Case
Report
Mycobacterium
sherrisii
visceral
disseminated
infection
in
an
African
HIV-infected
adolescent
Francesco
Santoro
a,*
,
Giulia
Santoro
b,
Annalisa
Del
Giudice
b,
Rossella
Perna
b,
Francesco
Iannelli
a,
Maria
Immacolata
Spagnuolo
c,
Eugenia
Bruzzese
c,
Andrea
Lo
Vecchio
c,*
a
LaboratoryofMolecularMicrobiologyandBiotechnology(LAMMB),DepartmentofMedicalBiotechnologies,UniversityofSiena,Siena,Italy
b
UOCMicrobiologyandVirology,OspedalideiColli–AOV.Monaldi,Naples,Italy
c
SectionofPaediatrics,DepartmentofTranslationalMedicalScience,UniversityofNaplesFedericoII,Naples,Italy
1. Introduction
Mycobacterium sherrisii is an opportunistic pathogen mainly associatedwithHIVinfection.1Ithasrecentlybeenrecognizedasa
speciesphylogeneticallyrelatedtoMycobacteriumsimiae.2Afew
casesofdisseminated3orlocalized4infectionhavebeenreported
intheliterature,someoftheminnon-HIVpatients.5
2. Casereport
A 17-year-old, HIV-infected, severely malnourished Eritrean femalewashospitalizedinJanuary2014foraclinicalevaluationin thePaediatricsDepartmentoftheUniversityofNaplesFedericoII. Thegirl had beendiagnosed withHIV in Eritrea and had been startedonantiretroviraltherapy(ART)in2011.In2013shewas admitted to a local hospital in Eritrea withchronic diarrhoea,
abdominaldiscomfort,vomiting,haematemesis,andalow-grade fever.Shewasdiagnosedwithpulmonarytuberculosis(TB)onthe basisofpositiveacid-fastsmearsandwasstartedonathree-drug anti-TB regimen lasting 3 months, followed by rifabutin for another4months.
UponarrivalinItaly,thegirlwasseverelymalnourishedwitha weight of 23.78kg (Z-score 13.3), height of 132cm (Z-score 4.78),bodymassindex(BMI)of13.6kg/m2(BMI-for-agebelow thefirstpercentile),andpubertalretardation(TannerstageB1,G1, PH1).DespitegoodcompliancewithARTandanHIVloadof<40 HIVRNAcopies/ml,herCD4+cellcountwas261/
m
l(12%oftotal lymphocytes),definingAIDS(stageC3accordingtotheUSCenters forDiseaseControlandPreventionpaediatricclassification6).Aphysicalexaminationrevealedreducedlungbasalventilation, increasedrespiratoryfrequency(36breaths/min),anddecreased thoracicexcursion.Theabdomenwastenseandtherewaspainon palpationoftheleftside.ThepresenceofhighC-reactiveprotein (CRP; 88mg/dl), hyperfibrinogenemia (644mg/dl), normocytic anaemia (haemoglobin11.3g/dl), and thepersistent low-grade eveningfever(37.88C)suggestedachronicsystemicinflammatory process.
InternationalJournalofInfectiousDiseases45(2016)43–45
ARTICLE INFO Articlehistory:
Received27November2015
Receivedinrevisedform11January2016 Accepted13February2016
CorrespondingEditor:EskildPetersen, Aarhus,Denmark. Keywords: Mycobacteriumsherrisii Non-tuberculousmycobacteria HIV Abscess Children gyrB SUMMARY
AcaseofvisceraldisseminatedinfectionbyMycobacteriumsherrisiiinanAfricanHIV-infectedadolescent
withmultipleabdominalabscessesisreported.Despitemultipledrugresistancetofirst-lineantibiotics
in vitro, long-term treatment with clarithromycin, moxifloxacin, and clindamycin, together with
appropriateantiretroviraltreatment,resultedinclinicalandradiologicalcureafter19monthsoftherapy
andfollow-up.
ß 2016TheAuthors.PublishedbyElsevierLtdonbehalfofInternationalSocietyforInfectiousDiseases.
ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(
http://creativecommons.org/licenses/by-nc-nd/4.0/).
* Correspondingauthors.
E-mailaddresses:santorof@unisi.it(F.Santoro),andrea.lovecchio@unina.it
(A.LoVecchio).
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.2016.02.011
1201-9712/ß2016TheAuthors.PublishedbyElsevierLtdonbehalfofInternationalSocietyforInfectiousDiseases.ThisisanopenaccessarticleundertheCCBY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).
At admission, the patient’s ART, consisting of lamivudine (4mg/kg twice daily), abacavir (8mg/kg twice daily), and lopinavir/ritonavir (12mg/kg twice daily of lopinavir), was reviewedandadjustedaccordingtoweightvariationandage.
High-resolution computed tomography (CT) of the thorax revealedaparenchymalconsolidationintheupperlobeoftheleft lung.Becauseofthepersistenthaematemesis,anupperendoscopy wasperformedtoruleoutgastrointestinalbleeding.Althoughthe girlhadnocough(hencenohaemoptysis),shereportedfrequent swallowingofmucus,mainlyatnight,strengtheningthesuspicionof arespiratoryaetiologyofthebleeding.InordertoruleoutTB,three consecutivegastricaspirationsandthreesputumsamplesweresent tothemycobacteriologylaboratory.Aninterferon-gammarelease assaywas‘non-reactive’,presumablyduetothelowlymphocyte count. As clinical and anamnestic data suggested a relapse of thepreviousTBinfection,treatmentwasstartedimmediatelywith isoniazid (10mg/kg/day), ethambutol (20mg/kg/day), pyrazina-mide(35mg/kg/day),andrifabutin(10mg/kg/day)inaccordance withrecentguidelines.7
Abdominal ultrasound and subsequent magnetic resonance imagingof theabdomenrevealedthepresenceof encapsulated abscesses of about 2030mm located in the para-aortic and mesentericlymphnodesandalargeabscess(8230mm)inthe leftpsoasmuscle.Thecapsulesoftheabscessesshowedsignificant contrast enhancement (Figure 1). Considering the previous ineffective anti-TBtreatment and thepersistence of symptoms andgeneralinflammationaftertheonsetoftreatment,thepsoas abscesswasdrainedpercutaneouslyandthematerialwassentto themicrobiologylaboratoryforfurtheranalysis.
Acid-faststainswereperformedonallspecimens.Specimens wereinoculatedontobothsolid(Lowenstein–Jensen)andliquid media(BACTECMGIT960).Smearsmadefromgastricaspiration werenegative,whilethesmearfromtheabscessdrainagematerial waspositiveforacid-fastbacilli(>10bacilli/field).Twooutofthree gastricaspirationspecimensyieldedgrowthintheliquidmedium after6and7days,whiletheabscessdrainagematerialgrewon solid medium after 30 days of incubation. Both isolates were identified as M. simiae by GenoType Mycobacterium AS (Hain Lifescience,GmbH,Nehren,Germany).Therapywasthusmodified bytheadditionoforalclarithromycinandthediscontinuationof bothisoniazidandpyrazinamide.
Duringthefirst7daysofthistherapy,thepatientexperienced aninitialimprovement(CRP25mg/dl,fever378C);however,she thenbegantohavehighfeversandanincreaseininflammatory markers.Ultrasoundoftheleftpsoasshowedanincreaseinthe size of the abscesses and therefore a permanent drain was positioned.
Inordertoconfirmtheaetiologicaldiagnosis,PCR amplifica-tionandsequencingofaninternalfragment(964bp)ofthe16S rDNAwasperformedonthetwogastricaspirateisolates.BLAST sequence analysis (http://blast.ncbi.nlm.nih.gov/Blast.cgi) with the16SribosomalRNAsequencedatabaseshowed100%identity with the sequence of M. sherrisii ATCC BAA-832 (GenBank AY353699). Furthermore, a 1282-bp fragment of the gyrase subunit B (gyrB) gene was amplified and sequenced with primersIF882 (50-CAYGCSGGCGGCAAGTTCG-30) andIF883(50
-GCCATCARSACGATCTTGTG-30).Thesequenceshowed92%
iden-tity with the gyrB gene from M. simiae strain KPM 1403 (GenBankAB014182)andwasdepositedatGenBank(accession numberKT182936).Thisconfirmedthe16Ssequencingspecies identification.
Antibiotictherapywasagainmodified,switchingfromoralto intravenousclarithromycinandaddingamikacin(30mg/kg/day),3
andsuccessivelymoxifloxacin(10mg/kg/day)andco-trimoxazole (15mg/kg/day).Duringthefirst10daysofthismultidrugtherapy, thepatientexperiencedageneralimprovement,withresolutionof thefeverandareductionintheinflammatorymarkers.However, thepatientdevelopedpancytopeniaandseverehypoacusis(with auditory brainstem response threshold shifts), thus both co-trimoxazoleandamikacinwerediscontinued.
Inaccordancewiththerecommendationsforthetreatmentof multidrug-resistantmycobacterialinfections,7empirictreatment withlinezolid(20mg/kg/day)wasaddedandtherewasaninitial clinicalimprovementinthefeverandpain.However,duetothe limitedresponsewithregardtoinflammationandtotherelapseof symptoms,linezolidwasdiscontinuedafter18daysoftreatment. Despite the relapsing–remitting pattern, the patient still complained of abdominal pain, fever, and rare episodes of haematemesis.
InApril2014,after3monthsofhospitalizationanddespitethe persistenceofthelow-gradefever,abdominalpain,andlowgrade inflammation(CRP10.7mg/l),thepatientreturnedtoEritreaon
Figure1.Magneticresonanceimagingoftheabdomenbefore(a)andafter(b)intravenousgadoliniumcontrastinjection.Thelargerabscessformationsareindicatedwith arrows.
F.Santoroetal./InternationalJournalofInfectiousDiseases45(2016)43–45 44
ART(lamivudine,abacavir,andlopinavir/r).Atailoredantibiotic therapywasplannedconsistingoforalclindamycin,moxifloxacin, andclarithromycin(switchedtooralafterintravenous adminis-tration),considering(1) theinvitroantimicrobial susceptibility profile(Table1),(2)thesideeffectsshownduringhospitalization, and (3) the availability of drugs in the country of origin. The progressionoftheHIVinfectionwascheckedwith viro-immuno-logicalmarkers,whilethemycobacterialinfectionwasmonitored byperiodicbloodsamplingandCToftheabdomen.
Aslowandprogressiveimprovementwasregisteredafterthe patient’sreturnfromEritrea,withclinicalamelioration, improve-mentsintheabdominaldistensionandpain,andresolutionofthe vomiting,haematemesis,andfeverwithin2monthsofdischarge. An abdominal CT scan performed after 1 year of treatment demonstrated complete resolution of the psoas abscess and a significant reduction in the other abdominal lesions. As of November2015,thegirlwasin goodoverall clinicalcondition, hadgained12kginweight(weight36kg,Z-score4.3)and13cm inheight(height145cm,Z-score2.7),and washavingregular menstrualcycles.
3. Discussion
The diagnosis of non-tuberculousmycobacterial infections is routinely performed with commercial kits, such as GenoType MycobacteriumASorINNOLiPA(Innogenetics,Ghent,Belgium); however,inthecasepresentedhere,thediagnosisofM.sherrisii infectionrequired16SrDNAsequencing.Theantimicrobial suscep-tibilitypatternshowedresistancetomultiplefirst-lineantibiotics, includingmostofthoseusedfortheempiricaltreatmentof non-tuberculous mycobacterial infections(i.e., isoniazid,ethambutol, ciprofloxacin,andlinezolid).Afternumerous antibiotic modifica-tions, a long-term antibiotic regimen including clindamycin, clarithromycin,andmoxifloxacinwasabletocontrol,andappears tohavecured,theinfection.Thiswasevidencedbythesignificant weightgainandpubertaldevelopment.EffectivecontroloftheHIV infection(HIVRNAcopies<40/mlandCD4+18%,435cells/
m
l)was also likely tohave been an important factor in the favourable outcome.Ethicalapproval:Notrequired.Informedconsenttoreportthe clinicaldataanonymouslywasprovidedbythecaregivers.
Conflictofinterest:Theauthorsreportnoconflictofinterest. References
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Table1
InvitroantimicrobialsusceptibilityoftheMycobacteriumsherrisiiisolatea
Antibiotic MIC(mg/ml) Interpretativecategory
Isoniazid 4 -Streptomycin 32 -Ethambutol 16 R Rifampicin 4 R Amikacin 16 S Clarithromycin 4 S Ciprofloxacin 16 R Linezolid 32 R Moxifloxacin 2 S
MIC,minimuminhibitoryconcentration;R,resistant;S,susceptible.
a MICvalueswereinterpretedaccordingtotheClinicalandLaboratoryStandards
Institute(CLSI)criteria.TherearenoCLSIinterpretativecriteriaforisoniazidand streptomycin.
