Pediatric Osteomyelitis

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.

Staphylococcus aureus is the most common pathogen, followed by Streptococcus 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.[1, 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, 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, and Peptostreptococcus rarely cause osteomyelitis.

United States statistics

The exact frequency is unknown as osteomyelitis is not a reportable disease.

International statistics

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

Race-, sex-, and age-related demographics

Few studies have commented on race differences.

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.

One half of cases occur in preschool-aged children.

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.

Morbidity/mortality

As noted in recent studies, patients may develop deep vein thrombosis and fractures.[5, 1, 6, 7]

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. In a Swedish study of 430 children with acute osteomyelitis, severe complications occurred in 14 children and 5 of them required intensive care.[8]

Monitor patients for septic thrombophlebitis, venous thrombosis, and pathologic fractures.[9]

Leg-length discrepancy is due to involvement of the growth plate with infection.

Discuss age-appropriate care with the patient to ensure compliance with medical therapy.

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

Long bones, including the femur, tibia, and humerus, are most commonly affected.

Fever, localized 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.

It is important to differentiate uncomplicated versus complicated osteomyelitis: single bone versus two or more bones involved with soft tissue infection, as this will help determine the risk of complications to monitor patient for.[9]

 

To confirm a clinical diagnosis of osteomyelitis, adequate radiologic and laboratory data are necessary. A blood culture and serum C-reactive protein are recommended as first line. 

The white blood cell (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 in local area of practice.

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 or send off for K kingae PCR testing. 

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

Magnetic resonance imaging

Magnetic resonance imaging (MRI) 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.

A study by Schallert et al found that children with joint effusions identified by MRI, in the setting of metaphyseal osteomyelitis, should be presumed to have septic arthritis until proven otherwise.[11]

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.[12, 13]

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.

Gallium scanning

This study is usually not recommended because of lower specificity and exposure to higher levels of radiation.

Ultrasonography

Ultrasonography 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.[5, 1, 7]

Bloood cultures should always be drawn on these children. Bone aspiration may be necessary to identify the pathogen if needed.

The study on 250 children by McNeil et al examined the impact of interventional radiology (IR) and surgically obtained cultures in the diagnosis and management of acute hematogenous osteomyelitis. The study found that IR or operating room culture was the only means of identifying a pathogen in 80 of 216 cases (37%), and the results changed antibiotic therapy in 85% of patients. The authors further added that IR can be used effectively to obtain bone cultures in children with acute hematogenous osteomyelitis not requiring open surgical drainage. IR was able to obtain cultures in difficult to acess areas important to obtaining a positive culture and resulted in a shorter hospital stay. The most common pathogen isolated was Staphyloccus aureus (32.5% MRSA, 9.8% MSSA) and no Kingella cases were reported.[14]

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 24-48 hours of initiation of appropriate antimicrobial treatment, consider bone aspiration to drain the pus, in consultation with the pediatric orthopedic surgeon.[9]

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.[15]

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. It is helpful to look at the local antibiogram to determine what are the MRSA rates as well as clindamycin susceptibilities for both MRSA and MSSA. If patients are moderately to severely ill in areas of clindamycin resistance greater than 10-20%, vancomycin, daptomycin, ceftaroline, or linezolid may be used.[9]

Linezolid has good Gram-positive coverage, including MRSA, and 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.[16]

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 3-6 weeks until normalization of the C-reactive protein level.[17, 18]

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 aid with management.[19] The severity of disease in infections with organisms carrying the Panton-Valentine leukocidin (PVL) gene is also increasing.[3]

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 for empiric antibiotic therapy. This additional treatment is commonly used in children younger than 3 years.

The use of a third-generation cephalosporins alone to treat osteomyelitis is not recommended as it is not optimal regimen 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.

Consultation with a pediatric orthopedic surgeon and a pediatric infectious diseases specialist is 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. Aerobic and anaerobic culture samples may be performed to aid with diagnostic workup as well as pathology.

Diet

No specific diet is recommended.

Activity

Weight bearing and aggressive physical activity should be restricted until the infection and treatment course are completed, as noted recently in S aureus infections.[6]

Woods CR, Bradley JS, Chatterjee A, Copley LA, Robinson J, Kronman MP, et al. Clinical Practice Guideline by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America: 2021 Guideline on Diagnosis and Management of Acute Hematogenous Osteomyelitis in Pediatrics. J Pediatric Infect Dis Soc. 2021 Sep 23. 10 (8):801-844. https://read.qxmd.com/doi/10.1093/jpids/piab027

Class Summary

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

Nafcillin (Nafcil, Nallpen, Unipen)

Interferes with bacterial cell wall synthesis during active multiplication, causing cell wall death and resultant bactericidal activity against susceptible bacteria.

Clindamycin (Cleocin)

Inhibits bacterial protein synthesis by its action at the bacterial ribosome. The antibiotic binds preferentially to the 50S ribosomal subunit and affects the process of peptide chain initiation.

Cefazolin (Ancef, Kefzol)

First-generation semisynthetic cephalosporin that arrests bacterial cell wall synthesis, inhibiting bacterial growth. Primarily active against skin flora, including S aureus. Typically used alone for skin and skin-structure coverage.

Vancomycin (Vancocin)

Inhibits cell wall synthesis. It is accomplished by binding to carboxyl units on peptide subunits containing free D-alanyl-D-alanine.

Cefotaxime (Claforan)

Third-generation cephalosporin with gram-negative spectrum. Lower efficacy against gram-positive organisms. Binds to PBPs, inhibiting bacterial cell wall growth.

Ceftriaxone (Rocephin)

Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Binds to PBPs, inhibiting bacterial cell wall growth.

Cefuroxime (Kefurox, Zinacef)

Second-generation cephalosporin maintains gram-positive activity that first-generation cephalosporins have. Binds to PBPs, inhibiting bacterial cell wall growth

Ceftazidime (Ceptaz, Fortaz, Tazicef, Tazidime)

Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Binds to PBPs, inhibiting bacterial cell wall growth.

Tobramycin (Nebcin)

Inhibits protein synthesis by irreversibly binding to bacterial 30S and 50S ribosomes.

Gentamicin (Garamycin)

Inhibits protein synthesis by irreversibly binding to bacterial 30S and 50S ribosomes.

Trimethoprim/sulfamethoxazole (Bactrim, Septra)

Trimethoprim/sulfamethoxazole inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid.

Cephalexin (Keflex, Panixine Disperdose)

Provide close follow-up care throughout treatment with weekly measurements of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, liver function tests, and complete blood cell (CBC) counts to monitor response and diagnose antibiotic-related neutropenia.

Patients with complicated osteomyelitis are encouraged to be followed up for 1 year for those at risk for long-term adverse sequelae.[9]

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 CRP levels to the reference range govern duration of treatment. Prescribe a minimum antibiotic course of 3 weeks; this is adequate except for patients with methicillin-resistant Staphylococcus aureus (MRSA) infection, for whom 4-6 weeks of therapy are often required.

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. Family structure and ease of compliance should be factored into the treatment route of administration and frequency. Family need to understand the commitment to the treatment prescribed in terms of frequency and timing and the risk if this is not met. 

Studies have reported successful treatment of acute uncomplicated osteomyelitis with 3-5 days of intravenous antibiotics and 16-18 days of oral antibiotics.[20, 18] 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 

• Availability of oral antibiotic capable of achieving adequate serum level

• 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.