BACKGROUND

Osteomyelitis is an inflammatory process of the bone and bone marrow that is generally due to a bacterial infection. The most common form in childhood is acute hematogenous osteomyelitis (AHO); 50% of cases occur in children younger than 5 years.^1,2 The incidence of AHO is approximately 60 in 100,000 children,³ and boys are about twice as likely to be affected as girls.^1,2 The majority of cases occur in long bones, with the femur and tibia accounting for almost half of all cases. Most cases are limited to a single site.

Staphylococcus aureus is the most commonly identified organism, accounting for 60% to 89% of cases of AHO,^4,5 with group A beta-hemolytic streptococci (GABHS) next in frequency. In the past, Haemophilus influenzae accounted for 5% to 7% of cases,^1,4,5 but the advent of effective immunization has decreased this incidence dramatically. Streptococcus pneumoniae is a relatively uncommon organism in patients with AHO. Kingella kingae is a common cause of osteomyelitis in the Middle East and is being recognized increasingly in the United States. Osteomyelitis due to K. kingae tends to occur in young children (<4 years) following an upper respiratory tract infection or stomatitis. Group B Streptococcus and enteric gram-negative organisms such as Escherichia coli may be identified in neonates with osteomyelitis but are rare in older children. Salmonella species are commonly identified in patients with sickle cell disease, and Pseudomonas aeruginosa is often identified in cases of osteochondritis following puncture wounds of the feet. Mycobacteria and fungi are rare causes of osteomyelitis. Bartonella henselae is an atypical cause of osteomyelitis, which occurs in patients with cat scratch disease.

PATHOPHYSIOLOGY

Several routes of infection are hypothesized in the pathogenesis of osteomyelitis. In children, most cases result from hematogenous spread after a transient episode of bacteremia. About one-third of patients report a history of blunt trauma,⁴ which increases the likelihood of seeding an infection during an episode of bacteremia (due to disruptions in the microcirculation in the medullary bone). Less likely, osteomyelitis may result from direct inoculation of bacteria into bone, which may occur during surgery or as a result of penetrating trauma.

Osteomyelitis most commonly begins in the metaphysis of long bones, which are highly vascular structures. Certain bacteria such as S. aureus adhere to bone by expressing receptors (adhesions) for a component of the bone matrix. Growing colonies of bacteria surround themselves with a protective glycocalyx, shielding them from circulating white blood cells. As infection advances, cortical bone is destroyed, and infection and inflammation may extend into the subperiosteal space.

The periosteum in young infants is thin and is not tightly adherent to the underlying bone. As a result, the periosteum is more likely to perforate, spreading infection into the surrounding tissues. In young infants, blood vessels extend into the epiphyses, which increase the likelihood of growth plate damage as well as septic arthritis. The hips and shoulders are common sites of epiphyseal infection.

CLINICAL PRESENTATION

Patients often present after experiencing symptoms for days to weeks, most commonly complaining of fever and pain at the affected site. Infants and toddlers may present with irritability, refusal to bear weight on, or use, an extremity, or limp. Neonates with osteomyelitis may present with pseudoparalysis (refusal to move) of the affected extremity. Erythema, warmth, and swelling of the affected site may be noted. The lower extremities account for most cases, followed by the humerus and pelvis. A subacute presentation, often for weeks or months, is associated with a so-called Brodie abscess. Chronic osteomyelitis is now uncommon (and it should be the goal of clinicians to never allow children to develop this condition); signs of inflammation can last for life if not properly treated.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis for osteomyelitis includes cellulitis, septic arthritis, toxic synovitis, thrombophlebitis, trauma, fracture, rheumatologic diseases such as juvenile rheumatoid arthritis, pain crisis in sickle cell disease, Ewing sarcoma, osteosarcoma, and leukemia.

EVALUATION AND DIAGNOSIS

A complete blood count is likely to reveal a leukocytosis with a left shift, as well as reactive thrombocytosis. Inflammatory markers such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are usually elevated and can be used to follow response to therapy. It is important to try to identify the microbial etiology of bone infection, as the culture and susceptibility data will inform the choice of antimicrobial therapy. Blood cultures should always be performed as part of the initial evaluation before initiating antibiotic therapy. The organism will be found in blood in about a third of cases.⁶ Needle aspiration is likely to yield an organism in approximately 70% of cases,^4,7 whereas blood cultures are positive in 36% to 55% of cases.^2,7 For the most part, culture-negative cases behave similarly to cases in which a pathogen is identified.⁸ Open procedures involving metaphyseal drilling may enhance the yield and can also be therapeutic. Table 105-1 lists the most common causes of osteomyelitis by age.

The value of various imaging techniques are summarized in Table 105-2. For plain radiographs (Figure 105-1), the yield depends on the duration of active disease. In the first 3 days, these films may reveal soft tissue swelling; by days 3 to 7, swelling of the surrounding muscle leads to obliteration of the normally translucent fat planes. Osteolytic lesions are generally not apparent until days 10 to 21, at which point there has been greater than 50% loss of bone density.⁹ In contrast, patients presenting with discitis may show narrowing of the disc space early on, with involvement of the vertebral bodies later.

Nuclear scintigraphy (bone scan) is helpful in young patients who are unable to verbalize the location of their pain, when multiple sites are suspected, and in differentiating osteomyelitis from cellulitis (see Figure 105-1). Technetium-99m methylene diphosphonate has increased uptake in areas of osteoblastic activity, and the three-phase bone scan is the study of choice. The technetium scan is not specific for infection and may be abnormal with fractures, tumors, and other bone pathology. Tagged leukocyte scans (e.g. indium 111 or technetium-99m) are more specific for infection but are laborious, time consuming, and may yield false positive results.

CT allows a cross-sectional assessment and can reveal areas of cortical bone destruction, periosteal reaction, sequestration, and soft tissue abscesses. Images should be obtained with and without enhancement. CT involves significant radiation exposure and will not be necessary in most cases of pediatric osteomyelitis.

With a reported sensitivity as high as 97%,¹⁰ MRI is becoming the modality of choice in patients with a high suspicion for osteomyelitis. Edema and exudate of the medullary space may be noted in early osteomyelitis (Figure 105-2). Coronal or sagittal images are especially useful for planning surgical procedures and assessing the growth plates and epiphyses. Gadolinium enhancement is recommended.

TREATMENT

Upon admission, an orthopedist should be consulted, especially if imaging reveals subperiosteal or soft tissue abscesses, sequestra, intramedullary purulence, or involvement of the growth plate. The surgeon’s role includes performing the diagnostic procedure, decompression and drainage (when necessary), and long-term follow-up in complicated cases. In some institutions, interventional radiology (IR) may be consulted in order to obtain appropriate specimens.

Empirical therapy should cover S. aureus and GABHS. Traditionally, a semisynthetic penicillinase-resistant penicillin was recommended; however, over the past 15 years there has been a sharp increase in the number of cases of community-acquired methicillin-resistant S. aureus (MRSA) infections. In most communities in the United States, the incidence of MRSA is high enough that beta-lactam antibiotics cannot be used as initial empiric therapy for osteomyelitis (although in other parts of the world with a smaller burden of MRSA, these agents still play a role). For patients who are more seriously ill, and certainly if the blood culture is positive, vancomycin should be considered for empirical therapy until sensitivities are available. If vancomycin is used to treat osteomyelitis, a potentially severe infection, trough concentrations between 15 and 20 μg/mL should be targeted, in order to ensure adequate bacterial killing. Alternatively, clindamycin may be used in the child who presents with less severe illness, and is associated with less toxicity and there is no requirement to measure levels. However, clinicians should be aware of increasing resistance of S. aureus to this agent. Clindamycin resistance in S. aureus can be either constitutive or inducible; in either case, it should not be used for osteoarticular infections. Up to a third of methicillin-susceptible S. aureus (MSSA) and a quarter of MRSA are clindamycin resistant in some communities. Knowing local susceptibility data is therefore important.