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«Bone and Joint Infections in Children Kathleen Gutierrez, MD Department of Pediatrics, Division of Pediatric Infectious Disease, Stanford University ...»

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Pediatr Clin N Am 52 (2005) 779 – 794

Bone and Joint Infections in Children

Kathleen Gutierrez, MD

Department of Pediatrics, Division of Pediatric Infectious Disease,

Stanford University School of Medicine, Stanford, CA 94305, USA

Bone and joint infections are a significant cause of morbidity in infants and

young children. Although many principles regarding pathogenesis, diagnosis, and

treatment of infection have remained constant over the years, other aspects of this

important pediatric diagnosis are continuing to evolve. This article reviews current information regarding pathogenesis, epidemiology, and microbiology of pediatric bone and joint infections and the clinical presentation, diagnosis, and treatment of these infections.

Osteomyelitis Osteomyelitis is inflammation of the bone caused by infection with bacterial

or fungal organisms. Osteomyelitis often is categorized into three different types:

(1) acute hematogenous osteomyelitis; (2) osteomyelitis secondary to contiguous spread of infection after trauma, puncture wounds, surgery, or joint replacement;

and (3) osteomyelitis secondary to vascular insufficiency [1]. Acute hematogenous osteomyelitis is seen most often in children. Osteomyelitis caused by contiguous spread of infection is less common in children, and infection secondary to vascular insufficiency is rare in children.

Pathogenesis Acute hematogenous osteomyelitis results from symptomatic or asymptomatic bacteremia. Because of its rich vascular supply, the metaphysis of the bone is most often involved. The infecting organism travels to metaphyseal capillary E-mail address: mdkat@stanford.edu 0031-3955/05/$ – see front matter D 2005 Elsevier Inc. All rights reserved.

doi:10.1016/j.pcl.2005.02.005 pediatric.theclinics.com 780 gutierrez loops, where it replicates and causes local inflammation. As the bacteria replicate, they travel through vascular tunnels and adhere to cartilaginous matrix.

Staphylococcus aureus is the most common cause of infection perhaps because of its capacity to express bacterial adhesions that promote attachment to extracellular bone matrix. This organism also is able to evade host defenses, attack host cells, and colonize bone persistently [1].

The bony metaphyses of children younger than 18 months are vascularized by the transphyseal vessels. Because these vessels enter the epiphysis and ultimately the joint space, young children are believed to have a higher risk of joint space infection complicating osteomyelitis. One clinical study found the incidence of adjacent joint involvement to be the same, however, in children older than 18 months compared with children younger than 18 months [2]. The authors speculated that some cases ofjoint involvement could be due to subperiosteal spread of infection into the joint space or that an adjacent site of osteomyelitis may predispose an adjacent joint to hematogenous seeding.

Animal models show that bone infection is more likely after bacteremic animals sustain trauma to the affected area. These animal models may explain why a history of trauma is elicited in approximately 30% children before onset of symptoms [3]. Contiguous osteomyelitis in children is seen in the setting of trauma; animal bites; puncture wounds; and direct extension of infection from an infected sinus, mastoid bone, or dental abscess.

Epidemiology

The exact incidence of childhood osteomyelitis in the United States is unknown. Other countries report a decrease in the diagnosis in recent years [4].

Approximately 50% of cases of osteomyelitis occur in the first 5 years of life.

Boys are more likely than girls to be affected. The long bones of the lower extremities are most often involved, although any bone may be affected.

Microbiology

The type of infecting organism depends on the age of the child and underlying medical problem (Table 1). S. aureus is the most common cause of osteomyelitis in all age groups, accounting for 70% to 90% of infections. Infection caused by methicillin-resistant S. aureus (MRSA) is becoming an increasingly common problem. One group of investigators identified 59 patients with musculoskeletal infections caused by S. aureus over a 2-year period at their center. More than half of the patients described were infected with community-acquired MRSA (CA-MRSA) [5].

In addition to S. aureus, young infants may develop osteomyelitis caused by Streptococcus agalactiae or enteric gram-negative bacteria. Organisms other than S. aureus causing infection in older children include Streptococcus pyogenes, bone and joint infections

–  –  –

Streptococcus pneumoniae, and Kingella kingae [6]. S. pyogenes causes approximately 10% of cases of acute hematogenous osteomyelitis with a peak incidence of disease in preschool-age and early school–age children [7]. Children with S. pyogenes osteomyelitis often have a recent history of varicella infection and present with higher fever and white blood cell (WBC) counts compared with children infected with S. aureus.

Children with osteomyelitis caused by S. pneumoniae are younger than children infected with S. aureus and S. pyogenes. They are more likely to have joint involvement [8]. The proportion of bone infections caused by S. pneumoniae is relatively small (approximately 1–4%); the impact of heptavalent pneumococcal conjugate vaccine on the incidence of osteomyelitis is limited.





K. kingae is reported as a pathogen with increasing frequency [9]. A cluster of bone and joint infections caused by K. kingae at a daycare center underscores the importance of this organism in children with musculoskeletal infections [10].

K. kingae is a fastidious gram-negative coccobacillary bacterium found in normal respiratory flora. Infection with this organism often is preceded by an upper respiratory tract infection or stomatitis; disrupted respiratory mucosa may facilitate invasion and hematogenous dissemination.

There has been a substantial decrease in musculoskeletal infections secondary to Haemophilus influenzae type b (Hib) as a result of an effective immunization program against this pathogen. Hib infection is rare in a completely immunized child, although other serotypes are reported to cause bone and joint infections.

Puncture wounds to the foot may result in osteomyelitis caused by mixed flora, including Pseudomonas, S. aureus, enteric gram-negative bacteria, and anaerobes. The source of bacteria is usually from moist colonized soles of tennis shoes. A series of cases describes osteomyelitis of the metatarsals occurring as a result of toothpick puncture injuries. The organisms isolated included skin and environmental organisms; others have reported infection with mouth organisms as a result of toothpick injuries [11].

782 gutierrez Anaerobes are a rare cause of pyogenic osteomyelitis in healthy children.

Predominant organisms are Bacteroides, Fusobacterium, Clostridium, and Peptostreptococcus. Anaerobic osteomyelitis can occur as the result of a bite, chronic sinusitis, mastoiditis, or dental infection.

Organisms causing bone infection in children with sickle cell disease include Salmonella and S. aureus and less commonly Escherichia coli, Hib, Shigella, and S. pneumoniae. Unusual causes of osteomyelitis include infection with Mycobacterium, Bartonella, Coxiella burnetii, or fungi (Table 2). The specific etiology of osteomyelitis is not determined in many cases; nonetheless, resolution after empirical therapy for S. aureus is usual [12].

Clinical manifestations

Most children with acute hematogenous osteomyelitis are symptomatic for less than 2 weeks. Symptoms include complaints of acute, persistent, and increasing pain over the affected bone. Osteomyelitis in an infant may present as irritability or reluctance to move the affected limb. Fever is usually present.

Swelling or redness of the soft tissue over the affected bone may be seen. In one study, patients with culture-positive osteomyelitis were more likely than patients

–  –  –

with culture-negative osteomyelitis to have a history of antecedent trauma, changes in skin overlying the bone, associated cellulites, or high fever [12].

Pelvic osteomyelitis is reported in 1% to 11% of all cases of acute hematogenous osteomyelitis and typically affects older children [13]. Symptoms include hip, buttock, low back, or abdominal pain. Fever may be absent. Findings on physical examination include tenderness of the pelvic bones, pain with hip movement, decreased range of motion at the hip, and refusal or inability to bear weight. Any bone in the pelvis may be involved, but the ilium tends to be affected most often, presumably because of its rich blood supply. Symptoms and findings frequently are nonspecific and poorly localized and often are attributed to other diagnoses, such as pyogenic arthritis of the hip or appendicitis. Establishing the correct diagnosis often is delayed.

Osteomyelitis in a neonate is an uncommon but serious infection. It often results from hematogenous spread of microorganisms in patients with indwelling venous catheters. Presenting signs and symptoms include fever, irritability, refusal to move the affected limb, and redness and swelling over the affected area. Diagnosis may be delayed because of nonspecific signs of illness. Infection involving multiple bones and contiguous joints and soft tissue is common.

The differential diagnosis of bone pain in children includes trauma, malignancy, and bone infarction in patients with sickle cell disease. Differentiation between bone infection and infarction in a child with sickle cell anemia is difficult because in both cases the acute onset of fever and bone pain is common.

In addition, a patient may have infarction that predisposes to infection.

Chronic recurrent multifocal osteomyelitis is a poorly understood inflammatory illness characterized by recurrent bone pain and fever. Girls are predominantly affected and have radiologic evidence of multiple, often symmetric bone lesions involving primarily the long bones and clavicles. Associated findings include psoriasis vulgaris and palmoplantar pustulosis.

Diagnosis

The diagnosis of osteomyelitis depends primarily on clinical findings and corroborative laboratory and radiographic results. The WBC count may be normal or increased. Erythrocyte sedimentation rate (ESR) is elevated in 80% to 90% of cases, and C-reactive protein (CRP) is elevated in 98% of cases. ESR generally peaks 3 to 5 days after admission, and CRP peaks within 48 hours of admission. CRP typically returns to normal 7 to 10 days after appropriate therapy.

ESR may remain elevated for 3 or 4 weeks, even with appropriate therapy [14].

Patients who require surgical incision and drainage procedures may have prolonged time to normalization of ESR or CRP [15].

Every attempt should be made to establish a microbiologic diagnosis. A bacteriologic diagnosis can be made in 50% to 80% of cases if blood and bone cultures are obtained. In the case of culture-negative osteomyelitis that is not responding as expected to empirical therapy, a bone biopsy specimen should be 784 gutierrez obtained for histopathologic staining and for culture for bacteria, mycobacteria, and fungi. Inoculation of bone or abscess material directly into an aerobic blood culture bottle facilitates isolation of K. kingae. Cultures for K. kingae and other fastidious organisms may need to be incubated longer than usual laboratory protocol [6].

Plain films show soft tissue swelling in the first few days of illness. Periosteal and lytic changes in the bone generally are not seen until substantial bone destruction has occurred, usually 10 to 21 days after onset of symptoms. In some cases of proven bacterial osteomyelitis, bone changes are never seen on plain film, presumably because prompt diagnosis and treatment prevented extensive bone destruction.

The sensitivity of skeletal scintigraphy, using technetium-labeled methylene diphosphonate isotope, is 80% to 100%. Radionuclide bone scans usually are positive within 48 to 72 hours of onset of symptoms. In some cases of osteomyelitis, vascular supply to the bone is compromised, with decreased uptake of technetium to the affected area, resulting in a ‘‘cold scan.’’ Some experts prefer bone scan as the initial study in the evaluation of suspected uncomplicated osteomyelitis of the long bones. It is less expensive than MR imaging, sedation of the child is generally not necessary, and it is particularly useful when multifocal osteomyelitis is suspected or the exact location of infection is not obvious on physical examination [16,17]. Radionuclide scans may be positive in other illnesses that result in increased osteoblastic activity, including malignancy, trauma, cellulitis, postsurgery, and arthritis.

MR imaging gives excellent resolution of bone and soft tissue. It is particularly useful for visualizing soft tissue abscess associated with osteomyelitis, bone marrow edema, and bone destruction. Contrast enhancement with gadolinium is used to look for areas of abscess formation [18]. If pelvic or vertebral body osteomyelitis is suspected, MR imaging is the imaging study of choice. MR imaging gives better spatial resolution than bone scan and is preferred if a surgical procedure to diagnose or drain an abscess is necessary. Limitations of MR imaging include the need for sedation in younger children, high cost, and inability to assess easily whether other bones are affected.

Differentiating bone infarction versus infection can be difficult in a child with sickle cell disease. In both situations, children present with fever and bone pain and have elevated inflammatory markers. Biopsy and culture of affected bone is often necessary to establish the diagnosis. Some authors have used the pattern of MR imaging contrast enhancement to distinguish acute medullary bone infarction from osteomyelitis [19].

Treatment Successful treatment of osteomyelitis depends on the appropriate selection and administration of antibiotic therapy and surgical intervention as needed.

Empirical selection of antibiotics depends on the age of the child and the clinical bone and joint infections

–  –  –

situation (Table 3). Infants 0 to 2 months old with osteomyelitis should be treated with antibiotics that have excellent coverage against S. aureus, S. agalactaiae, and enteric gram-negative bacteria.



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