Bone and Joint Infections

Osteoarticular infections are infections in the bone (osteomyelitis) or joint (septic arthritis). Osteomyelitis and septic arthritis should be considered in the differential diagnosis of patients with a constellation of the following symptoms:

• fever

• joint or bone pain

• swelling

• limited range of motion

• refusal to bear weight

Etiology of Osteoarticular Infections

The source of osteoarticular infection can be:

• hematogenous seeding of bacteria

• direct inoculation secondary to trauma

• spreading from adjacent tissue

• concurrent septic arthritis

In children, infection is most often secondary to hematogenous spread. Approximately 15%-50% of osteoarticular infections involve both the bone and joint. When both bone and joint are involved, the clinical course tends to be prolonged.

Causative pathogens of osteoarticular infections vary based on risk factors (e.g., age and comorbidities) and include the following:

• Staphylococcus aureus is a frequent cause of osteoarticular infections in children. Other causes include Streptococcus pyogenes (group B streptococcus) and Streptococcus pneumoniae.

• Salmonella: Children living in developing countries and children with sickle cell disease are at increased risk of osteoarticular infection due to Salmonella species.

• Kingella kingae can cause subacute osteoarticular infections, typically in children younger than 3 years. Children with Kingella kingae infection often have a history of a preceding upper respiratory infection.

• Group B streptococcus can cause osteomyelitis in children younger than 4 months.

• Mycobacterial species and fungi rarely cause osteoarticular infections in healthy children but can be seen in immunocompromised children.

• Borrelia burgdorferi (Lyme disease) can present with monoarticular arthritis and should be considered in areas where Lyme disease is endemic.

Osteomyelitis

In high-income countries, the incidence of osteomyelitis in children is 10 to 80 per 100,000 person-years and the incidence of septic arthritis is about 4 to 10 per 100,000 person-years. Males and children living in low-income countries have higher rates of osteomyelitis. The consequences of untreated osteomyelitis can be severe.

Symptoms

Symptoms of osteomyelitis include:

• fever

• limping

• refusal to bear weight

• focal tenderness

• swelling around a long bone

Diagnosis

Osteomyelitis can affect any bone but most often affects the long bones of the arms and legs. The skeletal distribution of osteomyelitis in children is shown in the figure below.

(Source: Acute Osteomyelitis in Children. N Engl J Med 2014.)

Evaluation and Diagnosis

The top section of the following algorithm describes the approach to the diagnosis of osteomyelitis in children.

(Source: Acute Osteomyelitis in Children. N Engl J Med 2014.)

Laboratory tests: Noninvasive diagnostic testing should precede initiation of antibiotics and include routine blood culture, a complete blood count, inflammatory markers, sedimentation rate, and C-reactive protein (CRP) level.

CRP level can be used to determine the degree of inflammation. Erythrocyte sedimentation rate (ESR) may increase rapidly but declines more slowly than CRP level. Both inflammatory markers are followed closely to assist with duration of therapy and response to treatment.

Blood cultures should be performed on all patients with suspected osteomyelitis, although only about 30%-40% of blood culture results will ultimately be positive. Identifying the pathogen causing the infection is important to inform targeted antimicrobial therapy. Ideally, blood cultures and bone or tissue samples should be collected before starting antibiotics. Studies of bone and tissue cultures have demonstrated organism recovery up to 65% of the time even if the patient has previously received antibiotics.

Imaging: Radiographic findings can take 2 to 3 weeks to become apparent. Therefore, a normal x-ray does not rule out acute osteomyelitis (see algorithm above). Magnetic resonance imaging (MRI) is considered the best imaging method to detect osteomyelitis early in the disease course. You can view graphs that demonstrate expected CRP, ESR, leukocyte, and radiographic changes associated with adequate treatment of osteomyelitis here.

(Source: Acute Osteomyelitis in Children. N Engl J Med 2014.)

Differential diagnosis: In children presenting with bone pain and tenderness, fracture, rheumatologic disease, and malignancy also should be considered. Children with joint swelling may have reactive arthritis from a preceding or concurrent infection.

Management

Management of osteomyelitis involves a combination of antibiotics and surgery. Patients typically require intravenous antibiotics followed by a course of oral antibiotics. Duration of treatment is typically 3 to 4 weeks (see bottom half of algorithm above), with longer courses indicated in patients with complicated osteomyelitis or in cases caused by difficult-to-treat or aggressive bacterial pathogens.

Antibiotic choice depends on local susceptibilities, pathogen identification, patient risk factors, and oral bioavailability (see table below).

Transition from intravenous to high-dose oral therapy should take place for most children at the time of hospital discharge with documentation of improvement of clinical symptoms (e.g., fever, pain), appropriate trending of inflammatory markers, and assured follow-up. For more-complicated cases, outpatient antibiotic therapy administered through a peripherally inserted central catheter (PICC) line is appropriate,

Surgical intervention may be required in some instances for diagnostic and therapeutic purposes. Surgical indications for osteoarticular infections include source control, microbiologic diagnosis, and preservation of function.

Clinical course: Children generally recover well following osteomyelitis, and mortality in developed countries is rare. However, delayed treatment may correlate with a worse outcome.

Septic Arthritis

Septic arthritis is a bacterial infection of the joint that can be associated with infection at other sites, including the bone. The incidence of septic arthritis in developed countries is 4 to 10 per 100,000 children. Most infections involve the hips, knees, and ankles. Children with septic arthritis often have a history of preceding trauma.

Symptoms

Children will often present with generalized malaise, fever, and limp. They may have swelling, tenderness, and erythema of the joint.

Evaluation and Diagnosis

The differential diagnosis of septic arthritis includes trauma, hemarthrosis, rheumatoid arthritis, rheumatic fever, malignancy, and toxic synovitis.

Laboratory evaluation of a child with suspected septic arthritis should include CRP level, ESR, CBC with differential, and blood culture. X-rays of the affected joint should be obtained. Ultrasound can be done to determine if a joint effusion is present, especially in joints such as the hip, where an effusion may be difficult to detect with physical examination alone.

Because 15% to 50% of patients with septic arthritis have concurrent osteomyelitis, MRI should be performed to rule out bone infection. Older age, elevated CRP level, longer duration of symptoms, lower platelet count, and elevated absolute neutrophil count have been found to be predictive of adjacent infection.

Arthrocentesis or joint aspiration should be performed, and aspirated fluid should be sent for gram stain, aerobic and anaerobic culture, and cell count and differential. Polymerase chain-reaction (PCR) testing of fluid to rule out Lyme disease or Kingella infection may be indicated in some cases. Aspirated fluid with glucose level <40 mg/dL, leukocyte count >50,000/mm³, and neutrophil predominance is most consistent with septic arthritis.

Management

Untreated septic arthritis can lead to severe complications, including avascular necrosis, joint destruction, and sepsis. For this reason, septic arthritis is considered a surgical emergency, and patients should undergo arthrotomy, irrigation, and debridement.

Ideally, empiric antibiotics should be started after blood and joint fluids are collected for culture. Empiric treatment should include S. aureus coverage based on local susceptibilities. Consideration for coverage of K. kingae, Salmonella, and other gram-negative bacteria should be based on history and patient risk factors.

Although patients are started on intravenous antibiotics initially, they can quickly be transitioned to oral antibiotics after they demonstrate clinical improvement. Typical treatment duration for uncomplicated septic arthritis is 3 weeks.