Pediatric infections can pose a diagnostic challenge to the clinician. Children are often unable to give an accurate history, and although parents can give insight into the child's normal behavior, they cannot articulate what the child is feeling. Pediatric osteomyelitis can be particularly difficult to diagnose due to its nonspecific presentation, and patients often present without any specific history of trauma to the involved extremity. Acute hematogenous osteomyelitis (AHO) is the most common musculoskeletal infection in children,1 with an annual rate of 1 in 5,000 in children younger than age 13 years in the United States.1,2 The worldwide annual incidence ranges from 1 in 1,000 to 1 in 20,000.2
Osteomyelitis can occur due to 1 of 3 different mechanisms: hematogenous spread from bacteremia; direct inoculation from penetrating trauma; or spread from local infection. In children, hematogenous spread is the most common mechanism of osteomyelitis.1 Most cases of pediatric AHO begin in the metaphysis,2 where sluggish blood flow and a discontinuous endothelium result in an increased risk of bacterial deposition into the bone marrow.1 The most commonly involved sites are those with the fastest growing metaphyses, due to their high vascularity.1 The femur has the highest rate of osteomyelitis (27%), followed by the tibia (22%), humerus (12%), and hands and feet (13%).2 The infection initially starts in the marrow. Progressive accumulation of purulence within the marrow causes increased pressure.1 This increased pressure subsequently allows the infection to then spread toward the cortex and subperiosteal space through Volkmann's canals and the Haversian system.1,2 Elevation of the periosteum can result in a subperiosteal abscess, whereas infarction of cortical bone can lead to formation of a sequestrum.2 In an effort to confine the infection, reactive periosteal bone is formed, thus creating an involucrum around the sequestrum.2 Once this involucrum-sequestrum is formed, eradication of infection without surgical intervention is futile. The avascular nature of the sequestrum prevents penetration of antibiotics and acts as a necrotic nidus for persistent bacterial proliferation. In children younger than age 2 years, transphyseal blood vessels can allow spread of infection into the epiphysis and subsequently into the joint, resulting in septic arthritis.1,2 However, after age 2 years, the physis is fairly avascular and the risk of adjacent septic arthritis is decreased.
An 11-year-old girl presented to the emergency department with a 10-day history of worsening left knee pain after a fall. Her knee pain was also associated with fever. Her parents were treating her pain with acetaminophen and ibuprofen. However, on the day of presentation to the emergency department, she began to have spiking fevers and refused to bear weight on the leg. Vital signs at presentation were a temperature of 104.2°F, heart rate of 116 beats per minute, respiratory rate of 20 breaths per minute, and blood pressure 120/75 mm Hg. Physical examination revealed erythema, warmth, and tenderness about the proximal tibia with painful range of motion of the knee. Radiographs showed soft tissue swelling and a knee effusion without bone destruction or periosteal reaction (Figure 1). Laboratory testing showed white blood cell count of 21,000/mm3, erythrocyte sedimentation rate (ESR) of 103 mm/hr, and C-reactive protein (CRP) of 242 mg/dL. Blood cultures were drawn at the time of admission. Magnetic resonance imaging (MRI) of the tibia showed a T1 hypointense region in the proximal tibia corresponding to an area of hyperintensity on T2-weighted images and a large subperiosteal abscess (Figure 2 and Figure 3). A diagnosis of osteomyelitis was made.
(A) Anteroposterior and (B) lateral views of the tibia and fibula showing soft tissue swelling without any bony destruction.
Axial magnetic resonance imaging cuts of the tibia and fibula. (A) T1 hypointensity within the surrounding subperiosteal space (white arrows). (B) T2 hyperintensity in the subperiosteal space around the tibia (white arrows). (C) Postcontrast axial cut showing rim-enhancing lesion in the subperiosteal space (white arrows) and heterogeneous lesion in the medullary canal (asterisk) representing subperiosteal abscess and intraosseous abscess, respectively.
Sagittal postcontrast T2-weighted magnetic resonance imaging cut of the tibia showing heterogeneous lesion within the proximal tibia metaphysis (asterisk) and a rim-enhancing lesion in the proximal subperiosteal space (white arrows).
The orthopedics department was consulted and they aspirated the knee. The patient was admitted and taken to the operating room for emergent irrigation and debridement of the tibia. Frank pus was seen in the subperiosteal space and gross purulence within the shaft of the tibia. She was transferred to the pediatric intensive care unit (PICU) postoperatively due to sepsis. Broad-spectrum antibiotics were started after intraoperative cultures were obtained. During her hospitalization she required two more visits to the operating room for persistent purulent drainage. Blood cultures remained positive for 3 days after presentation despite early debridement and initiation of antibiotics. Blood and intraoperative cultures grew methicillin-resistant Staphylococcus aureus (MRSA). Knee aspirate was negative for infection. The patient gradually improved throughout the remainder of her hospital course and she was discharged home on hospital day 13 with a peripherally inserted central catheter line and a tailored antibiotic regimen.
Acute Hematogenous Osteomyelitis
Common organisms causing pediatric AHO include S. aureus, Streptococcus pyogenes, Streptococcus pneumonia, and, more rarely, Kingella kingae.1–3K. kingae can be seen in children ages 6 months to 4 years and is a fastidious organism requiring special culture medium for isolation.4 Group B streptococcus and gram-negative rods can commonly be seen in neonates, whereas Salmonella is more commonly seen in the immunocompromised and in children with sickle cell disease.2 However, S. aureus is, overall, the most common pathogen causing pediatric AHO.2
MRSA is a more worrisome organism due to its increased virulence. Strains of MRSA osteomyelitis are particularly aggressive because of the presence of the Panton-Valentine leukocidin (PVL) gene.5,6 PVL encodes an exotoxin that results in lysis of neutrophils, which are the critical cell of the inflammatory response and a key component in the defense against bacterial pathogens.6 This antimicrobial defense mechanism of MRSA (and now of some emerging methicillin-sensitive S. aureus strains) contributes to local tissue necrosis and increased virulence by creating pores in the cell membrane of skin or mucosa.5,7 Children with MRSA osteomyelitis have been shown to have higher serum inflammatory markers, higher and more prolonged fever, and greater lengths of hospital stay compared with other pathogens.3,8
In addition to their musculoskeletal manifestations, children with MRSA osteomyelitis have systemic complications that are not commonly seen in the pediatric population, such as deep venous thrombosis, septic pulmonary emboli, and septic thrombophlebitis.8 In a study of 27 children with MRSA musculoskeletal infections, Vander Have et al.9 found that 12 of 27 patients required care in the PICU, with 4 patients requiring extracorporeal membrane oxygenation within 24 hours of presentation due to multisystem organ failure. Clinicians must be aware of these complications and remain vigilant in monitoring for their development. Children with MRSA osteomyelitis also tend to remain bacteremic, with positive blood cultures for several days despite being on appropriate antibiotics.8 This persistent bacteremia can allow infection to spread to other areas and predispose children to developing infections distant to the index source.
Children with AHO often present with vague symptoms of fever and malaise. They can have pain with swelling of the affected extremity; however, this is not always the case. Older children who are able to give a good history may be able to localize their symptoms. If the lower extremity is affected, they may ambulate with an antalgic gait. In the early stages of AHO, the symptoms may seem benign, and a misdiagnosis of a muscle strain may be made.
Younger children, however, tend to stop bearing weight soon after the onset of pain. If the upper extremity is involved, parents may note pseudoparalysis of the affected extremity.
Diagnostic evaluation with laboratory tests and imaging is vitally important. Laboratory tests to be obtained include complete blood count with differential, ESR, CRP, and blood cultures. Elevations in CRP usually start within 4 to 6 hours after infection and peak in 24 to 72 hours.2 Although CRP is a useful test to evaluate for AHO, it can be elevated in other inflammatory states (eg, rheumatoid arthritis, lupus, tumors, synovitis). ESR and CRP together have a sensitivity of 98%; however, their specificity is quite low.3,4 If both ESR and CRP are within normal limits, a diagnosis of AHO is much less likely, although not impossible.3 In addition, consideration should be made to a diagnosis of osteomyelitis in the young child with a cellulitic extremity and extremely elevated inflammatory markers.4 Blood cultures should be obtained before the initiation of antibiotics. They have been shown to be positive in 30% to 60% of cases of AHO; however, use of repeated blood cultures has not been shown to increase the yield of a positive culture, especially after initiation of antibiotics.2 If the patient is stable enough to tolerate it, cultures from the suspected site of infection should also be obtained prior to initiation of antibiotics in an effort to increase the yield of the offending pathogen.2 If infection with K. kingae is suspected, the aspirate should be sent in an aerobic blood culture bottle and plated on blood and chocolate agar to increase the likelihood of isolation.4
Radiologic examination is of critical importance in confirming the diagnosis of pediatric AHO. First-line imaging should consist of plain radiographs of the painful extremity. X-rays are most useful in ruling out other causes of limb pain, such as tumor or trauma, rather than in diagnosing osteomyelitis. Radiographic findings of osteomyelitis include soft tissue swelling (within 48 hours of infection), periosteal reaction (within 5–7 days of infection), and osteolysis.2 Osteolysis requires a 30% to 50% reduction in bone density and can take up to 14 days to be seen on plain radiographs.2
MRI with and without contrast has proven to be effective in diagnosing AHO even in its very early stages.4 Studies have shown MRI to have a sensitivity of 88% to 100% and specificity of 75% to 100% for diagnosing osteomyelitis.2 Advantages of MRI include lack of radiation (in contrast to bone scans), ability to detect subtle changes at the onset of infection, and the ability to detect intraosseous abscesses, subperiosteal abscesses, joint effusions, and pyomyositis.3 In addition to being effective in diagnosing osteomyelitis, MRI is also useful for determining need for surgery and guiding the extent of surgical decompression required.1,4 It provides multiplanar images and can identify fluid within the marrow or in extraosseous soft tissues.2 In young patients, sedation may be necessary to obtain an MRI, and the MRI may need to be delayed due to the patients overall medical condition. Once stabilized, MRI should be obtained to guide surgical management.4 If the treating facility is unable to safely obtain an MRI in a pediatric patient with high suspicion of osteomyelitis, strong consideration should be given to transferring the patient to a tertiary care facility.
Approaching the treatment of pediatric AHO is multidisciplinary. It should involve pediatric emergency room physicians, general pediatricians, pediatric infectious disease doctors, musculoskeletal radiologists, pediatric orthopedists, and all ancillary staff. The goal in pediatric AHO is expedient diagnosis and rapid initiation of treatment in an effort to stabilize the patient or prevent the development of sepsis. The mainstay of treatment includes antibiotic administration.
Surgery is often indicated if there is a focus of infection that requires decompression. However, with the increased incidence of MRSA osteomyelitis, the indications for surgical intervention have changed significantly. Because patients often have a collection of pus (either intraosseous or subperiosteal), surgical decompression is usually required. Arnold et al.8 found that 91% of patients with MRSA bone and joint infections required surgical debridement, whereas Vander Have et al.9 found that 100% of patients with musculoskeletal infection required operative intervention, with 16 of 27 requiring multiple debridements.
Broad-spectrum intravenous (IV) antibiotics should be initiated once a diagnosis has been made and cultures obtained. Treatment guidelines from the Infectious Diseases Society of America recommend vancomycin (15 mg/kg every 6 hours) or clindamycin (40 mg/kg per day divided every 6–8 hours) as the first-line therapy for acute hematogenous MRSA osteomyelitis.10 Treatment duration should be for a minimum of 4 to 6 weeks;4,10 oral antibiotics are acceptable if cultures show a clindamycin-susceptible strain.10 The Infectious Diseases Society of America also states that surgical debridement of intraosseous or adjacent soft tissue abscesses is a critical component to effective therapy.10 If, however, surgery is deferred initially, close clinical observation should be performed and surgical intervention indicated if the patient shows clinical or laboratory signs of worsening infection.4 Early “step-down” therapy can be considered after clinical improvement and may avoid the need for parenteral antibiotics upon discharge. A retrospective study by Zaoutis et al.11 looked at 1,021 children discharged on IV antibiotics compared with 948 children discharged on oral antibiotics for pediatric AHO. Failure rates were similar in both groups, and patients discharged on IV antibiotics had higher complication rates due to the indwelling catheter.11
Regardless of the initiated treatment, long-term sequelae of osteomyelitis exist. Complications related to prolonged use of IV antibiotics include bacteremia from the indwelling catheter or readmission for catheter-associated issues.11 As such, early step-down therapy is an attractive option. However, oral antibiotics are not without their risks and can include diarrhea, rash, nausea, thrombocytosis, and antibiotic-induced neutropenia.2 Complications from the infection itself include growth arrest, chronic osteomyelitis, and pathologic fracture.2 As a result, children must be monitored periodically with serial radiographs by a pediatric orthopedist to allow for early recognition of these late complications.
AHO is the most common musculoskeletal infection in children. The clinician should maintain a high index of suspicion for AHO in the febrile child with generalized malaise and a painful or swollen limb. MRSA osteomyelitis is increasing in incidence, and successful eradication of infection requires prompt evaluation and initiation of care. Diagnosis and treatment requires a coordinated, multidisciplinary approach. Laboratory evaluation and radiographic imaging are crucial to the diagnosis of pediatric osteomyelitis, with MRI being the most sensitive and specific imaging modality for both diagnosis and surgical planning. Broad-spectrum IV antibiotics and early surgical intervention are the mainstays of treatment for pediatric MRSA osteomyelitis due to its increased virulence, and repeat debridements in the operating room are often necessary. Children should be closely monitored for complications unrelated to the musculoskeletal, such as deep venous thrombosis or septic pulmonary emboli.
- Pugmire BS, Shailam R, Gee MS. Role of MRI in the diagnosis and treatment of osteomyelitis in pediatric patients. World J Radiol. 2014;6(8):530–537. doi:10.4329/wjr.v6.i8.530 [CrossRef]
- Song KM, Sloboda JF. Acute hematogenous osteomyelitis in children. J Am Acad Orthop Surg. 2001;9(3):166–175. doi:10.5435/00124635-200105000-00003 [CrossRef]
- Thomsen I, Creech CB. Advances in the diagnosis and management of pediatric osteomyelitis. Curr Infect Dis Rep. 2011;13(5):451–460. doi:10.1007/s11908-011-0202-z [CrossRef]
- Copley LA. Pediatric musculoskeletal infection: trends and antibiotic recommendations. J Am Acad Orthop Surg. 2009;17(10):618–626. doi:10.5435/00124635-200910000-00004 [CrossRef]
- Ritz N, Curtis N. The role of Panton-Valentine leukocidin in Staphylococcus aureus musculoskeletal infections in children. Pediatr Infect Dis J. 2012;31(5):514–518. doi:10.1097/INF.0b013e31824f18cb [CrossRef]
- DeLeo FR, Otto M, Kreiswirth BN, Chambers HF. Community-associated methicillin-resistant Staphylococcus aureus. Lancet. 2010;375(9725):1557–1568. doi:10.1016/S0140-6736(09)61999-1 [CrossRef]
- Pendleton A, Kocher MS. Methicillin-resistant staphylococcus aureus bone and joint infections in children. J Am Acad Orthop Surg. 2015;23(1):29–37. doi:10.5435/JAAOS-23-01-29 [CrossRef]
- Arnold SR, Elias D, Buckingham SC, et al. Changing patterns of acute hematogenous osteomyelitis and septic arthritis: emergence of community-associated methicillin-resistant Staphylococcus aureus. J Pediatr Orthop. 2006;26(6):703–708. doi:10.1097/01.bpo.0000242431.91489.b4 [CrossRef]
- Vander Have KL, Karmazyn B, Verma M, et al. Community-associated methicillin-resistant Staphylococcus aureus in acute musculoskeletal infection in children: a game changer. J Pediatr Orthop. 2009;29(8):927–931. doi:10.1097/BPO.0b013e3181bd1e0c [CrossRef]
- Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3):285–292. doi:10.1093/cid/cir034 [CrossRef]
- 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. doi:10.1542/peds.2008-0596 [CrossRef]