brazjinfectdis2020;24(1):89–91
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
Letter
to
the
editor
Septicemia
in
an
immunocompetent
adult
in
the
Czech
Republic
caused
by
Corynebacterium
diphtheriae
nontoxigenic
strain
biotype
mitis:
emergence
of
invasive
cases
in
Western
Europe
DearEditor:
InvasivediseasescausedbyCorynebacteriumdiphtheriaoccur very rarelyand whenthey involve Corynebacterium diphthe-rianontoxigenic strains, they can cause atypical course of thedisease.InthelastyearsseveralarticlesfromPoland,1,2
Germany,3 Czech Republic,4 and France5 have reported
invasivediseases caused byCorynebacteriumdiphtheria non-toxigenicstrainssuggestingaspreadofthesepathogens in WesternEurope(Table1).
Hereinwepresenta30-year-oldmalesoccerplayerwith septicemiaassociatedwithadiagnosisofosteomyelitisofthe pubicsymphysis.Theagent,Corynebacteriumdiphtheriae non-toxigenicstrain,biotypemitis,wasidentifiedbyserialblood cultures.
Previouslyhealthy, the manwas admittedto the Emer-gency Department of Infectious Diseases of the Hospital na Bulovce (Nemocnice na Bulovce) in Prague with fever, headache and groin pain. There was no history of recent tick bites, exposures to sick contacts or animal exposure, illicitdruguse, ortravel outsideCzech Republic.On physi-calexamination,histemperaturewas38.1◦C,bloodpressure 98/50, heart rate 118, and he manifested lower abdomi-naltenderness and pain. There were no further abnormal findings.Laboratoryexaminationshowedelevated inflamma-toryparameters, C reactive protein 159mg/l(normal value <8mg/l).Thewhitebloodcountwas14,200cells/mm3withno
shifttotheleft,thrombocytopenia80×109/L(normalvalue
range150.000–450.000109/L),andcreatinine 140mg/L
(nor-malvaluerange50–90mg/L).Urineanalysiswasnormaland culturenegative;aplainabdominalradiographwasnormal.
Clinicalre-evaluationshowedlocalizedtendernessinthe pubicarea.Inamoredetailedhistory,thepatientreportedthat forthelastyear,hehadtrainedextensivelyasasoccerplayer
(at leastsixtimes aweek).Afterexercisingheexperienced paininthepubicregionandstiffnessfortwodays.A contrast-enhancedabdominalandpelviccomputedtomographywas performedandidentifiedbonydestructiononthemarginsof thesymphysispubis,suggestingosteitispubis.The diagno-sisofsymphysispubisosteomyelitiswasthenconfirmedby magneticresonanceimaging(MRI)ofthepubicregion.
Four blood samples were drawn during the first dayof hospitalizationformicrobiologicalevaluation,andempirical intravenous antibiotictherapy (co-amoxicillinand gentam-icin) wasstarted.Allfourblood cultures(BDBACTECTMFX [Becton Dickinson] bottles)showeda richgrowth of Gram-positiverods,identifiedasCorynebacteriumdiphtheriasensitive to penicillin, oxacillin, ampicillin, cefalotin, erythromycin, clindamycin,cotrimoxazole,tetracycline,andofloxacin.The isolatedstrainwasconfirmedbytheNationalReference Lab-oratoryforPertussisandDiphtheriaoftheNationalInstitute ofPublicHealth,Prague.
ThestrainwasidentifiedasC.diphtheriaebiotypemitis, non-toxigenicstrain.Thestrainwascharacterizedbybiochemical method(APICoryne,BioMérieux,France)andbymass spec-trometry(MALDITOF,BrukerDaltonics,USA).Diphtheriatox genewasscreenedbyreal-timePCR.
Uponresultsoftheantibiogram,antibioticde-escalation toG-penicillinwas adopted.Fever andinflammatoryblood markers normalized after one weekof intravenous antibi-otictreatment,butthesevere painwasstillpresent,which indicatedsurgicalrevisionanddebridementofthepurulent cavityofospubis.Histologicalexaminationofbiopsy speci-mensshowedbonydestruction,osteolysisandfibroticzones withclustersofhistiocyteswithsignsofacuteosteomyelitis, cultivationofexcochleatedbonetissueweresterile.
Postoperative recovery went without any complications andthepatientwasdischargedhomeafter30daysof
hospi-90
braz j infectdis.2020;24(1):89–91Table1–ReportedcasesofCorynebacteriumdiphtheriaenontoxigenicstrainsepticemiainEurope.
Country No.ofpatients Medianage Underlyingconditions Clinicaldiagnosis/source Outcome
Germany 9 40 homelessness,drug
abuse,alcoholabuse
1endocarditis,2 bacteremia,and6 sepsis. 100%survivdewith antibiotictherapy Poland 28 38 smoker, homelessness,drug abuse
28septicemia 100%survivedwith
antibiotictherapy
Czechrepublic 2 32 unidentified 1osteomyelitisand
1endocarditis
100%survivedwith antibiotictherapy
France 7 30 drugabuse,AIDS 1endocarditis 1fatalcase,6
survivedwith antibiotictherapy
talization.Antibiotictreatmentwascontinuedorallyforthree weeks (cotrimoxazole). The patient did well after surgery and had no complications.He was then seen inthe clinic afteronemonth,twomonths,fourmonths,andsixmonths and magnetic resonance imaging (MRI) assessments were performed each time. So far, these measures havecaused himanoticeablereliefandhehassincethenreturnedtohis dailyroutinesdespitesomeoccasionalpain.
According to data from medical databases, this is the second report of septicemia caused by C. diphtheriae non-toxigenic strain in an immunocompetent adult in Czech Republic.
C. diphtheriae nontoxigenic strain can produce atypical
manifestations ofa disease and it is a rare cause of sep-sis in immunocompetent patients because of high rate of immunizationcoverageagainstdiphtheria,asisthecasein the Czech Republic. It isrelatively rare in immunocompe-tentpatients, aswellasingeographic areaswithno cases reported of diphtheria and other C. diphtheriae infections. CasesofsepticemiabyC.diphtherianontoxigenicstrainwere however reported in other European countries, suggesting thatnontoxigenicCorynebacterium diphteriaestrains are suf-ficiently pathogenic tocause disease.Thediagnosis of our patientwassurprisingashedoesnotbelongtoany ofthe mentionedtypicalriskgroups(gynecologicorurologicsurgery, pelvicmalignancy,intravenous drug use, and immunodefi-ciency)andnoconnectionbetweenbacteremia,skinlesions orotherriskfactorswasfound.Thebacteriumwasreportedto havedevelopedresistancetocommonlyusedantibiotics,but fortunately,inourcase,itshowedgoodsensitivitytothese antibiotics.
The pathogenesis of infection caused by nontoxigenic
Corynebacterium diphteriae is unknown and requires
inves-tigation. Weknow that current vaccine against diphtheria containsthetoxoidsoitprotectsonlyagainstthe toxigenic-itybutnotagainsttheinvasivenessofC.diphtheria.Itisthus importantto show that infections connected with C.
diph-theriacan occurinanimmunizedpopulation.Itispossible
that thehigh rate ofimmunization withdiphtheriatoxoid mayplaceselectivepressureonthemicroorganismtodevelop otherpathogenicityfactors.Forthisreason,wemustconsider
thisbacteriumasapotentialpathogeninimmunized popula-tions.
Consent
Writteninformedconsentwasobtainedfromthepatientfor publicationofthiscasereport.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
Acknowledgements
The authors would like to thank Ms Kamila Etchegoyen Rosolová,PhDHeadofCenterforAcademicWritinginPrague, fortherevisionofthemanuscript.
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1.CzajkaU,WiatrzykA,MosiejE,Formi ´nskaK,ZasadaAA. ChangesinMLSTprofilesandbiotypesofCorynebacterium diphtheriaeisolatesfromthediphtheriaoutbreakperiodtothe periodofinvasiveinfectionscausedbynontoxigenicstrainsin Poland(1950-2016).BMCInfectDis.2018;18:121.
2.ZasadaAA.Nontoxigenichighlypathogeniccloneof
Corynebacteriumdiphtheriae,Poland,2004–2012.EmergInfect Dis.2013;19:1870–2.
3.DangelA,BergerA,KonradR,BischoffH,SingA. geographicallydiverseclustersofnontoxigenic
Corynebacteriumdiphtheriaeinfection,Germany,2016-2017. EmergInfectDis.2018;24:1239–45.
4.Je ˇzekP,ZavadilováJ,KolínskáR, ˇSvecP,GuttwirthJ,PetráˇsP. [Corynebacteriumimitansisolatedfrombloodcultureina patientwithsuspectedbacteremia—thefirstisolationfrom humanclinicalmaterialintheCzechRepublic].KlinMikrobiol InfekcLek.2014;20:98–101.
5.Billard-PomaresT,RouyerC,WalewskiV,etal.Diagnosisin Franceofanon-toxigenictoxgene-bearingstrainof
CorynebacteriumdiphtheriaeinayoungmalebackfromSenegal. OpenForumInfectDis.2017;4:ofw271.
brazj infect dis.2020;24(1):89–91
91
RicardoMassmann(Dr.) a,∗,JanaZavadilováb,
JanaDrozenová(Dr.)c,DavidFiksad, DitaSmíˇsková(Dr.)e
aDepartmentofInfectious,ParasiticandTropicDiseasesofthe Hos-pitalNaBulovceandthirdFacultyofMedicine,CharlesUniversityin Prague,CzechRepublic
bHeadoftheNationalReferenceLaboratoryforPertussisand Diph-theria,at the National Institute of Public Health,Prague, Czech Republic
cDepartmentofmicrobiologyoftheHospitalNaBulovce,Prague, CzechRepublic
dStudent ofMedicine attheSecondFacultyofMedicine, Charles UniversityinPrague,Czechrepublic
eDepartmentofInfectious,ParasiticandTropicDiseasesofthe Hos-pitalNaBulovceandSecondFacultyofMedicine,CharlesUniversity inPrague,CzechRepublic
∗Correspondingauthor.
E-mailaddress:ricardo.massmann@bulovka.cz
(R.Massmann).
Availableonline21January2020 1413-8670/
©2020SociedadeBrasileiradeInfectologia.Publishedby ElsevierEspa ˜na,S.L.U.Thisisanopenaccessarticleunder theCCBY-NC-NDlicense(http://creativecommons.org/ licenses/by-nc-nd/4.0/).
