Case
Report
Mycobacterium
chelonae,
an
‘atypical’
cause
of
an
LVAD
driveline
infection
Stefan
Roest
a,1,
Hannelore
I.
Bax
b,c,1,
Nelianne
J.
Verkaik
b,
Jasper
J.
Brugts
a,
Alina
A.
Constantinescu
a,
Chantal
C.
de
Bakker
a,
Ozcan
Birim
d,
Kadir
Caliskan
a,
Olivier
C.
Manintveld
a,*
a
DepartmentofCardiology,ThoraxCentre,ErasmusMC,UniversityMedicalCentreRotterdam,Rotterdam,TheNetherlands
b
DepartmentofMedicalMicrobiologyandInfectiousDiseases,ErasmusMC,UniversityMedicalCentreRotterdam,Rotterdam,TheNetherlands
c
DepartmentofInternalMedicine,DivisionofInfectiousDiseases,ErasmusMC,UniversityMedicalCentreRotterdam,Rotterdam,TheNetherlands
d
DepartmentofCardio-ThoracicSurgery,ThoraxCentre,ErasmusMC,UniversityMedicalCentreRotterdam,Rotterdam,TheNetherlands
ARTICLE INFO Articlehistory:
Received11December2019
Receivedinrevisedform27December2019 Accepted2January2020
Keywords: Drivelineinfection Leftventricularassistdevice Mycobacteriumchelonae
ABSTRACT
Wedescribethefirstpatientwithaleftventricularassistdevice(LVAD)drivelineinfectioncausedby Mycobacteriumchelonaepresentingwithpersistentinfectiondespiteconventionalantibiotics.Treatment wassuccessfulwithsurgicaldebridement,drivelineexitrelocation,anda4-monthperiodofantibiotics. Inthecaseofaculture-negativeLVADdrivelineinfection, non-tuberculousmycobacteriashouldbe considered.Thiscaseillustratesthatmultidisciplinarycollaborationisessentialinprovidingoptimalcare forLVADpatients.
©2020TheAuthors.PublishedbyElsevierLtdonbehalfofInternationalSocietyforInfectiousDiseases. ThisisanopenaccessarticleundertheCCBY-NC-NDlicense( http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction
Inaselectedgroupofpatientswithend-stageheartfailure,a leftventricularassistdevice(LVAD)isimplanted.Thenumberof LVADimplantationsisrisingrapidly (deByetal.,2018;Kormos etal.,2019).Oneofthemostcommoncomplicationsisadriveline infection.Theincidenceof LVAD-associatedinfection(including drivelineinfection) is around28% in the first12 months post-implantation (de By et al., 2018; Kormos et al., 2019). Early diagnosis and appropriate treatment is important in order to preventanascendinginfection,includingLVADpumpinfections, whichareassociatedwithincreasedmorbidityandmortality(de Byetal.,2018;Kormosetal.,2019;Simeonetal.,2017).Thisreport describes the case of a patient with a rare cause of an LVAD drivelineinfection.
Casereport
A 56-year-old Caucasian male with a history of ischemic cardiomyopathy, diabetes, and an LVAD (HeartMate II, Abbott)
since2015asabridgetotransplant,presentedattheoutpatient clinicwithpainandapurulentdischargeatthedrivelineexit3.5 yearspost-LVADimplantation.Therewasnofeverorredness,and hisC-reactiveprotein(CRP)levelwaslowat0.6mg/l.Thepatient was treated with oral levofloxacin 500 mg twicedaily after a bacterialculture of thewound fluid was obtained. Asa conse-quence,hewasdeemednoteligibleforhearttransplantationat thattime.
Twoweekslater,thepatientreturnedtotheoutpatientclinic with a persistent purulent discharge from the driveline exit withoutsystemicsymptomsandwithnegativebacterialcultures. Thepatientwasadmittedandtreatedwithintravenousantibiotics. Bacterial,mycobacterial, andfungal cultureswereobtainedand incubated for a prolonged period of time (14 days) for the identification of potential fastidious and/or slowly growing microorganisms.Anultrasoundwasperformed,demonstratinga fluid collection around the driveline over a length of 15 cm. Subsequently,apositronemissiontomography–computed tomog-raphy(PET-CT)scanwasperformedtoevaluatetheextentofthe infection(Akinetal.,2018)andshoweduptakeinthe subcutane-ous tissuesurroundingthe LVADdrivelinecompatiblewiththe ultrasoundfindings(Figure1A).Sinceregularmicrobialcultures remainednegative,thepatientwasdischargedwithoutantibiotics. After6days,routinebacterialculturesbecamepositive(Figure 1B).Matrix-assisted laserdesorption/ionization (MALDI) identi-fiedMycobacteriumchelonae, and acid-fast stainingshowedthe
* Correspondingauthorat:DepartmentofCardiology,ThoraxCentre,Erasmus MC,UniversityMedicalCentreRotterdam,RoomRg-431,DoctorMolewaterplein40, 3015GD,Rotterdam,TheNetherlands.
E-mailaddress:o.manintveld@erasmusmc.nl(O.C. Manintveld).
1
StefanRoestandHanneloreI.Baxcontributedequallytothismanuscript.
https://doi.org/10.1016/j.ijid.2020.01.002
1201-9712/©2020TheAuthors.PublishedbyElsevierLtdonbehalfofInternationalSocietyforInfectiousDiseases.ThisisanopenaccessarticleundertheCCBY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).
InternationalJournalofInfectiousDiseases92(2020)127–129
ContentslistsavailableatScienceDirect
International
Journal
of
Infectious
Diseases
presenceofmycobacteria(Figure1C).Reverselineblot hybridiza-tionconfirmedthe MALDIfindings, showinga bandingpattern fittingMycobacteriumchelonae/Mycobacteriumabscessuscomplex/ Mycobacterium immunogenum. Further molecular identification with partial gene sequencing of the 16S–23S rRNA internal transcribedspacer(ITS)regionconfirmedM.chelonaeasthecause ofthedrivelineinfection.Thepatientwasreadmittedandstarted on imipenem 500 mg four times daily intravenously and clarithromycin500mgtwicedailyorally,basedonsusceptibility results. After 2 weeks of adequate antimicrobial treatment, surgical debridement was performed with relocation of the drivelineexittotherightsideoftheabdomen.Negativepressure wound therapy (vacuum-assisted closure) was initiated at the locationoftheold,infectedexitsite(Figure1D,E).
After surgicalexploration,imipenemandclarithromycinwere continuedforoneadditionalweek,afterwhichclarithromycinwas combinedwith doxycycline100mg twicedailyorally. Thetotal durationofantibiotictherapywas4months.Todate(8.5months afterstoppingantibiotics),noinfectionrecurrencehasoccurredand thepatientisconsideredeligibleforhearttransplantationagain. Discussion
LVAD-associated infections are serious infections associated withhighmorbidityandmortality(deByetal.,2018;Kormosetal., 2019; Simeon et al., 2017). LVAD-associated infections can be dividedintodrivelineinfectionsandascendingorpumpinfections. Early diagnosis is important in order to initiate appropriate antimicrobialtherapy withor without surgical debridement to prevent disease progression. Causative pathogens of
LVAD-associated infections are mainly Staphylococcus aureus and coagulase-negative staphylococci, which cause approximately 50%ofinfections,butPseudomonasaeruginosaand Enterobacter-iaceae infectionshavealsobeendescribed (Simeonet al.,2017; Nienaberetal.,2013;Kusneetal.,2017).LVADinfectionscausedby non-tuberculousmycobacteria(NTM)areextremelyrare.Recently, NunezBretonetal.reportedtwocasesofdrivelineinfectioncaused by M. abscessus (Nunez Breton et al., 2018). Mycobacterium chimaera was reported in two patients in the context of a worldwide outbreak of infected heater cooler units (Balsam et al., 2017).Here, we describe the first patientwith an LVAD drivelineinfectioncausedbyM.chelonae.
NTMare ubiquitous environmental organisms found in soil, dust, and water. Together with M. abscessus complex and Mycobacteriumfortuitum,M.chelonaeisthemostclinicallyrelevant specieswithinthegroupofrapidlygrowingNTM(RGM).RGMare characterizedbytheabilitytogrowonsolidculturemediawithin sevendays,asopposedtotheslowlygrowingNTM,whichusually require more than seven days for growth. In general, it is recommendedthatculturesareobtainedinspecificliquidmedia aswellassolidmediawhenthereisaclinicalsuspicionofNTM infection(Griffithetal.,2007).Furthermore,itis recommended that low temperature settings are used, as for several NTM, includingM.chelonae,theoptimal growthtemperatureis30C. Interestingly,inourcase,cultureofthepusfromtheexitsiteon routinebacterialmediumwaspositiveondaysix,whiletheliquid and solid cultures on specific mycobacterial culture media remained negative. This might be due to the decontamination procedure,whichisroutinelyperformedwhennon-sterile speci-mens arepreparedfor mycobacterialdiagnostics. Althoughthis
Figure1.(A)TransversePET-CTviewshowingclear18F-FDGuptakeinthesubcutaneoustissuesurroundingthedriveline.(B)GrowthofMycobacteriumchelonaeonchocolate
agar.(C)Acid-fastacidstainingshowingthepresenceofmycobacteria.(D)Drivelinerelocationprocedure;theasterisk(*)markstheinfectedpartoftheLVADdriveline.(E) Negativepressurewoundtherapyafterdrivelinerelocation.
procedure is important for reducing contamination with other microorganisms,itmayhamperthedetectionofNTMandRGMin particular (Griffithet al., 2007).Therefore, includingprolonged incubationonnon-specificbacterialculturemediamightincrease thedetectionrateofNTM,aswasthecaseforourpatient.Oncea mycobacterialcultureispositive,properspeciesidentificationis crucial,sincesusceptibilityandoptimaltreatmentregimensdiffer betweendifferentNTMand betweendifferentRGM.Ingeneral, treatmentrequiresacombination of antibioticagentsbased on susceptibilityresultsforatleastfourmonthsinthecaseofskinand soft tissue infections (Griffith et al., 2007). Our patient was successfully treated with a 4-month combination antibiotic regimen, surgical debridement, and driveline relocation. Since NTMincludingRGMhavethetendencytoformbiofilms,removing theforeignmaterialin thecase ofNTMinfectionsofprosthetic materialseemsprudentwheneverfeasible(Sousaetal.,2015).
MeasurestopreventtherecurrenceofNTMinfectioncouldnot beestablished,asspecificriskfactors(e.g.,hot tubexposureor saunavisits)werenotidentified.Furthermore,suchexposuresare notallowedinthispatientpopulation.
In conclusion, in patients with an LVAD driveline infection unresponsivetoconventionalantibioticregimensandwithnegative bacterialculturesonnon-selectiveculturemedia,NTMandRGMin particularshouldbeconsideredasacause.Furthermore,theuseof selective culture media including prolonged incubation in non-selectiveculturemediaatdifferenttemperaturesmightincreasethe yield.Thecombinationofprolongedantibiotictherapyandsurgical debridementanddrivelinerelocationseemsaprudentapproach. Nevertheless,amultidisciplinaryapproachshouldbeusedineach casetodeterminetheoptimalmanagement of LVAD-associated NTM infections.
Funding
Noneoftheauthorsreceivedfundingforthiscasereport.
Ethicalapproval
Noethicalapprovalwasneeded.Writtenconsentwassignedby thepatient.
Conflictofinterest
Allauthorsdeclarenoconflictofinterest. References
AkinS,MuslemR,ConstantinescuAA,ManintveldOC,BirimO,BrugtsJJ,etal. 18F-FDG PET/CT in the diagnosis and management of continuous flow left ventricularassistdeviceinfections:acaseseriesandreviewoftheliterature. AsaioJ2018;64:e11–9.
Balsam LB,LouieE, HillF,Levine J,Phillips MS.Mycobacterium chimaeraleft ventricularassistdeviceinfections.JCardSurg2017;32:402–4.
deByT,MohacsiP,GahlB,ZittermannA,KrabatschT,GustafssonF,etal.The EuropeanRegistryforPatientswithMechanicalCirculatorySupport (EURO-MACS) of the EuropeanAssociation for Cardio-Thoracic Surgery (EACTS): secondreport.EurJCardiothoracSurg2018;53:309–16.
GriffithDE,AksamitT,Brown-ElliottBA,CatanzaroA,DaleyC,GordinF,etal.An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007;175:367–416.
KormosRL,CowgerJ,PaganiFD,TeutebergJJ,GoldsteinDJ,JacobsJP,etal.The Society of Thoracic Surgeons Intermacsdatabase annual report: evolving indications,outcomes,andscientificpartnerships. JHeartLungTransplant 2019;38:114–26.
KusneS,MooneyM,Danziger-IsakovL,KaanA,LundLH,LysterH,etal.AnISHLT consensusdocumentforpreventionandmanagementstrategiesformechanical circulatorysupportinfection.JHeartLungTransplant2017;36:1137–53.
NienaberJJ,KusneS,RiazT,WalkerRC,BaddourLM,WrightAJ,etal.Clinical manifestationsandmanagementofleftventricularassistdevice-associated infections.ClinInfectDis2013;57:1438–48.
NunezBretonJD,HernandezG,SimkinsJ,ChaparroSV.Mycobacteriumabscessusleft ventricleassistdevicedrivelineinfections:anemergingpathogen?.Transpl InfectDis2018;20:e12957.
Simeon S,Flecher E,RevestM,NiculescuM,RousselJC,MichelM,etal.Left ventricularassistdevice-relatedinfections:amulticentricstudy.ClinMicrobiol Infect2017;23:748–51.
SousaS,BandeiraM,CarvalhoPA,DuarteA,JordaoL.Nontuberculousmycobacteria pathogenesisandbiofilmassembly.IntJMycobacteriol2015;4:36–43. S.Roestetal./InternationalJournalofInfectiousDiseases92(2020)127–129 129