Journal of the American Academy of Orthopaedic Surgeons166

The annual rate of acute hematog-enous osteomyelitis in childrenunder the age of 13 in the UnitedStates is estimated to be approxi-mately 1:5,000.1 Population studiesshow a worldwide incidence rang-ing from 1:1,000 to 1:20,000,2 makingthis an uncommon, but not a rare,problem. Half of all cases of acutehematogenous osteomyelitis occurin children under the age of 5.3 Neo-natal osteomyelitis is estimated tooccur in 1 to 3 infants per 1,000intensive-care-nursery admissions.3

Before the advent of antibiotics,bacterial osteomyelitis in childrencarried mortality rates of 20% to50%.2,4 Advances in antibiotictreatment, diagnostic modalities,and surgical management have

made death uncommon, but mor-bidity due to delays in diagnosisand inadequate treatment continueto result in permanent sequelaeand poor outcomes in as many as6% of affected children.4,5 Failureof cultures to demonstrate patho-genic bacteria in many patients,poor understanding of the patho-physiology of bone infections, andemerging antibiotic resistance haveled to the development of manydifferent empirical treatments.However, recent advances in theevaluation and management ofacute hematogenous osteomyelitisand a thorough understanding ofthis disease entity will help toensure accurate diagnosis andprompt treatment.

Basic Science

The etiology and pathophysiologyof bone infections are still incomplete-ly defined. Introduction of bacteriainto bone can occur by direct inocu-lation, hematogenous spread frombacteremia, or local invasion from acontiguous focus of infection. A his-tory of trauma is common. Mostlong-bone infections occur in themetaphyseal portions of tubularbones of the lower extremities (Fig. 1).The majority of infections involveonly a single bone; involvement attwo or more sites is very uncommonexcept in neonatal infections.

Infection spreads via Volkmann’scanals or the haversian bone systemthrough the metaphyseal bone tothe subperiosteal space. Elevationof the periosteum can result in ab-scess formation. In severe cases,infarction of cortical bone may leadto the formation of a sequestrumand chronic osteomyelitis.

Septic arthritis can occur in jointsin which the metaphysis is intra-

Dr. Song is Assistant Director of OrthopedicSurgery, Children’s Hospital and RegionalMedical Center of Seattle, Seattle, Wash. Dr.Sloboda is Resident in Orthopaedic Surgery,Madigan Army Medical Center, Tacoma, Wash.

Reprint requests: Dr. Song, Department ofOrthopedic Surgery, Children’s Hospital andRegional Medical Center of Seattle, 4800 SandPoint Way NE, Seattle WA 98105.

Copyright 2001 by the American Academy ofOrthopaedic Surgeons.

Abstract

Acute hematogenous osteomyelitis in children is a relatively uncommon butpotentially serious disease. Improvements in radiologic imaging, most notablymagnetic resonance imaging, and a heightened awareness of this condition haveled to earlier detection and resultant marked decreases in morbidity and mortal-ity. Staphylococcus aureus, which has the ability to bind to cartilage, pro-duce a protective glycocalyx, and stimulate the release of endotoxins, accountsfor 90% of infections in all age groups. Infections with Haemophilus influen-zae have become rare in immunized children. A careful history and a thoroughphysical examination remain important. Positive cultures are obtained in only50% to 80% of cases; the yield is improved by the use of blood cultures andevolving molecular techniques. Improvements in antibiotic treatment havelessened the role of surgery in managing these infections. Sequential intra-venous and high-dose oral antibiotic therapy is now an accepted modality.Evaluation of response to treatment by monitoring C-reactive protein levels hasdecreased the average duration of therapy to 3 to 4 weeks with few relapses.The emergence of antibiotic resistance, particularly resistance to methicillinand vancomycin by S aureus organisms, is of increasing concern. Long-termsequelae and morbidity are primarily due to delays in diagnosis and inadequatetreatment.

J Am Acad Orthop Surg 2001;9:166-175

Acute Hematogenous Osteomyelitis in Children

Kit M. Song, MD, and John F. Sloboda, MD

Kit M. Song, MD, and John F. Sloboda, MD

Vol 9, No 3, May/June 2001 167

articular (e.g., hip, shoulder, andankle). It has been estimated that10% to 16% of cases of septic arthri-tis are secondary to bacterial osteo-myelitis. The avascular physis gen-erally limits extension of infectioninto the epiphysis except in neo-nates and infants. Blood vesselscross the physis until approximately15 to 18 months of age, with thepotential for concomitant septic ar-thritis. This may be present in asmany as 75% of cases of neonatalosteomyelitis.3

Fewer than 20% of infectionsoccur in nontubular bones. The cal-caneus and pelvis are the most com-mon sites. Infections in the flatbones (e.g., the skull, scapula, ribs,and sternum) and the spine are rare.2

Staphylococcus aureus is by farthe most common pathogen causingacute hematogenous osteomyelitisin all age categories. It has been im-plicated in as many as 89% of all in-fections. Streptococcus pneumoniae,group A Streptococcus, and coagulase-negative staphylococci are more age-and disease-specific. Group B strepto-cocci have been found with greaterfrequency in neonates, but accountfor only 3% of infections in this agegroup.3 Infections with these patho-gens generally result in a single focusof infection, unlike neonatal infec-tions with group A streptococci andS aureus. The introduction of a vac-cine against Haemophilus influenzaetype b has led to a marked decline inthe incidence of infections by thisorganism from 2% to 5% of all boneinfections to nearly 0% in immu-nized children.1-3,5-7

Avian models of bone infectionmost closely mimic what is observedin humans and have provided infor-mation about the pathophysiologyof bone infections. Gaps in the en-dothelium of growing metaphysealvessels allow the passage of bacteriathat then adhere to type I collagen inthe hypertrophic zone of the growthplate. Staphylococcus aureus surfaceantigens appear to play a key role inthis local adherence, while endotox-ins suppress local immune response.An extensive glycocalyx surround-ing each bacterium enhances adhe-sion of other bacteria and may beprotective against antibiotic treat-ment. Bacterial proliferation thenoccurs, occluding vascular tunnelswithin 24 hours. Abscesses appearafter 48 hours, with local tissuenecrosis and extension beyond thecalcifying area of the growth plate.Four to eight days after infection,localized sequestra of dead cartilage

are formed, and infection extendsbeyond the metaphysis. Furtherbone destruction may be mediatedby prostaglandin production as aresult of S aureus infection.8,9

Diagnosis

Bacterial osteomyelitis in childrenmust be differentiated from thewide range of conditions that maypresent with clinical symptoms andsigns mimicking infection (Table 1).

Figure 1 Sites of acute osteomyelitis in 657children with single-site involvement.(Adapted with permission from GutierrezKM: Osteomyelitis, in Long SS, PickeringLK, Prober CG [eds]: Principles and Practiceof Pediatric Infectious Diseases. New York:Churchill Livingstone, 1997, p 529.)

Ulna 3%

Pelvis 9%

Radius4%

Humerus 12%

Tibia 22%

Fibula 5%

Femur 27%

Hands andfeet 13%

Table 1Differential Diagnosis of aPainful, Swollen Extremity in a Child

Systemic conditionsAcute rheumatic feverChronic recurrent multifocal

osteomyelitisFungal arthritisGaucher’s diseaseHenoch-Schönlein purpuraHistiocytosisLeukemiaPrimary bone malignant tumorsReactive arthritisReiter’s syndromeRound cell tumorsSarcoidosisSeptic arthritisSickle cell diseaseSystemic juvenile rheumatoid

arthritisTuberculosis

Nonsystemic conditionsCellulitisFracture/nonaccidental traumaHemangioma/lymphangiomaHistiocytosisLegg-Perthes diseaseOsteochondrosisOveruse syndromesReactive arthritisReflex neurovascular dystrophySlipped capital femoral epiphysisStress fracture/toddler’s fractureSubacute osteomyelitisTransient synovitis

Acute Hematogenous Osteomyelitis in Children

Journal of the American Academy of Orthopaedic Surgeons168

The history and physical examina-tion findings associated with acutehematogenous osteomyelitis are sen-sitive but rarely specific. The mostfrequent clinical findings are fever,pain at the site of infection, and lim-ited use of the affected extremity.Constitutional symptoms, such aslethargy and anorexia, are less com-mon. The degree of abnormalitydoes not correlate with the extent ofinfection, and older children willoften have more subtle symptoms.Most patients will have had symp-toms for less than 2 weeks.

On physical examination, signsare often age-dependent. Neonateshave a thin periosteum that is easi-ly penetrated by infection and as aresult frequently have swelling atthe affected site and irritability onmovement of the limb. Infants andyoung children will have point ten-derness with limited ability to bearweight or use the extremity. Olderchildren, with their thicker metaph-yseal cortex and densely adherentperiosteum, will generally havepoint tenderness and a mild limp.Cellulitis is occasionally presentand may be a manifestation of anunderlying abscess.1-4,6,10

Serologic StudiesSerologic studies that should be

ordered when evaluating a childwith possible acute hematogenousosteomyelitis include a completeblood cell (CBC) count with differ-ential and peripheral smear, eryth-rocyte sedimentation rate (ESR), C-reactive protein (CRP) determina-tion, and blood cultures. As mostblood counts are automated, in-spection of the peripheral smearcan be helpful in eliminating thepossibility of leukemia. The whiteblood cell (WBC) count will be ele-vated in 31% to 40% of patients withacute hematogenous osteomyeli-tis6,11,12; the ESR, in up to 91%.6,11-13

Several authors have reportedon the usefulness of the CRP levelin making the diagnosis and fol-

lowing response to treatment ofacute hematogenous osteomye-litis.12-14 On presentation, it is ele-vated in as many as 97% of pa-tients. The degree of rise of theCRP has not been correlated withseverity of infection. The CRP risesmore rapidly than the ESR afteronset of infection, with synthesisbeginning within 4 to 6 hours afterinjury and peaking after 24 to 72hours (Fig. 2). Failure of the CRPlevel to fall rapidly after initiationof treatment has been predictive oflong-term sequelae.15 Unlike theESR, the CRP concentration is inde-pendent of the physical propertiesof cells and is a direct quantitativemeasurement. Similar to the ESR,it will rise and fall after surgery,trauma, or systemic illnesses, aswell as in patients with benign andmalignant tumors, thereby limitingits usefulness in some situations.16,17

Both the ESR and CRP are frequentlyelevated in neonatal infections,18

but the response to treatment ofthese indices has not yet been doc-umented.

Radiologic EvaluationRadiography remains an essential

tool for diagnosing and managingosteomyelitis in children and shouldbe performed in every case of sus-pected infection. The sensitivity andspecificity of radiographs rangefrom 43% to 75% and from 75% to83%,19 respectively (Fig. 3). Soft-tissue swelling will be evident with-in 48 hours of the onset of infection.Periosteal new-bone formation maybe evident by 5 to 7 days. Osteolyticchanges require bone mineral loss ofat least 30% to 50% and may take 10days to 2 weeks after the onset ofsymptoms to develop.19,20

Technetium-99m bone scintigra-phy is useful in the setting of nor-mal radiographs and clinical suspi-cion of osteomyelitis (Figs. 4, A; 5,B). It can be positive within 24 to 48hours of the onset of symptoms.The reported sensitivity rangesfrom 84% to 100% for detection ofosteomyelitis; the specificity, from70% to 96%.19 Aspiration of bonehas not been shown to create afalse-positive result if bone scintig-

100

160

140

120

80

60

40

20

0

0

Days Days

Osteomyelitis alone Osteomyelitis withadjacent arthritis

CRP, mg/LESR, mm/hr

CRP, mg/LESR, mm/hr

5 10 15 20 25 30

100

160

140

120

80

60

40

20

0

0 5 10 15 20 25 30

CRP

ESR

CRP

ESR

Figure 2 Rise and fall of erythrocyte sedimentation rate (ESR) and C-reactive protein(CRP) level in 50 patients with osteomyelitis with and without associated septic arthritis.Shaded areas indicate the normal range of values. Bars indicate 1 SD. (Reproduced withpermission from Unkila-Kallio L, Kallio MJT, Peltola H: The usefulness of C-reactive pro-tein levels in the identification of concurrent septic arthritis in children who have acutehematogenous osteomyelitis: A comparison with the usefulness of the erythrocyte sedi-mentation rate and the white blood-cell count. J Bone Joint Surg Am 1994;76:848-853.)

Kit M. Song, MD, and John F. Sloboda, MD

Vol 9, No 3, May/June 2001 169

raphy is carried out within 24 hoursof aspiration. The use of pinhole-collimated views and single-photon-emission computed tomography(SPECT) (Fig. 5, C) can increase bothsensitivity and specificity.21 In theearly stages of an infection, scintig-raphy may show decreased uptakebecause of the relative ischemiacaused by the increased pressurefrom the presence of purulent mate-rial (Fig. 3). Such “cold” scans havebeen reported to have a positive pre-dictive value of 100%, comparedwith a positive predictive value of83% for “hot” scans.21,22 Scintigraphyis of more limited use in neonatal in-fections, with reported sensitivityranging from 30% to 86%; radiogra-phy may be more sensitive in thissetting.2,3,10

Gallium scanning, although moresensitive for infection than Tc-99mscanning, delivers a higher amountof radiation, may take up to 48hours to perform, and is not specificfor infection. Scanning with indium-111–tagged WBCs can be helpfulin those rare situations in whichosteomyelitis is suspected but the

Tc-99m scan appears normal.2,19 Itrequires preparation time and cantake as long as 24 hours to perform.Monoclonal antibody scans havebeen investigated, but are as yet ofunproven benefit.2

Magnetic resonance imaging hasa reported sensitivity of 88% to100% and a specificity of 75% to100% in the detection of osteomye-litis. The positive-predictive valuesfor MR imaging and Tc-99m scin-tigraphy are comparable (85% and83%).20 However, MR imaging canprovide biplanar images of the in-fected site and is superior to scintig-raphy and CT for depicting themarrow cavities of long bones andadjacent soft tissues. It is most use-ful for detecting spinal and pelvicinfections (Fig. 5, D) and for plan-ning surgical approaches for de-bridement when a subperiosteal orsoft-tissue abscess may be pres-ent.19-21,23,24 Characteristic T1- andT2-weighted images can be used todifferentiate acute, subacute, andchronic osteomyelitis.24 T1-weightedand short-tau inversion recovery(STIR) images are most useful for

the detection of acute osteomyelitis(Fig. 4). The use of gadolinium en-hancement can aid in identifyingsinus tracts and distinguishing cel-lulitis from abscess.19 Like scintig-raphy, MR imaging is limited by alack of specificity; the signal pat-terns seen with fractures, boneinfarction, tumors, postsurgicalchanges, bone contusions, and sym-pathetic edema are similar.24

Computed tomography has beenmost useful in the detection of gasin soft-tissue infections and in theidentification of sequestra in casesof chronic osteomyelitis.19,21 It isalso useful in diagnosing and accu-rately defining the location of pelvicand spinal infections after localiza-tion with scintigraphy (Fig. 5). Fordeep infections, needle localizationprior to biopsy or debridement canbe helpful.

Ultrasonography is attractive forevaluating the possibility of boneand joint infections in childrenbecause of its low cost, relative avail-ability, and noninvasive nature, aswell as because there is no ionizingradiation involved and no need for

Figure 3 A, Radiograph of a child with a swollen forearm, elevated temperature, and elevated CRP value. B, Technetium bone scan per-formed on day of presentation was interpreted as normal, although it shows a “cold” left radius (i.e., area of decreased radionuclide uptake).C, Follow-up radiograph at 6 weeks shows periosteal elevation of the entire radius. D, Follow-up radiograph at 3 months demonstrates seg-mental bone loss in the radius.

A B C D

Acute Hematogenous Osteomyelitis in Children

Journal of the American Academy of Orthopaedic Surgeons170

sedation. It has been used to detectintra-articular, soft-tissue, and sub-periosteal fluid collections prior totheir appearance on plain radio-graphs. However, the lack of speci-ficity, dependence on operator skill,and inability to image marrow orshow cortical detail of bone havelimited the usefulness of ultrasoundcompared with MR imaging or CT.

An algorithm for radiologicevaluation of suspected bone infec-tions is shown in Figure 6. Radiog-raphy should be the initial study.If positive, MR imaging, CT, or

ultrasonography can be used to de-fine the infected area and to plansurgical approaches if needed. Ifthe results of any of those studiesare negative, scintigraphy can bevery helpful in isolating the infectedarea, after which one of the othermodalities can be used to provideadditional information for treat-ment planning.

Bacterial CulturesObtaining cultures of organisms

directly from sites of bone infectionin order to focus antibiotic treat-

ment is critical to effective manage-ment.2,3,25 However, direct cultureof the affected bone results in isola-tion of the bacterial agent in only48% to 85% of cases.5,6,26,27 Giventhe potentially low yield from cul-tures and the reluctance to performinvasive procedures on distressedchildren, it may be tempting not toperform bone aspiration. Neverthe-less, concerns about emerging anti-biotic resistance by bacteria makethe identification of pathogens andthe use of organism-specific treat-ment desirable.

Aspiration is easily performedthrough thin metaphyseal bonewith an 18-gauge spinal needle, andthe central trocar can be used to dis-engage any bone plugs created bypassage through the cortex. Localinfiltration of lidocaine into the tis-sues combined with intravenoussedation is generally effective. Theaspiration of bone through an over-lying area of cellulitis has not beenshown to cause osteomyelitis. Directculture of cellulitic areas yields apositive culture in fewer than 10%of cases,28 with Staphylococcus andStreptococcus species being mostcommonly isolated.

Blood cultures are positive in 30%to 60% of cases of acute osteomye-litis in children.1,4,6,27 The use ofmultiple blood cultures has not beenshown to increase the likelihood ofhaving a positive culture, especiallyif the samples were drawn after theinitiation of antibiotic treatment.The combination of blood and directcultures provides the highest yield,but in many cases treatment of pre-sumed infections will be empirical,based on clinical and radiographiccriteria.

Most bacterial cultures will bepositive within 48 hours of speci-men collection. However, fastidi-ous organisms may take as long as 7days to become positive. A surveyof hospitals in one area showed thatcultures are held an average of 5days before being discarded.

A B

C D

Figure 4 A, Technetium bone scan shows acute osteomyelitis in the distal left femur. B, T1-weighted MR image also demonstrates acute osteomyelitis, which was confirmed bybiopsy and treated with intravenous antibiotics. C, A STIR MR image further demon-strates acute osteomyelitis. D, Gradient-echo MR image illustrates growth arrest due tothe infection.

Kit M. Song, MD, and John F. Sloboda, MD

Vol 9, No 3, May/June 2001 171

The relatively low yield of stan-dard bacterial cultures has stimulatedinterest in using molecular tecniquesfor detection and speciation of bacte-rial and viral infections. Molecularmethods have been shown to bemore sensitive than standard culturetechniques for detecting pathogensand can do so even in the absence ofviable organisms. These techniquesfall into two broad categories: non-amplified and amplified. With non-amplified techniques, direct bindingof a target molecule is done with alabeled oligonucleotide probe ormonoclonal antibody, followed bydetection of the probe agent withradiolabeling, enzyme-linked immu-nosorbent assay, or chemolumines-cence. These methods are specificand applicable when looking for aparticular organism.

With amplified techniques, geo-metric amplification of the target

molecule is achieved by usingenzyme-driven reactions. The mostcommon of these techniques is thepolymerase chain reaction (PCR).The basis of these methods is to tar-get a portion of bacterial DNA orRNA that is not present in humancells. A probe or primer specific tothat region of DNA or RNA is in-troduced, which on binding pro-motes binding of a polymerase thatreplicates the target region in aseries of temperature-dependentcycles. The amplified products arethen identified by gel electrophoresis.Much recent work has focused on thehighly conserved area of DNA thatcodes for the 16s ribosomal RNAsubunit. There is enough gene se-quence variation within this area toallow differentiation among bacterialspecies and from human DNA.29,30

Polymerase chain reaction hasproduced some promising results

in diagnosing periprosthetic infec-tions and septic arthritis, but a highfalse-positive rate has been ob-served.31 The PCR method has beenfound to be very sensitive for thedetection of infection when a primerfor a specific organism is used. Incases of polymicrobial infection orinfection due to an unknown bacter-ial strain, the use of universal prim-ers that amplify all bacterial speciespresent is being developed. Identi-fication of the amplified genetic ma-terial remains difficult.

Treatment

The management of acute hematog-enous osteomyelitis is largely non-operative. The role of surgery is toimprove the local environment byremoving infected devitalized boneand soft tissue, decompressing a

Acetabularroof

Proximalfemur

A B

C D E

Figure 5 A, AP radiograph of a 15-year-old girl with right hip pain. B, Technetium bone scan of hips with pinhole collimation. C, SPECT images of the right hip show lesion in the supra-acetabular area. D, MR image depicts pelvic osteomyelitis. E, Brodie’s abscessof the acetabulum was localized on this CT scan prior to biopsy.

large abscess cavity, and facilitatingantibiotic delivery. If antibiotictreatment is initiated before signifi-cant bone and soft-tissue necrosishas occurred, it is more likely to besuccessful without the need for sur-gical treatment.

Antibiotic TherapyMost recent studies of antibiotic

treatment of acute hematogenousosteomyelitis have emphasized asequential parenteral-oral antibioticregimen.2,3,5,12,13 Due to the lowyield of culture techniques, empiricaltreatment based on known epidemi-ologic trends in different age groupsand at-risk populations will often benecessary (Table 2).

Empirical antibiotic coverageshould always include coverage for Saureus, as this is the most commonpathogen in all age groups. For neo-

natal osteomyelitis, treatment tar-geting group B streptococci andGram-negative rods should beadded. Children less than 4 years ofage need antibiotic coverage for H in-fluenzae type b if the immunizationprogram has not been completed orthe history is uncertain. For fullyimmunized children, the most likelypathogens are S aureus, Streptococcuspyogenes, and S pneumoniae. For im-munocompromised children withsickle cell disease, broad-spectrumcoverage to include Salmonella spe-cies should be included.

Children with human immuno-deficiency virus (HIV) infectionhave a propensity for infection by Spneumoniae. However, to date, thereis no evidence to suggest that pre-senting signs and symptoms or re-covery from infection are affected bycoinfection by HIV. Broad-spectrum

coverage is suggested for HIV-positive children due to the widerange of organisms reported.2

Antibiotic selection should sub-sequently be altered according tothe results of culture and sensitivitytesting. There are concerns aboutemerging antibiotic resistance.Methicillin- and cephalosporin-resistant S aureus organisms havebeen reported in as many as 20% ofcommunity-acquired bone and jointinfections.32,33 Recently, emergenceof vancomycin-resistant S aureus inJapan and parts of the United Stateshas raised the specter of emergingbacterial strains for which there areno known antibiotic treatments.34

The duration and route of ad-ministration of antibiotic treatmenthave previously been empirical, withthe length of intravenous therapyranging from 4 to 8 weeks. The du-

Acute Hematogenous Osteomyelitis in Children

Journal of the American Academy of Orthopaedic Surgeons172

Negative

Bone scan

Positive

Negative Positive

Negative Positive

Positive Negative

Radiographicevaluation

Antibiotictherapy

Antibiotic therapy

Antibiotic therapy

Biopsy, surgicaldebridement

Biopsy, surgicaldebridement

Consideraspiration

Suspicion of osteomyelitis (clinical/serologic evidence)

No clinicalimprovement

in 48 hr

MR imaging,CT, or ultrasound;

reassess diagnosis

MR imaging, CT, or ultrasound for

abscess/sequestrum

Figure 6 Algorithm for radiologic evaluation and treatment when acute hematogenous osteomyelitis is suspected.

Kit M. Song, MD, and John F. Sloboda, MD

Vol 9, No 3, May/June 2001 173

ration of antibiotic treatment hasnot been related to the presence orabsence of positive blood or directcultures; antibiotic sensitivity orresistance of the bacteria; degree ofelevation of the WBC count, CRP, orESR; presence or absence of puru-lent material; or symptoms at pre-sentation. Authors of earlier studiessuggested that a total duration oftreatment of less than 3 weeks isassociated with a higher rate of re-lapse.35 Although previously con-troversial, the need to complete atleast a 3-week oral antibiotic regi-men has become accepted.5,6,12-14,25

Success of treatment correlatesmost closely with an adequateserum level of the antibiotic, ratherthan the route of administration.25

Doses that are two to three timesthe package recommendation aregenerally necessary to ensure apeak serum titer greater than orequal to 1:8.2,25 Inability to reliablytake oral medications, poor oralabsorption, poor response to intra-venous therapy, inadequate moni-toring of antibiotic levels, and inad-equate improvement of the localenvironment by surgery have beenimplicated in treatment failures

using this approach.2,6,25 Early treat-ment protocols suggested transitionto oral antibiotics once clinical im-provement was observed, with treat-ment continuing until normalizationof the ESR.25

Peltola et al12 documented suc-cessful treatment of acute hematog-enous osteomyelitis in childrenfrom 3 months to 14 years old witha very short course of intravenousantibiotics followed by oral therapy.The authors utilized changes in theCRP level to guide treatment. Ini-tiation of oral treatment resulted ina rapid fall in the CRP and an im-provement in the clinical course.Treatment was discontinued whenthe CRP level and ESR normalized.The average length of intravenoustreatment was 5 days, and the totalduration of treatment averaged 23days. A more controversial issue inthis study was the absence of serummonitoring of antibiotic levels. Theauthors used very high doses ofcefadroxil (150 mg per kilogram ofbody weight per day in four doses)or clindamycin, which is readilyabsorbed. No failures of treatmentwere seen in this study with a mini-mum follow-up period of 1 year.

In our institution over the past 5years, we have utilized a protocolwhereby empirical treatment is startedwith high-dose intravenous cefazolinafter obtaining local and/or bloodcultures for all bone and joint infec-tions. A regimen of 100 to 150 mg/kg/day is started, with doses admin-istered every 8 hours. Serial valuesfor CRP are checked. Once clinicalimprovement is seen and the CRPlevel approaches normal, oral cepha-lexin therapy is started at a dosage of150 mg/kg/day, with doses every 6hours. Peak serum levels are checkedafter the fourth dose. If the responseis adequate, the patient is discharged,and antibiotic treatment is continueduntil the ESR normalizes. A weeklyoutpatient CBC count with differentialis obtained to monitor for the develop-ment of antibiotic-induced neutrope-nia. In our series of 40 consecutivepatients treated in this manner, theaverage length of antibiotic treatmentwas 21 days. There were no relapses.

There are no reports of neonateswith osteomyelitis being treated byintravenous-oral regimens. Seriouspermanent sequelae occur in 6% to50% of affected children due to themultiple sites of involvement (in

Table 2Common Pathogens and Recommended Antibiotic Therapy

Age Likely Organisms Intravenous Antibiotic Treatment Oral Antibiotic Therapy (in 4 doses)

Neonate Staphylococcus aureus Nafcillin, 150-200 mg/kg/day and Dicloxacillin, 75-100 mg/kg/day orBeta-hemolytic Streptococcus Gentamicin, 5.0-7.5 mg/kg/day or Cephalexin, 100-150 mg/kg/day or

(group A, group B) Cefotaxime, 150 mg/kg/day Clindamycin, 30 mg/kg/dayGram-negative rods

Infant/ S aureus Non-Hib-immunized: Dicloxacillin, 75-100 mg/kg/day ortoddler Haemophilus influenzae Nafcillin, 150 mg/kg/day and Cephalexin, 100-150 mg/kg/day or<3 yr old type b (Hib) Cefotaxime, 100-150 mg/kg/day Clindamycin, 30 mg/kg/day

Pneumococci Single-agent treatment: Streptococci Cefuroxime, 150-200 mg/kg/day

Child S aureus Hib-immunized: Dicloxacillin, 75-100 mg/kg/day or≥3 yr old Cefazolin, 100-150 mg/kg/day or Cephalexin, 100-150 mg/kg/day or

Nafcillin, 150-200 mg/kg/day or Clindamycin, 30 mg/kg/dayClindamycin, 30-40 mg/kg/day

Acute Hematogenous Osteomyelitis in Children

Journal of the American Academy of Orthopaedic Surgeons174

20% to 50% of cases) and the highrate of concomitant septic arthritis.Because neonates are more prone togeneralized sepsis, have less consis-tent oral antibiotic absorption, andhave a less predictable radiographicand serologic response to treatment,it has generally been recommendedthat the entire course of treatmentbe intravenous.3,4,10

Uncomplicated pelvic and verte-bral osteomyelitis or diskitis2-4,36

and calcaneal osteomyelitis37 in chil-dren have been successfully treatedwith antibiotics without surgical in-tervention. The necessary durationof antibiotic treatment regimens isfrequently longer than for osteomy-elitis in an extremity, although thesurgical indications are the same.

Surgical TreatmentThe indications for surgical inter-

vention have been controversial.38,39

The primary aim of surgery is to im-prove the local environment for anti-biotic delivery. A “hole-in-bone” ap-pearance has not been shown tomandate surgical intervention un-less there is aspiration of purulentmaterial. Rates of surgical interven-tion have decreased with the adventof better antibiotic treatment for os-teomyelitis, the heightened aware-ness that has led to earlier detectionof infections, and a shift toward moresubacute forms of osteomyelitis,which do not routinely require sur-gical debridement.40 The cited rates

of surgical intervention in earlierstudies ranged from 22%39 to ashigh as 83%,25 compared with 8% to45% in more recent series.6,12,38 Thepresence of subperiosteal, associatedsoft-tissue, or bone abscess on aspi-ration; an obvious osseous seques-trum; failure to respond to antibiotictherapy; and concomitant septicarthritis in a deep joint are generallyrecognized indications for surgicalintervention.2,4,6,12,25,38,39

Complications

Major complications related to os-teomyelitis are becoming less com-mon. Recurrent infection, chronicosteomyelitis, pathologic fracture,and growth disturbance have beenlinked to late recognition and inad-equate treatment of acute hematog-enous osteomyelitis.5 Children whopresent with combined osteomye-litis and septic arthritis have beenobserved to have a more prolongedcourse of recovery13 and a greaterpotential for growth disturbanceand long-term sequelae.2,3

Excessive surgical debridementcan also cause pathologic fracture andgrowth arrest with subsequent limb-length discrepancy or angular defor-mity.4 Complications associated withantibiotic treatment have been few.Diarrhea, nausea, rash, thrombocyto-sis, transient changes in liver en-zymes, and antibiotic-induced neu-

tropenia have been observed withhigh-dose oral antibiotic therapy.25

Summary

The management of acute hematog-enous osteomyelitis has been greatlyimproved by enhanced imagingcapabilities and advances in antibi-otic therapy. Early recognition andprompt intervention will decreasethe morbidity associated with thiscondition. Initial evaluation shouldinclude plain radiography; serologicstudies, including ESR, CRP, CBCcount with differential and smear;blood cultures; and, when possible,aspiration of the suspected site.

Empirical intravenous treatmentbased on the known epidemiologyof age-specific pathogens should bestarted, with antibiotic selectionmodified on the basis of the cultureresults. Sequential intravenous-oraltherapy is now accepted, with tran-sition based on the clinical and/orCRP response to treatment. Moni-toring of serum antibiotic levels iscontroversial, but may be helpful toensure adequate treatment.

Surgical treatment is warrantedif there is aspiration of purulentmaterial from the suspected site, anobvious area of necrotic bone, orfailure to rapidly respond to antibi-otic therapy. Generally good out-comes with few long-term compli-cations can be expected.

References

1. Sonnen GM, Henry NK: Pediatric boneand joint infections: Diagnosis and anti-microbial management. Pediatr ClinNorth Am 1996;43:933-947.

2. Krogstad P, Smith AL: Osteomyelitisand septic arthritis, in Feigin RD,Cherry JD (eds): Textbook of PediatricInfectious Diseases, 4th ed. Philadelphia:WB Saunders, 1998, vol 1, pp 683-704.

3. Gutierrez KM: Osteomyelitis, in LongSS, Pickering LK, Prober CG (eds):Principles and Practice of Pediatric In-

fectious Diseases. New York: ChurchillLivingstone, 1997, pp 528-536.

4. Morrissy RT: Bone and joint sepsis, inMorrissy RT, Weinstein SL (eds):Lovell & Winter’s Pediatric Orthopaedics,4th ed. Philadelphia: Lippincott-Raven, 1996, vol 1, pp 579-624.

5. Karwowska A, Davies HD, Jadavji T:Epidemiology and outcome of osteo-myelitis in the era of sequential intra-venous-oral therapy. Pediatr Infect DisJ 1998;17:1021-1026.

6. Scott RJ, Christofersen MR, RobertsonWW Jr, Davidson RS, Rankin L,Drummond DS: Acute osteomyelitisin children: A review of 116 cases. JPediatr Orthop 1990;10:649-652.

7. Bowerman SG, Green NE, Mencio GA:Decline of bone and joint infectionsattributable to Haemophilus influenzaetype b. Clin Orthop 1997;341:128-133.

8. Norden CW: Lessons learned fromanimal models of osteomyelitis. RevInfect Dis 1988;10:103-110.

Kit M. Song, MD, and John F. Sloboda, MD

Vol 9, No 3, May/June 2001 175

9. Cunningham R, Cockayne A, Humph-reys H: Clinical and molecular aspectsof the pathogenesis of Staphylococcusaureus bone and joint infections. J MedMicrobiol 1996;44:157-164.

10. Wong M, Isaacs D, Howman-Giles R,Uren R: Clinical and diagnostic fea-tures of osteomyelitis occurring in thefirst three months of life. Pediatr InfectDis J 1995;14:1047-1053.

11. Faden H, Grossi M: Acute osteomye-litis in children: Reassessment of etio-logic agents and their clinical charac-teristics. Am J Dis Child 1991;145:65-69.

12. Peltola H, Unkila-Kallio L, Kallio MJT,Finnish Study Group: Simplifiedtreatment of acute staphylococcalosteomyelitis of childhood. Pediatrics1997;99:846-850.

13. Unkila-Kallio L, Kallio MJT, Peltola H:The usefulness of C-reactive proteinlevels in the identification of concur-rent septic arthritis in children whohave acute hematogenous osteomye-litis: A comparison with the usefulnessof the erythrocyte sedimentation rateand the white blood-cell count. J BoneJoint Surg Am 1994;76:848-853.

14. Roine I, Faingezicht I, Arguedas A,Herrera JF, Rodríguez F: Serial serumC-reactive protein to monitor recoveryfrom acute hematogenous osteomye-litis in children. Pediatr Infect Dis J1995;14:40-44.

15. Roine I, Arguedas A, Faingezicht I,Rodriguez F: Early detection ofsequela-prone osteomyelitis in chil-dren with use of simple clinical andlaboratory criteria. Clin Infect Dis1997;24:849-853.

16. Larsson S, Thelander U, Friberg S: C-reactive protein (CRP) levels after elec-tive orthopedic surgery. Clin Orthop1992;275:237-242.

17. Foglar C, Lindsey RW: C-reactive pro-tein in orthopedics. Orthopedics 1998;21:687-691.

18. Benitz WE, Han MY, Madan A, Rama-

chandra P: Serial serum C-reactiveprotein levels in the diagnosis of neo-natal infection [abstract]. Pediatrics1998;102:E41.

19. Boutin RD, Brossmann J, Sartoris DJ,Reilly D, Resnick D: Update on imag-ing of orthopedic infections. OrthopClin North Am 1998;29:41-66.

20. Jaramillo D, Treves ST, Kasser JR,Harper M, Sundel R, Laor T: Osteo-myelitis and septic arthritis in chil-dren: Appropriate use of imaging toguide treatment. AJR Am J Roentgenol1995;165:399-403.

21. Mandell GA: Imaging in the diagnosisof musculoskeletal infections in chil-dren. Curr Probl Pediatr 1996;26:218-237.

22. Tuson CE, Hoffman EB, Mann MD:Isotope bone scanning for acute osteo-myelitis and septic arthritis in children.J Bone Joint Surg Br 1994;76:306-310.

23. Mazur JM, Ross G, Cummings RJ,Hahn GA Jr, McCluskey WP: Useful-ness of magnetic resonance imagingfor the diagnosis of acute musculo-skeletal infections in children. J PediatrOrthop 1995;15:144-147.

24. Gylys-Morin VM: MR imaging of pe-diatric musculoskeletal inflammatoryand infectious disorders. Magn ResonImaging Clin N Am 1998;6:537-559.

25. Nelson JD, Bucholz RW, Kusmiesz H,Shelton S: Benefits and risks of sequen-tial parenteral-oral cephalosporin ther-apy for suppurative bone and joint in-fections. J Pediatr Orthop 1982;2:255-262.

26. Dahl LB, Hoyland AL, Dramsdahl H,Kaaresen PI: Acute osteomyelitis inchildren: A population-based retro-spective study 1965 to 1994. Scand JInfect Dis 1998;30:573-577.

27. Tröbs RB, Möritz RP, Bühligen U, et al:Changing pattern of osteomyelitis ininfants and children. Pediatr Surg Int1999;15:363-372.

28. Epperly TD: The value of needle aspi-ration in the management of cellulitis.J Fam Pract 1986;23:337-340.

29. Hoeffel DP, Hinrichs SH, Garvin KL:Molecular diagnostics for the detectionof musculoskeletal infection. ClinOrthop 1999;360:37-46.

30. Tompkins LS: The use of molecularmethods in infectious diseases. N EnglJ Med 1992;327:1290-1297.

31. Mariani BD, Martin DS, Levine MJ,Booth RE Jr, Tuan RS: Polymerasechain reaction detection of bacterialinfection in total knee arthroplasty.Clin Orthop 1996;331:11-22.

32. Abbasi S, Orlicek SL, Almohsen I,Luedtke G, English BK: Septic arthri-tis and osteomyelitis caused by peni-cillin and cephalosporin-resistantStreptococcus pneumoniae in a children’shospital. Pediatr Infect Dis J 1996;15:78-83.

33. Gwynne-Jones DP, Stott NS: Commu-nity-acquired methicillin-resistantStaphylococcus aureus: A cause of mus-culoskeletal sepsis in children. JPediatr Orthop 1999;19:413-416.

34. Perl TM: The threat of vancomycinresistance. Am J Med 1999;106:26S-37S.

35. Dich VQ, Nelson JD, Haltalin KC:Osteomyelitis in infants and children:A review of 163 cases. Am J Dis Child1975;129:1273-1278.

36. Highland TR, LaMont RL: Osteomye-litis of the pelvis in children. J BoneJoint Surg Am 1983;65:230-234.

37. Jaakkola J, Kehl D: Hematogenouscalcaneal osteomyelitis in children. JPediatr Orthop 1999;19:699-704.

38. LaMont RL, Anderson PA, Dajani AS,Thirumoorthi MC: Acute hematoge-nous osteomyelitis in children. JPediatr Orthop 1987;7:579-583.

39. Cole WG, Dalziel RE, Leitl S: Treatmentof acute osteomyelitis in childhood. JBone Joint Surg Br 1982;64:218-223.

40. Hamdy RC, Lawton L, Carey T, WileyJ, Marton D: Subacute hematogenousosteomyelitis: Are biopsy and surgeryalways indicated? J Pediatr Orthop1996;16:220-223.