Osteomyelitis

Basics

Description

  • Infection of any bone
  • Most commonly occurs in the metaphysis of a long bone (especially the distal femur or proximal tibia)

Epidemiology

  • One of the most common invasive bacterial infections in children, accounting for 1% of all pediatric hospitalizations
  • One third occurs in children <2 years of age, and ~50% of cases occur in children ≤5 years of age.
  • A history of minor trauma to the affected site is common but of unclear significance.
  • Boys are more commonly affected than girls (2:1 ratio).

Pathophysiology

  • Hematogenous spread is most common in children (inoculation of bone during an episode of bacteremia). The infecting organism enters the bone via a nutrient artery and then is deposited in the metaphysis due to its rich vascular supply. The organism replicates in metaphyseal capillary loops, causes local inflammation, spreads through vascular tunnels, and adheres to the bone matrix. Increased pressure in the metaphysis allows pus to perforate through the cortex and lift the periosteum.
  • In newborns and young infants, rupture of pus into the adjacent joint space is more common because blood vessels connect the metaphysis and epiphysis.
  • Local spread from a contiguous focus of infection and direct inoculation (e.g., penetrating injury) are less common mechanisms of infection.

Risk Factors

  • Sickle hemoglobinopathy
  • Primary or acquired immunodeficiency, especially chronic granulomatous disease (CGD), and HIV
  • Bone trauma (open fractures, puncture wounds, bites, surgical manipulation)
  • Implanted orthopedic devices or indwelling vascular catheters
  • Pressure ulcers

Etiology

  • Staphylococcus aureus is responsible for 70–90% of osteomyelitis in all age groups, with MRSA an increasingly common problem.
  • Streptococcus pyogenes accounts for ~10% of osteomyelitis and is more common in preschool and early school–aged children.
  • Streptococcus pneumoniae causes ~10% of osteomyelitis in children <3 years old, although a decline in pneumococcal infections has been seen with widespread vaccination. Conversely, S. pneumoniae remains an important cause of osteomyelitis in children infected with HIV.
  • Kingella kingae, a gram-negative organism found in the respiratory tract, is an important pathogen in children age <3 years, especially in those that attend day care centers.
  • Group B Streptococcus, gram-negative enterics, and Candida spp. are important causative organisms in neonates.
  • Salmonella spp. can be the cause in children with sickle cell disease and in patients from or traveling to tropical countries.
  • Pseudomonas aeruginosa is a common cause following puncture wounds to the foot.
  • There has been a significant decline in the incidence of Haemophilus influenzae type b (Hib) osteomyelitis since immunization with the Hib conjugate vaccine became widespread.
    • Prior to widespread vaccination, this organism was an important cause of bone and joint infection in children and infants <2 years.
  • Other more unusual pathogens may be seen in patients with specific risk factors (e.g., coagulase-negative staphylococci in the presence of prosthetic material, anaerobes after animal or human bites, Aeromonas after injuries sustained in fresh water settings).
  • In a significant percentage of cases, a definitive causative microorganism is not identified. The use of antibiotic prior to collection of samples, presence of fastidious organisms, low inoculum, or inappropriately collected samples, may be a factor in culture-negative osteomyelitis.
  • Infections after open fractures or puncture wounds may be polymicrobial.

Diagnosis

History

  • Persistent, increasing pain and tenderness over the affected bone
  • Restricted use of the involved limb (pseudoparalysis may be the only sign in a neonate), refusal to bear weight, or limp
  • Fever, malaise, anorexia, irritability
  • Children with vertebral and pelvic osteomyelitis may complain of poorly localized pain for several weeks, often resulting in delay in the diagnosis and treatment.
  • In some patients, osteomyelitis will have an indolent, subacute presentation with the development of a minimally symptomatic abscess within the bone, eponymously known as a “Brodie abscess.”

Physical Exam

  • Swelling, warmth, and erythema of the soft tissues over the affected bone may be noted.
  • Exaggerated immobility/pain with micromotion of an adjacent joint suggests pyogenic arthritis (alternatively or in addition to osteomyelitis).
  • Multifocal osteomyelitis may be seen in neonates and in children with S. aureus sepsis syndrome.

Differential Diagnosis

  • Trauma
  • Cellulitis
  • Soft tissue abscess
  • Pyomyositis or fasciitis
  • Septic arthritis
  • Congenital syphilis
  • Aseptic bone necrosis or bone infarction (sickle cell disease)
  • Tumor (e.g., Ewing sarcoma, osteoid osteoma, eosinophilic granuloma)
  • Acute leukemia, neuroblastoma with bone invasion
  • Chronic recurrent multifocal osteomyelitis (CRMO)
  • Inflammatory arthritis or juvenile idiopathic arthritis
  • Transient synovitis
  • Bone cyst

Diagnostic Tests and Interpretation

Initial Tests

  • The white blood cell count may be normal or elevated.
  • Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels are usually elevated, although in certain cases, such as puncture wounds, they may be normal.
  • Blood cultures are positive in ~50% of patients.
  • Bone needle aspiration cultures are positive in ~60–70% of cases.
  • Some uncommon bacteria-causing osteomyelitis are fastidious and difficult to culture; they may require molecular methods to establish the diagnosis (e.g., polymerase chain reaction).
  • Plain radiographs may show deep soft tissue swelling early in the course of infection and may help to suggest or exclude alternative diagnoses. Evidence of bone destruction and periosteal elevation are not typically seen until 10 to 14 days after the onset of symptoms.
  • MRI is sensitive and specific and offers superior anatomic resolution, making it a more useful modality for surgical planning and for identification of intraosseous, subperiosteal, and soft tissue abscesses.
  • Bone scans are useful if the site of infection is poorly localized or if there is concern for multifocal osteomyelitis. However, they may be positive in other illnesses that cause osteoblastic activity.

Diagnostic Procedures/Other

  • Biopsy or aspiration of the infected bone (or an associated abscess) for Gram stain and culture is useful for determining the etiologic organism. Inoculating a portion of an aspirated sample into a blood culture bottle enhances yield for K. kingae.
  • If a plan is in place to rapidly obtain a bone culture in a clinically stable patient, it is reasonable to defer initiation of antibiotic therapy until after the culture specimen is secured.
  • Biopsy may help differentiate osteomyelitis from noninfectious bone pathology.

Treatment

Medication (Drugs)

  • Empiric antibiotics should cover the most likely pathogens considering patient age, history of presentation, physical findings, and underlying medical conditions.
  • Empiric therapy should always include an agent directed against S. aureus, usually nafcillin, oxacillin, or a 1st-generation cephalosporin. However, in areas where the rate of methicillin resistance among community S. aureus isolates exceeds 10%, an antibiotic effective against community-acquired MRSA should be selected (i.e., clindamycin or vancomycin).
  • When clindamycin is considered for treatment of an identified MRSA isolate, the D-test (to exclude inducible macrolide, lincosamide, and streptogramin B resistance) should be performed by the clinical microbiology laboratory.
  • Clindamycin and vancomycin are also usually effective against S. pneumoniae and S. pyogenes but are not effective in vitro against K. kingae. The latter organism is usually susceptible to most β-lactam antibiotics (penicillins and cephalosporins).
  • In addition to antistaphylococcal coverage, a 3rd-generation cephalosporin, such as ceftriaxone or cefotaxime, should be used to cover Salmonella spp. in patients with sickle cell disease.
  • Gram-negative coverage should also be added to the empiric regimen for neonates.
  • If the patient recently had a foot puncture wound, coverage for P. aeruginosa should be considered.
  • If an organism is isolated and susceptibilities determined, antibiotic therapy should be modified based on the susceptibility profile.

Issue for Referral

The treatment of osteomyelitis should be done in consultation with an infectious disease specialist.

Diagnostic Procedures/Other

  • If an intraosseous, subperiosteal, or soft tissue abscess is present, surgical debridement may be necessary in addition to antibiotic therapy.
  • Surgical debridement is important in the management of osteomyelitis that is secondary to a puncture wound.

Inpatient Consideratons

  • Traditionally, 4 to 6 weeks of antibiotics have been recommended. Newer data is emerging suggesting that for non-MRSA hematogenous osteomyelitis, 20 days of therapy may be sufficient. However, this may require the use of more frequent dosing schedules as well as higher doses.
  • Total treatment duration should be individualized based on the extent of infection, the promptness and completeness of surgical debridement (when indicated), the rate of clinical response, the presence or absence of distant foci of infection, and the patient’s underlying risk factors and comorbid conditions.
  • After an initial period of parenteral antibiotic administration, many patients can be transitioned to an oral regimen to complete therapy (assuming the availability of an oral antibiotic with an appropriate spectrum of activity and adequate bone penetration as well as patient’s ability to adhere to and absorb an oral regimen). This sequential IV–oral approach reduces the risk of complications (e.g., catheter-associated bloodstream infection, catheter malfunction, and thrombosis) associated with the prolonged presence of a central venous catheter.
  • The decline in CRP alongside improvement in clinical signs may be a good indicator of when it is safe to transition to oral therapy.

Ongoing Care

Follow-Up Recommendations

  • Most children who receive appropriate treatment have no long-term sequelae.
  • Inflammatory markers (ESR and CRP) are typically measured serially until they normalize during the course of antibiotic therapy.
  • Patients should be followed to ensure medication compliance, adequacy of treatment, side effects of therapy, and continued growth of the involved extremity.

Complications

  • Septic arthritis
  • Recurrence or progression to chronic osteomyelitis in ~5% of patients
  • Disturbances of bone growth, limb length discrepancy
  • Arthritis
  • Pathologic fractures

Additional Reading

  1. Arnold JC, Cannavino CR, Ross MK, et al. Acute bacterial osteoarticular infections: eight-year analysis of C-reactive protein for oral step-down therapy. Pediatrics. 2012;130(4):e821–e828.  [PMID:22966033]
  2. Dodwell E. Osteomyelitis and septic arthritis in children: current concepts. Curr Opin Pediatr. 2013;25(1):58–63.  [PMID:23283291]
  3. Harik NS, Smeltzer MS. Management of acute hematogenous osteomyelitis in children. Expert Rev Anti Infect Ther. 2010;8(2):175–181.  [PMID:20109047]
  4. Kaplan SL. Osteomyelitis in children. Infect Dis Clin North Am. 2005;19(4):787–797.  [PMID:16297732]
  5. Keren R, Shah SS, Srivastava R, et al. Comparative effectiveness of intravenous vs oral antibiotics for postdischarge treatment of acute osteomyelitis in children. JAMA Pediatr. 2015;169(2):120–128.  [PMID:25506733]
  6. Pääkkönen M, Peltola H. Bone and joint infections. Pediatr Clin North Am. 2013;60(2):425–436.  [PMID:23481109]
  7. Peltola H, Pääkkönen M, Kallio P, et al. Short- versus long-term antimicrobial treatment for acute hematogenous osteomyelitis of childhood: prospective, randomized trial on 131 culture-positive cases. Pediatr Infect Dis J. 2010;29(12):1123–1128.  [PMID:20842069]
  8. Yagupsky P. Kingella kingae: from medical rarity to an emerging paediatric pathogen. Lancet Infect Dis. 2004;4(6):358–367.  [PMID:15172344]
  9. Zaoutis T, Localio AR, Leckerman K, et al. Prolonged intravenous therapy versus early transition to oral antimicrobial therapy for acute osteomyelitis in children. Pediatrics. 2009;123(2):636–642.  [PMID:19171632]

Codes

ICD-9

  • 730.20 Unspecified osteomyelitis, site unspecified
  • 730.00 Acute osteomyelitis, site unspecified
  • 730.10 Chronic osteomyelitis, site unspecified
  • 730.25 Unspecified osteomyelitis, pelvic region and thigh
  • 730.26 Unspecified osteomyelitis, lower leg

ICD-10

  • M86.9 Osteomyelitis, unspecified
  • M86.00 Acute hematogenous osteomyelitis, unspecified site
  • M86.10 Other acute osteomyelitis, unspecified site
  • M86.8X5 Other osteomyelitis, thigh
  • M86.60 Other chronic osteomyelitis, unspecified site
  • M86.50 Other chronic hematogenous osteomyelitis, unspecified site
  • M86.659 Other chronic osteomyelitis, unspecified thigh
  • M86.259 Subacute osteomyelitis, unspecified femur
  • M86.8X9 Other osteomyelitis, unspecified sites

SNOMED

  • 60168000 Osteomyelitis (disorder)
  • 409780002 Acute osteomyelitis (disorder)
  • 40970001 Chronic osteomyelitis (disorder)
  • 1551001 osteomyelitis of femur (disorder)
  • 67322009 Subacute osteomyelitis (disorder)

FAQ

  • Q: Can children with osteomyelitis present without fever and with normal CBCs and inflammatory markers?
  • A: Fever along with leukocytosis and elevated inflammatory markers (CRP and ESR) are common in children who have acute hematogenous osteomyelitis. However, children with subacute or chronic osteomyelitis and with other forms of osteomyelitis, such as puncture wound osteochondritis, may not exhibit these findings.
  • Q: What is the imaging modality of choice in a child suspected of having acute hematogenous osteomyelitis?
  • A: MRI is the most sensitive and specific imaging study to detect acute osteomyelitis. Plain films do not reveal periosteal elevation for at least 10 to 14 days after infection. A bone scan is less specific than MRI and does not reveal extraosseous features of infection.

Authors

Blanca E. Gonzalez, MD


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