Background

Osteomyelitisisinflammationofthebonecausedbyaninfectingorganism.Although
boneisnormallyresistanttobacterialcolonization,eventssuchastrauma,surgery,
the presence of foreign bodies, or the placement of prostheses may disrupt bony
integrityandleadtotheonsetofboneinfection.Osteomyelitiscanalsoresultfrom
hematogenous spread after bacteremia. When prosthetic joints are associated with
infection, microorganisms typically grow in biofilm, which protects bacteria from
antimicrobialtreatmentandthehostimmuneresponse.
Earlyandspecifictreatmentisimportantinosteomyelitis,andidentificationofthe
causativemicroorganismsisessentialforantibiotictherapy. [1] Themajorcauseof
bone infections is Staphylococcus aureus. Infections with an open fracture or
associatedwithjointprosthesesandtraumaoftenmustbetreatedwithacombination
ofantimicrobialagentsandsurgery.Whenbiofilmmicroorganismsareinvolved,asin
jointprostheses,acombinationofrifampinwithotherantibioticsmightbenecessary
fortreatment.
Anatomy
Thebonyskeletonisdividedintotwoparts:theaxialskeletonandtheappendicular
skeleton.Theaxialskeletonisthecentralcoreunit,consistingoftheskull,vertebrae,
ribs,andsternum;theappendicularskeletoncomprisesthebonesoftheextremities.
Thehumanskeletonconsistsof213bones,ofwhich126arepartoftheappendicular
skeleton,74arepartoftheaxialskeleton,andsixarepartoftheauditoryossicles.
Hematogenous osteomyelitis most commonly involves the vertebrae, but infection
mayalsooccurinthemetaphysisofthelongbones,pelvis,andclavicle.Vertebral
osteomyelitisinvolvestwoadjacentvertebraewiththecorrespondingintervertebral
disk.(Seetheimagebelow.)Thelumbarspineismostcommonlyaffected,followed
bythethoracicandcervicalregions.
Posttraumatic osteomyelitis begins outside the bony cortex and works its way in
toward the medullary canal, typically found in the tibia. Contiguousfocus
osteomyelitisoftenoccursinthebonesofthefeetinpatientswithdiabetesmellitus
andvascularcompromise.
Pathophysiology
Bone is normally resistant to infection. However, when microorganisms are
introduced into bone hematogenously from surrounding structures or from direct
inoculationrelatedtosurgeryortrauma,osteomyelitiscanoccur.Boneinfectionmay
result from the treatment of trauma, which allows pathogens to enter bone and
proliferateinthetraumatizedtissue.Whenboneinfectionpersistsformonths,the
resultinginfectionisreferredtoaschronicosteomyelitisandmaybepolymicrobial.
Althoughallbonesaresubjecttoinfection,thelowerextremityismostcommonly
involved.[1,2]
Someimportantfactorsinthepathogenesisofosteomyelitisincludethevirulenceof
theinfectingorganism,underlyingdisease,immunestatusofthehost,andthetype,
location,andvascularityofthebone.Bacteriamaypossessvariousfactorsthatmay

contributetothedevelopmentofosteomyelitis.Forexample,factorspromotedbyS
aureusmaypromotebacterialadherence,resistancetohostdefensemechanism,and
proteolyticactivity.[3]
Hematogenousosteomyelitis
Inadults,thevertebraearethemostcommonsiteofhematogenousosteomyelitis,but
infectionmayalsooccurinthelongbones,pelvis,andclavicle.[4]
Primaryhematogenousosteomyelitisismorecommonininfantsandchildren,usually
occurringinthelongbonemetaphysis.However,itmayspreadtothemedullarycanal
orintothejoint.Wheninfectionextendsintosofttissue,sinustractsmayeventually
form.Secondaryhematogenousosteomyelitisismorecommonandoccurswhena
childhoodinfectionisreactivated.Inadults,thelocationisalsousuallymetaphyseal.
Saureusisthemostcommonpathogenicorganismrecoveredfrombone,followedby
Pseudomonas and Enterobacteriaceae. Less common organisms involved include
anaerobe gramnegative bacilli. Intravenous drug users may acquire pseudomonal
infections. Gastrointestinal or genitourinary infections may lead to osteomyelitis
involving gramnegative organisms. Dental extraction has been associated with
viridansstreptococcalinfections.Inadults,infectionsoftenrecurandusuallypresent
withminimalconstitutionalsymptomsandpain.Acutely,patientsmaypresentwith
fever,chills,swelling,anderythemaovertheaffectedarea.[2,5]
Contiguousfocusandposttraumaticosteomyelitis
The initiating factor in contiguousfocus osteomyelitis often consists of direct
inoculation of bacteria via trauma, surgical reduction and internal fixation of
fractures,prostheticdevices,spreadfromsofttissueinfection,spreadfromadjacent
septicarthritis,ornosocomialcontamination.Infectionusuallyresultsapproximately
onemonthafterinoculation.
Posttraumaticosteomyelitismorecommonlyaffectsadultsandtypicallyoccursinthe
tibia.ThemostcommonlyisolatedorganismisSaureus.Atthesametime,localsoft
tissue vascularity may be compromised, leading to interference with healing.
Comparedwithhematogenousinfection,posttraumaticinfectionbeginsoutsidethe
bony cortex and works its way in toward the medullary canal. Lowgrade fever,
drainage,andpainmaybepresent.Lossofbonestability,necrosis,andsofttissue
damagemayleadtoagreaterriskofrecurrence.[4,5]
Septic arthritis may lead to osteomyelitis. Abnormalities at the joint margins or
centrally,whichmayarisefromovergrowthandhypertrophyofthesynovialpannus
andgranulationtissue,mayeventuallyextendintotheunderlyingbone,leadingto
erosions andosteomyelitis.Onestudydemonstrated that septicarthritis inelderly
persons most commonly involves the knee and that, despite most of the patients
havingahistoryofsurgery,38%developedosteomyelitis.Septicarthritisismore
commoninneonatesthaninolderchildrenandisoftenassociatedwithmetaphyseal
osteomyelitis.Althoughrare,gonococcalosteomyelitismayariseinaboneadjacent

toachronicallyinfectedjoint.
Patients with vascular compromise, as in diabetes mellitus, are predisposed to
osteomyelitisowingtoaninadequatelocaltissueresponse.[4]
Infectionismostoftencausedbyminortraumatothefeetwithmultipleorganisms
isolated from bone, including Streptococcus species, Enterococcus species,
coagulasepositiveandnegativestaphylococci,gramnegativebacilli,andanaerobic
organisms.Footulcersallowbacteriatoreachthebone.Patientsmaynotexperience
any resulting pain, because of peripheral neuropathy, and may present with a
perforatingfootulcer,cellulitis,oraningrowntoenail.
Physical examination may reveal decreased sensation, poor capillary refill, and
decreaseddorsalispedisandposteriortibialpulses.Treatmentisaimedatsuppressing
infectionandimprovingvascularity.However,mostpatientsdeveloprecurrentornew
bone infections. Resection or amputation of the affected tissue is sometimes
necessary.Debridement,incisionanddrainage,andtendonlengtheningareattempted
first.
Vertebralosteomyelitis
Theincidenceofvertebralosteomyelitisgenerallyincreasesprogressivelywithage,
with most affected patients being older than 50 years. Although devastating
complicationsmayresultfromadelayindiagnosis,vertebralosteomyelitisisrarely
fatal since the development of antibiotics. The infection usually originates
hematogenously and involvestwo adjacent vertebrae with the corresponding
intervertebraldisk.Thelumbarspineismostcommonlyaffected,followedbythe
thoracicandcervicalregions.[4,1]
Potentialsourcesofinfectionincludeskin,softtissue,respiratorytract,genitourinary
tract,infectedintravenoussites,anddentalinfections.Saureusisthemostcommon
isolated organism. However, Pseudomonas aeruginosa is more common in
intravenousdrugusers.
Mostpatientswithvertebralosteomyelitispresentwithlocalizedpainandtenderness
oftheinvolvedvertebraewithaslowprogressionover3weeksto3months.Fever
maybepresentinapproximately50%ofpatients.Fifteenpercentofpatientsmay
have motor and sensory deficits. Laboratory studies may reveal peripheral
leukocytosis and an elevated erythrocyte sedimentation rate. Extension of the
infectionmayleadtoabscessformation.[4]
Osteomyelitisinchildren
Acutehematogenousosteomyelitisusuallyoccursafteranepisodeofbacteremiain
whichtheorganismsinoculatethebone.Themostcommonorganismsisolatedin
thesecasesincludeSaureus,Streptococcuspneumoniae,andHaemophilusinfluenza
typeb(lesscommonsincetheuseofvaccineforHinfluenzatypeb).

Acute hematogenous S aureus osteomyelitis in children can lead to pathologic

fractures.Thiscanoccurinabout5%ofcaseswitha72daymeantimefromdisease
onsettofracture.[8]
Inchildrenwithsubacutefocalosteomyelitis(seetheimagebelow),Saureusisthe
mostcommonlyisolatedorganism.
GramnegativebacteriasuchasPseudomonasspeciesorEscherichiacoliarecommon
causes of infection after puncture wounds of the feet or open injuries to bone.
Anaerobescanalsocauseboneinfectionafterhumanoranimalbites.
Osteomyelitisintheneonateresultsfromhematogenousspread,especiallyinpatients
withindwellingcentralvenouscatheters.Thecommonorganismsinosteomyelitisof
the neonate include those that frequently cause neonatal sepsis, namely group B
Streptococcus species, and E coli. Infections in the neonate can involve multiple
osseoussites,andapproximatelyhalfofthecasesalsoinvolveeventualdevelopment
ofsepticarthritisintheadjacentjoint.
Childrenwithsicklecelldiseaseareatanincreasedriskforbacterialinfections,and
osteomyelitis is the second most common infection in these patients. The most
common organisms involved in osteomyelitis in children with sickle cell anemia
includeSalmonellaspecies,Saureus,Serratiaspecies,andProteusmirabilis.
Etiology
Posttraumaticosteomyelitisaccountsforasmanyas47%ofcasesofosteomyelitis.
Othermajorcausesofosteomyelitisincludevascularinsufficiency(mostlyoccurring
inpersonswithdiabetes;34%)andhematogenousseeding(19%).
Motor vehicle accidents, sports injuries, and the use of orthopedic hardware to
managetraumaalsocontributetotheapparentincreaseinprevalenceofposttraumatic
osteomyelitis.Osteomyelitismaycomplicatepuncturewoundsofthefoot,occurring
in1.8%6.4%ofpatientsfollowinginjury.
Epidemiology
Approximately20%ofadultcasesofosteomyelitisarehematogenous,whichismore
commoninmalesforunknownreasons.
Theincidenceofspinalosteomyelitiswasestimatedtobe1in450,000in2001.In
subsequentyears,however,theoverallincidenceofvertebralosteomyelitisisbelieved
tohaveincreasedasaconsequenceofintravenousdruguse,increasingageofthe
population,andhigherratesofnosocomialinfectionduetointravasculardevicesand
other instrumentation. [14, 15] The overall incidence of osteomyelitis is higher in
developingcountries.
Prognosis
Inadequate therapy may lead to relapsing infection and progression to chronic
infection.Becauseoftheavascularityofbone,chronicosteomyelitisiscurableonly
withradicalresectionoramputation.Thesechronicinfections mayrecuras acute

exacerbations,whichcanbesuppressedbydebridementfollowedbyparenteraland
oralantimicrobialtherapy.Rarecomplicationsofboneinfectionincludepathologic
fractures, secondary amyloidosis, and squamous cell carcinoma at the sinus tract
cutaneousorifice.
Clinicalsymptomps
Osteomyelitisisoftendiagnosedclinicallywithnonspecificsymptomssuchasfever,
chills,fatigue,lethargy,orirritability.Theclassicsignsofinflammation,including
localpain,swelling,orredness,mayalsooccurandnormallydisappearwithin57
days.
Chronic posttraumatic osteomyelitis requires a detailed history for diagnosis,
includinginformationregardingtheinitialinjuryandpreviousantibioticandsurgical
treatment. Weightbearing and function of the involved extremity are typically
disturbed.Localpain,swelling,erythema,andedemamayalsobereported.
PhysicalExamination
Onphysicalexamination,scarsorlocaldisturbanceofwoundhealingmaybenoted
alongwiththecardinalsignsofinflammation. [2] Rangeofmotion,deformity,and
local signs of impaired vascularity are also sought in the involved extremity. If
periostealtissuesareinvolved,pointtendernessmaybepresent.[5]
In children, the clinical presentation of osteomyelitis can be challenging for
physicians because it can present with only nonspecific signs and symptoms and
because the clinical findings are extremely variable. Children may present with
decreased movement and pain in the affected limb and adjacent joint, as well as
edemaanderythemaovertheinvolvedarea.Inaddition,childrenmayalsopresent
withfever,malaise,andirritability.Newbornswithosteomyelitismaydemonstrate
decreasedmovementofalimbwithoutanyothersignsorsymptoms.
Complications
Themostcommoncomplicationinchildrenwithosteomyelitisisrecurrenceofbone
infection.Althoughadverseoutcomesarecommonwithdelaysintreatment,chronic
infection may still develop in 510% of patients treated appropriately. Common
complicationsinchildrenyoungerthan18monthsincludebonedestruction,chronic
osteomyelitis, and impaired bone growth, especially when the growth plate is
affected.Althoughrare,extremebonedestructionorthinningofthecortexcanleadto
pathologicfractures.Whencentrallyplacedintravenouscathetersareusedincases
that require prolonged antibiotic treatment intravenously, catheterassociated
complicationscanoccur.However,theuseofperipherallyinsertedcentralvenous
cathetershasdecreasedthiscomplication.
Inastudyof17,238Taiwanesepatientsnewlydiagnosedwithchronicosteomyelitis
from2000to2008whowereidentifiedonthebasisofTaiwaneseNationalHealth
Insurance (NHI) inpatient claims, Tseng et al found chronic osteomyelitis to be
associatedwithanincreasedriskofdementia,particularlyamongtheyoungerpatients
studied.
Laboratory
A complete blood count (CBC)is useful for evaluating leukocytosis and anemia.

Leukocytosisiscommoninacuteosteomyelitisbeforetherapy.Theleukocytecount
rarely exceeds 15,000/L acutely and is usually normal in chronic osteomyelitis.
ErythrocytesedimentationrateandCreactiveproteinlevelsareusuallyincreased.
Bloodculturesarepositiveinonly50%ofcasesofosteomyelitis. Theyshouldbe
obtainedbeforeoratleast48hoursafterantibiotictreatment.Althoughsinustract
culturesdonotpredictthepresenceofgramnegativeorganisms,theyarehelpfulfor
confirmingSaureus.
Bonebiopsyleadstoadefinitivediagnosisbyisolationofpathogensdirectlyfromthe
bonelesion.[5]Bonebiopsyshouldbeperformedthroughuninfectedtissueandeither
beforetheinitiationofantibioticsormorethan48hoursafterdiscontinuance.
ImagingStudies
Radiography
Conventional radiography is the initial imaging study at presentation of acute
osteomyelitis.Itishelpfultointerpretcurrentandoldradiographstogether.(Seethe
imagebelow.)

Osteomyelitis, chronic. Image in a 56yearold man with diabetes shows chronic

osteomyelitisofthecalcaneum.Noteairinthesofttissues.
ViewMediaGallery

Radiographicfindingsincludeperiostealthickeningorelevation,aswellascortical
thickening, sclerosis, and irregularity. Other changes include loss of trabecular
architecture,osteolysis,andnewboneformation.Thesechangesmaynotbeevident
until57daysinchildrenand1014daysinadults.Plainfilmsshowlyticchanges
after at least 50%75% of the bone matrix is destroyed. Therefore, negative
radiographicstudiesdonotexcludethediagnosisofacuteosteomyelitis.
Healingfractures,cancers,andbenigntumorsmayappearsimilarlyonplainfilm.
Subtlechangesmayindicatecontiguousfocusorchronicosteomyelitis.
Computedtomography
Computedtomography(CT)isusefulforguidingneedlebiopsiesinclosedinfections
and for preoperative planning to detect osseous abnormalities, foreign bodies, or
necroticboneandsofttissue.Itmayassistintheassessmentofbonyintegrity,cortical
disruption,andsofttissueinvolvement.Itmayalsorevealedema.Intraosseousfistula
andcorticaldefectsthatleadtosofttissuesinustractsarealsodemonstratedonCT.
AlthoughCTmayplayaroleindiagnosisofosteomyelitis,thescatterphenomenon
may resultin significantloss ofimageresolutionwhenmetalis near the areaof
inflammation.
Magneticresonanceimaging
Magnetic resonance imaging (MRI) is a very useful modality in detecting
osteomyelitis and gauging the success of therapy because of high sensitivity and
excellentspatialresolution.Theextentandlocationfosteomyelitisisdemonstrated
alongwithpathologicchanges ofbonemarrow andsofttissue. [4] (Seetheimage
below.)

Osteomyelitis,chronic.T1andT2weightedsagittalMRIsshowbonemarrowedema
inL1andobliterationofthediskspacebetweenL1andL2.
ViewMediaGallery
MRIshowsalocalizedmarrowabnormalityinosteomyelitis.T1weightedimages
typically show decreased signal intensity, whereas T2weighted images produce
increasedsignalintensity.[4]IncreasedintensityonT2weightedimagesmayindicate

sinus tracts, which extend from marrow and bone to skin through soft tissue. A
decreasedintensityonT1weightedimageswithnochangeonT2weightedimages
mayindicatesurgicalorposttraumaticscarringofbonemarrow.
Ultrasonography
Thepresenceoffluidcollectionadjacenttothebonewithoutinterveningsofttissue
usuallysuggestsosteomyelitis.Otherfindingsonultrasonographyincludeelevation
andthickeningoftheperiosteum.
Nuclearmedicineimaging
Threephasebonescanningishelpfulinevaluatingacuteosteomyeliticanddoubtful
diskitis. However, the specificity of this procedure is decreased in secondary
osteomyelitis.Thebonescanmayrevealincreasedmetabolicactivityinosteomyelitis,
butthisfindingisindistinguishablefromposttraumaticinjuryorfollowingsurgeryor
cancer.[4,1](Seetheimagebelow.)

Osteomyelitis, chronic. Threephase technetium99m diphosphonate bone scans

(staticcomponent)showincreasedactivityintheheelandinthefirstandsecondtoes
andinthefifthtarsometatarsaljoint.
ViewMediaGallery
Oneapproachmakesuseofwhitebloodcells(WBCs)labeledwithtechnetium99m
(99mTc) hexamethylpropylene amine oxime (99mTcHMPAO) or indium111 (111In)
oxime.Thismethod,whenusedinthecombinationof 111InoximeWBCscanwith
99m
Tcsulfur colloid bone marrow scan, is helpful for evaluating infections of hip
prostheses. Isotope accumulates in areas of increased blood flow and new bone

formationinthe 99mTcpolyphosphatescan.Anegativetestresultmayindicatean
impairedbloodsupplytotheaffectedarea.Whenredmarrowispresent(ie,axial
skeletonandspine),WBCscanningislesssensitiveforimaging.[4,1]
Galliumcitrateattachestotransferrin,whichthenleaksintoinflamedareasfromthe
bloodstream. Increased uptake may occur in infection, cancer, and sterile
inflammatoryconditions.Performingatechnetium99mscanalongwiththegallium
67(67Ga)citratescanmayhelpdistinguishboneandsofttissueinflammationand
showbonedetail.[4,1]
Intheassessmentofinflammationofspinallesions,2[ 18F]fluoro2deoxyDglucose
(18FFDG) positron emission tomography (PET) may provide highresolution
tomographic images and may represent an alternative to 67Ga citrate scanning.
However,comparisonwithCTorMRIisessential.[1]
DiagnosticProcedures
Open bone biopsy with histopathologic examination and culture is the criterion
standardforthemicrobiologicdiagnosisofosteomyelitis.Thisproceduremaynotbe
necessaryifbloodculturesarepositivewithconsistentradiologicfindings.Needle
biopsymayalsobeusedtoobtainboneforanalysis.
Whenclinicalsuspicionishighbutbloodculturesandneedlebiopsyhaveyielded
negativeresults,arepeatneedlebiopsyoranopenbiopsyshouldbeperformed.A
bonesamplecanbecollectedatthetimeofdebridementforhistopathologicdiagnosis
inpatientswithcompromisedvasculature.Toobtainaccuratecultures,bonebiopsy
must be performed through uninvolved tissue. Cultures of the sinus tract may be
usefulifSaureusandSalmonellaspeciesareisolated.[22,23]
HistologicFindings
Acute osteomyelitis presents with acute inflammatory cells, edema, vascular
congestion,andsmallvesselthrombosis.Inearlydisease,infectionextendsintothe
surroundingsofttissue,whichcompromisesthevascularsupplytothebone,aswell
ashostresponse,surgery,and/orantibiotictherapy.
Largeareasofdeadbonemayformifbothmedullaryandperiostealbloodsupplies
are compromised. Necrotic bone shows extensive resorption and inflammatory
exudatesonbonebiopsyandappearswhiterthanlivingboneowingtothelossof
bloodsupply.Thedevelopmentofgranulationtissueoccursatthesurfaceofdead
bone,whichisbrokendownbyproteolyticenzymes,includingpolymorphonuclear
leukocytes,macrophages,andosteoclasts.Thisoccursmostrapidlyatthejunctionof
living and necrotic bone. A sequestrum is formed when dead cortical bone is
graduallydetachedfromlivingbone.
Chronicosteomyelitispresentswithpathologicfindingsofnecroticbone,formation
ofnewbone,andpolymorphonuclearleukocyteexudation,whichisjoinedbylarge
numbersoflymphocytes,histiocytes,andoccasionalplasmacells.
Theformationofnewboneoccursoverweeksormonthsasavascularreactiontothe
infection.Newbonearisesfromthesurvivingfragmentsofperiosteum,endosteum,

andcortexintheregionofinfectionalongtheintactperiostealandendostealsurfaces.
It may also occur when periosteum forms an involucrum, which is dead bone
surroundedbyasheathoflivingbone.Involucrummayleadtosinustractsdueto
perforations that allow pus to enter surrounding soft tissues and ultimately skin
surface.Anewshaftformsasthedensityandthicknessofinvolucrumincreases.
Asaresultofinflammatoryreactionandatrophydisuseduringtheactiveperiodof
osteomyelitis,survivingboneintheareaofinfectionusuallybecomesosteoporotic.
Bonedensityincreasespartiallyfromreuseastheinfectionsubsidesandextensive
transformationofbonemayoccurtoconformtoareasofnewmechanicalstresses.
Overtime,oldlivingboneandnewlyformedbonemayappearsimilarandmightbe
indistinguishable,especiallyinchildren.

Staging
Twoclassificationsystemsarecommonlyusedforosteomyelitis.
In1970,Waldvogeletalclassifiedboneinfectionsonthebasisofpathogenesisand
proposed the original osteomyelitis staging system. This system classifies bone
infectionsaseitherhematogenousorosteomyelitissecondarytoacontiguousfocusof
infection. Contiguousfocus osteomyelitis is further classified according to the
presenceorabsenceofvascularinsufficiency.Bothhematogenousandcontiguous
focusosteomyelitismaythenbeclassifiedaseitheracuteorchronic.
In2003,CiernyMaderetaldevelopedtheirstagingsystem,whichatpresentismore
commonly used. This system considers host immunocompetence in addition to
anatomicosseousinvolvementandhistologicfeaturesofosteomyelitis. Thefirstpart
ofthesystemspecifiesfourstages,asfollows:

Stage1diseaseinvolvesmedullaryboneandisusuallycausedbyasingleorganism
Stage2diseaseinvolvesthesurfacesofbonesandmayoccurwithdeepsofttissue
woundsorulcers
Stage3diseaseisanadvancedlocalinfectionofboneandsofttissuethatoftenresults
from a polymicrobially infected intramedullary rod or open fracture; stage 3
osteomyelitisoftenrespondswelltolimitedsurgicalinterventionthatpreservesbony
stability
Stage4osteomyelitisrepresentsextensivediseaseinvolvingmultiplebonyandsoft
tissuelayers;stage4diseaseiscomplexandrequiresacombinationofmedicaland
surgicaltherapies,withpostsurgicalstabilizationasanessentialpartoftherapy
ThesecondpartoftheCiernyMaderclassificationsystemdescribesthephysiologic
statusofthehost,asfollows:
ClassAhostshavenormalphysiologic,metabolic,andimmunefunctions
ClassBhostsaresystemically(Bs)orlocally(Bl)immunocompromised;individuals
withlocalandsystemicimmunedeficienciesarelabeledasBls
InClassChosts,treatmentposesagreaterriskofharmthanosteomyelitisitself;the
stateofthehostisthestrongestpredictorofosteomyelitistreatmentfailure,andthus
the physiologic class of the infected individual is often more important than the

anatomicstage[5]

Other classification systems have been proposedfor longbone osteomyelitis.The

Gordon classification classifies longbone osteomyelitis on the basis of osseous
defects,usinginfectedtibialnonunionsandsegmentaldefects,asfollows[26]:
TypeAincludestibialdefectsandnonunionswithoutsignificantsegmentalloss
TypeBincludestibialdefectsgreaterthan3cmwithanintactfibula
TypeCincludestibialdefectsofgreaterthan3cminpatientswithoutanintactfibula

The Ger classification is used to address the physiology of the wound in

osteomyelitis,whichiscategorizedasfollows[27,28]:
Simplesinus
Chronicsuperficialulcer
Multiplesinuses
Multipleskinlinedsinuses
Bone infection persists if appropriate woundmanagement is not undertaken. It is
importanttocoveropentibialfractureswithsofttissueearlyinthediseasetoprevent
infectionandulceration.

TheWeilandclassificationcategorizeschronicosteomyelitisasawoundwithexposed
bone,positivebonecultureresults,anddrainageformorethan6months. [29] This
systemalsoconsiderssofttissueandlocationofaffectedbone.Itdoesnotrecognize
chronicinfectionifwounddrainagelastslessthan6months.Weilandetalspecified
thefollowingthreetypes:
TypeIosteomyelitiswasdefinedasopenexposedbonewithoutevidenceofosseous
infectionbutwithevidenceofsofttissueinfection
Type II osteomyelitis showed circumferential, cortical, and endosteal infection,
demonstrated on radiographs as a diffuse inflammatory response, increased bone
density, and spindleshaped sclerotic thickening of the cortex; other radiographic
findingsincludedareasofbonyresorptionandoftenasequestrumwithasurrounding
involucrum
Type III osteomyelitis revealed cortical and endosteal infection associated with a
segmentalbonedefect
TheKellyclassificationconsidersthefollowingtypesofosteomyelitisinadults:
Hematogenousosteomyelitis
Osteomyelitisinafracturewithunion
Osteomyelitisinafracturewithnonunion
Postoperativeosteomyelitiswithoutfracture
Thissystememphasizestheetiologyoftheinfectionalongwithitsrelationtofracture
healing.
ApproachConsiderations
Surgery is indicated forosteomyelitis if the patient has not responded to specific
antimicrobial treatment, if there is evidence of a persistent soft tissue abscess or

subperiostealcollection,orifconcomitantjointinfectionissuspected.Debridementof
necrotictissues,removalofforeignmaterials,andsometimesskinclosureofchronic
unhealedwoundsarenecessaryinsomecases.
Although vertebral osteomyelitis does not usually necessitate surgical treatment,
indicationsincludefailuretorespondtoantimicrobialtherapy,neuralcompression,
spinalinstability,ordrainageofepiduralorparavertebralabscesses.
TheInfectiousDiseasesSocietyofAmericahaspublishedclinicalpracticeguidelines
forthediagnosisandtreatmentofnativevertebralosteomyelitisinadults,including
recommendationsregardingantibiotictherapyandsurgicalintervention.
MedicalTherapy
Antibiotictreatmentshouldbebasedontheidentificationofpathogensfrombone
culturesatthetimeofbonebiopsyordebridement. [1, 4] Boneculturesareobtained
first, and suspected pathogens are then covered by initiation of a parenteral
antimicrobialtreatment.However,treatmentmaybemodifiedoncetheorganismis
identified. Parenteral and oral antibiotics may be used alone or in combination
dependingonmicroorganismsensitivityresults,patientcompliance,andinfectious
diseaseconsultation.
Prophylactictreatmentwiththebeadpouchtechniquehasbeensuggestedinopen
fracturestoreducetheriskofinfection,withsystemicantibioticssupplementedwith
antibioticbeadscomparedtousingsystemicantibioticsalone.
Local antibiotic therapy with gentamicinimpregnated Septopal beads,
thoughavailable in Europe, is controversial. [32] Factors involved in the debate
include the length of implantation, the need for removal, and the choice of
nonabsorbable versus bioabsorbable delivery vehicles. Prolonged implantation of
antibioticbeads andspacersremainscontroversialowingtotheriskofsecondary
infectionanddevelopmentofresistantorganisms.Secondaryinfectionstemsfromthe
beads,whichmayserveasaforeignbodyuponcompleteelutionofantibiotic.
Traditionally,antibiotictreatmentofosteomyelitisconsistsofa4to6weekcourse.
[ ]
4 Animal studies and observations show that bone revascularization after
debridementtakesabout4weeks.
Oralantibioticsthathavebeenproventobeeffectiveincludeclindamycin,rifampin,
trimethoprimsulfamethoxazole, and fluoroquinolones. Clindamycin is given orally
afterinitialintravenoustreatmentfor12weeksandhasexcellentbioavailability.Itis
active against most grampositive bacteria, including staphylococci. Linezolid is
active against methicillinresistant staphylococci and vancomycinresistant
Enterococcus.Itinhibitsbacterialproteinsynthesis,hasexcellentbonepenetration,
andisadministeredintravenouslyororally.
Oralquinolonesareoftenusedinadultsforgramnegativeorganisms.Quinolones
haveexcellentoralabsorptionandmaybeusedassoonaspatientisabletotakethem.
Rifampinhasanoptimalintercellularconcentrationandagoodsensitivityprofilefor
methicillinresistant staphylococci. It is used in combination with cell wall active
antibioticstoachievesynergistickillingandtoavoidrapidemergenceofresistant

strains.
Empirictherapyisnecessarywhenitisnotpossibletoisolateorganismsfromthe
infectionsite. [1] Hospitalacquiredinfectionsareusuallyderivedfrommethicillin
resistant staphylococci. Infections contracted outside the hospital are often
polymicrobialwiththepresenceofgramnegativebacteria.
Parenteral antibiotics should be administered for several weeks, often requiring
patientstoremaininthehospitalforanextendedduration.Atthistime,oraltherapyis
indicatedonlyinchildrenwhosecomplianceiscertain.Infectionmayfailtoimprove
owing to the ability of bacteria to resist antibiotics. Some bacteria, such as S
epidermidis inprosthesisinfections,adheretoabiofilmthatprotectstheorganism
fromphagocytosisandimpedesdeliveryoftheantibiotic.
Rifampinmustalwaysbeusedincombinationwithotherantibioticsforprosthesis
infectionsbecauseitactsonthebiofilmandavoidsrecurrence.Infectionmayrecurif
rifampinisnotusedwithinafewweekstoamonthoftreatment.
Suppressiveantibiotictherapyshouldalsobedirectedbybonecultureandisgiven
orally when surgery is contraindicated. [4] Good bioavailability, low toxicity, and
adequatebonepenetrationareimportantfactorsintreatment.Iftheinfectionrecurs
after 6 months of suppressive antibiotic treatment, a new, lifelong regimen of
suppressivetherapymaybetried.
Extensivestudiesofsuppressivetherapywithadministrationofrifampin,ofloxacin,
fusidicacid,andtrimethoprimsulfamethoxazolefor69monthshavebeenperformed
in patients with infected orthopedic implants. Studies have shown that, after
discontinuationofantibiotics,norecurrenceofinfectionoccurredin67%ofpatients
treatedwithtrimethoprimsulfamethoxazole,55%ofpatientstreatedwithrifampin
andfusidicacid,and50%ofpatientstreatedwithrifampinandofloxacin.
SurgicalTherapy
Preoperativeplanning
The CiernyMader classification system (see Workup) plays an important role in
guidingtreatment.Asdescribedabove,stage1and2diseaseusuallydonotrequire
surgical treatment, whereas stage 3 and 4 respond well to surgical treatment. In
CiernyMaderclassChosts,treatmentmaybemoreharmfulthantheosteomyelitis
itself.[5]
Operativetreatmentconsistsofadequatedrainage,extensivedebridementofnecrotic
tissue,managementofdeadspace,adequatesofttissuecoverage,andrestorationof
bloodsupply.[4]Whenafractureandstablehardwareareinvolved,surgeryisusedto
treat a residual infection after suppressing the infection until the fracture heals.
Techniques involve secondstage hardware removal followed by treatment of an
infectednonunion,oftenwithanexternalfixator.Externalfixators,plates,screws,and
rodsmaybeusedtorestoreskeletalstabilityattheinfectionsite. [4] Sincehardware
tends to become secondarily infected, external fixation is preferred over internal

fixation.
Remissionorcureismostlikelywithextensivedebridement,obliterationofdead
space,removalofanyhardware,andappropriateantibiotictherapy.
Debridementofallnonviableorinfectedtissueiscriticalbecauseretainednecroticor
infecteddebriscanresultinosteomyelitisrecurrence.Bonedebridementisperformed
until punctuate bleeding is noted. [4] The remaining tissue is still considered
contaminatedevenafteradequatedebridementofnecrotictissue.Studieshaveshown
thatmarginalresectionmaybesufficientinnormalhosts.However,incompromised
hosts,extensiveresectionseemstobemuchmoreimportant.
Deadspacereferstothesofttissueandbonydefectleftbehindafterdebridement. [4]
Appropriatemanagementofthisspaceisnecessarytoreducetheriskofpersistent
infectionfrompoorvascularizationoftheareaandtomaintaintheintegrityofthe
skeletalpart.Deadspacemustbefilledwithdurablevascularizedtissue,sometimes
fromthefibulaorilium.Antibioticimpregnatedbeadsmaybeusedfortemporary
sterilizationofdeadspace.Vancomycin,tobramycin,andgentamicinaresomeofthe
commonantibioticsusedinthesebeads.Within24weeks,thebeadsmaybereplaced
withcancellousbonegraft.
Becausetwomajoraimsofsurgicaltreatmentincluderesectionofnecroticboneand
thorough debridement of intraosseous and soft tissue fistula, CT scanning is
sometimesperformedwhenplanningasurgicalinterventionandforguidingsurgery.
Preoperatively, CT scanning is helpful to characterize bone quality, demonstrate
intraosseousfistula,anddetectdevitalizedboneareas,orcorticaldefectsthatleadto
softtissuesinustracts.[2]
Whenosteomyelitisinvolvesafracture,itisalsoimportanttoincludeaworkuptobe
sure the fracture has healed. Antibioticimpregnated beads may be used as an
effectivemeasuretomaintainsteriledeadspaceuntiladefinitivesurgicalprocedure
canbeperformed.
InordertoapplytheIlizarovmethodsuccessfullyandtopreventdamagetovital
nervesandbloodvessels,preoperativeplanningishelpfulwithcarefulattentionto
"safezones"duringwireinsertion.Itisimportanttoadjusttheskintopreventtension
on the skinwire interface. Correction of the deformity or lengthening is better
achievedbyappropriatelyconstructingtheIlizarovframe.[33]
Ilizarovmethod
TheIlizarovmethod,developedbyG.A.Ilizarovin1951,promotesbonegrowth
throughdistractionosteogenesisusingaspecializeddeviceandsystematicapproach.
This technique has facilitated limb lengthening, decreased the incidence of many
complications,anddecreasedthelevelofsurgicalinterventionnecessary.
The Ilizarov method involves the use of a tissuesparing, cortical osteotomy
osteoclasistechniquethatpreservestheosteogenicelementsinthelimb.Tocreatea

preliminarycallusthatcanbelengthened,Ilizarovadvocatedadelayofseveraldays
beforeinitiatingdistraction.Ahighfrequency,smallstepdistractionrhythmpermits
regenerationofgoodqualityboneandlesssofttissuecomplicationssuchasnerve
and vessel injury. An advantage of using this procedure is that it minimizes the
prevalence of nonunion andthus further bone grafting by producing goodquality
boneformation.
The risk of repeat osteotomy and osteoclasis is also decreased owing to less
prematureconsolidationofthelengthenedsegment.[34]However,Ilizarovtechniques
areoftennottoleratedwellbypatients,andotheroptions,includingamputation,may
bepreferred.
TheIlizarovexternalfixatorisapopulardevicethatiscomposedofwires,fixation
bolts, rings, threaded rods, hinges, and plates, together allowing customized
assemblies.Althoughthisapparatusisstiffforbendingandtorsion,itislessstifffor
axialloading.Thisfeatureisthoughttohelppromoteosteogenesis.[33]
TheIlizarovmethodisbasedontheconceptof"tensionstress,"inwhichgradual
distractionstimulatesboneproductionandneogenesis.TheIlizarovdeviceisattached
tothedistalorproximalportionoftheaffectedbone.Boneregeneratesasthescrew
and wire mechanism moves the healthy bone fragment at a maximal rate of
approximately0.25mm4timesperdayforanoverallrateof1mmperday.Gentle
distraction allows bone formation and decreases the need for supplemental bone
graftingandinternalfixation.Thedistractionforcepermitstissuefibersandcellsto
becomeorientedinthesamedirectionasthedistractionvector,whichisthoughtto
mimictheprocessofnaturalbonegrowth.[33]
Nonunions, malunions, or defects of any length can be treated and may also be
correctedusingtheIlizarovmethod.Atthesametime,theIlizarovtechniqueislabor
intensiveandmayrequireatleast8monthsoftreatment.Inaddition,thefixatorpins
can be uncomfortable and often become infected. Amputation is an option if
reconstructionisnotsuitable.
Woundclosure
Toarrestinfection,itisnecessarytoprovideadequatesofttissuecoverage. [4] Over
smallsofttissuedefects,asplitthicknessskingraftmaybeplaced,whereaslarge
softtissue defects may be covered with local muscle flaps and free vascularized
muscle flaps. Rotation of a local muscle with its neurovascular supply must be
possibleanatomicallyforthatproceduretobesuccessful.
Theseflapsbringinabloodsupply,whichisimportantforhostdefensemechanisms,
newboneregeneration,deliveryofantibiotics,andhealing.Theyalsomaybeusedin
combination with antibiotics and surgical debridement of necrotic and infected
tissues.Thefibulaandiliaccrestarecommondonorsitesforfreeflaps.
Adjunctivehyperbaricoxygentherapy

Adjunctive hyperbaric oxygen therapy can promote collagen production,

angiogenesis,andhealinginanischemicorinfectedwound.[4]
Complications
TheIlizarovtechniqueisusuallywelltoleratedbythepatient,withlittleassociated
pain.Afewcomplicationsthathavebeenreportedincludepintractinfectionsand
cellulitis, flexion contractures above and below the frame, limb edema, and bone
fragmentrotationwithmalunion.[35]
The complication rate may bedecreased byfuture trends to improve the Ilizarov
method. [34] Some goals include improving the technique to prevent pintrack
infectionsandosteomyelitis,prematureordelayedconsolidationofbone,angularor
axial deviation of the new bone, joint contracture or instability, neurovascular
compromise,andpsychologicaladjustmentreactions.
LongTermMonitoring
Afteracorticotomyismadeforbonelengthening,alatencyperiodisrequiredbefore
distraction.OncedistractionhasbegunusingtheIlizarovtechnique,newboneshould
beapparentwithin34weeks.Afterobtainingtheappropriatelengthorcorrectingthe
angular deformity, the apparatus remains in place until completion of the
consolidation phase. During the postoperative period, it is necessary to adjust or
modifytheassembly,andtheapparatusisremovedwhenthegoalisachieved.[33]
Becausetheapparatusmaybeinplaceforanextendedperiod,evenuptoayear,
specialpostoperativeconsiderationsareimportant. [33] Painmanagementmaybea
challengebecauseofthedurationofmildtomoderatepostoperativepain.Toprevent
flexioncontractures ofthesurroundingjoints,akeyelementis intensivephysical
therapy and splinting techniques. Successful treatment also requires psychological
support and family counseling. Some problems to be cautious of during the
postoperativeperiodincludepintrackinfections,prematureordelayedconsolidation,
jointcontractures,andpinbreakagethatmayrequirereplacement.
Imaging studies in the followup period are most useful in patients who have
equivocalorworseclinicalstatusattheendoftherapy.
IDSAGuidelinesforNativeVertebralOsteomyelitisinAdults
TheInfectiousDiseasesSocietyofAmerica(IDSA)haspublishedclinicalpractice
guidelinesforthediagnosisandtreatmentofnativevertebralosteomyelitis(NVO)in
adults, including recommendations regarding antibiotic therapy and surgical
intervention.[31]Theserecommendationsarestructuredonthebasisofanswersto13
clinicalquestions,asfollows.
Clinicaldiagnostics

WhenshouldthediagnosisofNVObeconsidered?
Inpatientswithneworworseningbackorneckpainandfever
In patients with new or worsening back or neck pain and elevated erythrocyte
sedimentationrate(ESR)orCreactiveprotein(CRP)

Inpatientswithneworworseningbackorneckpainandbloodstreaminfectionor
infectiveendocarditis
Potentially,inpatientswhopresentwithfeverandnewneurologicsymptomswithor
withoutbackpain
Potentially,inpatientswhopresentwithnewlocalizedneckorbackpain,followinga
recentepisodeofStaphylococcusaureusbloodstreaminfection
WhatistheappropriatediagnosticevaluationforsuspectedNVO?
Recommended: a pertinent medical and motor/sensory neurologic examination in
patientswithsuspectedNVO
Recommended:bacterial (aerobic and anaerobic) blood cultures (two sets) and
baselineESRandCRPinallpatientswithsuspectedNVO
Recommended: magnetic resonance imaging (MRI) of thespine in patients with
suspectedNVO
Suggested:acombinationspinegallium/Tc99bonescanorcomputedtomography
(CT)orpositronemissiontomography(PET)inpatientswithsuspectedNVOwhen
MRI cannot be obtained (eg, implantable cardiac devices, cochlear implants,
claustrophobia,orunavailability)
Recommended:bloodculturesandserologictestsfor Brucella sp.inpatientswith
subacuteNVOresidinginendemicareasforbrucellosis
Suggested:fungal blood cultures in patients with suspected NVO and at risk for
fungalinfection(epidemiologicriskorhostriskfactors)
Suggested:purifiedproteinderivative(PPD)testorobtaininganinterferongamma
release assay in patients with subacute NVO and at risk for Mycobacterium
tuberculosis NVO (ie, originating or residing in endemic regions or having risk
factors)
May be considered: in patients with suspected NVO, evaluation by an infectious
diseasespecialistandaspinesurgeon
Whenshouldanimageguidedaspirationbiopsyoradditionalworkupbeperformed?
Recommended:imageguidedaspirationbiopsyinpatientswithsuspectedNVO(on
thebasisofclinical,laboratory,andimagingstudies)whenamicrobiologicdiagnosis
for a known associated organism ( S aureus, Staphylococcus lugdunensis, and
Brucellasp.)hasnotbeenestablishedbybloodculturesorserologictests
Notadvised:imageguidedaspirationbiopsyinpatientswithSaureus,Slugdunensis,
orBrucellasp.bloodstreaminfection(BSI)suspectedofhavingNVOonthebasisof
clinical,laboratory,andimagingstudies
Not advised: imageguided aspiration biopsy in patients with suspected subacute
NVO(highendemicsetting)andstronglypositiveBrucellaserology(strong,low).
Howlongshouldantimicrobialtherapybewithheldbeforeimageguideddiagnostic
aspirationbiopsyinsuspectedNVO?
Recommended:immediate surgical intervention and initiation of empiric
antimicrobial therapy in patients with neurologic compromise with or without
impendingsepsisorhemodynamicinstability
When is it appropriate to send fungal/mycobacterial/brucellar cultures or other
specializedtestingafterimageguidedaspirationbiopsyinsuspectedNVO?
Suggested:additionoffungal,mycobacterial,orbrucellarculturesonimageguided
biopsyandaspirationspecimensinpatientswithsuspectedNVOifepidemiologic,

hostriskfactors,orcharacteristicradiologiccluesarepresent
Suggested:additionoffungalandmycobacterialculturesandbacterialnucleicacid
amplification testing (NAAT) to appropriately stored specimens if aerobic and
anaerobicbacterialculturesrevealnogrowthinpatientswithsuspectedNVO
Whenisitappropriatetosendspecimensforpathologicexamination afterimage
guidedaspirationbiopsyinsuspectedNVO?
Recommended:fromallpatients(ifadequatetissuecanbesafelyobtained)tohelp
confirm NVO and guide further diagnostic testing, especially in the setting of
negativecultures
Whatisthepreferrednextstepwithnondiagnosticimageguidedaspirationbiopsy
andsuspectedNVO?
Recommended:intheabsenceofconcomitantBSI,asecondaspirationbiopsyifthe
original imageguided aspiration biopsy specimen grew a skin contaminant
(coagulasenegativestaphylococci[except Slugdunensis],Propionibacterium sp.,or
diphtheroids)
Recommended: with a nondiagnostic first imageguided aspiration biopsy and
suspectedNVO,furthertestingtoexcludedifficulttogroworganisms(eg,anaerobes,
fungi,Brucellasp.,ormycobacteria)
Suggested:withsuspectedNVOandanondiagnosticimageguidedaspirationbiopsy
and laboratory workup, either repeating a second imageguided aspiration biopsy,
performingpercutaneousendoscopicdiscectomyanddrainage(PEDD),orproceeding
withanopenexcisionalbiopsy
Clinicaltherapy

Whenshouldempiricantimicrobialtherapybestarted?
Suggested: in patients with normal and stable neurologic examination and stable
hemodynamics,holdempiricantimicrobialtherapyuntilamicrobiologicdiagnosisis
established
Suggested:inpatientswithhemodynamicinstability,sepsis,septicshock,orsevereor
progressive neurologic symptoms, initiate empiric antimicrobial therapy in
conjunctionwithanattemptatestablishingamicrobiologicdiagnosis
Whatistheoptimaldurationofantimicrobialtherapy?
Recommended:totaldurationof6weeksofparenteralorhighlybioavailableoral
antimicrobialtherapyformostpatientswithbacterialNVO
Recommended:totaldurationof3monthsofantimicrobialtherapyformostpatients
withNVOduetoBrucellasp.
Whataretheindicationsforsurgicalintervention?
Recommended:surgicalinterventioninpatientswithprogressiveneurologicdeficits,
progressivedeformity,andspinalinstabilitywithorwithoutpaindespiteadequate
antimicrobialtherapy
Suggested: surgical debridement with or without stabilization in patients with
persistentorrecurrentBSI(withoutanalternativesource)orworseningpaindespite
appropriatemedicaltherapy

Notadvised:surgicaldebridementand/orstabilizationinpatientswhohaveworsening
bony imaging findings at 46 weeks in the setting of improvement in clinical
symptoms,physicalexamination,andinflammatorymarkers
Clinicalfollowup

Howshouldfailureoftherapybedefinedintreatedpatients?
Suggested:persistentpain,residualneurologicdeficits,elevatedmarkersofsystemic
inflammation, or radiographic findings alone do not necessarily signify treatment
failureintreatedpatients
What roles do systemic inflammatory markers and MRI play in followup after
treatment?
Suggested: monitoring ESR, CRP, or both after approximately 4 weeks of
antimicrobialtherapy,inconjunctionwithaclinicalassessment
Not recommended: routinely ordering a followup MRI in patients who exhibit a
favorableclinicalandlaboratoryresponsetoantimicrobialtherapy
Suggested: performing a followup MRI to assess evolutionary changes of the
epiduralandparaspinalsofttissuesinpatientswhoarejudgedtohaveapoorclinical
responsetotherapy
Howshouldsuspectedtreatmentfailurebeapproached?
Suggested:obtainingESRandCRPvalues;unchangedorincreasingvaluesafter4
weeksoftreatmentshouldincreasesuspicionfortreatmentfailure
Recommended:obtainingafollowupMRIwithemphasisonevolutionarychangesin
theparaspinalandepiduralsofttissuefindings
Suggested:inpatientswithclinicalandradiographicevidenceoftreatmentfailure,
obtaining additional tissue samples for microbiologic (bacteria, fungal, and
mycobacterial)andhistopathologicexamination,eitherbyimageguidedaspiration
biopsyorthroughsurgicalsampling
Suggested:inpatientswithclinicalandradiographicevidenceoftreatmentfailure,
consultationwithaspinesurgeonandaninfectiousdiseasephysician