AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Osteomyelitis, or inflammation of the bone, is usually caused by bacterial infection. Bone infections in children are primarily hematogenous in origin, although cases secondary to penetrating trauma, surgery, or infection in a contiguous site are also reported.

Pathophysiology

Approximately 50% of cases occur in preschool-aged children. Young children primarily experience acute hematogenous osteomyelitis because of the rich vascular supply in their growing bones. Circulating organisms tend to start the infection in the metaphyseal ends of the long bones because of the sluggish circulation in the metaphyseal capillary loops. The presence of vascular connections between the metaphysis and the epiphysis makes infants particularly prone to arthritis of the adjacent joint. Involvement of the shoulder joint or hip joint is also noted when the intracapsular metaphyseal end of the humerus or femoral is infected. If untreated, infection can also spread to the subperiosteal space after traversing the cortex.

Frequency

United States

The exact frequency is not known because osteomyelitis is not a reportable disease.

International

Chronic osteomyelitis is frequently reported in developing countries where medical and surgical treatment modalities are not commonly accessible.

Mortality/Morbidity

As noted in recent studies, patients may develop deep vein thrombosis.^{1, 2}

Race

The disease is more common among black children.

Sex

A preponderance in males is observed in all age groups. Factors related to increased incidence in males may include increased trauma due to risk-taking behavior or other physical activities that predispose to bone injury.

Age

One half of cases occur in preschool-aged children.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Long bones, including the femur, tibia, and humerus, are most commonly affected.
• Fever, bone pain, swelling, redness, and guarding the affected body part are common.
• Inability to support weight and asymmetric movement of extremities are often early signs in newborns and young infants.

Physical

• Painful focal swelling with cardinal signs of inflammation is often present.
• In a cooperative patient, the clinician may be able to elicit focal point tenderness over the affected bone.
• Draining sinus and bone deformity are both rare in acute disease. When present, these symptoms suggest subacute or chronic infection.
• Movements of the adjoining joint may be restricted due to joint involvement or associated soft tissue inflammation.
• Cellulitis, subcutaneous abscess, fractures, and bone tumors should be considered in the differential diagnosis. In newborns and infants in whom osteomyelitis may present as a pseudoparalysis, also consider CNS disease (eg, poliomyelitis), cerebral hemorrhage, trauma, scurvy, and child abuse.

Causes

• Staphylococcus aureus is the most common pathogen, followed by Streptococcus pneumoniae and Streptococcus pyogenes. Community-associated methicillin-resistant S aureus (CA-MRSA) is also an increasing problem and is the most common cause in many regions.^{2, 3, 4}
• Gram-negative bacteria and group B streptococci are frequently seen in newborns.
• Pseudomonas aeruginosa is often associated with osteomyelitis and osteochondritis following penetrating wounds of the foot through a tennis shoe.
• Children who are immunocompromised are prone to infection with various fungi and bacteria.
• Bony lesions due to Bartonella henselae (cause of catscratch disease) have also been reported.
• Salmonella is an important cause of osteomyelitis in children with sickle cell disease and other hemoglobinopathies.
• Kingella kingae, a fastidious gram-negative rod, is increasingly recognized as a cause of osteoarticular infections, particularly in the first 2 years of life and following a respiratory tract infection.
• Anaerobes such as Bacteroides, Fusobacterium, Clostridium, and Peptostreptococcus rarely cause osteomyelitis.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Chondrosarcoma
Discitis
Osteoblastoma
Osteochondroma
Stress fractures
Eosinophilic granuloma
Cellulitis
Subcutaneous abscess
Nervous system disease (eg, polio)
Cerebral hemorrhage
Trauma
Bone infarction in patients with sickle cell disease

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• To confirm a diagnosis of osteomyelitis, adequate radiologic and laboratory data are necessary.
• In most cases, the etiologic agent is identified if blood, bone, and joint aspirate cultures are obtained before any antibiotics are given.
• Obtain bone and joint fluid aspirate for Gram staining because the aspirate itself can be bactericidal. The yield of K kingae is improved by inoculating synovial fluid directly into blood culture bottles.
• The WBC count is elevated in only one half of patients.
• The C-reactive protein and erythrocyte sedimentation rate (ESR) are almost always elevated (except in small bones infections).
• Consider performing a bone biopsy if the patient does not respond to therapy.

Imaging Studies

• Radiography
• • Plain radiography usually only reveals soft tissue swelling and loss of normally visible tissue planes; however, radiography can be useful in revealing bone tumors, fractures, and healing fractures.
  • Osteopenia, lytic lesions, and periosteal changes are late radiographic signs; their absence does not exclude a diagnosis of acute osteomyelitis.
• Three-phase technetium radionuclide bone scanning
• • Through enhanced uptake of the radioisotope, this procedure reveals increased osteoblastic activity of the infected bone and distinguishes osteomyelitis from deep cellulitis.
  • Technetium bone scanning has a false-negative rate of as much as 20%, particularly in the first few days of illness.
  • Fractures, bone tumors, and surgery also cause enhanced technetium uptake.
• MRI
• • This test is increasingly used to define bone involvement in patients with  negative bone scan findings.
  • Changes in bone marrow caused by inflammation result in an area of low signal intensity within bright fatty marrow. These abnormalities need to be correlated with the clinical picture before a diagnosis is made because they are not specific for osteomyelitis.
• Indium scanning: This test, which uses indium-labeled leukocytes, is also useful, although it has limitations in newborns, infants, and patients with neutropenia.
• Gallium scanning: This study is usually not recommended because of lower specificity and exposure to higher levels of radiation.
• Ultrasonography: Clinical suspicion for deep vein thrombosis should be especially high in patients with osteomyelitis caused by CA-MRSA who have an elevated C-reactive protein level. Doppler venous ultrasonography is the first imaging study indicated in such cases. However, routine screening is not yet recommended.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Optimal antibiotic selection, adequate dosing, and a sufficiently prolonged antibiotic course with monitoring for clinical response and for the toxicity of therapy are essential. Promptly initiate antibiotic treatment, preferably after obtaining blood and bone aspirates for culture. Initially, select one or more antimicrobial agents that provide adequate coverage for common pathogens.
• The usual choice is an antistaphylococcal antibiotic; nafcillin, vancomycin, clindamycin, and cefazolin are the preferred agents.
• Consider vancomycin as an alternative to clindamycin for empiric therapy in patients who live in communities that have a higher incidence of penicillin-resistant S pneumoniae or CA-MRSA. Reports of CA-MRSA osteomyelitis are increasing worldwide. The severity of disease in infections with organisms carrying the Panton-Valentine leukocidin (PVL) gene is also increasing.⁴
• Although Haemophilus influenzae type b (Hib) disease has virtually disappeared from the Hib-immune population, third-generation cephalosporins (eg, cefotaxime, ceftriaxone) are used in addition to nafcillin or clindamycin. This additional treatment is commonly used in children younger than 3 years. Do not use third-generation cephalosporins alone to treat osteomyelitis because they are not optimal for treating serious S aureus infections.
• Cefuroxime, a second-generation cephalosporin, can be used as a single agent against both methicillin-sensitive S aureus and Hib.
• The increasing incidence of penicillin-resistant S pneumoniae warrants the use of a clindamycin and cefotaxime/ceftriaxone combination in infants and children.
• When treating neonatal osteomyelitis, consider nafcillin and tobramycin or nafcillin and cefotaxime combinations to provide coverage of bacteria from the Enterobacteriaceae family, in addition to group B streptococci and S aureus.
• In children and adolescents with penetrating trauma of the foot, perform surgical debridement before considering antipseudomonal treatment.
• For further details, see Follow-up.

Surgical Care

• Bone aspiration may be necessary to identify the pathogen.
• Consider bone biopsy if other diagnoses are possible (eg, tumors).
• Joint aspiration is recommended if signs and symptoms suggest pathology near shoulder or hip joints. This is critical because arthrotomy is indicated if evidence of hip or shoulder arthritis is present.
• If signs and symptoms do not begin to resolve within 48-72 hours of initiation of appropriate antimicrobial treatment, consider repeat bone aspiration to drain the pus, in consultation with the orthopedic surgeon.

Consultations

• Consultation with an orthopedic surgeon and infectious diseases specialist is necessary in the management of osteomyelitis.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• For successful treatment, ensure that high-dose antimicrobials are used for an optimal period and provide close follow-up care for the patient. When antibiotics are used for less than 3 weeks, recurrence rates are higher.
• Clinical response, etiologic agent, and return of the ESR and C-reactive protein levels to the reference range govern duration of treatment. Prescribe a minimum antibiotic course of 4 weeks; most patients receive treatment for 4-8 weeks, depending on the pathogen, clinical course, and laboratory parameters.
• Once the pathogen is identified and antibiotic susceptibility results are available, consider modifying antibiotic therapy.
• Sequential intravenous-to-oral antibiotic regimens have proven safe and effective for treatment of bone and joint infections. Once symptoms and signs of inflammation have subsided and the ESR has started to fall, consider switching to oral antibiotics.
• Studies have reported successful treatment of acute uncomplicated osteomyelitis with 4 days of intravenous antibiotics and 30 days of oral antibiotics.⁵ Further studies are needed to aid with universal recommendations. The treatment regimen of choice is based on the clinical progression and the location of the osteomyelitis in the child.
• Ensure the following criteria are met before switching from intravenous to oral therapy:
• • Availability of etiologic agent and reliable laboratory to perform serum-cidal assay (Schlichter test)
  • Availability of oral antibiotic capable of achieving adequate serum levels; usually 2-3 times usual oral dose
  • Absence of GI disease causing poor absorption of antibiotic
  • Family compliance (critical to success)
• In older children, giving higher oral dosages of antibiotics is often not possible because they exceed the maximum allowable doses.
• If the patient does not meet the above criteria for high-dose oral antibiotic course, continue treatment at home after establishing a peripherally inserted central catheter (PICC) line or another reliable venous access. Parents often find it easier to administer intravenous antibiotics less frequently than every 6 hours. Cefazolin (Ancef, Kefzol), ceftazidime (Ceptaz, Fortaz, Tazicef, Tazidime), ceftriaxone (Rocephin), aminoglycosides, and clindamycin (Cleocin) provide this dosing convenience.
• The patient may require repeat aspiration of the bone if fever, pain, and swelling fail to respond promptly or if radiography reveals significant periosteal elevation or periosteal abscess.
• If chronicity of illness leads to necrotic bone, surgical debridement is usually required.

Further Outpatient Care

• Provide close follow-up care throughout treatment with weekly measurements of ESR, C-reactive protein levels, liver function tests, and CBC counts to monitor response and diagnose antibiotic-related neutropenia.
• Oral antibiotic dosages may need to be increased to keep peak serum-cidal levels of 1:8 or greater. If serum-cidal levels are not adequate with oral antibiotics, the patient may need parenteral treatment.

Complications

• Possible complications from osteomyelitis include disturbances in bone growth, limb-length discrepancies, arthritis, abnormal gait, and pathologic fractures. In patients with chronic osteomyelitis, bone necrosis and fibrosis can occur.

Prognosis

• Despite adequate treatment and appropriate surgical intervention, 5-10% of patients may experience recurrence.
• Aggressively treat any recurrence in consultation with an orthopedic surgeon and infectious diseases specialist. Recurrences may lead to chronic osteomyelitis with discharging sinuses and other systemic sequelae.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• The importance of compliance and careful follow-up should be stressed to the family and documented.
• Delayed treatment or lowered dosage results in higher incidence of chronic osteomyelitis and complications associated with it. Therefore, prognostic factors relevant to each case must be discussed with the family regarding both initiation and completion of treatment.

Special Concerns

• Neonatal osteomyelitis
• • S aureus, enteric gram-negative bacilli (eg, Escherichia coli, Klebsiella species), and group B streptococci are common pathogens.
  • Intravenous sites, scalp electrodes, and puncture wounds are often predisposing factors. Diagnosis may be delayed because swelling and erythema may not be evident at onset.
  • Decreased movement (pseudoparalysis) of the affected area may be the only symptom. As many as 50% of affected newborns may have multiple bone involvement. Associated arthritis is also common.
  • Unlike radiographic findings in older children, plain radiography of newborns often reveal a lytic area at the time of diagnosis.
  • Perform a complete evaluation for serious bacterial infection before initiating empirical treatment with antibiotics (eg, nafcillin and gentamicin, nafcillin and cefotaxime).
  • A significant number of patients develop permanent sequelae due to involvement of the adjacent joint and damage to the cartilaginous growth plate.
• Puncture wound osteochondritis
• • Osteochondritis often develops 3-7 days after puncture wounds of the foot.
  • When the puncturing object passes through the shoe, P aeruginosa is often the infecting pathogen.
  • Patients who present soon after the puncture wound occurs should be evaluated by an orthopedic surgeon for a thorough debridement that includes obtaining bacterial cultures.⁶
  • S aureus is a common pathogen, but a patient who receives a brief course of antistaphylococcal antibiotics often presents later with painful swelling and focal tenderness.
  • Bone scanning and MRI reveal the pathology and assist in locating the site for aspiration or biopsy.
  • If treatment is initiated soon after injury, a short course of 10-12 days of antipseudomonal therapy is adequate. If significant bone pathology is revealed on MRI, a longer course of 4-5 weeks is usually required.
  • Aminoglycoside and antipseudomonal penicillin or ceftazidime in combination are recommended for initial treatment before susceptibility results are available.
  • If aminoglycoside agents are continued beyond 5-7 days, evaluating hearing, performing urinalysis, and monitoring BUN and creatinine levels is essential.
  • Experienced orthopedic surgeons should provide follow-up care for these patients because foot pathology can be associated with persistent pain.
• Other bone infections
• • Vertebral and pelvic osteomyelitis is relatively uncommon in children. The signs and symptoms are generally nonspecific, and delay in diagnosis often occurs. Various imaging studies help to reveal the pathology, and S aureus and gram-negative enteric bacteria are often isolated.
  • Various Salmonella species have been reported in vertebral osteomyelitis. Bone and joint infections due to Salmonella are also common in patients with various hemoglobinopathies, including sickle cell disease. Consider performing a bone biopsy to rule out a bone infarction.
  • Consider discitis in the differential diagnosis when a patient presents with focal tenderness or a gibbus deformity of the spine. The etiology of discitis is not well defined. S aureus and other pathogens have been reported in a few cases, and some investigators attribute infection to trauma. Often, these patients are treated with a 4- to 8-week course of antistaphylococcal antibiotics, even if cultures of the aspirate are negative.
  • Mycobacteria and various fungi also cause osteomyelitis. Careful history, histopathologic diagnosis, purified protein derivative (PPD) skin test findings, and biopsy findings assist in arriving at this diagnosis. Patients need specific treatment of considerably longer duration, depending on the etiologic agent and susceptibility results.
  • Chronic recurrent multifocal osteomyelitis (CRMO) is an ill-defined disease of uncertain etiology. Patients present with low-grade fever and swelling over affected bones; flat bones are frequently involved. Bone scanning reveals increased uptake in several bones, and blood culture and aspirate culture findings are often negative for bacteria. Consider histiocytosis X, leukemia, and neuroblastoma in the differential diagnosis. Antimicrobial treatment has no effect on the course, and treatment with steroids is controversial. In a case report by Ozbek et al, one patient was noted to have salmon-colored conjunctival lesions with CRMO that responded to systemic steroids.⁷
  • In a recent case report, 2 cases of chronic osteomyelitis caused by Actinomyces were noted to have characteristic findings that included multifocal, lytic, sclerotic bone lesions on imaging findings with soft tissue involvement.⁸ Isolating this anaerobic bacteria is difficult because culture findings are only 50% positive, and bone biopsy findings may or may not reveal characteristic sulfur granules.
  • In subacute osteomyelitis, patients may present with fever of unknown origin and do not have any signs of local inflammation. Occasionally, patients present with erythema nodosum, and the search for the cause leads to a diagnosis of subacute osteomyelitis. WBC count and other laboratory parameters may not be abnormal. Radiography and bone scanning may aid in the diagnosis. Aspiration of bone to identify the etiologic agent and an evaluation for tuberculosis, fungal disease, and other unusual pathogens are essential before an appropriate anti-infective agent can be selected. The duration of treatment is usually longer (2-3 mo) depending on the clinical course and evidence of healing as demonstrated by radiologic findings.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: May 7, 2008