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Fatal nosocomial meningitis caused by Mycoplasma hominis in an adult patient: case report and review of

the literature

Sophie Reissier, Romain Masson, François Guérin, Gerald Viquesnel, Joëlle Petitjean-Lecherbonnier, Sabine Pereyre, Vincent Cattoir, Christophe Isnard

To cite this version:

Sophie Reissier, Romain Masson, François Guérin, Gerald Viquesnel, Joëlle Petitjean-Lecherbonnier, et al.. Fatal nosocomial meningitis caused by Mycoplasma hominis in an adult patient: case report and review of the literature. International Journal of Infectious Diseases, Elsevier, 2016, 48, pp.81-83.

�10.1016/j.ijid.2016.05.015�. �hal-02632170�

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Case Report

Fatal nosocomial meningitis caused by Mycoplasma hominis in an adult patient: case report and review of the literature

Sophie Reissier

a

, Romain Masson

b

, Franc ¸ois Gue´rin

a

, Ge´rald Viquesnel

b

,

Joe¨lle Petitjean-Lecherbonnier

c

, Sabine Pereyre

d,e

, Vincent Cattoir

a

, Christophe Isnard

a,

*

aDepartmentofMicrobiology,CHUdeCaen,Av.CoˆtedeNacre,14033CaenCedex9,France

bDepartmentofAnaesthesiologyandCriticalCareMedicine,CHUdeCaen,Caen,France

cDepartmentofVirology,CHUdeCaen,Caen,France

dUniversityofBordeaux,INRA,USCEA3671MycoplasmaandChlamydiaInfectionsinHumans,Bordeaux,France

eDepartmentofBacteriology,CHUdeBordeaux,Bordeaux,France

1. Introduction

Mycoplasmahominisisawell-knownbacteriumcolonizingthe genito-urinary tract, especially in sexually active adolescent females. Extragenitalinfections arerare. Todate,only 16cases ofcentralnervoussystem(CNS) infectioncaused byM.hominis have been described since 1950 (Table 1).1–15 A new case of meningitis caused by this bacterium in an adult, following a neurosurgicalprocedure,isreportedhere.

2. Casereport

A39-year-oldmanwithahistoryofuntreatedhypertension, chronic alcoholism, and active smoking was admitted to the emergencydepartmentaftera lossofconsciousnesslinkedtoa history ofa fall. Injuries includeda subarachnoid haemorrhage (FishergradeIII)duetoarupturedpericallosalleftarteryaneurism, which wasembolized whendiagnosed. An externalventricular

drain(EVD)wasplacedandsuprapubiccatheterizationwasalso performed.Ontransfertotheintensivecareunit(ICU),thepatient wasinitiallyafebrile.Neurologicalandrespiratoryfailureoccurred 1weeklater(day8)andthepatientrequiredtrachealintubation.

Antibiotherapy consisting of piperacillin–tazobactam plus line- zolid was given for 3 days, and this was then switched to ceftriaxone plus linezolid due to a suspicion of nosocomial pneumonia. The pneumonia was confirmed by culture of the Combicath, which harboured 104 CFU/ml Streptococcus pneumoniae. Computed tomography (CT) perfusion imaging revealedaperi-aneurysmalhaematomaandspasmsoftheanterior cerebral arteries (ACA) and rightmiddle cerebral artery(MCA), without surgical indication. Arteriography confirmed a severe vasospasmofthebilateralACAanMCA,andendovasculartherapy withmilrinoneandnimodipinewasstarted.

Between days 8 and 12, several febrile episodes occurred despitetheantibioticsprescribed forthesuspectedpneumonia.

Multiplecerebrospinalfluid(CSF)samples(days8,10,11,and12) wereanalyzedandreturnedsterile.Acellcountwasnotperformed because of the haemorrhagic nature of the samples; direct examination was also negative. On day 13, in view of this presentation of aseptic meningitis, the patient was started on InternationalJournalofInfectiousDiseases48(2016)81–83

ARTICLE INFO Articlehistory:

Received25March2016

Receivedinrevisedform12May2016 Accepted12May2016

CorrespondingEditor:EskildPetersen, Aarhus,Denmark.

Keywords:

Mycoplasmahominis Meningitis Nosocomial

Centralnervoussystem Molecularidentification

SUMMARY

MeningitisduetoMycoplasmahominisinadultsisrarelydescribed,withonlythreecaseshavingbeen reportedtodate.Acaseoffatalmeningitisina39-year-oldpatientafteraneurosurgicalprocedurefora subarachnoidhaemorrhageisreportedherein.Identificationandtreatmentweresignificantlydelayed becauseoftherarityoftheaetiologyanddifficultyidentifyingthisorganismwiththeroutinelyused conventional methods, such as Gram staining and agar growth on standardagar plates.Clinical proceduresandthetreatmentof‘culture-negative’centralnervoussysteminfectionsisarealchallenge forclinicalmicrobiologistsandclinicians,andM.hominishastobeconsideredasapotential,although veryuncommon,pathogen.

ß2016TheAuthor(s).PublishedbyElsevierLtdonbehalfofInternationalSocietyforInfectiousDiseases.

ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by- nc-nd/4.0/).

* Correspondingauthor.Tel.:+33231063327;fax:+33231064573.

E-mailaddress:isnard-c@chu-caen.fr(C.Isnard).

ContentslistsavailableatScienceDirect

International Journal of Infectious Diseases

j o urn a l hom e pa ge : ww w. e l s e v i e r. c om/ l o ca t e / i j i d

http://dx.doi.org/10.1016/j.ijid.2016.05.015

1201-9712/ß2016TheAuthor(s).PublishedbyElsevierLtdonbehalfofInternationalSocietyforInfectiousDiseases.ThisisanopenaccessarticleundertheCCBY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).

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treatmentwithmeropenemplusvancomycinfor14daysandthe EVDwaschanged.AnalysisoftheCSFsamplescollectedondays 16,17,and20showedadecreaseintheleukocytecount(2.3,0.53, and 0.33109/l, respectively)and all bacterialcultures of CSF samplesremainedsterile.

Follow-upimagingonday21showedmoderatehydrocephaly withischemicareasinbothterritoriesoftheACA.Sedationofthe patientwasthen ended,anda neurologicalevaluationrevealed tetraparesisandvaryingresponsestosimpleorders.AnewEVD wasplacedonday22tomanagethehydrocephaly.CSFcollected duringtheprocedurewasstillabnormal(0.74109leukocytes/l with94% neutrophils).Atthesametime, serologicaltesting for HIV,hepatitisCvirus,andhepatitisBviruswasdone;alltestswere negative.Cytomegalovirus(CMV)serologyintheCSFwaspositive forIgGand IgMsuggestingreactivation intheCSF.Mycological cultureswereallnegative,includingthoseforCryptococcus.PCRof CSFsamplesformycobacterialinfections,Mycoplasmapneumoniae, Chlamydiapneumoniae,CMV,herpessimplexvirus,varicellazoster virus,andenteroviruswerealsonegative.Nevertheless,duetothe presenceoftinymicrocoloniesonbloodagarplates,16SrRNAgene sequencingwas performed directly from thecolonies. The CSF sampleobtainedonday33waspositiveforMycoplasmahominisby quantitativereal-timePCR(yidCgene)16.

Selective agar for M. hominis (A7 Mycoplasma; bioMe´rieux, Marcyl’Etoile,France)wasusedtocultureaCSFsampleandwas positive,showingthetypical‘friedegg’colonies.Anantibiogram performed using a Mycofast RevolutioN kit (Elitech, Puteaux, France) revealed sensitivity to clindamycin, tetracycline, levo- floxacin,andmoxifloxacin andconfirmedintrinsicresistance to erythromycin. All CSF samples from day 22 to day 34 were recoveredand cultured on specific agar plates for Mycoplasma spp. All of these specimens were positive for M.

hominis. Interestingly, identification by matrix-assisted laser desorption/ionizationtime-of-flight massspectrometry(MALDI- TOFMS)wasnotpossible,evenafteracetonitrileextraction.

Oncethediagnosishadbeenmade,moxifloxacinwasaddedto theother antibiotics from day 34 today 49. Three days after introducing the treatment, the patient’s neurological status

declined.Magneticresonanceimaging(MRI) performedtheday aftershowedcorticallaminarnecrosisassociatedwithtetraven- tricular hydrocephaly. Due to the lack of improvement, the patient’s critical condition, and the severe irreversible lesions, theethicsstaffdecidedtolimitfurthertherapeuticproceduresand thepatientdiedonday80.

3. Discussion

M. hominis is found in the human urogenital tract with a prevalence of approximately 15% and is mainly involved in urogenital infections and neonatal infections. Nevertheless, the pathogenicityofthisspeciesmaybedifficulttoassessbecauseitis often present as a commensal organism. Although rare, extra- genital infections have beendescribed, such as bone and joint infectionsandCNSinfections,especiallyinnewborninfantsand immunocompromised patients. In adults, only16 cases ofCNS infectionhavebeendescribedsince1950,with13casesofbrain abscesses and three cases of meningitis (two postoperative infections and one secondary to septic arthritis)11–13,15 (Table1).Inallcasesdescribed,thepatientspresentedcontribut- ingfactorssuchasaheadtrauma,neurosurgery,orgenitourinary ordeliverymanipulations.Inthecasepresentedhere,thepatient sufferedasubarachnoidhaemorrhageandhadaurinarycatheter, two important comorbidities for CNS infections caused by M.

hominis.

ThelackofbacterialcellwallcomponentsmakesM.hominis undetectablebyGramstaining.Bacterialcultureisveryslow(2–5 days)andrequiresspecificagarplatesenrichedwitharginine.On appropriatemedia,M.hominisproducestypicalfriedeggshaped colonies.Cultureisthegoldstandardprocedureforidentification, nevertheless only a few microbiology laboratories have used specific agar for M. hominis in meningitis cases. Blood culture systems appear to be ineffective for the detection of M.

hominis. Studies have reported identification using MALDI-TOF MS,14andmoleculartechniquessuchas16SrRNAgenesequencing andreal-timePCR.11,16Inthecasereportedhere,identificationof M.hominis wasperformed usingTaqMan quantitativereal-time Table1

CasesofCNSinfectioncausedbyMycoplasmahominisinadultsreportedintheliterature1–15

Case Age(years)/sex Sample Diagnosis Diagnosistechnique(s) Author,year

1 20/M Abscess PTbrainabscess Culture Paineetal.,1950

2 29/M Abscess PObrainabscess Culture Payanetal.,1981

3 76/M CSF POmeningitis Culture McMahonetal.,1990

4 18/F CSF POmeningitis Culture CohenandKubak,1997

5 22/F Abscess PPbrainabscess ELISA Zhengetal.,1997

6 40/F Abscess Brainabscess 16SrDNA

Culture

Houseetal.,2003

7 17/F CSF,blood PPbrainabscess Culture Douglasetal.,2003

8 40/M Abscess PTbrainabscess 16SrDNA Kupilaetal.,2006

9 48/M CSF,bonegraft PObrainabscess 16SrDNA

Culture

McCarthyandLooke,2008

10 17/F Abscess,softtissues PObrainabscess Culture McCarthyandLooke,2008

11 41/F Abscess Postabortionbrainabscess 16SrRNA AlMasalmaetal.,2011

12 48/F CSF PObrainabscess 16SrRNA

Culture

Leeetal.,2012

13 26/M CSF Meningitis(secondarytoSA) 16SrDNA

Culture

Satoetal.,2012

14 40/M Abscess PTbrainabscess 16SrDNA

Culture

Henao-Martı´nezetal.,2012

15 43/M Intracranialpressure

sensor

Subduralhematoma Culture

MALDI-TOFMS

Pailhorie`setal.,2014

16 21/F Biopsy Spinalabscessafterperidural

procedure

16SrDNA Culture

Hosetal.,2015

17 39/M CSF POmeningitis SpecificqPCR

Culture

Thiscase,2016

CSF,cerebrospinalfluid;CNS,centralnervoussystem;F,female;M,male;MALDI-TOFMS,matrix-assistedlaserdesorption/ionizationtime-of-flightmassspectrometry;PO, postoperative;PP,post-partum;PT,post-traumatic;SA,septicarthritis.

S.Reissieretal./InternationalJournalofInfectiousDiseases48(2016)81–83 82

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PCR and specific agar culture. Interestingly, MALDI-TOF MS (Microflex; Bruker, Bremen, Germany) failed to identify M.

hominis.Itisassumedthatgrowthonbloodagarplatesdoesnot allowidentification,becauseallpreviouscasesthatwereidentified byMALDI-TOFMSreportedgrowthonspecificagar,suchasPPLO mediumandHayflickarginine medium.14Moreover,M.hominis spectrausedforMALDI-TOFidentificationwerenotavailableinthe initialBrukersoftwarelibrary.

M.hominis is intrinsically resistanttoa variety of antibiotic classes such as

b

-lactams, glycopeptides, fosfomycin, sulfona- mides,and macrolides.The major antibiotics active against M.

hominisarethetetracyclines,lincosamides,chloramphenicol,and fluoroquinolones.Inthecasepresentedhere,anantibiogramwas performedandrevealedsusceptibilitytoclindamycin,tetracycline, levofloxacin,andmoxifloxacin.AsM.hominisCNSinfectionsmay result in aseptic lymphocytic meningitis syndrome, which is treatedempiricallywithantibioticsactiveonthebacterialcellwall suchasthird-generationcephalosporins,thechangetoappropriate targetedtherapeuticmanagementcouldbedelayedsignificantly.

In this case, the patient received appropriate antibiotherapy 24 days after the onset of symptoms. Fluoroquinolones (e.g., moxifloxacinandlevofloxacin)havebeendescribedasproviding effectivetherapywithsignificantCNSpenetration,9,11andtheside effects areless significantcompared tothose ofother effective therapeuticssuchaschloramphenicolorcyclins.

Inconclusion, this case ofM.hominis meningitis showsthat empiricalantibiotictreatmentfornosocomialasepticmeningitis hasahighchanceoffailureandthatthenewtechniqueofreal-time PCRappearstobemoreeffectiveandfasterthanroutinebacterial culture.Despitethedeathofthispatient,moxifloxacincouldbe considered effective against M. hominis, as hasbeen described previouslyinotherstudies.M.hominisshouldbeconsideredasa causativeagentofCNSinfectionafterneurosurgicalprocedures, especiallyifthereisnorapidresponsetoantimicrobialtherapyand routinecultureofCSFsamplesremainsnegative.

Conflictofinterest:Theauthorsdeclarethattheyhavenoconflict ofinterest.

References

1.PaineJrTJ,MurrayR,PerlmutterI,FinlandM.Brainabscessandmeningitis associatedwithpleuropneumonia-likeorganism:clinicalandbacteriological observationsinacasewithrecovery.AnnInternMed1950;32:554–62.

2.Payan DG,SeigalN,MadoffS.Infectionofabrainabscess ofMycoplasma hominis.JClinMicrobiol1981;14:571–3.

3.McMahonDK,DummerJS,PasculleAW,CassellG.ExtragenitalMycoplasma hominisinfectionsinadults.AmJMed1990;89:275–81.

4.CohenM,KubakB.Mycoplasmahominismeningitiscomplicatingheadtrauma:

casereportandreview.ClinInfectDis1997;24:272–3.

5.Zheng X,Olson DA,TullyJG,WatsonHL,CassellGH,GustafsonDR,etal.

Isolation of Mycoplasma hominis from a brain abscess. J Clin Microbiol 1997;35:992–4.

6.HouseP,DunnJ,CarrollK,MacDonaldJ.Seedingofacavernousangiomawith Mycoplasmahominis:casereport.Neurosurgery2003;53:749–52.discussion 752–7.

7. DouglasMW,FisherDA,LumGD,RoyJ.Mycoplasmahominisinfectionofa subduralhaematomaintheperipartumperiod.Pathology(Phila)2003;35:

452–4.

8.KupilaL,Rantakokko-JalavaK,JalavaJ,PeltonenR,MarttilaRJ,KotilainenE,etal.

BrainabscesscausedbyMycoplasmahominis:aclinicallyrecognizableentity?

EurJNeurol2006;13:550–1.

9.McCarthyKL,LookeDF.Successfultreatmentofpost-neurosurgicalintracranial Mycoplasmahominisinfectionusinggatifloxacin.JInfect2008;57:344–6.

10.AlMasalmaM,DrancourtM,DufourH,RaoultD,FournierPE.Mycoplasma hominisbrainabscessfollowinguteruscurettage:acasereport.JMedCaseRep 2011;5:278.

11.LeeEH,WinterHL,vanDijlJM,MetzemaekersJD,ArendsJP.Diagnosisand antimicrobialtherapyofMycoplasmahominismeningitisinadults.IntJMed Microbiol2012;302:289–92.

12. SatoH,IinoN,OhashiR,SaekiT,ItoT,SaitoM,etal.Hypogammaglobu- linemicpatientwithpolyarthritismimickingrheumatoidarthritisfinally diagnosedassepticarthritis caused by Mycoplasma hominis. Intern Med 2012;51:425–9.

13.Henao-Martı´nezAF,YoungH,Nardi-KorverJJ,BurmanW.Mycoplasmahominis brainabscesspresentingafteraheadtrauma:acasereport.JMedCaseRep 2012;6:253.

14.Pailhorie`sH,RabierV,EveillardM,MahazaC,Joly-GuillouML,ChennebaultJM, etal.AcasereportofMycoplasmahominisbrainabscessidentifiedbyMALDI- TOFmassspectrometry.IntJInfectDis2014;29:166–8.

15.HosNJ,BauerC,LiebigT,PlumG,SeifertH,HamplJ.Autoinfectionasacauseof postpartumsubduralempyemaduetoMycoplasmahominis.Infection2015;43:

241–4.

16.Fe´randonC, Peuchant O,JanisC, Benard A,RenaudinH,PereyreS, etal.

Developmentofareal-timePCRtargetingtheyidCgeneforthedetectionof Mycoplasmahominisandcomparisonwithquantitativeculture.ClinMicrobiol Infect2011;17:155–9.

S.Reissieretal./InternationalJournalofInfectiousDiseases48(2016)81–83 83

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