The
Brazilian
Journal
of
INFECTIOUS
DISEASES
w w w . e l s e v i e r . c o m / l o c a t e / b j i d
Case
report
Primary
pyomyositis
and
disseminated
septic
pulmonary
emboli:
a
reactivated
staphylococcal
infection?
Savvoula
Savvidou
a,∗,
Emmanouil
Kalogiannis
a,
Kalliopi
Tsakiri
a,
Maria
Gavra
a,
Afroditi
Tsona
a,ba1stDepartmentofInternalMedicine,“Papageorgiou”GeneralHospitalofThessaloniki,Greece bDepartmentofInfectiousDiseases,AHEPAUniversityHospitalofThessaloniki,Greece
a
r
t
i
c
l
e
i
n
f
o
Articlehistory:
Received7January2014 Accepted18March2014 Availableonline30April2014
Keywords:
Pyomyositis
Staphylococcusaureus
Septicpulmonaryemboli Reactivation
a
b
s
t
r
a
c
t
Staphylococcalpyomyositisisasevereinvasivesofttissueinfectionwithhighmortality ratethatisincreasinglybeingrecognizedevenintemperateclimates.Inmostcases predis-posingfactorsareidentifiedthatincludeeithersourceofskinpenetrationor/andimpaired hostimmunocompetence.Acaseofprimary,community-acquiredpyomyositisoftheleft iliopsoasmuscleina59-year-oldimmunecompetentwoman,whichwascomplicatedwith septicpulmonaryemboliwithin24hafterhospitaladmission,ispresented.Thepatientwas subjectedtoabscessdrainageundercomputedtomographyguidance.Bothpusaspiration andbloodculturesrevealedmethicillin-susceptibleStaphylococcusaureus.Giventhe abso-luteabsenceofpredisposingfactorsandaremotehistoryofstaphylococcalosteomyelitis inthesameanatomicalregion53yearsago,reactivationofastaphylococcalsofttissue infection waspostulated.Systematicreviewoftheliteraturerevealed afewinteresting casesofreactivatedstaphylococcalinfectionafterdecadesoflatency,althoughtheexact pathophysiologicalmechanismsstillneedtobeelucidated.
©2014ElsevierEditoraLtda.Allrightsreserved.
Introduction
Primarypyomyositisisanacutebacterialinfection character-izedbysuppurationwithinlargeskeletalmusclesmanifesting assingleormultipleabscesses.1–3Staphylococcusaureusisthe leadingcausative agent(70–90% ofallcases).Thisinvasive softtissueinfectionwastraditionallyencounteredintropical
∗ Correspondingauthorat:RingRoadN.Efkarpia-Thessaloniki,Thessaloniki,Greece.
E-mailaddress:ssavidou@med.auth.gr(S.Savvidou).
countries,whereconcomitantparasiticinfections,nutritional deficiencies and repetitive lower extremity trauma due to barefootedwalkingmayhavecontributedtoitspathogenesis.1 Intemperateclimates,primarypyomyositishadbeen consid-eredrare,withonly98casesbeingreportedinNorthAmerica from1971to1992.1,2Currently,manycasesarebeingreported worldwide with increasedincidence and high mortalityof around 10%,which may reach 20–60%inshortterms with
http://dx.doi.org/10.1016/j.bjid.2014.03.002
concomitantsepsis.4,5Predisposingfactorsarealmostalways identified, and include either skin penetration (for exam-pleintravenousdruguse,intramuscularinjections,external woundsortrauma,underlyingskindisease)orimpairedhost immunocompetencelikeinfectionwithhuman immunodefi-ciencyvirus,diabetesmellitus,malignancy,connectivetissue diseases,cirrhosis,andimmunosuppressivetherapy.2
Apartfromhostpredisposingfactors,recentadvancesin microbiology have linked invasive soft tissue staphylococ-calinfections with theproduction ofthe Panton–Valentine leukocidin(PVL)toxin.6,7 PVL isa member ofthe synergo-hymenotropic family of exotoxins that destroy leukocytes bycreating pores inthe cell membrane and induce tissue necrosisat the site ofinfection.6 Thistoxin isbelieved to beapotentfactorofvirulencethatcontributessignificantly toincreasedmorbidityandmortalityfromboth methicillin-sensitive(MSSA) and methicillin-resistant S.aureus(MRSA) infections.7 Further studies have also concluded that pro-ductionofPVL isassociatedwithhigherrates ofrecurrent invasivestaphylococcalinfectionsirrespectiveofmethicillin susceptibility.7
In this study we report an interestingcase of primary, community-acquired pyomyositis in a Greek immunecom-petent woman, whichwas rapidly complicatedwith septic pulmonary emboli. Given the absolute absence of pre-disposing factors and a remote history of staphylococcal osteomyelitis in the same anatomical region 53 years ago, reactivationofalatentstaphylococcalsofttissueinfectionwas postulated.Systematicreviewoftheliteraturerevealedafew interestingcasesofreactivatedstaphylococcalinfections,8–14 although the distinct pathophysiological mechanisms still needtobeelucidated.
Case
report
A59-year-oldwoman wasreferred toourhospitalbecause ofhigh temperature,orthostatichypotensionandleftthigh pain.Thepatientwasingoodconditionuntil15daysearlier, whenbackpainreflectingtothelefthipandthighdeveloped. Thepainworsenedgraduallyandtwodaysearlierfever devel-opedaccompaniedwithchills,sweats,andextremefatigue. The patient was temporally relieved from symptoms after receivingantipyreticagents.Thenextdaytemperaturerose to39.5◦C,andthepatientpresentedunbearablethighpain. Shewasfinallyreferredtohospitalforfurtherinvestigation.
Thepatient was a mother and was working as admin-istrativeemployee inanother hospital. Shewas notunder medicationforanyillness.Shementionedasurgical proce-duretotheleftiliumduetostaphylococcalosteomyelitis53 yearsago,attheageofsix.Thepatientreportedno concomi-tant diseases or skin infection, no recent trauma, bites or intramuscularinjections.Thepatientwasasmokeranddid notexercisestrenuously.
On admission, the initial evaluation of the vital signs revealedhypotensionwithsystolicpressureof70mmHgwhile lyingdown, pulse of90 beats per minute,normal temper-ature, and respiratory rate of 15 breaths per minute with oxygen saturation of 96%. Chest X-ray and electrocardio-gram were normal. Clinicalexamination revealed nothigh
Fig.1–Computedtomographyofthelowerabdomen showinganabscesswithintheleftileopsoasmuscle.
sensitivity,butthepatientreportedpaintothelefthipand thighthatwasexacerbatedwhenperformingmovement.The remainingexaminationwasnormal.Initiallaboratory inves-tigationshowedmildlyelevatedwhitebloodcellcountwith neutrophilicpredominance, elevatedinflammatorymarkers (erythrocytesedimentationrate,C-reactiveprotein, procalci-tonin),andonlymildlyelevatedliverenzymesandcreatinine kinase.
Duringthefirsthoursofhospitalization,thepatientwas foundfebrile, and blood cultureswereobtained. Antipyret-icsandempiricalantibioticsagainstbothGram-positiveand Gram-negative microorganisms were administered. Whole body imagingwithcomputed tomography(CT)revealed an abscess within the left iliopsoas muscle (Fig. 1), and few smalleronesinthegluteusmuscle,findingsthatwere con-firmed withmagnetic resonance imaging(MRI) (Fig. 2).No adjacent bonechangeswere detected.Abscesswasdrained underCTguidance,and pusaspirationwassenttoculture. Hours later the patient complained fornew-onset sudden bilateralpleuriticpainwithaccompanieddifficultyin breath-ing.Onauscultation,abnormalbreathsoundswithcrackles and diffuse rhonchi rapidly developed, while hypoxia was
Fig.2–Magneticresonanceimagingoftheabscess (T2-weighted,coronalsection).
Fig.3–Computedtomographyofthethoraxshowing bilaterallunginfiltrates.
observedinoxymetry.NewX-rayshowedbilateralopacities, andnewCTofthethoraxrevealedthepresenceofnodular infiltratesinbothpulmonaryfields(Fig.3).Differential diag-nosisincludedsepticpulmonaryembolioracuterespiratory distresssyndrome(ARDS).Investigationforright-sided endo-carditiswithtrans-eosophagealechocardiogram,aswellasfor thrombosisinthelowerextremitiesprovednegative.Despite allactions,thepatient’shealthwasdeterioratingandhewas broughttotheIntensiveCareUnitduetoacuterespiratory failurerequiringmechanicalventilation.Onthe fifthday, a methicillin-susceptiblestrainofS.aureuswasisolatedfrom bloodandpus,whileculturesofskinandnareswerenegative. Thepatientimprovedunderanti-staphylococcal chemother-apywithlinezolid600mgintravenously,andfourdayslater, shewasweanedfromtheventilator.RepeatedCTwithin15 daysrevealedreductionofthe iliopsoasabscessand ofthe cavitationofthenodularlunginfiltrates(Fig.4),confirming thediagnosisofsepticpulmonaryembolidueto staphylococ-calpyomyositis.Shecontinuedonintravenousantibioticsfor fourweeksfollowedbyfourweeksoforaltreatment.Repeated CTwithinthreemonthsaftertheendoftreatmentshowed completedisappearanceofabscesses.
Fig.4–Highresolutioncomputedtomographyofthe thoraxshowingcavitationofpreviouslesions.
Discussion
Primary pyomyositis is an intriguing disease, as skeletal muscles are intrinsically resistant to bacterial infections.2 However,undercertaincircumstances,S.aureuscan practi-callyinvadeallmusclegroupsbybeingseededfromtransient bacteremia,and withoutanapparent spreadfrom contigu-ousstructures.3Ontheotherhand,whenabscessesextend intomusclesfromadjoiningtissuessuchasboneor subcu-taneoustissues,orarisefromprevioussepticemia,theterm “secondarypyomyositis”ismoreappropriatetodefinedisease pathogenesis.2
Staphylococcalpyomyositisisclinicallydividedintothree consecutive stages:the invasive stage,withlocal symptoms and low-grade fever, the suppurative stage, with abscess formation, and the late stage, with dissemination of the infection, ifthe abscessremains untreatedinthe previous stages.2,3 Bacteriemia,sepsis,acuterenalfailure,ARDS,and metastatic abscesses are some of the complications that have been described.2,15 Septicpulmonary emboli are usu-ally associated with right-sided endocarditis or deep vein thrombosis/thrombophlebitis.However,evenintheabsence ofprofoundintravascularsources,septicpulmonaryemboli mayrepresentmetastaticabscessestothelungsarisingfrom primarydeeptissueinfectionssuchasosteomyelitis,septic arthritis,andrarelypyomyositis.15
A key feature of staphylococcal skin and soft tissue infections is recurrence, which is estimated to occur in approximately 30%ofallcases.16 These casesincludeboth
relapses,whichrefertoincompletelytreatedprimaryepisodes thatresultfrom theemergence oftheoriginal microorgan-ism, or re-infections, which describe infections with a new microorganism.17Traditionally,athresholdof6-monthtime intervalhasbeenusedtodistinguishclinicallyrelapsefrom re-infection,althoughonlymolecularfingerprintingofthe iso-latedbacteriacanprovidedefinitediscrimination.17
Inadditiontothewell-substantiatedstaphylococcal recur-rence, there are several reports of invasive staphylococcal infectionsintheliterature–primarilyosteomyelitis–where staphylococcusremainedsurprisinglylatentforaverylong periodoftime–overadecadeordecades.8–14These observa-tions were reportedarbitrarilyasstaphylococcalreactivations,
and notas simplerelapsing, persistentor recurrent infec-tions.In thecase ofosteomyelitis, ithad been taughtthat “osteomyelitiswhichhaditsonsetinthepre-penicillineracouldnever beconsideredcured”.9
Atthattime,authorswere notabletoprovidesolid evi-denceor explaintheexact pathophysiologicalmechanisms of this staphylococcal latency. Later it was shown that S. aureushastheabilitytotransformintoanatypical intracellu-larpathogen.Similarlytothebacteriaembeddedinbiofilms, when internalized, staphylococcus can change its charac-teristics,astoremain metabolicallyinactiveor todecrease its susceptibility tocertain antibiotics.In theexperimental study by Krut et al.,18 it was shown that only rifampicin was able to eliminate completely intracellular S. aureus
fromnon-phagocyticcells,whilelinezolid,clindamycin,and azithromycin induced a state of intracellular persistence, and vancomycin failed to prevent host cells from dying.
Furthermore,in order toexplainstaphylococcal dormancy, research has been focused on the role of the Accessory GeneRegulator(AGR)system.Inparticular,activationofthe AGR system is responsible for the synthesis of virulence factors,suchasexoproteins/cytotoxins,leadingtothe sub-sequent development of the abscess lesion and bacterial survival. Investigating the AGR activation kinetics, Wright etal.reportedan“eclipsephase”whichprobablyrepresentsa metabolicshut-downofvirulentstrainsalthoughtheir intra-cellularsurvivalremainedintact.19 Thishypothesismay in partexplainhow Staphylococcus canremain latent intracel-lularly for long periods of time, but it does not elucidate what happens during reactivation. In this setting,none of the authors reporting cases of late reactivations was able toprovideanypossibleexplanationorsuggestprecipitating factors,asall reactivationsoccurredunexpectedlyin previ-ouslyhealthy,immunecompetentpatientswithoutevidence ofrecenttraumaorskincontamination.
Certainly,onecouldarguethattheabovementionedcases representre-infectionsandnotreactivations.Infact, Uc¸kay etal.20reportedthreecasesofrecurrentosteomyelitiscaused bydifferentbacterialstrainsorotherbacteria,suggestingthat formerly infected and altered bone surface might present a region of diminished resistance fora newinfection. On the other hand,in another caseofrecurrent osteomyelitis after75years8anoldsinustractduringsurgerywasfound, whichhadnotbeendrainedinthefirstplace.Culturesfrom the bone and tract grew only S. aureus, which was sensi-tive,asexpected,toallantibiotics.Investigatorsproceededto sequencetyping,whichplacedtheisolatedstrainamongthe ST30S.aureusclone,believedtohavebeenspread through-out the worldduring the 1950sand 1960s, and,therefore, providedevidenceofstaphylococcalreactivated osteomyeli-tis.
Inourcase,this identification couldnothavebeen per-formed.Asnomedicalrecordswereavailable,weonlyhada historyofastaphylococcalosteomyelitiswhenthepatientwas sixyearsoldforwhichshewasoperatedon.Administration ofantibiotics inthe mid-1950s in Greeceis also question-able.Reactivationofstaphylococcalinfectionwaspostulated becauseofthefollowing:
(i) Thepatientwaspreviouslyhealthyand immunecompe-tent,andnopredisposingfactorswereidentified. (ii) Culturesfromnostrilsandskinfoldsturnedoutnegative
forS.aureus,rejecting thehypothesisofprevious colo-nization.
(iii) Thepatientpresentedwithatwo-weekhistoryof non-specificsymptoms – time consistentwith early stages ofprimarypyomyositis–untilshedevelopedtheseptic complicationsofthelatestage.
(iv) Recurrenceofstaphylococcalinfectionbeganinthesame anatomicalregion(leftilium)andpossiblyexpandedinto theneighboringmusclegroupsasabscessesoftheleft ileopsoasandglutealmuscles.
(v) Septicpulmonaryemboliarisingfromprimary pyomyosi-tiswereconsistentwiththeabsenceofbothright-sided endocarditisandthrombosisofthelowerextremities. (vi) Pusandbloodculturesidentifiedamethicillin-sensitive
staphylococcalstrain,althoughincidenceratesofMRSA
inGreeceareamongstthehighestinEurope,estimated tobeover40%.
Themaincounterargumenttoourprimaryhypothesisthat thiscaserepresentsareactivatedstaphylococcalsofttissue infectionisthattherewasnoevidenceofosteomyelitisinthe presentMRI.AsinthereportofStevensetal.,10recurrenceof hiposteomyelitiswithsecondarypyomyositisoftheadjoining muscleswouldbeaprobablecasescenariothatcouldexplain staphylococcalreactivation.Instead,ourfindingssuggestthat eitherMRIwasunabletoshowanunderlyingosteomyelitisor that Staphylococcusremainedquiescent fromprevious seed-ingintomicro-abscessesofthesurroundingmuscles.Ifthis isthecase,thatmakesourreportthefirstcaseofreactivated staphylococcalpyomyositis.
Conclusion
Staphylococcal pyomyositis is a dangerous infection with highmortalitythatisincreasinglybeingrecognizedevenin temperateclimates.Diagnosisshouldbeimmediateand man-agement should be aggressive, in order to prevent sepsis and spreadofmetastaticabscesses.If completeeradication fails, recurrence manifesting either as relapse or even as reactivationistobeanticipated.Finally,futurestudiesshould focusonthepathophysiologyofstaphylococcallatencyand theprecipitatingfactorsthatmayleadtoitsreactivation.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
r
e
f
e
r
e
n
c
e
s
1.BurdetteSD,WatkinsRR,WongKK,MathewSD,MartinDJ, MarkertRJ.Staphylococcusaureuspyomyositiscomparedwith non-Staphylococcusaureuspyomyositis.JInfect.
2012;64:507–12.
2.ChauhanS,JainS,VarmaS,ChauhanS.Tropicalpyomyositis (myositistropicans):currentperspective.PostgradMedJ. 2004;80:267–70.
3.OlsonDP,SoaresS,KanadeSV.Community-acquiredMRSA pyomyositis:casereportandreviewoftheliterature.JTrop Med.2011,http://dx.doi.org/10.1155/2011/970848.
4.BlockAA,MarshallC,RatcliffeA,AthanE.Staphylococcal pyomyositisinatemperateregion:epidemiologyandmodern management.MedJAust.2008;189:323–5.
5.JacobssonG,NasicS.Long-termoutcomeofinvasive
Staphylococcusaureusinfections.ScandJInfectDis. 2012;44:350–4.
6.BocchiniCE,HultenKG,MasonJrEO,GonzalezBE, HammermanWA,KaplanSL.Panton–Valentineleukocidin genesareassociatedwithenhancedinflammatoryresponse andlocaldiseaseinacutehematogenousStaphylococcus aureusosteomyelitisinchildren.Pediatrics.2006;117:433–40.
7.HallMJ,SteerJA,KeenanJ.Panton–Valentineleukocidin
Staphylococcusaureusosteomyelitisoftheadulttibia–acase report.AnnRCollSurgEngl.2010;92:W17–9.
8.LibratyDH,PatkarC,TorresB.Staphylococcusaureus
reactivationosteomyelitisafter75years.NEnglJMed. 2012;366:481–2.
9. ScullyRE,MarkEJ,McNeelyWF,McNeelyBU.Caserecordsof theMassachusettsGeneralHospital(case6-1993).NEngJ Med.1993;328:422–8.
10.StevensQE,SeiblyJM,ChenYH,DickermanRD,NoelJ, KattnerKA.Reactivationofdormantlumbar
methicillin-resistantStaphylococcusaureusosteomyelitisafter 12years.JClinNeurosci.2007;14:585–9.
11.WidmerA,BarraudGE,ZimmerliW.Reactivationof
Staphylococcusaureusosteomyelitisafter49years.Schweiz MedWochenschr.1988;118:23–6.
12.DonatiL,QuadriP,ReinerM.Reactivationofosteomyelitis causedbyStaphylococcusaureusafter50years.JAmGeriatr Soc.1999;47:1035–7.
13.KorovessisP,FortisAP,SpastrisP,DroutsasP.Acute osteomyelitisofthepatella50yearsafterakneefusionfor septicarthritis:acasereport.ClinOrthop.1991;272:205–7.
14.Evliyao ˘gluC,BademciG,YucelE,KeskilS.Pott’spuffytumor ofthevertexyearsaftertraumainadiabeticpatient:case report.Neurocirugia(Astur).2005;16:54–7.
15.LinMY,RezaiK,SchwartzDN.Septicpulmonaryemboliand bacteremiaassociatedwithdeeptissueinfectionscausedby community-acquiredmethicillin-resistantStaphylococcus aureus.JClinMicrobiol.2008;46:1553–5.
16.KimHK,ThammavongsaV,SchneewindO,MissiakasD. Recurrentinfectionsandimmuneevasionstrategiesof
Staphylococcusaureus.CurrOpinMicrobiol.2012;15:92–9.
17.ChuVH,SextonDJ,CabellCH,etal.Repeatinfective endocarditis:differentiatingrelapsefromreinfection.Clin InfectDis.2005;41:406–9.
18.KrutO,SommerH,KrönkeM.Antibiotic-inducedpersistence ofcytotoxicStaphylococcusaureusinnon-phagocyticcells.J AntimicrobChemother.2004;53:167–73.
19.Wright3rdJS,JinR,NovickRP.Transientinterferencewith staphylococcalquorumsensingblocksabscessformation. ProcNatlAcadSciUSA.2005;102:1691–6.
20.Uc¸kayI,AssalM,LegoutL,etal.Recurrentosteomyelitis causedbyinfectionwithdifferentbacterialstrainswithout obvioussourceofreinfection.JClinMicrobiol.2006;44:1194–6.
