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.

Approximately 50% of cases occur in preschool-aged children. Young children primarily experience acute hematogenous osteomyelitis due to 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 make 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 StatesThe exact frequency is unknown as osteomyelitis is not a reportable disease.

InternationalChronic 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 and fractures.[1, 2, 3, 4]

Race

Few studies have commented on race diffferences.

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.

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.

Often, patients are able to localize the infected bone on examination, owing to pain. Symptoms include focal swelling with cardinal signs of inflammation with or without fever and

focal point tenderness over the affected bone. It is important to note whether the adjacent joint is involved by assessing the range of motion of the joint and signs of inflammation. Arthritis found on examination may be a reactive inflammatory response or a sign of an infected joint.

Draining sinus and bone deformity are both rare in acute disease. When present, these symptoms suggest subacute or chronic osteomyelitis.

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.

Staphylococcus aureus is the most common pathogen, followed byStreptococcus pneumoniae and Streptococcus pyogenes. Community-associated methicillin-resistant S aureus (CA-MRSA) continues to be a major and most common cause in many regions of the United States.[2, 5, 6, 7]

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, in

addition to common pathogens. 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, andPeptostreptococcus rarely cause osteomyelitis

Acute Lymphoblastic Leukemia Acute Myelocytic Leukemia Animal Bites Arthritis, Septic Brucellosis Catscratch Disease Child Abuse & Neglect: Physical Abuse Ewing Sarcoma and Primitive Neuroectodermal Tumors Gaucher Disease Gonorrhea

Haemophilus influenzae infection Neuroblastoma Osteosarcoma Polyarteritis Nodosa Scurvy Serum Sickness

To confirm a clinical diagnosis of osteomyelitis, adequate radiologic and laboratory data are necessary.

The WBC count is elevated in only one half of patients with or without thrombocytosis. The C-reactive protein and erythrocyte sedimentation rate (ESR) are almost always elevated

(except in small bones infections). There are many methods to attempt to recover the organism causing the bone infection, such as

blood, bone, or joint aspirate cultures. It is important to obtain these cultures before any antibiotics are given.

However, at times cultures may be negative or difficult to obtain and therapy should be guided by the most common causes.

If one is able to obtain bone and/or joint fluid aspirate for culture, a Gram stain is vital, as the procedure itself can be bactericidal.

Consult with the microbiology laboratory prior to obtaining cultures to ensure proper culture mediums and technique are used.

If a clinician is considering, Kingella kingae, notify the microbiology department as recovery is improved by inoculating synovial fluid directly into blood culture bottles.

Consider performing a bone biopsy if the patient does not respond to standard therapy.

Radiography Initial films may be normal, with or without soft tissue swelling. Bone destruction occurs 10-15

days later and then can be appreciated on radiographs.[8, 9]

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.

Chronic recurrent multifocal osteomyelitis, fractures, bone tumors, and surgery also cause enhanced technetium uptake.

It is an inexpensive test without need for sedation and with relatively quick turnaround. MRI

This test remains the criterion standard, especially in early infections. On T2-weighted images, increased marrow intensity with surrounding inflammation is

suggestive of osteomyelitis. Gadolinium contrast is important to help elucidate edema from an

abscess.[10] These abnormalities need to be correlated with the clinical picture before a diagnosis is made, as 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: This modality is difficult to use in acute cases of osteomyelitis, with limitations based on

availability, technician-dependent results, and an inability to differentiate fluid patterns as infectious versus traumatic.

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.[1, 2, 4]

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, knee,

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 bone aspiration to drain the pus, in consultation with the orthopedic surgeon.

An osteomyelitis staging system is present in the literature for adult treatment and diagnosis of osteomyelitis. The Cierny-Mader classification is the newest system to account for host factors to aid with treatment. It categorizes the first part by anatomical involvement of infection, such as type 1 as medullary osteomyelitis and host type A as a normal host.[11]

Optimal antibiotic selection, adequate dosing, and a sufficiently prolonged antibiotic course with monitoring for clinical response and for the toxicity of therapy are essential. The decision must be tailored to the age of the patient, local resistance patterns, pathogen suspected, and compliance with the agent prescribed.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, until therapy can be narrowed.The usual choice is an antistaphylococcal antibiotic; nafcillin, vancomycin, clindamycin, and cefazolin are the preferred agents. Clindamycin may be used if resistance is less than or equal to 10% in the community setting after D-testing is performed.Linezolid is one of the newer medications on the market approved for skin and soft tissue infections, with Gram-positive coverage, including MRSA. It has excellent oral bioavailability and additional studies supporting its varied use. However, it is an expensive option and not well studied in the treatment of osteomyelitis.[12]

Intravenous therapy is still recommended for initial treatment. Various studies have started oral therapy after a few days of intravenous therapy. The entire duration of treatment remains between 4-6 weeks until normalization of the C-reactive protein level.[13, 14]

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, with IDSA guidelines now available to aide with management.[15] The severity of disease in infections with organisms carrying the Panton-Valentine leukocidin (PVL) gene is also increasing.[6]

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, if they are the suspected pathogens.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 vancomycin and gentamicin 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. Infection can occur days to weeks before initial presentation, as history is vital to the diagnosis.

As mentioned above, patients may require a bone biopsy to ensure a correct diagnosis and appropriate antimicrobial therapy. Consultation with orthopedic surgeons is helpful in determining whether surgery is necessary for diagnosis and treatment.

Consultation with an orthopedic surgeon and infectious diseases specialist are helpful in the management of osteomyelitis.

Intervention radiologists with a focus on bone pathology would be very helpful to obtain a bone biopsy in a difficult location under fluoroscopic guidance.Weight bearing and aggressive physical activity should be restricted until the infection and treatment course are completed, as noted recently in S aureusinfections.

Antibiotics

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 4-6 weeks, depending on the pathogen, clinical course, and laboratory parameters.

Once the pathogen is identified and antibiotic susceptibility results are available, consider narrowing 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/CRP has started to fall, consider switching to oral antibiotics in a nontoxic child.

Studies have reported successful treatment of acute uncomplicated osteomyelitis with 4 days of intravenous antibiotics and 30 days of oral antibiotics.[16, 14]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 long-term 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. Newer, expensive antibiotics may also be used such as linezolid and daptomycin.

The patient may require repeat aspiration of the bone if fever, pain, and swelling or 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.

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.It is important to ensure familial compliance with proper dosing of antibiotics when choosing an appropriate oral regimen.

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.

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.