OVERVIEW: What every practitioner needs to know

Are you sure your patient has Osteomyelitis? What are the typical findings for this disease?

Osteomyelitis is defined an inflammation of bone and bone marrow that is generally caused by the presence of infection. It is considered to be “acute” if it is diagnosed within 2 weeks of the onset of symptoms or “subacute” if symptoms have been present for more than 2 weeks at the time of presentation. Acute and subacute osteomyelitis may evolve into a chronic process leading to extensive necrosis of the bone.

Osteomyelitis occurs most commonly during the first 2 decades of life with 50% of children with osteomyelitis being under the age of 5 years. The incidence is higher in children with sickle cell disease and in some immunocompromised patient populations.

The clinical findings of osteomyelitis vary depending on the age of the child, the duration of the process, and the location of the infection.

Continue Reading

A. In neonates with osteomyelitis, up to 50% will have multifocal bone involvement. Clinical findings may be minimal but may include:

1. Mild irritability, low grade fever, decreased feeding

2. Septic appearance with no localized findings

3. Diffuse, edema, erythema, warmth and swelling of a limb

4. Guarding of an effected limb with markedly decreased movement (pseudoparalysis)

5. Severe discomfort with passive movement or touch

6. Regional adenopathy

7. Sign of hip/proximal femur involvement results in a leg that is flexed at the hip, abducted, and externally rotated – “frog leg” position

B. In older infant and child, clinical findings include:

1. Fever, chills, malaise, nausea/vomiting

2. Refusal to use the affected extremity (refusal to walk or limps)

3. Pain with passive and/or active movement of the involved extremity

4. Localized or point tenderness over the involved site (may precede overlying swelling, erythema and warmth)

5. Regional adenopathy

C. In adolescent, clinical findings include:

1. Similar to those for a child

2. Function of affected extremity is less restricted

3. Point tenderness over the involved site may only be present at rest

What other disease/condition shares some of these symptoms?


Bone contusion

Nondisplaced fracture (traumatic or stress)

Sickle cell crisis

Histiocytosis X

Inflammation in severe arthritis

Autoinflammatory diseases


What caused this disease to develop at this time?

Bacteria may reach the bone by 3 routes:

a. hematogenous spread from a primary focus (main mechanism accounting for 90% of the cases in children under 16 years of age)

b. contiguous spread from adjacent tissue (e.g., cellulitis)

c. direct inoculation into the site (e.g., surgery or trauma)

Hematogenous osteomyelitis occurs as a complication of bactermia. Blood-borne bacteria localize to the metaphyseal end of the bone adjacent to the epiphyseal growth centers. The nutrient artery that supplies the bone divides into branches and then into a narrow plexus of capillaries that make sharp loops in the area of the epiphyseal plate before entering a system of large sinusoidal vessels supplying the metaphysis. Sluggish blood flow and an absence of lining reticuloendothelial cells are predisposing factors for microvascular thrombosis and bacterial growth. Occult or minor trauma or embolization cause thrombosis of the slow-flowing vessels providing a breeding ground for blood-borne bacteria.

Bacteria are able to proliferate in this avascular area, protected from host defenses resulting in a localized cellulitis of the bone marrow. Polymorphonuclear leukocytes and bacterial products accumulate under pressure leading to further vascular thrombosis, pressure necrosis of the bone, and death of small islands of bone.

As the process continues, the infection may:

i. Spread into the metaphyseal cortex and under the periosteum leading to the development of a subperiosteal abscess

ii. Spread along the marrow cavity and the periosteum into a joint space, resulting a septic joint; or

iii. Rupture through the periosteum into adjacent muscle, resulting in a soft tissue infection.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

1. Complete blood count with platelets and differential – leukocytosis and/or left shift may be seen, thrombocytosis may be seen.

2. Blood culture – may yield causative organism in 50-80% of cases of acute hematogenous osteomyelitis.

3. Culture of bone – may yield causative organism in 50-80% of cases with acute hematogenous osteomyelitis.

4. C-reactive protein (CRP) – elevated in up to 95-100% of patients with osteomyelitis.

5. Erythrocyte sedimentation rate (ESR) – elevated in up to 90% of patients with osteomyelitis.

Would imaging studies be helpful? If so, which ones?

In the neonate, physical examination findings alone are sufficient to make the diagnosis of osteomyelitis. Plain film radiographs are usually abnormal when clinical signs are present. Destruction of cortical bone and periosteal new bone formation might be seen on plain films in this age group.

In the older child or adolescent, radiographic studies that can help confirm the diagnosis of osteomyelitis include:

1. Plain film radiographs – the earliest abnormalities may be seen within the first 3 days of onset of symptoms and include deep soft tissue swelling and obliteration of the tissue planes around the affected bones due to muscle edema. Osteolytic lesions do not become evident until 40% to 50% of the bone has been demineralized; therefore, at least 10 days to 3 weeks are required after the onset of the infection before periosteal elevation from subcortical purulence, lytic bone lesions and periosteal new bone formation are evident. However, negative plain films even at 10 to 14 days DO NOT RULE OUT the presence of osteomyelitis. Sclerosis of bone is seen when the infection has been present for over a month.

2. Radionuclide imaging:

a. Bone scanning techniques using technetium TC 99m phosphate or diphosphate compounds are more sensitive and can be used earlier in the infection, before bony changes are apparent on plain films. Abnormalities may be detected as early as 48-72 hours from the start of the infection. In osteomyelitis, increased isotope uptake is seen in areas of infection; “cold” spots (where there is no isotope uptake) are seen in areas of ischemia, necrosis, or abscess.

If there is an associated cellulitis/soft tissue infection, uptake occurs during the early phase of the bone scan but does not persist in the later phases; however, inflammation associated with cellulitis and fractures may make interpretation of the scan results more difficult. The reported sensitivity of technetium bone scan is between 80% to 100%, however, the sensitivity in neonates and young infants is much lower due to the limited amount of mineralization in their bones. Bone scan can be normal in up to 20% of children with osteomyelitis in the first few days of illness. There is a fair amount of radiation involved in performing a bone scan.

b. Gallium and indium tagged WBC scans may be used in the diagnosis of osteomyelitis. Gallium scan is positive in diseases characterized by increased bone turnover but a major limitation is that it is not specific for osteomyelitis. Indium scan reflects migration of white blood cells into areas of inflammation but a major limitation is its poor localization of infection (e.g., bone versus soft tissue) and its decreased sensitivity in diagnosing infections in the central skeleton. Both gallium and indium studies involve a relatively high radiation exposure.

3. Magnetic resonance imaging (MRI) – MRI is the most sensitive test to use very early in the course of the infection. The reported sensitivity of MRI is between 92% to 100% for the detection of osteomyelitis. Normal fatty bone marrow produces a bright signal on T1-weighted MRI images. Changes in marrow caused by infection and inflammation produce an area of low signal intensity within the bright fatty marrow indicating areas of bone marrow cellulitis. Areas of low signal intensity in infected marrow seen on T1-weighted image change to bright signal intensity in the T2-weighted image. MRI can also detect signal alterations in soft tissue and is especially useful in differentiating cellulitis from osteomyelitis. It also can detect abnormalities within 48 hours of infection onset.

If you are able to confirm that the patient has Osteomyelitis, what treatment should be initiated?

The need for surgical therapy should be considered in all patients with osteomyelitis. Patients with soft tissue, subperiosteal, and intramedullary abscesses seen on imaging studies should have drainage via surgical or interventional radiology techniques and cultures should be sent of the material to confirm a microbiologic diagnosis. Sequestra, if present, should be removed and contiguous foci of infection should be debrided.

Appropriate antibiotic selection is critical for the successful treatment of osteomyelitis. Things that should be considered in the choice of the agent include: the age of the child, presence of underlying medical conditions, suspected pathogens and their antimicrobial susceptibility patterns, and safety and efficacy of the antibiotic. The empiric therapy chosen should always have potent activity against S. aureus (including MRSA if geographic area has > 10% MRSA incidence) and group A streptococcus and should be administered intravenously. (See Table I)

Table I.
Population Antibiotic Therapy
Neonate Vancomycin or nafcillin plus cefotaxime, Vancomycin or nafcillin plus gentamicin; linezolid for resistant Gram-positive organisms
Under 3 years Clindamycin or vancomycin or cefazolin or nafcillin plus cefotaxime or ceftriaxone (if patient incompletely immunized against Hib or status unknown); cefuroxime; linezolid for resistant Gram-positive organisms 
Over 3 years Clindamycin or vancomycin or cefazolin or nafcillin; linezolid for resistant Gram-positive organisms
Hemoglobinopathies Cefotaxime or ceftriaxone or ampicllin plus an aminoglycoside
Immunocompromised or patients with puncture wounds of foot Ceftazidime plus an aminoglycoside; fluoroquinolone (ciprofloxacin or levofloxacin)

Therapy should be tailored once the causative organism identified and antibiotic susceptibilities available. For the treatment of acute hematogenous osteomyelitis, duration of parenteral antibiotic therapy is a minimum of 4 weeks. The exception to this is with puncture wound osteomyelitis due to Pseudomonas aeruginosa. In these cases, if the infection is recognized early and management involved surgical debridement, the duration of therapy is 10 to 14 days.

Antibiotic therapy should be continued until the patient has a peripheral WBC count, ESR, and/or CRP that has returned to baseline, and serial radiographs indicating significant improvement and/or resolution of the infection.

The treatment of acute hematogenous osteomyelitis with a combination of initial parenteral therapy followed by oral antibiotic therapy is becoming more common. There are some advantages associated with completing therapy with a course of oral antibiotics such as decreasing the cost, discomfort, and potential hazards of long-term parenteral therapy; however, this is not feasible for every patient. Criteria that are used for determining whether switching to oral therapy is feasible include:

a. Patient has been afebrile for 48 to 72 hours with no other systemic symptoms,

b. A significant reduction in local signs and symptoms of the infections,

c. Adequate surgical debridement,

d. Definitive identification of an organism or response of the presumed organism to antibiotic therapy,

e. Determination of appropriate serum concentrations of the antibiotic,

f. Patient able to swallow and retain the medication, and most importantly,

g. Presence of a reliable care taker that will be compliant with the medication course.

What are the adverse effects associated with each treatment option?

Antibiotic therapy with the beta-lactam antibiotics may be associated with rash, diarrhea, oral and diaper area candidiasis, reversible neutropenia and thrombocytopenia.

Aminoglycoside antibiotics may be associated with nephrotoxicity and ototoxicity so monitoring serum levels are important. Minor side effects include rash and drug fever.

Clindamycin therapy maybe associated with nausea, vomiting and diarrhea. Pseudomembranous colitis due to C. difficile is rare.

Vancomycin may cause nephrotoxicity and ototoxicity and can cause phlebitis if the drug is injected rapidly. If the drug is injected too rapidly, a transient rash may develop on the upper body with itching which occurs due to histamine release (“red-man syndrome”) – this resolves with slowing of the infusion and administration of oral antihistamines.

Fluoroquinolones may cause gastrointestinal upset, dizziness, headaches, cardiac dysrhythmias and in various toxicity studies in immature animals has been shown to cause cartilage damage to weight-bearing joints. There is no conclusive data on these findings in children.

Linezolid may cause diarrhea, headache, nausea, vomiting, transient leukopenia and thrombocytopenia. Very long term use has been associated with peripheral neuropathy and optic neuropathy.

What are the possible outcomes of Osteomyelitis?

When treated appropriately, the majority of children recover completely from their infection with no long term sequelae.

The complications that may be seen include:

1. Physical deformity/disability with impairment of limb growth and function.

2. Pathologic fractures at the infection site.

3. Secondary bacteremia from the infection site with seeding of secondary sites if the initial infection is not properly treated.

4. Chronic osteomyelitis, usually from inadequately treated acute osteomyelitis.

What causes this disease and how frequent is it?

Osteomyelitis is an inflammation of bone that is usually caused by a pyogenic organism. It occurs in about 1 in 5,000 children under 13 years of age and boys are 2.5 times more likely to develop osteomyelitis compared to girls, possibly related to an increased incidence of minor trauma. In neonates, the incidence of osteomyelitis is estimated to be 1 to 3 cases in 1,000 intensive case nursery admissions. Risk factors for disease include: prematurity, low birthweight, bacteremia, preceding infection(s), and the presence of intravenous or umbilical catheters.

Staphylococcus aureus is the primary etiologic organism causing acute hematogenous osteomyelitis in all age groups accounting for 70% to 90% of all cases. This includes methicillin-sensitive and methicillin-resistant strains. Beta-hemolytic group A streptococcus (Streptococcus pyogenes) is the second most common entity.

Other organisms commonly associated with acute hematogenous osteomyelitis include:

1. Neonatal population – Streptococcus agalactiae (group B streptococcus, especially serotype III), enteric Gram negative bacilli, coagulase negative staphylococci (premature infants), Candida species, polymicrobial infections.

2. Outside neonatal period – Streptococcus pneumoniae; Haemophilus influenzae type b (children less than 2 years); Salmonella species (children with hemoglobinopathies), Escherichia coli, Shigella species, Klebsiella species, Kingella kingae,
Pseudomonas aeruginosa (immunocompromised host, also associated with puncture wound of the calcaneus through sole of sneaker – produces more of an osteochondritis),
Aspergillus species (immunocompromised hosts).

Special manifestations of osteomyelitis:

a. Vertebral osteomyelitis accounts for about 1% to 3% of all cases of osteomyelitis and is usually hematogenous. It is more common in boys, and the presentation is insidious. Primary symptoms include fever, back pain and stiffness, weakness, and generalized malaise. Children may present with poorly localized chest (thoracic vertebra) abdominal or leg pain (lumbar vertebra). The vagueness and nonspecific nature of complaints associated with vertebral osteomyelitis may delay the diagnosis for up to several months. Clinically, vertebral osteomyelitis may mimic discitis but can usually be differentiated on plain film (greater vertebral endplate involvement) or by MRI. Most cases are caused by
S. aureus.

b. Pelvic osteomyelitis often has a subacute presentation and diagnosis may be difficult to establish. It can mimic appendicitis and urinary tract infections. Children with pelvic osteomyelitis may present with fever, gait abnormalities and limp, poorly localized hip or abdominal pain, and tenderness over the sciatic notch or buttock. Point tenderness and pain with hip movement can be elicited in only 50% of patients on physical examination. Diagnosis is often delayed for prolonged periods of time.

c. Contiguous focus osteomyelitis occurs through spread of infection from adjoining infected tissue to bone. The femur and the tibia are the most common sites of involvement. The microorganisms are often introduced during a traumatic injury that results in an open fracture or during open reduction and internal fixation of a fracture.

d. Epiphyseal osteomyelitis occurs through hematogenous spread of the microorganisms to the epiphyses by transphyseal vessels. After 15 to 18 months of age, these vessels are lost, and the physis acts as a physical barrier to the spread of infection from the metaphysis. However, bacteria may also get to the site by venous sinusoids via terminal branches of the epiphyseal arteries. Epiphyseal osteomyelitis may be acute or chronic. Acute manifestations include joint swelling, pain, limp, and other symptoms which prompt an evaluation for an osteoarticular infection.

How do these pathogens/genes/exposures cause the disease?

See ‘What caused this disease to develop at this time?’.

What complications might you expect from the disease or treatment of the disease?

See ‘What are the possible outcomes of Osteomyelitis’.

Are additional laboratory studies available; even some that are not widely available?

How can osteomyelitis be prevented?

What is the evidence?

Ash, JM, Gilday, DL. “The futility of bone scanning in neonatal osteomyelitis: Concise communication”. J Nucl Med. vol. 21. 1980. pp. 417-420.

Asmar, BI. “Osteomyelitis in the neonate”. Infect Dis Clin N Am. vol. 6. 1992. pp. 117-132.

Blyth, MJG, Kincaid, R, Craigen, MAC. “The changing epidemiology of acute and subacute haematogenous osteomyelitis in children”. J Bone Joint Surg [Br]. vol. 83. 2001. pp. 99-102.

Bradley, JS, Kaplan, SL, Tan, TQ. “Pediatric pneumococcal bone and joint infections”. Pediatrics. vol. 102. 1998. pp. 1376-1382.

Burnett, MW, Bass, JW, Cook, BA. “Etiology of osteomyelitis complicating sickle cell disease”. Pediatrics. vol. 101. 1998. pp. 296

Capitanio, MA, Kirkpatrick, JA. “Acute roentgen observations in acute osteomyelitis”. AJR. vol. 108. 1970. pp. 488

Correa, AG, Edwards, MS, Baker, CJ. “Vertebral osteomyelitis in children”. Pediatr Infect Dis J. vol. 12. 1993. pp. 228

Chung, T. “Magnetic resonance imaging in acute osteomyelitis in children”. Pediatr Infect Dis J. vol. 21. 2002. pp. 869-870.

Demopulos, GA, Bleck, EE, McDougall, IR. “Role of radionuclide imaging in the diagnosis of acute osteomyelitis”. J Pediatr Orthop. vol. 8. 1988. pp. 558-565.

Feigin, RD, Pickering, LK, Anderson, D. “Clindamycin treatment of osteomyelitis and septic arthritis in children”. Pediatrics. vol. 55. 1975. pp. 213

Fleisher, GR, Paradise, JE, Plotkin, SA. “Falsely normal radionuclide scans for osteomyelitis”. Am J Dis Child. vol. 134. 1980. pp. 499

Fletcher, BD, Scoles, PV, Nelson, AD. “Osteomyelitis in children: detection by magnetic resonance”. Radiology. vol. 150. 1984. pp. 57

Frederiksen, B, Christiansen, P, Knudsen, FU. “Acute osteomyelitis and septic arthritis in the neonate: risk factors and outcome”. Eur J Pediatr. vol. 152. 1993. pp. 577

Gillespie, WJ. “The epidemiology of acute haematogenous osteomyelitis of childhood”. Int J Epidemiol. vol. 14. 1985. pp. 600

Ibia, Eo, Imoisili, M, Pikis, A. “Group A beta-hemolytic streptococcal osteomyelitis in children”. Pediatrics. vol. 112. 2003. pp. e22

Jacobs, RF, McCarthy, RE, Elser, JM. ” osteochondritis complicating puncture wounds of the foot in children: a 10-year evaluation”. J Infect Dis. vol. 160. 1989. pp. 657

Kaplan, SL. “Osteomyelitis in children”. Infect Dis Clin North Am. vol. 19. 2005. pp. 787

Kaplan, SL, Deville, JG, Yogev, R. “Linezolid versus vancomycin for treatment of resistant gram-positive infections in children”. Pediatr Infect Dis J. vol. 22. 2003. pp. 677

Karwowska, A, Davies, D, Jadavji, T. “Epidemiology and outcome of osteomyelitis in the era of sequential intravenous-oral therapy”. Pediatr Infect Dis J. vol. 17. 1998. pp. 1021

Kiang, KM, Ogunmodede, F, Juni, BA. “Outbreak of osteomyelitis/septic arthritis caused by among child care center attendees”. Pediatrics. vol. 116. 2005. pp. e206

Krogstad, P, Feigin, RD, Cherry, JD, Demmler-Harrison, GJ, Kaplan, SL. “Osteomyelitis”. Feigin and Cherry's Textbook of Pediatric Infectious Diseases. 2009. pp. 725-742.

Lebel, MH, Nelson, JD. “
type b osteomyelitis in infants and children”. Pediatr Infect Dis J. vol. 7. 1988. pp. 250

Lew, DP, Waldvogel, FA. “Osteomyelitis”. N Engl J Med. vol. 336. 1997. pp. 999-1007.

Martinez-Aguilar, G, Avalos-Mishaan, A, Hulten, K. “Community acquired, methicillin-resistant and methicillin-susceptible musculoskeletal infections in children”. Pediatr Infect Dis J. vol. 23. 2004. pp. 701

Mazur, JM, Ross, G, Cummings, RJ. “Usefulness of magnetic resonance imaging for the diagnosis of acute musculoskeletal infections in children”. J Pediatr Orthop. vol. 15. 1995. pp. 144

Moumile, K, Merckx, J, Glorion, JC. “Bacterial aetiology of acute osteoarticular infections in children”. Acta Paediatr. vol. 94. 2005. pp. 419

Mustafa, MM, Saez-Llorens, X, McCracken, GH. “Acute hematogenous pelvic osteomyelitis in infants and children”. Pediatr Infect Dis J. vol. 9. 1990. pp. 416

Nelson, JD. “Acute osteomyelitis in children”. Infect Dis Clin North Am. vol. 4. 1990. pp. 513

Raz, R, Miron, D. “Oral ciprofloxacin for treatment of infection following nail puncture wounds of the foot”. Clin Infect Dis. vol. 21. 1995. pp. 194

Schauwecker, DS, Park, HM, Mock, BH. “Evaluation of complicating osteomyelitis with Tc-99m MDP, In-111 granulocytes, and Ga-67 citrate”. J Nucl Med. vol. 25. 1984. pp. 849

Sullivan, DC, Rosenfield, NS, Ogden, S. “Problems in the scintigraphic detection of osteomyelitis in children”. Radiology. vol. 135. 1980. pp. 731

Syrogiannopoulos, GA, Nelson, JD. “Duration of antimicrobial therapy for acute suppurative osteoarticular infections”. Lancet. vol. 1. 1988. pp. 37

Tien, I. “Update on the management of skin, soft-tissue, and osteoarticular infections in children”. Curr Opin Pediatr. vol. 18. 2006. pp. 254

Unkila-Kallio, L, Kallio, MJ, Eskola, J. “Serum C-reactive protein, erythrocyte sedimentation rate, and white blood cell count in acute hematogenous osteomyelitis of children”. Pediatrics. vol. 93. 1994. pp. 59

Wald, ER, Mirro, R, Gartner, JC. “Pitfalls on the diagnosis of acute osteomyelitis by bone scan”. Clin Pediatr. vol. 19. 1980. pp. 597

Weber-Chrysochoou, C, Corti, N, Goetschel, P. “Pelvic osteomyelitis: a diagnostic challenge in children”. J Pediatr Surg. vol. 42. 2007. pp. 553

Wong, M, Isaacs, D, Howman-Giles, R. “Clinical and diagnostic features of osteomyelitis occurring in the first three months of life”. Pediatr Infect Dis J. vol. 14. 1995. pp. 1047

Yagupsky, P, Erlich, Y, Ariela, S. “Outbreak of Kingella Kingae skeletal system infections in children in daycare”. Pediatr Infect Dis J. vol. 25. 2006. pp. 526