Pediatric acute hematogenous osteomyelitis.
An 8 year old male presents with fever, chills, malaise, fatigue and pain over the left clavicle. The patient has been experiencing decreased range of motion of left arm due to pain. There is no report of recent trauma and no reported significant previous medical history.
Upon palpation during physical examination, tenderness is present over the medial aspect of the left clavicle with mild soft tissue swelling. Edema and erythema are present. The patient moves all extremities well but does not wish to move the left arm.
Laboratory findings reveal a normal WBC count with a left shift; 73 neutrophils, 16 bands and 1 metamyelocyte. ESR and CRP are both elevated at 38 and 12.40 respectively. X-ray of the left clavicle indicates no recent fracture or dislocation. MRI findings are consistent with osteomyelits, sternoclavicular septic arthritis and soft tissue abscess.
Culture results from the incision and drainage indicate Staph sensitive bacteria. The patient is started on appropriate antibiotic treatment. After five days of IV antibiotics, a PICC line is placed, allowing the patient to be discharged while continuing with the antimicrobial therapy.
Acute hematogenous osteomyelitis (AHOM) is a serious pyogenic infection of rapid onset primarily in children; affecting nearly 7% of children with boys twice as often as girls. The long bones of the lower extremity are the most commonly involved, although any bone may be affected. Because Staphylococcus aureus is responsible for approximately 70% of AHOM cases, empirical therapy is usually directed against this pathogen. Prompt diagnosis and appropriate treatment greatly reduce the risk of long term sequelae.
Osteomyelitis (OM) by definition is any inflammation of the bone often as a result of bacterial infection (1,6,9). There are three ways infection of the bone can occur (4,7,13):
* hematogenous seeding from bacteremia
* direct introduction as a result of trauma or surgery
* contiguous spread from nearby infected tissue
Osteomyelitis is categorized as either acute or chronic according to duration but more importantly by histopathological findings. With chronic osteomyelitis, patients often do not display symptoms until up to six weeks after invasion of the infective agent. The presence of necrotic bone is the primary histopathological finding related to chronic infection. Often, chronic osteomyelitis develops secondary to contiguous soft tissue infection, likely due to the increase in the number of diabetic patients with foot infections and peripheral vascular disease (5). Acute OM, more common in children, can result in inflammatory bone changes and symptoms appear more rapidly, usually within fourteen days of onset (2,5). Acute osteomyelitis in children is a serious pyogenic infection that is frequently due to hematogenous seeding as a result of (6,9) asymptomatic bacteremia (1).
Because acute hematogenous osteomyelitis is not a reportable disease, the exact incidence is unknown (12). It is estimated that industrialized countries have an annual incident rate of 8 children per every 100,0007. Some data suggest the incidence is as high as 7% (6) with boys affected twice as often as girls (7). Patients with hemoglobinopathies and those who are immunocompromised are at greater risk than the general population. Half of those affected are preschool age with 25% being under the age of one year (2,9,12,13). AHOM is rare in neonates but can occur as a complication in critically ill newborns (13).
AHOM often occurs at one site only (13) and more commonly affects the long bones of the lower extremity (9,15). Two-thirds of all cases involve the femur, tibia or humerus (6); although the femur is the most commonly affected of all bones. The vertebrae (1,2), clavicle and pelvic bones are rarely involved in AHOM (1).
AHOM is more prevalent in children (1) due to characteristics of the growing pediatric bones (13). There are three main regions of the pediatric long bones (3):
1. Epiphysis--the end of the long bone
2. Physis (epiphyseal growth plate)--cartilage cells that create solid bone with growth
3. Metaphysis (growing region)--the wide area below the physis that is closest to the shaft or the diaphysis
Children are more susceptible to AHOM because their bones have a nutrient rich arterial supply to the metaphysis (2,5,9). The metaphysis consists of spongy, porous bone which has an almost honeycomb-like structure, allowing for easy passage of infectious organisms (4). Infection often begins in the metaphyseal end of the long bones due to slow circulation through the metaphyseal capillary loops and sinusoidal veins where the physis adjoins the metaphysis (1,2,4,9,13). This vascular channel lacks a well-developed reticuloendothelial system (RES) allowing for an ideal location for pathogens to deposit (2,4,13) and replicate while evading host defenses (2). This seeding of bacteria in the metaphyseal portion of tubular bones leads to rapid onset of AHOM (1).
Pathogens are identified in only about half of all OM infections (13); of the pathogens isolated, Staphylococcus aureus is responsible for 70-90% of all cases (2,4,5,6,7,9). The majority of AHOM caused by S. aureus are due to MSSA, but the incidence of MRSA is increasing in many countries (2). The high prevalence of S. aureus is attributed to its unique virulence characteristics (9,13). Some strains of S. aureus are able to adhere to extracellular bone matrix and colonize in the bone where it is protected from host defenses and is able to attack host cells (2,9,13). Due to the poorly developed RES of the pediatric long bones (2,4,13), an inflammatory response leads to accumulation of pus and debris at the infection site. This creates increased pressure which further occludes the vasculature, thereby increasing stasis and allowing for the development of subperiosteal abscess (2).
After S. aureus, the next most common pathogens in children are Group A streptococcus (S. pyogenes), Streptococcus pneumoniae, Kingella kingae and Haemophilus influenza b (Hib). These microorganisms are responsible for 10-20% of AHOM cases involving children ages one to five years (2,4,9,13). Group A strep is the second most commonly identified pathogen in AHOM and is responsible for approximately 10% of all AHOM cases (9). AHOM caused by this bacteria has been associated with recent varicella infections (2,9) and these patients tend to have a higher fever and white blood cell count than those with S. aureus (9). S. pneumoniae, isolated in only 1-4% of AHOM cases (9), is more common in young children under two years old (2,9) and these patients are more likely to experience joint involvement (9). AHOM infection from K. kingae, normal flora of the respiratory tract, often follows upper respiratory infection or stomatitis, possibly due to disrupted respiratory mucosa (9). In most industrialized countries, Haemophilus influenza b has been nearly eliminated as a causative agent of AHOM due to the Hib vaccine (2,9).
Involvement of other organisms in AHOM is rare but not uncommon. Salmonella species are often responsible for AHOM in patients with sickle cell disease (4,5,9,13). Although rare, Group B strep is the likely culprit in newborns (2,4,5,13). AHOM caused by a puncture wound in the foot often results from Pseudomonas (2,9). Pseudomonas may also be found in immunocompromised patients (2), as well as fungal elements and mycobacterium (5).
AHOM is primarily diagnosed clinically by rapid onset of localized symptoms (5,9) and confirmed with the support of laboratory and radiological findings (2,9). This disease may present with a variety of symptoms and may affect any bone (7). The most common symptoms include fever, irritability and lethargy with erythema, swelling and tenderness over the affected site, and a decreased range of motion (5,7,10,11). These symptoms are often accompanied by an acute pain over the affected bone that is constant and gradually increasing in intensity (6,9). Unlike older kids with localized pain, young children may not be able to identify the exact location of pain (6), but they will exhibit signs and symptoms such as irritability, decreased appetite and refusal to use the affected limb (6,9,11). Because the long bones of the lower leg are most commonly involved, children will often present with a limp (6). AHOM should be considered in any child presenting with fever of unknown origin (7) or fever accompanied by localized pain (6,7).
Upon physical exam, a patient history is obtained inquiring about recent injury, trauma, surgery or recent infection (11). To differentiate AHOM from other conditions that present with similar symptoms, more diagnostic testing is often required (2,7). X-rays are often performed to rule out fracture of the affected bone (7). Because bone pain is often an initial complaint of leukemia, a peripheral blood smear is useful in differentiating this from malignancy. Radiological testing is helpful in differentiating it from the focal tenderness, erythema and edema often associated with cellulitis. Muscle spasms and the patient's refusal to move the limb or adjacent joint may be confused with septic arthritis. Distinguishing between the two can be difficult when AHOM occurs near a joint, especially since these two diseases can coexist in children (2). Because AHOM is characterized by localized bone tenderness, a lack of focal tenderness in conjunction with excessive joint immobility may lead to a diagnosis of septic arthritis (2,6).
Common laboratory testing that may aid in the diagnosis of AHOM include WBC count, ESR and CRP (2,9,11). The WBC count is not a reliable indicator of disease because it is often normal in AHOM, but it is useful in differentiating it from other disease processes (2,4,9). The acute phase reactants ESR and CRP are often increased in 90% of AHOM patients (2,9). ESR typically increases within 24 hours of onset and returns to normal slowly over three to four weeks even with appropriate treatment (2,9). CRP increases more rapidly, rising 6-10 hours after onset and decreases within 7-10 days with successful therapy (2,4). Because of its rapid return to normal, CRP is used to monitor efficacy of treatment (4,9).
Although pathogens are only isolated about half of the time (2,4,5,7,9), it is still important to collect blood cultures prior to commencing antibiotics (2,6). Blood cultures may be sterile if the patient has already received antibiotics but a gram stain may show the presence of bacteria. If the blood culture and gram stain are both negative, a histological analysis of the bone may reflect inflammation indicative of AHOM (2). Bone biopsy with culture and sensitivity is the gold standard of diagnosing AHOM (6,10). This is not always possible, though, because the pathogen may be hard to grow or empirical antibiotic treatment may have already begun (6). Routine use of bone aspiration or biopsy is controversial due to the high sensitivity of radiological tests, the likelihood of the pathogen based on the patient's age and because these invasive procedures can damage the growth plate of the bone (2). In a culture negative AHOM that is unresponsive to empirical therapy, a bone biopsy may be needed for histopathological stain and for cultures for mycobacterium and fungi (9).
All patients with bone pain should have plain radiographs performed in their diagnostic work-up (2). Plain films are useful in ruling out other causes of bone pain such as fracture (4,6). In the first few days of infection, swelling of soft tissue may be visible on x-rays, but bone changes may not be evident until there is presence of substantial bone destruction. Around 1-21 days after onset of symptoms is when these typical changes begin to appear, but with early diagnosis and treatment, destruction will likely be prevented and will never show up on X-rays (2,9).
Scintigraphy has more than 90% sensitivity in detecting OM (2,7,9) but only a specificity of 70-95% because it is difficult to distinguish OM infection from infection in surrounding joint or tissue (2). A false negative scan is possible when localized ischemia is present; therefore, a suspected false negative should be further investigated. Advantages of bone scan include; the ability to detect early stages of OM (within 48 hours of onset), rapid results with a high sensitivity, fairly inexpensive and sedation is usually not required. Advantages must be weighed against the following disadvantages; sensitivity is less than 30% in neonates, sensitivity and specificity are both low in the pelvis and vertebrae, a fairly high dose of radiation is administered and it's hard to distinguish between adjacent soft tissue infection and OM (2).
MRI is the best imaging method for detecting OM but not always the most practical selection (2). It has excellent resolution of bone and soft tissue (9) without exposure to radiation (6), but MRI is costly, not always readily available and children under seven often require sedation (2,6,9).
The most common complication of untreated or poorly managed AHOM is recurrence of infection which occurs in approximately 5% of all cases (9). Other complications, though rare, include bone deformity, permanent damage to bone (2,10), death and functional loss of limb (8). Factors influencing the risk of developing complications include delayed diagnosis, inadequate duration of antibiotics and a young age of the patient (2,9).
The most appropriate antibiotic treatment should be initiated as quickly as possible (6) with the desired outcome of destroying the pathogen with as minimal host tissue damage as possible (4). Empirical therapy is initiated prior to identification of the pathogen based on the likely infective organism according the patient's age and any underlying health concerns (2,4,7,9). Once identification and sensitivity results are obtained, the antimicrobial agent may need to be modified according to susceptibility tests (2,6,9). If there is no identification of the pathogen, empirical therapy is continued as long as the patient is improving. If however, the patient is not responding to empirical treatment, further investigative studies such as imaging bone biopsy for histopathology may be needed (2,9).
Because approximately 70% of AHOM result from S. aureus (5), empirical treatment often includes dual antibiotic therapy (11) with at least one antibiotic targeting this organism (5). Common antibiotics used are Nafcillin, Clindamycin, 1st generation Cephalosporin or Vancomycin (6). Special consideration must be given to the optimum antibiotic selection if MRSA is suspected or if the patient is allergic to penicillin (2,6). B-lactam antibiotics should not be considered if MRSA is a concern; Clindamycin or Vancomycin may be a better option depending on severity of infection and MRSA incidence in the community (6,9). For penicillin-allergic patients, 1st generation cephalosporin or clindamycin are often initial antibiotics of choice (2). Clindamycin is the preferred antibiotic among many physicians; side effects are acceptable at high doses, it has a short half-life, it is absorbed well and is able to penetrate the bone (7).
Currently, there are no random controlled studies for determining the optimal duration of antibiotic therapy (2,5). Most antibiotic treatments last 4-6 weeks (5,6,8,9,10,11) but recommendation of the route and duration is varied among physicians (8). Traditionally, children received IV therapy for 4-6 weeks with a switch to oral near the end of treatment (2,4,7). In recent years, IV therapy has been shortened to 3-7 days followed by another 3 weeks of oral therapy (2). Decreased patient discomfort, hospital stay and cost are several advantages of shortened IV therapy (2,8), but there are factors to consider when changing to oral therapy: appropriate oral medication must be available and the child must be able to take it by mouth and reliable caregivers must be available to closely monitor the child (4,9).
Duration of IV therapy depends on the severity of infection, clinical response to treatment and risk factors (9). There are no predetermined criteria for determining when to switch the patient from IV to oral treatment (6). CRP and clinical assessment are the best tools to evaluate the response to treatment and when to change to oral antibiotics (2). When the patient becomes afebrile, symptoms improve and CRP returns to normal, the patient is often then switched to oral antibiotics (6,9). In an otherwise healthy patient, this usually occurs about one week after effective IV therapy has begun (6). If CRP doesn't begin to decrease within 48-72 hours after starting IV antibiotics, treatment should be reevaluated (2). A CBC is often collected weekly to monitor the patient's response to treatment since prolonged antibiotic use can lead to neutropenia. Surgical intervention may be required if there is no response to IV treatment. Children with sickle cell disease may need multiple surgical drainage and debridement even with appropriate antibiotics (6).
AHOM is a serious infection of the bone, often resulting from hematogenous seeding from asymtomatic bacteremia. AHOM primarily involves the long bones of children. The unique anatomic characteristics of the pediatric bones allow bacteria in the blood supply settle and reproduce in the bone. S. aureus is the most common pathogen involved, but other pathogens are possible depending on age and health of the patient. Prompt recognition and early empirical treatment are key elements of successful treatment. Diagnosis relies heavily on clinical symptoms and is confirmed by laboratory and radiological results. Successful treatment involves administration of sequential parenteral-oral therapy of 4-6 weeks.
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1. Osteomyelitis can occur in all but which of the following ways?
A. Hematogenous seeding from bacteria
B. Direct innoculation from trauma or surgery
D. Contiguous spread from nearby infection
2. Which bones are more commonly affected by OM?
3. Which organism is responsible for the majority of AHOM cases?
A. S. aureus
B. K. kingae
C. S. pneumoniae
4. Which organism associated with AHOM often follows upper respiratory infection?
A. S. aureus
B. K. kingae
C. S. pneumoniae
5. Which pathogen seen in AHOM is more common in patients with sickle cell disease?
A. S. aureus
B. K. kingae
C. S. pneumoniae
6. Common symptoms of AHOM include:
D. All of the above
7. Which common laboratory test is used to monitor the efficacy of treatment?
D. None of the above
8. Which is the gold standard for diagnosing AHOM?
A. Bone biopsy with culture and sensitivity
C. Physical exam with patient history
9. Which is the best imaging method for detecting OM?
C. Plain radiograph
D. CT scan
10. Duration of IV therapy depends on:
A. Severity of infection
B. Clinical response to treatment
C. Risk factors
D. All of the above
(1.) Conrad, Dennis A. "Acute Hematogenous Osteomyelitis." Pedsinreview.aappublications.org. Pediatrics in Review. 2010, 31.11 Pg. 464. Web. 3 April, 2014.
(2.) Steer, Andrew C. and Jonathan R. Carapetis. "Acute Hematogenous Osteomyelitis in Children." Pediatric Drugs 2004, 6.6. 333-346. Web. 9 May, 2014.
(3.) Budd, Laura. "Pediatric Fractures." Learnpediatrics.com. 22 April, 2012. Web 9 May, 2014.
(4.) Ota, M.D. Floyd S. "Chapter XIX.4 Osteomyelitis." University of Hawaii Department of Pediatrics. January 2002. Web. 3 April, 2014.
(5.) Hatzenbuehler, John and Thomas J. Pullig. "Daignosis and Management of Osteomyelitis." Am Fam Physician. 2011, 84.9, 1027-1033. Web. 7 May, 2014.
(6.) Harik, Nada S. and Mark S. Smeltzer. "Management of Acute Hematogenous Osteomyelitis in Children." NIH Public Access. 2010, 8.2 175-181. Web. 3 April, 2014.
(7.) Peltola, Heikki and Markus Paakkonen. "Acute Osteomyelitis in Children." The New England Journal of Medicine 370.4. 2014, 352-360. Web. 7 May, 2014.
(8.) Le Saux, N., Howard, A., Barrowman, N., Gaboury, I., Sampson, M., and Moher D. "Shorter Courses of Parenteral Antibiotic Therapy Do Not Appear to Influence Response Rates for Children with Acute Hematogenous Osteomyelitis: A Systematic Review." BMC Infectious Diseases. 2002, 2.16. Web. 7 May, 2014.
(9.) Gutierrez, Kathleen. "Bone and Joint Infections in Children." Pediatric Clinics of North America. Elsevier Inc. 2005, 779794. Web. 9 May, 2014.
(10.) Orthopedic Surgery. Clinicalkey.com. n.d. Web. 3 April, 2014.
(11.) National Health Service in England. "Osteomyelitis." www.nhs.uk. 31 March, 2014. Web. 31 March, 2014.
(12.) Kalyoussef, Sabah. "Pediatric Osteomyelitis." Medscape Reference Drugs, Diseases and Procedures. 12, Feb 2014. Web. 31 March, 2014.
(13.) Krogstad, Paul. "Hematogenous Osteomyelitis in Children: Epidemiology, Pathogenesis and Microbiology." Wolters Kuwer Health. Uptodate.com. 10 Jan, 2014. Web. 9 April, 2014.
Vicki Pyles, MLS(ASCP), Ruston, LA; David Osafo, MD, Hematologist/ Oncologist, Ruston, LA
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|Author:||Pyles, Vicki; Osafo, David|
|Publication:||Journal of Continuing Education Topics & Issues|
|Article Type:||Case study|
|Date:||Jan 1, 2015|
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