinfectionin2010.Infect ControlHospEpidemiol2010;31(S1):S32–4.

[14]EUCASTdocumentshttp://www.eucast.org/astofbacteria/previousversions ofdocuments/clinicalbreakpointsbacteriav5.0[Accessed4October2016].

[15]LeeK,LimYS,YongD,YumJH,ChongY.EvaluationoftheHodgetestand theimipenem-EDTAdouble-disksynergytestfordifferentiatingmetallo-beta- lactamase-producingisolatesofPseudomonasspp.andAcinetobacterspp.JClin Microbiol2003;41(10):4623–9.

[16]Doi Y, PotoskiBA, Adams-Haduch JM,Sidjabat HE, Pasculle AW, Pater- son DL.Simpledisk-basedmethodfor detectionofKlebsiella pneumoniae carbapenemase-type␤-lactamasebyuseofaboronicacidcompound.JClin Microbiol2008;46:4083–6.

[17]WHOCollaboratingCentreforDrugStatisticsMethodology.GuidelinesforATC classiﬁcationandDDDassignment2013.Oslo,2012.http://www.whocc.no/

ﬁlearchive/publications/12013guidelines.pdf[Accessed31December2015].

[18]MagiorakosAP,SrinivasanA,CareyRB,CarmeliY,FalagasME,etal.Mul- tidrugresistant,extensivelydrug-resistantandpan-drug-resistancebacteria:

aninternationalexportproposalforinterminstandarddeﬁnitionsforacquired resistance.ClinMicrobiolInfect2012;18:268–81.

[19]FluitA,VerhoefJ,SchmitzFJ.EuropeanSENTRYParticipants:frequencyofisola- tionandantimicrobialresistanceofgram-negativeandgram-positivebacteria frompatientsinintensivecareunitsof25Europeanuniversityhospitalspartic- ipatingintheEuropeanarmoftheSENTRYantimicrobialsurveillanceprogram 1997–1998.EurJClinMicrobiolInfectDis2001;20(9):617–25.

[20]WroblewskaM,TownerKJ,MarchelH,LuczakM.Emergenceandspreadof carbapenem-resistantstrainsofAcinetobacterbaumanniiinatertiary-carehos- pitalinPoland.ClinMicrobiolInfect2007;13(5):490–6.

[21]VincentJL,RelloJ,MarshallJ,SilvaE,AnzuetoA,MartinCD,etal.International studyoftheprevalenceandoutcomesofinfectioninintensivecareunits.JAMA 2009;302:21(Reprinted).

[22]EuropeanCentre forDiseasePreventionandControl. Antimicrobialresis- tance andhealthcare-associatedinfections2014. Stockholm:ECDC; 2015.

http://ecdc.europa.eu/en/publications/Publications/antimicrobial-resistance- europe-2014.pdf[Accessed4October2016].

[23]Wisplinghhoff H, Bischoff T, Tallent SM,Seifert H, Wenzel RP, Edmond MB.NosocomialbloodstreaminfectionsinUShospitals:analysisof24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 2004;39:309–17.

[24]HanbergerH,ArmanD,GillH,JindrákV,KalenicS,KurczA,etal.Surveillance ofmicrobialresistanceinEuropeanIntensiveCareUnits:aﬁrstreportfrom theCare-ICUprogrammeforimprovedinfectioncontrol.IntensiveCareMed 2009;35:91–100.

[25]DuijnP.RecenttrendsinantibioticresistanceinEuropeanICU.CurrOpCrit Care2011;17:658–65.

[26]ChmielarczykA,Pilarczyk- ˙ZurekM,Kami ´nskaW,PobiegaM,RomaniszynD, ZiółkowskiG,etal.MolecularepidemiologyanddrugresistanceofAcinetobac- terbaumanniiisolatedfromhospitalsinsouthernPoland:ICUasariskfactor forXDRstrains.MicrobialDrugResistance2016;22(4):328–35.

[28]EuropeanCentre forDiseasePreventionandControl. Antimicrobialresis- tancesurveillanceinEurope.AnnualreportoftheEuropeanAntimicrobial ResistanceSurveillanceNetwork(EARS-Net)2013.Stockholm:ECDC;2014.

http://ecdc.europa.eu/en/publications/Publications/antimicrobial-resistance- surveillance-europe-2013.pdf[Accessed4October2016].

[29]MacKenieF,MonnetD,GouldI.Relationshipbetweenthenumberofdiffer- entantibioticsusedandthetotaluseofantibioticsinEuropeanhospitals.J AntimicrobChemother2006;58:657–60.

[30]HanbergerH,ArmanD,GillH,JindrákV,KalenicS,KurczA,etal.Surveillance ofmicrobialresistanceinEuropeanIntensiveCareUnits:aﬁrstreportfrom theCare-ICUprogrammeforimprovedinfectioncontrol.IntensiveCareMed 2009;35:91–100.

[31]EuropeanCentreforDiseasePreventionandControl.Surveillanceofantimi- crobial consumptioninEurope2012.Stockholm:ECDC;2014.http://ecdc.

europa.eu/en/publications/Publications/antimicrobial-consumption-europe- esac-net-2012.pdf[Accessed4October2016].

[32]OwensJrR,DonskeyCJ,GaynesRP,LooVG,MutoCA.Antimicrobial-associated riskfactorsforClostridiumdifﬁcileinfection.ClinInfectDis2008;46(suppl 1):S19–31.

[33]OwensJrR,DonskeyCJ,GaynesRP,LooVG,MutoCA,etal.Antimicrobialassoci- atedriskfactorsforClostridiumdifﬁcileinfections.ClinInfectDis2008;46(Suppl.

1):S19–31.

[34]LawrenceSJ,PuzniakLA,ShadelBN,GillespieKN,KollefMH,MundyLM.

Clostridiumdifﬁcileintheintensivecareunit:epidemiology,costs,andcolo- nizationpressure.InfectControlHospEpidemiol2007;28(2):123–30.

[35]Pituch H, Obuch-Woszczaty ński P,Lachowicz D, Wulta ńska D, Karpi ński P, Młynarczyk G, et al. Hospital-based Clostridium difficile infection surveillance reveals high proportions of PCR ribotypes 027 and 176 in different areas of Poland, 2011 to 2013. Euro Surveill 2015;20(38), http://dx.doi.org/10.2807/1560-7917.ES.2015.20.38.30025.

[36]RotimiVO,JamalWY,MokaddasEM,BrazierJS,JohnyM,DuerdenBI.Preva- lentPCRribotypesofclinicalandenvironmentalstrainsofClostridiumdifﬁcile isolated fromintensive-therapyunitpatientsin Kuwait.JMed Microbiol 2003;52:705–9.

[37]SalvaS,DuranN,RodriguezV,NietoL,SerraJ,RelloJ,etal.Clostridiumdifﬁ- cileintheICU:studyoftheincidence,recurrence,clinicalcharacteristicsand complicationsinaUniversityHospital.MedIntensiva2014;38:140–5.

[38]BradleyJS,NelsonJD,editors.2010–2011Nelson’sPocketBookofPediatric AntomicrobialTherapy.18thed.AmericanAcademyofPediatrics;2010.

[39]Baur D, Gladstone BP, Burkert F, Carrara E, Foschi F, Döbele S, et al.

Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difﬁ- cile infection: a systematic review and meta-analysis. Lancet Infect Dis 2017;16, http://dx.doi.org/10.1016/S1473-3099(17)30325-0, pii:

S1473-3099(17)30325-0.

[40]Barlam TF, Cosgrove SE, Abbo LM, MacDougall C, Schuetz AN, Septi- musEJ,etal.Implementinganantibioticstewardshipprogram:guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis 2016;62:e51–77, http://dx.doi.org/10.1093/cid/ciw118.