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Acute hematogenous osteomyelitis is characterized by the abrupt onset
of localized pain and tenderness at a single site, fever, and increased
inflammatory markers (erythrocyte sedimentation rate, C-reactive
protein). Imaging techniques and blood and bone cultures (if done) may
reveal findings consistent with bone changes in osteomyelitis and the
Initial empiric antibiotic therapy for acute hematogenous osteomyelitis
should be directed at gram-positive cocci, including methicillin-resistant
Staphylococcus aureus (MRSA). Protein binding and bone
concentrations of antibiotics are not critical factors in predicting
successful treatment, as long as the responsible pathogen is susceptible
to the chosen therapy, and treatment is given in high doses for long
If blood or bone cultures grow the likely pathogen, then therapy should
be de-escalated when possible based on organism susceptibilities.
Assuming no allergies, methicillin-sensitive Staphylococcus aureus
(MSSA) should be treated with oxacillin or nafcillin. The overall
duration of therapy (by intravenous [IV] route and possibly orally)
Osteomyelitis secondary to a contiguous focus of infection typically
occurs after trauma and the consequent orthopedic corrective surgery.
Common symptoms are pain, tenderness, erythema, and drainage at the
site of injury or infection. Imaging studies usually show bone changes
Secondary osteomyelitis is often polymicrobial. Surgical efforts should be
instituted to reassess the site of bone injury and infection, with deep
tissue or bone samples obtained for culture. Treatment is IV therapy for
at least 4 weeks, and the antibiotics chosen should depend on the
cultured organisms and their antibiotic susceptibilities.
Osteomyelitis associated with vascular insufficiency most often occurs in
patients with diabetes mellitus. Neuropathy and impaired blood flow lead
to the development of chronic lower extremity cellulitis and underlying
osteomyelitis. Multiple gram-positive and gram-negative aerobic and
anaerobic bacteria may be involved; thus, initial empiric treatment
typically includes vancomycin and an antipseudomonal beta-lactam.
Definitive therapy should be based on the results of deep surgical
cultures. Duration of treatment should be 6 or more weeks, with chronic
suppressive therapy considered thereafter.
Chronic osteomyelitis can present years later at a site of previous bone
infection and is usually characterized by a draining sinus tract from bone
to skin. Chronically infected dead bone is involved, and surgery is
important in removing necrotic bone when possible. Chronic
osteomyelitis is often polymicrobial, and the same organism (especially
S. aureus) that was causative of a previous bone infection could still be
involved in chronic infection. High-dose IV therapy directed at the
results of bone cultures for at least 6 weeks is recommended to offer
the best chances of preventing the extension of infection to adjacent
Prosthetic joint infection with adjacent bone osteomyelitis usually
requires surgical removal of the infected prosthesis for cure. Antibiotics
should be directed at the cultured bacteria from a joint aspirate or from
deep surgicalspecimens. The most common pathogens are S. aureus
and coagulase-negative staphylococci. In a situation in which the
prosthesis cannot be totally removed, lifelong, chronic suppressive oral
Nongonococcalseptic arthritis is characterized by fever, and the acute
onset of joint pain and effusion in a single joint. Infection is typically
acquired hematogenously from an originating site that may not always
be easily identified. S. aureus is the most common pathogen. Duration
of treatment should be 6 weeks, with oral therapy for the final 2 weeks.
Neisseria gonorrhoeae is the most common cause of polyarticular
arthritis in a young, sexually active adult. Skin lesions may also be
present in disseminated gonococcal infection (DGI). The diagnosis is
frequently based on the clinicalsyndrome and sexual history, because
joint fluid aspirate and blood cultures are frequently negative.
Intravenous ceftriaxone is the treatment of choice and should be
continued for 1 to 2 days after improvement begins. Treatment duration
Osteomyelitis is an inflammation of the bone marrow and surrounding bone
associated with infection. Any bone can be involved, and substantial morbidity is
possible even with early diagnosis and treatment. Despite the continued refinement of
diagnostic procedures (e.g., radionuclide imaging, computed tomography, magnetic
resonance imaging), advances in antimicrobial therapy, and the use of prophylactic
antibiotics before orthopedic procedures, osteomyelitis continues to be difficult to
Osteomyelitis can affect all age groups. The most common causative
microorganisms of acute osteomyelitis have historically been streptococci and
staphylococci. Staphylococcus aureus remains the most causative organism,
accounting for more than 50% of all cases, although the prevalence of infection
Bone may be infected by three routes: hematogenous spread of bacteria from a
distant infection site, direct infection of bone from an adjacent or contiguous source
of infection, and infection of bone secondary to vascular insufficiency. Table 73-1
summarizes characteristics associated with osteomyelitis.
osteomyelitis are considered to have chronic osteomyelitis.
The bone is divided into three sections: the epiphysis, located at the end of the bone;
the metaphysis (adjacent to the epiphysis and part of the epiphyseal growth plate);
and the diaphysis (midsection of the bone). The rapidly growing area of the bone is
supported by many blood vessels. Surrounding most of the bone is a fibrous, cellular
envelope. The external portion of this envelope is the periosteum, and the internal
Blood vessels that supply bone tissue are located predominantly in the epiphysis
and metaphysis of the bone. Nutrient arteries enter the bone at the metaphyseal side of
the epiphyseal growth plate and lead to capillaries that form sharp loops within the
growth plate. These capillaries lead to large sinusoidal veins that eventually exit the
metaphysis through a nutrient vein. Within the sinusoidal veins, blood flow is slowed
considerably, and infection is possible with bacterial colonization.
Differences in the vasculature of bone in different age groups lead to different
forms of osteomyelitis. In neonates and adults, vascular communications are present
between the metaphysis and epiphysis, which can allow infection to spread from
bone to the adjacent joint. During childhood, however, this area often is protected
from infection because the epiphyseal plate separates the vascular supply for these
Hematogenous osteomyelitis predominantly occurs in prepubertal children but may
be seen in older adults, patients with indwelling central catheters, and intravenous
1 Osteomyelitis in children tends to be acute, hematogenous, and is often
responsive to antibiotic therapy alone. In comparison, osteomyelitis in adults tends to
be subacute or chronic, commonly results from trauma, infection of prosthetic
devices, or other insult, and often requires surgical debridement in addition to
Infection in children develops primarily in the metaphysis of the rapidly growing
long bones of the body where the slowed blood flow allows bacteria to colonize and
multiply. The acute infectious process (e.g., edema, inflammation, small vessel
thrombosis) increases bone pressure, which compromises blood flow and eventually
leads to necrosis. Released cytokines alter bone integrity by promoting osteoclast
activity. Eventually, the elevated pressure and necrosis cause devitalized bone to
fragment from healthy bone (sequestra). With continued spread of the infection into
the outer layers of the bone and soft tissue, abscess and draining sinus tracts form.
Hematogenous infection in children most commonly occurs in the long bones with
a single focus in the femur and tibia.
1 Hematogenous osteomyelitis in neonates is an
especially serious disease that often involves multiple bones, especially the long
bones. Rapid infection spreading across the epiphyseal plate to the adjacent joint can
lead to septic arthritis, necessitating immediate and aggressive treatment. Vertebrae
involvement is seen more frequently in adults.
The most common organism causing hematogenous osteomyelitis is S. aureus,
responsible for up to 85% of pediatric cases.
4 The emergence of both hospital- and
community-associated strains of MRSA has challenged the management of
osteomyelitis. MRSA infections are associated with an increased risk of antibiotic
treatment failures and complications, including abscess formation, deep vein
thrombosis, and septic emboli.
5 Gram-negative bacilli (Escherichia coli, Klebsiella,
Proteus, Salmonella, and Pseudomonas) are responsible for an increasing number of
cases of osteomyelitis as well. Pseudomonas aeruginosa is more commonly seen in
patients with indwelling central catheters and in intravenous (IV) drug users, whereas
S. aureus and Salmonella species are common causes in patients with sickle cell
Site of Infection Vascular Insufficiency
Usual onset: pediatric or Predominantly pediatric Adult Adult
Sites of infection Tibia, femur (children);
Risk factors Bacteremia Surgery, trauma, cellulitis,
Common bacteria S. aureus, gram-negative
S. aureus, coagulasenegative staphylococci,
streptococci, gramnegative bacilli, anaerobic
Clinical findings Fever, chills, local
Clinical features of hematogenous osteomyelitis vary, depending on the patient’s
age and the infection site. In children, infection usually is characterized by an abrupt
onset of high fever and chills, localized pain, tenderness, and swelling. Systemic
symptoms often are absent in neonates, potentially delaying the diagnosis. A
diagnosis, therefore, must be made on the basis of localized symptoms such as edema
and restricted limb movement. Systemic symptoms are also less common in adults,
although patients with vertebral osteomyelitis can present with the insidious onset of
localized back pain and tenderness.
L.D. displays the usual signs and symptoms of acute hematogenous osteomyelitis in
children. She is a previously healthy child who experienced acute localized pain and
tenderness of the left distal femur, abrupt onset of high fever, and an elevated ESR
and CRP. Her plain radiographic studies were normal on two occasions; however,
destructive changes to bone often do not appear on plain radiographs for at least 10
to 14 days after onset of infection.
1 Hence, a normal plain film does not rule out acute
osteomyelitis if obtained within the first 2 weeks of infection. Diagnosis includes
radionuclide imaging (bone scans), computed tomography (CT), or MRI.
more sensitive than CT for the assessment of soft tissue and detecting early bone
marrow edema; however, it often requires sedation for children.
bone scan detection of osteomyelitis has been lowest when the infection was caused
by community-associated MRSA (CA-MRSA).
4 L.D.’s MRI scan on hospitalization
detected inflammation in the left distal femur. Although L.D. did not have a bone
biopsy sent for culture, her clinical picture, a positive MRI scan, and blood cultures
positive for S. aureus establish the diagnosis of osteomyelitis. The specific event that
caused bacteremia with dissemination to bone is unknown, as is often the case in
Laboratory tests that should be routinely obtained in every child suspected of
having osteomyelitis include a complete blood count (CBC), ESR, and serum CRP.
Although these tests are not specific for the diagnosis of osteomyelitis, they help
confirm the clinical diagnosis. An increased WBC count is consistent with
osteomyelitis, but leukocytosis is absent in many children with osteomyelitis at the
initial examination. Thus, L.D.’s WBC count of 8,000/μL is not unusual. In adults,
leukocytosis is more common in an acute infection rather than with recurrent or
chronic disease. Both ESR and CRP are nonspecific markers of systemic
Predisposing factors for hematogenous osteomyelitis include any risk factors for
bacteremia (e.g., indwelling catheters such as hemodialysis shunts and chronic
central venous catheters). Other risk factors that can potentially lead to bacteremia
and subsequently hematogenous osteomyelitis include IV drug use and a distant focus
of infection in the gastrointestinal or urinary tract. None of these factors exist in L.D.
In children such as L.D. who have no history of trauma, fractures, or penetrating
injury, the most common cause of acute hematogenous osteomyelitis is S. aureus and
the possibility of CA-MRSA must be considered.
CASE 73-1, QUESTION 2: What additional patient and diagnostic information should be obtained before
L.D. receives her first dose of antibiotics?
Before L.D. receives antibiotic therapy, she should be assessed for drug allergies,
especially penicillin allergy. Patient interviews, discussions with her parents, and a
comprehensive review of her medical record are necessary, especially with a history
of allergy. Details of an allergic reaction, including symptoms, onset of the reaction,
probable causative agent, treatment, and exposure to related antimicrobials should be
Cultures of blood and bone aspirate material optimally identify the pathogen and
must be part of the initial workup prior to the start of antibiotics. Cultures taken after
antibiotics have been initiated are often negative. Positive blood cultures are seen in
33%–50% of pediatric bone and joint infections.
In L.D.’s case, the positive blood culture and MRI establish the diagnosis of
osteomyelitis. If the blood cultures had been negative, however, a bone aspirate
would be recommended to identify the pathogen.
1 Once material has been obtained
for culture, empiric antibiotic therapy should start as soon as possible.
CASE 73-1, QUESTION 3: L.D. has no history of drug allergies. She took amoxicillin for the previous
The chosen agent should be administered IV at high doses to optimize drug
concentration in infected bone. Treatment should be initiated as soon as possible to
improve the chances for complete eradication of infection and to avoid the need for
surgery. Thus, empiric antibiotic therapy is often administered while bacterial
cultures are pending or before antibiotic susceptibility results are known.
Although cultures are pending or with negative cultures, the age of the child can
predict the likely pathogen and guide empiric antibiotic selection. For example, S.
aureus and Streptococcus species are commonly responsible for osteomyelitis in the
1 Kingella kingae, a facultatively anaerobic, gram-negative hemolytic
bacillus, is being detected with increasing frequency in children under 3 years of age,
especially in the day care setting.
8 Table 73-2 summarizes the common causative
organisms of acute hematogenous osteomyelitis in children and recommended drugs
Considering the epidemiology of L.D.’s infection and the blood cultures, she
should be treated for S. aureus osteomyelitis. In both children and adults, the number
of acute osteomyelitis cases caused by MRSA continues to increase.
vancomycin should be administered pending susceptibility results. Alternative
empiric therapy for L.D. with MRSA coverage includes daptomycin or linezolid.
Due to limited clinical experience, these two agents should be reserved for
vancomycin-intolerant cases. Clindamycin is not an option for L.D., but may be used
empirically for stable patients without bacteremia or intravascular infection.
The importance of antibiotic bone concentration when treating osteomyelitis is
unclear, and bone concentrations do not always predict outcome of therapy.
Theoretically, protein binding could influence clinical efficacy because free drug is
thought to diffuse from plasma into bone tissue and protein-bound drug does not.
However, cefazolin (for sensitive gram-positive cocci) and ceftriaxone (for sensitive
used. Therefore, antibiotic bone concentrations and protein binding of antibiotics (in
appropriate doses) are not significant factors in the selection of appropriate therapy
CASE 73-1, QUESTION 4: The S. aureus grown from L.D.’s blood culture is methicillin sensitive.
L.D. is not allergic to penicillin. Although vancomycin is active against MSSA, it
is inferior to β-lactams; thus, β-lactam-based therapy should be used for susceptible
6 De-escalating from vancomycin to oxacillin (or nafcillin) at 150
mg/kg/day every 6 hours is appropriate.
2 Nafcillin and oxacillin are therapeutically
equivalent and are given in similar doses; therefore, selection typically depends on
hospital formulary considerations. Her prior exposure to amoxicillin is irrelevant
except to establish the absence of a penicillin allergy.
Continuing to treat L.D. with IV oxacillin (or nafcillin) every 6 hours follows
treatment recommendations for MSSA osteomyelitis. Antistaphylococcal penicillins
are effective therapy with appropriate doses and duration. Changing L.D. to cefazolin
would allow slightly less frequent dosing (every 8 hours), a potential advantage for
home treatment. Vancomycin use should be discouraged in L.D.’s case because
cultures revealed a methicillin-sensitive organism, and vancomycin is more likely to
be associated with treatment failure.
In the absence of susceptibility results or of
methicillin resistance, IV vancomycin would be required for the duration of therapy.
Although the logistics of outpatient therapy in L.D. are being investigated, she should
remain on oxacillin while in the hospital.
CASE 73-1, QUESTION 5: Both of L.D.’s parents are employed, and their work schedules prevent them
hospital to receive her oxacillin?
Initially, all patients should receive IV antibiotics because early, aggressive
therapy offers the best chance to cure the infection. L.D., however, does not
necessarily need to stay in the hospital for the duration of therapy. A peripherally
inserted central catheter (PICC) can be placed, and antibiotics can be administered.
The decision to use home IV antibiotic administration must be decided in concert
with L.D.’s parents. If L.D.’s parents do not have the resources or are unwilling to
oversee IV treatment at home, L.D. should remain hospitalized for a minimum of 1
week to assess the efficacy of IV treatment. Transition to oral therapy should be
considered at discharge due to the frequency of PICC line complications and the cost
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