Acute Hematogenous Osteomyelitis in Children

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

Abstract
Acute hematogenous osteomyelitis in children is a relatively uncommon but potentially serious disease. Improvements in radiologic imaging, most notably magnetic resonance imaging, and a heightened awareness of this condition have led to earlier detection and resultant marked decreases in morbidity and mortality. Staphylococcus aureus, which has the ability to bind to cartilage, produce a protective glycocalyx, and stimulate the release of endotoxins, accounts for 90% of infections in all age groups. Infections with Haemophilus influenzae have become rare in immunized children. A careful history and a thorough physical examination remain important. Positive cultures are obtained in only 50% to 80% of cases; the yield is improved by the use of blood cultures and evolving molecular techniques. Improvements in antibiotic treatment have lessened the role of surgery in managing these infections. Sequential intravenous and high-dose oral antibiotic therapy is now an accepted modality. Evaluation of response to treatment by monitoring C-reactive protein levels has decreased the average duration of therapy to 3 to 4 weeks with few relapses. The emergence of antibiotic resistance, particularly resistance to methicillin and vancomycin by S aureus organisms, is of increasing concern. Long-term sequelae and morbidity are primarily due to delays in diagnosis and inadequate treatment. J Am Acad Orthop Surg 2001;9:166-175

Basic Science
The etiology and pathophysiology of bone infections are still incompletely defined. Introduction of bacteria into bone can occur by direct inoculation, hematogenous spread from bacteremia, or local invasion from a contiguous focus of infection. A history of trauma is common. Most long-bone infections occur in the metaphyseal portions of tubular bones of the lower extremities (Fig. 1). The majority of infections involve only a single bone; involvement at two or more sites is very uncommon except in neonatal infections. Infection spreads via Volkmanns canals or the haversian bone system through the metaphyseal bone to the subperiosteal space. Elevation of the periosteum can result in abscess formation. In severe cases, infarction of cortical bone may lead to the formation of a sequestrum and chronic osteomyelitis. Septic arthritis can occur in joints in which the metaphysis is intra-

The annual rate of acute hematogenous osteomyelitis in children under the age of 13 in the United States is estimated to be approximately 1:5,000.1 Population studies show a worldwide incidence ranging from 1:1,000 to 1:20,000,2 making this an uncommon, but not a rare, problem. Half of all cases of acute hematogenous osteomyelitis occur in children under the age of 5.3 Neonatal osteomyelitis is estimated to occur in 1 to 3 infants per 1,000 intensive-care-nursery admissions.3 Before the advent of antibiotics, bacterial osteomyelitis in children carried mortality rates of 20% to 50%. 2,4 Advances in antibiotic treatment, diagnostic modalities, and surgical management have

made death uncommon, but morbidity due to delays in diagnosis and inadequate treatment continue to result in permanent sequelae and poor outcomes in as many as 6% of affected children.4,5 Failure of cultures to demonstrate pathogenic bacteria in many patients, poor understanding of the pathophysiology of bone infections, and emerging antibiotic resistance have led to the development of many different empirical treatments. However, recent advances in the evaluation and management of acute hematogenous osteomyelitis and a thorough understanding of this disease entity will help to ensure accurate diagnosis and prompt treatment.

Dr. Song is Assistant Director of Orthopedic Surgery, Childrens Hospital and Regional Medical Center of Seattle, Seattle, Wash. Dr. Sloboda is Resident in Orthopaedic Surgery, Madigan Army Medical Center, Tacoma, Wash. Reprint requests: Dr. Song, Department of Orthopedic Surgery, Childrens Hospital and Regional Medical Center of Seattle, 4800 Sand Point Way NE, Seattle WA 98105. Copyright 2001 by the American Academy of Orthopaedic Surgeons.

166

Journal of the American Academy of Orthopaedic Surgeons

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

Humerus 12%

Pelvis 9%

Ulna 3% Radius 4%

Femur 27%

Hands and feet 13%

Tibia 22% Fibula 5%

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

articular (e.g., hip, shoulder, and ankle). It has been estimated that 10% to 16% of cases of septic arthritis are secondary to bacterial osteomyelitis. The avascular physis generally limits extension of infection into the epiphysis except in neonates and infants. Blood vessels cross the physis until approximately 15 to 18 months of age, with the potential for concomitant septic arthritis. This may be present in as many as 75% of cases of neonatal osteomyelitis.3

Fewer than 20% of infections occur in nontubular bones. The calcaneus and pelvis are the most common sites. Infections in the flat bones (e.g., the skull, scapula, ribs, and sternum) and the spine are rare.2 Staphylococcus aureus is by far the most common pathogen causing acute hematogenous osteomyelitis in all age categories. It has been implicated in as many as 89% of all infections. Streptococcus pneumoniae, group A Streptococcus, and coagulasenegative staphylococci are more ageand disease-specific. Group B streptococci have been found with greater frequency in neonates, but account for only 3% of infections in this age group.3 Infections with these pathogens generally result in a single focus of infection, unlike neonatal infections with group A streptococci and S aureus. The introduction of a vaccine against Haemophilus influenzae type b has led to a marked decline in the incidence of infections by this organism from 2% to 5% of all bone infections to nearly 0% in immunized children.1-3,5-7 Avian models of bone infection most closely mimic what is observed in humans and have provided information about the pathophysiology of bone infections. Gaps in the endothelium of growing metaphyseal vessels allow the passage of bacteria that then adhere to type I collagen in the hypertrophic zone of the growth plate. Staphylococcus aureus surface antigens appear to play a key role in this local adherence, while endotoxins suppress local immune response. An extensive glycocalyx surrounding each bacterium enhances adhesion of other bacteria and may be protective against antibiotic treatment. Bacterial proliferation then occurs, occluding vascular tunnels within 24 hours. Abscesses appear after 48 hours, with local tissue necrosis and extension beyond the calcifying area of the growth plate. Four to eight days after infection, localized sequestra of dead cartilage

are formed, and infection extends beyond the metaphysis. Further bone destruction may be mediated by prostaglandin production as a result of S aureus infection.8,9

Diagnosis
Bacterial osteomyelitis in children must be differentiated from the wide range of conditions that may present with clinical symptoms and signs mimicking infection (Table 1).

Table 1 Differential Diagnosis of a Painful, Swollen Extremity in a Child Systemic conditions Acute rheumatic fever Chronic recurrent multifocal osteomyelitis Fungal arthritis Gauchers disease Henoch-Schnlein purpura Histiocytosis Leukemia Primary bone malignant tumors Reactive arthritis Reiters syndrome Round cell tumors Sarcoidosis Septic arthritis Sickle cell disease Systemic juvenile rheumatoid arthritis Tuberculosis Nonsystemic conditions Cellulitis Fracture/nonaccidental trauma Hemangioma/lymphangioma Histiocytosis Legg-Perthes disease Osteochondrosis Overuse syndromes Reactive arthritis Reflex neurovascular dystrophy Slipped capital femoral epiphysis Stress fracture/toddlers fracture Subacute osteomyelitis Transient synovitis

Vol 9, No 3, May/June 2001

167

Acute Hematogenous Osteomyelitis in Children

The history and physical examination findings associated with acute hematogenous osteomyelitis are sensitive but rarely specific. The most frequent clinical findings are fever, pain at the site of infection, and limited use of the affected extremity. Constitutional symptoms, such as lethargy and anorexia, are less common. The degree of abnormality does not correlate with the extent of infection, and older children will often have more subtle symptoms. Most patients will have had symptoms for less than 2 weeks. On physical examination, signs are often age-dependent. Neonates have a thin periosteum that is easily penetrated by infection and as a result frequently have swelling at the affected site and irritability on movement of the limb. Infants and young children will have point tenderness with limited ability to bear weight or use the extremity. Older children, with their thicker metaphyseal cortex and densely adherent periosteum, will generally have point tenderness and a mild limp. Cellulitis is occasionally present and may be a manifestation of an underlying abscess.1-4,6,10 lowing response to treatment of acute hematogenous osteomyelitis.12-14 On presentation, it is elevated in as many as 97% of patients. The degree of rise of the CRP has not been correlated with severity of infection. The CRP rises more rapidly than the ESR after onset of infection, with synthesis beginning within 4 to 6 hours after injury and peaking after 24 to 72 hours (Fig. 2). Failure of the CRP level to fall rapidly after initiation of treatment has been predictive of long-term sequelae.15 Unlike the ESR, the CRP concentration is independent of the physical properties of cells and is a direct quantitative measurement. Similar to the ESR, it will rise and fall after surgery, trauma, or systemic illnesses, as well as in patients with benign and malignant tumors, thereby limiting its usefulness in some situations.16,17 Both the ESR and CRP are frequently elevated in neonatal infections, 18 but the response to treatment of these indices has not yet been documented.

Radiologic Evaluation Radiography remains an essential tool for diagnosing and managing osteomyelitis in children and should be performed in every case of suspected infection. The sensitivity and specificity of radiographs range from 43% to 75% and from 75% to 83%,19 respectively (Fig. 3). Softtissue swelling will be evident within 48 hours of the onset of infection. Periosteal new-bone formation may be evident by 5 to 7 days. Osteolytic changes require bone mineral loss of at least 30% to 50% and may take 10 days to 2 weeks after the onset of symptoms to develop.19,20 Technetium-99m bone scintigraphy is useful in the setting of normal radiographs and clinical suspicion of osteomyelitis (Figs. 4, A; 5, B). It can be positive within 24 to 48 hours of the onset of symptoms. The reported sensitivity ranges from 84% to 100% for detection of osteomyelitis; the specificity, from 70% to 96%.19 Aspiration of bone has not been shown to create a false-positive result if bone scintig-

Serologic Studies Serologic studies that should be ordered when evaluating a child with possible acute hematogenous osteomyelitis include a complete blood cell (CBC) count with differential and peripheral smear, erythrocyte sedimentation rate (ESR), Creactive protein (CRP) determination, and blood cultures. As most blood counts are automated, inspection of the peripheral smear can be helpful in eliminating the possibility of leukemia. The white blood cell (WBC) count will be elevated in 31% to 40% of patients with acute hematogenous osteomyelitis6,11,12; the ESR, in up to 91%.6,11-13 Several authors have reported on the usefulness of the CRP level in making the diagnosis and fol-

CRP, mg/L ESR, mm/hr 160 140

Osteomyelitis alone

CRP, mg/L ESR, mm/hr 160 140

Osteomyelitis with adjacent arthritis

120 100

120 100

CRP
80 80

CRP ESR
60 40 20 0

ESR
60 40 20 0 0 Days 5 10 15 20 25 30

0 Days

10

15

20

25

30

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 with permission from Unkila-Kallio L, Kallio MJT, Peltola H: The usefulness of C-reactive protein levels in the identification of concurrent septic arthritis in children who have acute hematogenous osteomyelitis: A comparison with the usefulness of the erythrocyte sedimentation rate and the white blood-cell count. J Bone Joint Surg Am 1994;76:848-853.)

168

Journal of the American Academy of Orthopaedic Surgeons

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

Figure 3 A, Radiograph of a child with a swollen forearm, elevated temperature, and elevated CRP value. B, Technetium bone scan performed 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 segmental bone loss in the radius.

raphy is carried out within 24 hours of aspiration. The use of pinholecollimated views and single-photonemission computed tomography (SPECT) (Fig. 5, C) can increase both sensitivity and specificity.21 In the early stages of an infection, scintigraphy may show decreased uptake because of the relative ischemia caused by the increased pressure from the presence of purulent material (Fig. 3). Such cold scans have been reported to have a positive predictive value of 100%, compared with a positive predictive value of 83% for hot scans.21,22 Scintigraphy is of more limited use in neonatal infections, with reported sensitivity ranging from 30% to 86%; radiography may be more sensitive in this setting.2,3,10 Gallium scanning, although more sensitive for infection than Tc-99m scanning, delivers a higher amount of radiation, may take up to 48 hours to perform, and is not specific for infection. Scanning with indium111tagged WBCs can be helpful in those rare situations in which osteomyelitis is suspected but the

Tc-99m scan appears normal.2,19 It requires preparation time and can take as long as 24 hours to perform. Monoclonal antibody scans have been investigated, but are as yet of unproven benefit.2 Magnetic resonance imaging has a reported sensitivity of 88% to 100% and a specificity of 75% to 100% in the detection of osteomyelitis. The positive-predictive values for MR imaging and Tc-99m scintigraphy are comparable (85% and 83%).20 However, MR imaging can provide biplanar images of the infected site and is superior to scintigraphy and CT for depicting the marrow cavities of long bones and adjacent soft tissues. It is most useful for detecting spinal and pelvic infections (Fig. 5, D) and for planning surgical approaches for debridement when a subperiosteal or soft-tissue abscess may be present.19-21,23,24 Characteristic T1- and T2-weighted images can be used to differentiate acute, subacute, and chronic osteomyelitis.24 T1-weighted and short-tau inversion recovery (STIR) images are most useful for

the detection of acute osteomyelitis (Fig. 4). The use of gadolinium enhancement can aid in identifying sinus tracts and distinguishing cellulitis from abscess.19 Like scintigraphy, MR imaging is limited by a lack of specificity; the signal patterns seen with fractures, bone infarction, tumors, postsurgical changes, bone contusions, and sympathetic edema are similar.24 Computed tomography has been most useful in the detection of gas in soft-tissue infections and in the identification of sequestra in cases of chronic osteomyelitis.19,21 It is also useful in diagnosing and accurately defining the location of pelvic and spinal infections after localization with scintigraphy (Fig. 5). For deep infections, needle localization prior to biopsy or debridement can be helpful. Ultrasonography is attractive for evaluating the possibility of bone and joint infections in children because of its low cost, relative availability, and noninvasive nature, as well as because there is no ionizing radiation involved and no need for

Vol 9, No 3, May/June 2001

169

Acute Hematogenous Osteomyelitis in Children

ment is critical to effective management.2,3,25 However, direct culture of the affected bone results in isolation of the bacterial agent in only 48% to 85% of cases.5,6,26,27 Given the potentially low yield from cultures and the reluctance to perform invasive procedures on distressed children, it may be tempting not to perform bone aspiration. Nevertheless, concerns about emerging antibiotic resistance by bacteria make the identification of pathogens and the use of organism-specific treatment desirable. Aspiration is easily performed through thin metaphyseal bone with an 18-gauge spinal needle, and the central trocar can be used to disengage any bone plugs created by passage through the cortex. Local infiltration of lidocaine into the tissues combined with intravenous sedation is generally effective. The aspiration of bone through an overlying area of cellulitis has not been shown to cause osteomyelitis. Direct culture of cellulitic areas yields a positive culture in fewer than 10% of cases,28 with Staphylococcus and Streptococcus species being most commonly isolated. Blood cultures are positive in 30% to 60% of cases of acute osteomyelitis in children. 1,4,6,27 The use of multiple blood cultures has not been shown to increase the likelihood of having a positive culture, especially if the samples were drawn after the initiation of antibiotic treatment. The combination of blood and direct cultures provides the highest yield, but in many cases treatment of presumed infections will be empirical, based on clinical and radiographic criteria. Most bacterial cultures will be positive within 48 hours of specimen collection. However, fastidious organisms may take as long as 7 days to become positive. A survey of hospitals in one area showed that cultures are held an average of 5 days before being discarded.

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 by biopsy and treated with intravenous antibiotics. C, A STIR MR image further demonstrates acute osteomyelitis. D, Gradient-echo MR image illustrates growth arrest due to the infection.

sedation. It has been used to detect intra-articular, soft-tissue, and subperiosteal fluid collections prior to their appearance on plain radiographs. However, the lack of specificity, dependence on operator skill, and inability to image marrow or show cortical detail of bone have limited the usefulness of ultrasound compared with MR imaging or CT. An algorithm for radiologic evaluation of suspected bone infections is shown in Figure 6. Radiography should be the initial study. If positive, MR imaging, CT, or

ultrasonography can be used to define the infected area and to plan surgical approaches if needed. If the results of any of those studies are negative, scintigraphy can be very helpful in isolating the infected area, after which one of the other modalities can be used to provide additional information for treatment planning.

Bacterial Cultures Obtaining cultures of organisms directly from sites of bone infection in order to focus antibiotic treat-

170

Journal of the American Academy of Orthopaedic Surgeons

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

A Acetabular roof

Proximal femur 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, Brodies abscess of the acetabulum was localized on this CT scan prior to biopsy.

The relatively low yield of standard bacterial cultures has stimulated interest in using molecular tecniques for detection and speciation of bacterial and viral infections. Molecular methods have been shown to be more sensitive than standard culture techniques for detecting pathogens and can do so even in the absence of viable organisms. These techniques fall into two broad categories: nonamplified and amplified. With nonamplified techniques, direct binding of a target molecule is done with a labeled oligonucleotide probe or monoclonal antibody, followed by detection of the probe agent with radiolabeling, enzyme-linked immunosorbent assay, or chemoluminescence. These methods are specific and applicable when looking for a particular organism. With amplified techniques, geometric amplification of the target

molecule is achieved by using enzyme-driven reactions. The most common of these techniques is the polymerase chain reaction (PCR). The basis of these methods is to target a portion of bacterial DNA or RNA that is not present in human cells. A probe or primer specific to that region of DNA or RNA is introduced, which on binding promotes binding of a polymerase that replicates the target region in a series of temperature-dependent cycles. The amplified products are then identified by gel electrophoresis. Much recent work has focused on the highly conserved area of DNA that codes for the 16s ribosomal RNA subunit. There is enough gene sequence variation within this area to allow differentiation among bacterial species and from human DNA.29,30 Polymerase chain reaction has produced some promising results

in diagnosing periprosthetic infections and septic arthritis, but a high false-positive rate has been observed.31 The PCR method has been found to be very sensitive for the detection of infection when a primer for a specific organism is used. In cases of polymicrobial infection or infection due to an unknown bacterial strain, the use of universal primers that amplify all bacterial species present is being developed. Identification of the amplified genetic material remains difficult.

Treatment
The management of acute hematogenous osteomyelitis is largely nonoperative. The role of surgery is to improve the local environment by removing infected devitalized bone and soft tissue, decompressing a

Vol 9, No 3, May/June 2001

171

Acute Hematogenous Osteomyelitis in Children

Suspicion of osteomyelitis (clinical/serologic evidence)

Radiographic evaluation

Negative

Positive

Bone scan Antibiotic therapy Negative Positive No clinical improvement in 48 hr Negative Positive Consider aspiration

MR imaging, CT, or ultrasound for abscess/sequestrum

Antibiotic therapy

Positive

Negative

MR imaging, CT, or ultrasound; reassess diagnosis

Biopsy, surgical debridement

Antibiotic therapy

Biopsy, surgical debridement

Figure 6

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

large abscess cavity, and facilitating antibiotic delivery. If antibiotic treatment is initiated before significant bone and soft-tissue necrosis has occurred, it is more likely to be successful without the need for surgical treatment.

Antibiotic Therapy Most recent studies of antibiotic treatment of acute hematogenous osteomyelitis have emphasized a sequential parenteral-oral antibiotic regimen. 2,3,5,12,13 Due to the low yield of culture techniques, empirical treatment based on known epidemiologic trends in different age groups and at-risk populations will often be necessary (Table 2). Empirical antibiotic coverage should always include coverage for S aureus, as this is the most common pathogen in all age groups. For neo-

natal osteomyelitis, treatment targeting group B streptococci and Gram-negative rods should be added. Children less than 4 years of age need antibiotic coverage for H influenzae type b if the immunization program has not been completed or the history is uncertain. For fully immunized children, the most likely pathogens are S aureus, Streptococcus pyogenes, and S pneumoniae. For immunocompromised children with sickle cell disease, broad-spectrum coverage to include Salmonella species should be included. Children with human immunodeficiency virus (HIV) infection have a propensity for infection by S pneumoniae. However, to date, there is no evidence to suggest that presenting signs and symptoms or recovery from infection are affected by coinfection by HIV. Broad-spectrum

coverage is suggested for HIVpositive children due to the wide range of organisms reported.2 Antibiotic selection should subsequently be altered according to the results of culture and sensitivity testing. There are concerns about emerging antibiotic resistance. Methicillin- and cephalosporinresistant S aureus organisms have been reported in as many as 20% of community-acquired bone and joint infections.32,33 Recently, emergence of vancomycin-resistant S aureus in Japan and parts of the United States has raised the specter of emerging bacterial strains for which there are no known antibiotic treatments.34 The duration and route of administration of antibiotic treatment have previously been empirical, with the length of intravenous therapy ranging from 4 to 8 weeks. The du-

172

Journal of the American Academy of Orthopaedic Surgeons

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

ration of antibiotic treatment has not been related to the presence or absence of positive blood or direct cultures; antibiotic sensitivity or resistance of the bacteria; degree of elevation of the WBC count, CRP, or ESR; presence or absence of purulent material; or symptoms at presentation. Authors of earlier studies suggested that a total duration of treatment of less than 3 weeks is associated with a higher rate of relapse.35 Although previously controversial, the need to complete at least a 3-week oral antibiotic regimen has become accepted.5,6,12-14,25 Success of treatment correlates most closely with an adequate serum level of the antibiotic, rather than the route of administration.25 Doses that are two to three times the package recommendation are generally necessary to ensure a peak serum titer greater than or equal to 1:8.2,25 Inability to reliably take oral medications, poor oral absorption, poor response to intravenous therapy, inadequate monitoring of antibiotic levels, and inadequate improvement of the local environment by surgery have been implicated in treatment failures

using this approach.2,6,25 Early treatment protocols suggested transition to oral antibiotics once clinical improvement was observed, with treatment continuing until normalization of the ESR.25 Peltola et al12 documented successful treatment of acute hematogenous osteomyelitis in children from 3 months to 14 years old with a very short course of intravenous antibiotics followed by oral therapy. The authors utilized changes in the CRP level to guide treatment. Initiation of oral treatment resulted in a rapid fall in the CRP and an improvement in the clinical course. Treatment was discontinued when the CRP level and ESR normalized. The average length of intravenous treatment was 5 days, and the total duration of treatment averaged 23 days. A more controversial issue in this study was the absence of serum monitoring of antibiotic levels. The authors used very high doses of cefadroxil (150 mg per kilogram of body weight per day in four doses) or clindamycin, which is readily absorbed. No failures of treatment were seen in this study with a minimum follow-up period of 1 year.

In our institution over the past 5 years, we have utilized a protocol whereby empirical treatment is started with high-dose intravenous cefazolin after obtaining local and/or blood cultures for all bone and joint infections. A regimen of 100 to 150 mg/ kg/day is started, with doses administered every 8 hours. Serial values for CRP are checked. Once clinical improvement is seen and the CRP level approaches normal, oral cephalexin therapy is started at a dosage of 150 mg/kg/day, with doses every 6 hours. Peak serum levels are checked after the fourth dose. If the response is adequate, the patient is discharged, and antibiotic treatment is continued until the ESR normalizes. A weekly outpatient CBC count with differential is obtained to monitor for the development of antibiotic-induced neutropenia. In our series of 40 consecutive patients treated in this manner, the average length of antibiotic treatment was 21 days. There were no relapses. There are no reports of neonates with osteomyelitis being treated by intravenous-oral regimens. Serious permanent sequelae occur in 6% to 50% of affected children due to the multiple sites of involvement (in

Table 2 Common Pathogens and Recommended Antibiotic Therapy Age Neonate Likely Organisms Intravenous Antibiotic Treatment Oral Antibiotic Therapy (in 4 doses) Dicloxacillin, 75-100 mg/kg/day or Cephalexin, 100-150 mg/kg/day or Clindamycin, 30 mg/kg/day Dicloxacillin, 75-100 mg/kg/day or Cephalexin, 100-150 mg/kg/day or Clindamycin, 30 mg/kg/day

Staphylococcus aureus Nafcillin, 150-200 mg/kg/day and Beta-hemolytic Streptococcus Gentamicin, 5.0-7.5 mg/kg/day or (group A, group B) Cefotaxime, 150 mg/kg/day Gram-negative rods S aureus Haemophilus influenzae type b (Hib) Pneumococci Streptococci S aureus Non-Hib-immunized: Nafcillin, 150 mg/kg/day and Cefotaxime, 100-150 mg/kg/day Single-agent treatment: Cefuroxime, 150-200 mg/kg/day Hib-immunized: Cefazolin, 100-150 mg/kg/day or Nafcillin, 150-200 mg/kg/day or Clindamycin, 30-40 mg/kg/day

Infant/ toddler <3 yr old

Child 3 yr old

Dicloxacillin, 75-100 mg/kg/day or Cephalexin, 100-150 mg/kg/day or Clindamycin, 30 mg/kg/day

Vol 9, No 3, May/June 2001

173

Acute Hematogenous Osteomyelitis in Children

20% to 50% of cases) and the high rate of concomitant septic arthritis. Because neonates are more prone to generalized sepsis, have less consistent oral antibiotic absorption, and have a less predictable radiographic and serologic response to treatment, it has generally been recommended that the entire course of treatment be intravenous.3,4,10 Uncomplicated pelvic and vertebral osteomyelitis or diskitis 2-4,36 and calcaneal osteomyelitis37 in children have been successfully treated with antibiotics without surgical intervention. The necessary duration of antibiotic treatment regimens is frequently longer than for osteomyelitis in an extremity, although the surgical indications are the same. of surgical intervention in earlier studies ranged from 22% 39 to as high as 83%,25 compared with 8% to 45% in more recent series.6,12,38 The presence of subperiosteal, associated soft-tissue, or bone abscess on aspiration; an obvious osseous sequestrum; failure to respond to antibiotic therapy; and concomitant septic arthritis in a deep joint are generally recognized indications for surgical intervention.2,4,6,12,25,38,39 tropenia have been observed with high-dose oral antibiotic therapy.25

Summary
The management of acute hematogenous osteomyelitis has been greatly improved by enhanced imaging capabilities and advances in antibiotic therapy. Early recognition and prompt intervention will decrease the morbidity associated with this condition. Initial evaluation should include plain radiography; serologic studies, including ESR, CRP, CBC count with differential and smear; blood cultures; and, when possible, aspiration of the suspected site. Empirical intravenous treatment based on the known epidemiology of age-specific pathogens should be started, with antibiotic selection modified on the basis of the culture results. Sequential intravenous-oral therapy is now accepted, with transition based on the clinical and/or CRP response to treatment. Monitoring of serum antibiotic levels is controversial, but may be helpful to ensure adequate treatment. Surgical treatment is warranted if there is aspiration of purulent material from the suspected site, an obvious area of necrotic bone, or failure to rapidly respond to antibiotic therapy. Generally good outcomes with few long-term complications can be expected.

Complications
Major complications related to osteomyelitis are becoming less common. Recurrent infection, chronic osteomyelitis, pathologic fracture, and growth disturbance have been linked to late recognition and inadequate treatment of acute hematogenous osteomyelitis.5 Children who present with combined osteomyelitis and septic arthritis have been observed to have a more prolonged course of recovery13 and a greater potential for growth disturbance and long-term sequelae.2,3 Excessive surgical debridement can also cause pathologic fracture and growth arrest with subsequent limblength discrepancy or angular deformity.4 Complications associated with antibiotic treatment have been few. Diarrhea, nausea, rash, thrombocytosis, transient changes in liver enzymes, and antibiotic-induced neu-

Surgical Treatment The indications for surgical intervention have been controversial.38,39 The primary aim of surgery is to improve the local environment for antibiotic delivery. A hole-in-bone appearance has not been shown to mandate surgical intervention unless there is aspiration of purulent material. Rates of surgical intervention have decreased with the advent of better antibiotic treatment for osteomyelitis, the heightened awareness that has led to earlier detection of infections, and a shift toward more subacute forms of osteomyelitis, which do not routinely require surgical debridement.40 The cited rates

References
1. Sonnen GM, Henry NK: Pediatric bone and joint infections: Diagnosis and antimicrobial management. Pediatr Clin North Am 1996;43:933-947. 2. Krogstad P, Smith AL: Osteomyelitis and septic arthritis, in Feigin RD, Cherry JD (eds): Textbook of Pediatric Infectious Diseases, 4th ed. Philadelphia: WB Saunders, 1998, vol 1, pp 683-704. 3. Gutierrez KM: Osteomyelitis, in Long SS, Pickering LK, Prober CG (eds): Principles and Practice of Pediatric Infectious Diseases. New York: Churchill Livingstone, 1997, pp 528-536. 4. Morrissy RT: Bone and joint sepsis, in Morrissy RT, Weinstein SL (eds): Lovell & Winters Pediatric Orthopaedics, 4th ed. Philadelphia: LippincottRaven, 1996, vol 1, pp 579-624. 5. Karwowska A, Davies HD, Jadavji T: Epidemiology and outcome of osteomyelitis in the era of sequential intravenous-oral therapy. Pediatr Infect Dis J 1998;17:1021-1026. 6. Scott RJ, Christofersen MR, Robertson WW Jr, Davidson RS, Rankin L, Drummond DS: Acute osteomyelitis in children: A review of 116 cases. J Pediatr Orthop 1990;10:649-652. 7. Bowerman SG, Green NE, Mencio GA: Decline of bone and joint infections attributable to Haemophilus influenzae type b. Clin Orthop 1997;341:128-133. 8. Norden CW: Lessons learned from animal models of osteomyelitis. Rev Infect Dis 1988;10:103-110.

174

Journal of the American Academy of Orthopaedic Surgeons

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

9. Cunningham R, Cockayne A, Humphreys H: Clinical and molecular aspects of the pathogenesis of Staphylococcus aureus bone and joint infections. J Med Microbiol 1996;44:157-164. 10. Wong M, Isaacs D, Howman-Giles R, Uren R: Clinical and diagnostic features of osteomyelitis occurring in the first three months of life. Pediatr Infect Dis J 1995;14:1047-1053. 11. Faden H, Grossi M: Acute osteomyelitis in children: Reassessment of etiologic agents and their clinical characteristics. Am J Dis Child 1991;145:65-69. 12. Peltola H, Unkila-Kallio L, Kallio MJT, Finnish Study Group: Simplified treatment of acute staphylococcal osteomyelitis of childhood. Pediatrics 1997;99:846-850. 13. Unkila-Kallio L, Kallio MJT, Peltola H: The usefulness of C-reactive protein levels in the identification of concurrent septic arthritis in children who have acute hematogenous osteomyelitis: A comparison with the usefulness of the erythrocyte sedimentation rate and the white blood-cell count. J Bone Joint Surg Am 1994;76:848-853. 14. Roine I, Faingezicht I, Arguedas A, Herrera JF, Rodrguez F: Serial serum C-reactive protein to monitor recovery from acute hematogenous osteomyelitis in children. Pediatr Infect Dis J 1995;14:40-44. 15. Roine I, Arguedas A, Faingezicht I, Rodriguez F: Early detection of sequela-prone osteomyelitis in children with use of simple clinical and laboratory criteria. Clin Infect Dis 1997;24:849-853. 16. Larsson S, Thelander U, Friberg S: Creactive protein (CRP) levels after elective orthopedic surgery. Clin Orthop 1992;275:237-242. 17. Foglar C, Lindsey RW: C-reactive protein in orthopedics. Orthopedics 1998; 21:687-691. 18. Benitz WE, Han MY, Madan A, Ramachandra P: Serial serum C-reactive protein levels in the diagnosis of neonatal infection [abstract]. Pediatrics 1998;102:E41. Boutin RD, Brossmann J, Sartoris DJ, Reilly D, Resnick D: Update on imaging of orthopedic infections. Orthop Clin North Am 1998;29:41-66. Jaramillo D, Treves ST, Kasser JR, Harper M, Sundel R, Laor T: Osteomyelitis and septic arthritis in children: Appropriate use of imaging to guide treatment. AJR Am J Roentgenol 1995;165:399-403. Mandell GA: Imaging in the diagnosis of musculoskeletal infections in children. Curr Probl Pediatr 1996;26:218-237. Tuson CE, Hoffman EB, Mann MD: Isotope bone scanning for acute osteomyelitis and septic arthritis in children. J Bone Joint Surg Br 1994;76:306-310. Mazur JM, Ross G, Cummings RJ, Hahn GA Jr, McCluskey WP: Usefulness of magnetic resonance imaging for the diagnosis of acute musculoskeletal infections in children. J Pediatr Orthop 1995;15:144-147. Gylys-Morin VM: MR imaging of pediatric musculoskeletal inflammatory and infectious disorders. Magn Reson Imaging Clin N Am 1998;6:537-559. Nelson JD, Bucholz RW, Kusmiesz H, Shelton S: Benefits and risks of sequential parenteral-oral cephalosporin therapy for suppurative bone and joint infections. J Pediatr Orthop 1982;2:255-262. Dahl LB, Hoyland AL, Dramsdahl H, Kaaresen PI: Acute osteomyelitis in children: A population-based retrospective study 1965 to 1994. Scand J Infect Dis 1998;30:573-577. Trbs RB, Mritz RP, Bhligen U, et al: Changing pattern of osteomyelitis in infants and children. Pediatr Surg Int 1999;15:363-372. Epperly TD: The value of needle aspiration in the management of cellulitis. J Fam Pract 1986;23:337-340. 29. Hoeffel DP, Hinrichs SH, Garvin KL: Molecular diagnostics for the detection of musculoskeletal infection. Clin Orthop 1999;360:37-46. 30. Tompkins LS: The use of molecular methods in infectious diseases. N Engl J Med 1992;327:1290-1297. 31. Mariani BD, Martin DS, Levine MJ, Booth RE Jr, Tuan RS: Polymerase chain reaction detection of bacterial infection in total knee arthroplasty. Clin Orthop 1996;331:11-22. 32. Abbasi S, Orlicek SL, Almohsen I, Luedtke G, English BK: Septic arthritis and osteomyelitis caused by penicillin and cephalosporin-resistant Streptococcus pneumoniae in a childrens hospital. Pediatr Infect Dis J 1996;15: 78-83. 33. Gwynne-Jones DP, Stott NS: Community-acquired methicillin-resistant Staphylococcus aureus: A cause of musculoskeletal sepsis in children. J Pediatr Orthop 1999;19:413-416. 34. Perl TM: The threat of vancomycin resistance. 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 Child 1975;129:1273-1278. 36. Highland TR, LaMont RL: Osteomyelitis of the pelvis in children. J Bone Joint Surg Am 1983;65:230-234. 37. Jaakkola J, Kehl D: Hematogenous calcaneal osteomyelitis in children. J Pediatr Orthop 1999;19:699-704. 38. LaMont RL, Anderson PA, Dajani AS, Thirumoorthi MC: Acute hematogenous osteomyelitis in children. J Pediatr Orthop 1987;7:579-583. 39. Cole WG, Dalziel RE, Leitl S: Treatment of acute osteomyelitis in childhood. J Bone Joint Surg Br 1982;64:218-223. 40. Hamdy RC, Lawton L, Carey T, Wiley J, Marton D: Subacute hematogenous osteomyelitis: Are biopsy and surgery always indicated? J Pediatr Orthop 1996;16:220-223.

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

Vol 9, No 3, May/June 2001

175