Osteomyelitis

78

SECTION K: Bone and Joint Infections

78

Osteomyelitis
Kathleen Gutierrez

Osteomyelitis is inflammation of bone. Bacteria are the usual etiologic agents, but fungal osteomyelitis occurs occasionally. Osteomyelitis in children primarily has hematogenous origin, occurring
less commonly as a result of trauma, surgery, or infected contiguous soft tissue. Osteomyelitis due to vascular insufficiency is rare
in children.

ACUTE HEMATOGENOUS OSTEOMYELITIS

Pathogenesis
Acute hematogenous osteomyelitis (AHO) is primarily a disease
of young children, presumably because of the rich vascular supply
of their rapidly growing bones.13 Infecting organisms enter the
bone through the nutrient artery and then travel to the metaphyseal capillary loops, where they are deposited, replicate, and
initiate an inflammatory response (Figure 78-1). Metaphyseal
localization results from sluggish blood flow, the presence of
endothelial gaps in the tips of growing metaphyseal vessels, and
lack of phagocytic cells lining the capillaries.36 Bacteria proliferate, spread through vascular tunnels, and are anchored to areas of
exposed cartilaginous matrix. Large colonies of bacteria surrounded by glycocalyx obstruct capillary lumens, impairing
phagocytosis and antibiotic penetration.7
Age-related differences in the anatomy of the bone and its blood
supply influence the clinical manifestations of osteomyelitis.2,3
Transphyseal vessels are present in most children younger than 18

months, providing a vascular connection between the metaphysis

and the epiphysis.8 As a result, in infants, infection originating in
the metaphysis can spread to the epiphysis and joint space. The
risk of ischemic damage to the growth plate is greater in the young
infant with osteomyelitis.9 Before puberty, the periosteum is not
firmly anchored to underlying bone. Infection in the metaphysis
of a bone can spread to perforate the bony cortex, causing sub
periosteal elevation and extension into surrounding soft tissue.
Bony destruction can spread to the diaphysis. By age of 2 years,
the cartilaginous growth plate usually prevents extension of infection to the epiphysis and into the joint space. When the metaphysis of the proximal femur or humerus is involved, however,
infection can extend into the hip or shoulder joint at any age,
because at these sites, the metaphysis is intracapsular.
Histologic features of acute osteomyelitis include localized suppuration and abscess formation, with subsequent infarction and
necrosis of bone. Segments of bone that lose blood supply and
become separated from viable bone are called sequestra. An involucrum is a layer of living bone surrounding dead bone.10 A Brodie
abscess is a subacute, well-demarcated focal infection, usually in
the metaphysis but sometimes in the diaphysis of bone.

Epidemiology
Approximately half of all cases of AHO occur in the first 5 years
of life.11 Boys are affected twice as frequently as girls, except in the
first year of life.11,12 One-third of patients have minor trauma to
the affected extremity before infection, but the specific importance
of this history is unclear, because virtually all young children
experience frequent mild trauma.13
The relative risk of developing osteomyelitis appears to be
higher in some populations. In one study, Polynesian and Maori
children were more likely to develop complicated osteomyelitis
with Staphylococcus aureus than other children in the same New
Zealand community.14 It is unclear whether genetic or socioeconomic or environmental factors accounted for this difference.

Microbiology

Figure 78-1. Gross specimen showing osteomyelitis of the proximal humerus

in a 6-week-old infant. Note metaphyseal location and bony destruction
(arrows). (Courtesy of S.S. Long.)

S. aureus is the most common cause of AHO.1,13,1521 Kingella

kingae, Streptococcus pneumoniae,22 and S. pyogenes23 are the organisms isolated in most other cases of AHO in children. K. kingae
and S. pneumoniae infections are most common in children less
than 3 years of age. S. pneumoniae accounts for a relatively small
proportion of infections, especially in the context of widespread
immunization with the pneumococcal conjugate vaccine.24,25 K.
kingae can be associated with small outbreaks of bone and joint
infections in childcare centers.20,26 Coagulase-negative staphylococci (CoNS) (almost exclusively as a complication of medical intervention), enteric gram-negative bacilli, and anaerobic bacteria
are uncommon causes of AHO. Bartonella henselae can cause
granulomatous infection of bone.2729 Actinomyces spp. cause facial
and cervical osteomyelitis.30 Infection with Serratia spp. and
Aspergillus spp. should be considered in children with chronic
granulomatous disease.31 Before widespread use of Haemophilus
influenzae type b (Hib) conjugate vaccines, 10% to 15% of cases
of osteomyelitis in children younger than 3 years were caused
by this organism.15,18 Invasive disease is rare in immunized
children.32
All references are available online at www.expertconsult.com

469

PART II Clinical Syndromes and Cardinal Features of Infectious Diseases: Approach to Diagnosis and Initial Management
SECTION K Bone and Joint Infections

Community-acquired methicillin-resistant Staphylococcus aureus

(CA-MRSA) AHO has been increasing dramatically.3336 Some
CA-MRSA isolates causing osteoarticular infection carry the genes
for PantonValentine leukocidin (PVL), a virulence factor or
marker for complicated infections.33,37,38

Clinical Characteristics and Differential Diagnosis

Most patients with AHO have symptoms for <2 weeks before they
are brought to medical attention, although a small proportion
have low-grade fever and intermittent bone pain for several
weeks.13,17 The most common manifestations are fever, pain at the
site of infection, and reluctance to use an affected extremity.18,39
Less common complaints are anorexia, malaise, and vomiting.
Physical findings consist of focal swelling, tenderness, warmth,
and erythema (usually over the metaphysis of a long bone). Rarely,
a draining fistulous tract develops over the affected bone.13 Tenderness out of proportion to soft-tissue findings suggests osteomyelitis rather than soft-tissue infection or cellulitis. Exaggerated
immobility of the joint and lack of point tenderness over the
metaphysis suggest pyogenic arthritis. Other causes of bone pain
are fracture, bone infarction secondary to hemoglobinopathy,
leukemia, vitamin deficiency, and bony neoplasms such as metastatic neuroblastoma and Ewing sarcoma.
Osteomyelitis most frequently occurs in the long bones (Figure
78-2), although in some series, 10% to 25% of cases involve short
or nontubular bones, including the pelvis, clavicle, calcaneus,
skull, ribs, and scapula.17,18,40 Multiple bones are involved in about
5% of cases.
Compared with methicillin-sensitive S. aureus (CA-MSSA),
patients with CA-MRSA infections have more protracted courses
of fever, as well as hospitalization, multiple foci of infection,
pyomyositis, and subperiosteal and intraosseous abscesses.36,38,41,42
A recent retrospective study demonstrated that four independent

predictive factors (temperature 38C, hematocrit <34%, WBC

count >12,000 cells/mm3 and C-reactive protein level >1.3mg/
dL) were useful in differentiating MRSA from MSSA osteomyelitis.
Prospective validation of this scoring system is pending.42a Patients
with PVL-positive CA-MRSA are at increased risk for deep-vein
thrombosis or septic emboli to the lungs.33,3537 Compared with
infection due to PVL-negative organisms, infection with PVLpositive S. aureus also appears more likely to result in chronic
osteomyelitis.33

Laboratory Diagnosis
Bacteriologic diagnosis can be confirmed in 50% to 80% of cases
of AHO; the yield is highest when multiple specimens, including
blood, bone, and joint fluid, are sampled.3,12,13,17,18,39 Cultures
obtained by imaging-guided bone biopsy are more likely to be
positive if larger volumes (>2mL) of purulent material are aspirated.43 Diagnosis of K. kingae infection is enhanced with intraoperative inoculation of culture material directly into liquid media
or onto agar plates or when polymerase chain reaction (PCR)
analysis is performed;20,21,44 cultures should be held for at least 7
to 10 days.
The erythrocyte sedimentation rate (ESR) is elevated in up to
90% of cases of osteomyelitis, and the C-reactive protein (CRP)
level in 98%.17,18,38,45 The mean ESR is 40 to 60mm/h, but levels
>100mm/h can occur. ESR generally peaks 3 to 5 days after initiation of therapy and returns to normal in approximately 3 weeks.
CRP levels peak by the second day (mean, 8.3mg/dL) and return
to normal (<2.0mg/dL) after approximately 1 week of therapy.45
Patients infected with PVL-positive versus PVL-negative S. aureus
are more likely to have positive blood cultures and higher ESR and
CRP levels at presentation.38 Higher levels of CRP at diagnosis may
predict greater risk of sequelae.46,47 The peripheral white blood cell
count can be elevated or normal; thrombocytosis can be noted,
especially if symptoms have been present for more than 1 week.

Radiologic Diagnosis
Plain Radiographs

Humerus
12%
Ulna
3%

Hands and
feet 13%

Radius
4%

Pelvis
9%

Radionuclide Scanning

Femur
27%

Tibia
22%

Fibula
5%

Figure 78-2. Sites of acute osteomyelitis in 657 children in whom a single

bone was involved. Shaded areas constitute sites of approximately 75% of
cases. Miscellaneous sites accounting for 5% are not shown. (Data collated
from references 12, 17, 18, and 39.)

470

Radiographic abnormalities in osteomyelitis reflect inflammation,

destruction, and new formation of bone.3,48 The earliest abnormalities, seen within the first 3 days of onset of symptoms, are
deep soft-tissue swelling and loss of the normally visible tissue
planes around the affected bone. Osteopenia or osteolytic lesions
from destruction of bone usually are not visible until approximately 50% of bone has been demineralized. Lytic lesions, perios
teal elevation due to subcortical purulence, and periosteal new
bone formation appear approximately 10 to 20 days after onset of
symptoms. Sclerosis of bone is seen when infection has been
present for longer than a month. If deep soft-tissue swelling is
noted on plain radiograph in a patient with a short history of
symptoms and with point tenderness over the affected metaphysis,
no further imaging studies are necessary to support the diagnosis
of osteomyelitis.

Radionuclide scans are useful in the early diagnosis of osteomyelitis, even when plain radiographs are normal. Technetiumlabeled methylene diphosphonate isotope is most frequently used
because its uptake by infected bone is enhanced when osteoblastic
activity is increased.
The reported sensitivity of technetium-99 bone scanning is
between 80% and 100% (Table 78-1),4953 (Figures 78-3 and 78-4).
The bone scan can be normal in 5% to 20% of children with
osteomyelitis in the first few days of illness.52,5456 Bone scan is less
expensive than MRI, and sedation usually is not required. Bone
scan is particularly useful when multifocal bone involvement is
suspected.57
A variety of disorders, including malignancy, deep soft-tissue
infection, cellulitis, pyogenic arthritis, trauma, fracture, and bone

Osteomyelitis

TABLE 78-1. Technetium Bone Scans for Osteomyelitis in Children

Studya
49

Tuson etal.
Hamdan etal.50
Howie etal.51
Sullivan etal.52
Bressler etal.53

Year

Patient Age

1994
1987
1983
1980
1984

6 months13 years
6 months14 years
6 weeks13 years
3 weeks15 years
<6 weeks

Sensitivity (%)
92
89
89
81b
100

Superscript numbers indicate references.

The 2 patients younger than 6 weeks of age had normal scans.

78

infarction, can result in positive scan results. Metaphyseal site of

maximal uptake and lack of uptake in bone on both sides of a
joint support the diagnosis of AHO, rather than pyogenic arthritis.
Diaphyseal uptake suggests tumor, trauma, or infarction.
In some cases of osteomyelitis, bone scans show areas of
decreased technetium uptake (cold scans), probably reflecting
compromised vascular supply to the bone from ischemia or
thrombosis;49,58 such findings make differentiation of osteomyelitis from infarction associated with sickle-cell disease difficult.
Patients with osteomyelitis and decreased uptake on bone scan
may have more complicated infection, frequently with thrombosis
and ischemic necrosis.58

Figure 78-3. Typical technetium-99 bone scan findings of acute osteomyelitis in a 4-year-old girl who had a 2-day history of fever, ankle pain, and swelling, and
refusal to bear weight. Plain radiograph was unremarkable. Triple-phase anterior images of bone scan show increased tracer activity in the region of the right
ankle in the angiographic (immediate) phase (A), increased tracer activity in the soft tissues in the region of the ankle in the blood pool (15-minute) phase (B), and
localization of tracer in the distal tibial metaphysis (arrow) without periarticular distribution in the delayed (2.5-hour) phase (C). Diagnosis was confirmed at surgery
with finding of subperiosteal pus; Streptococcus pyogenes was isolated. (Courtesy of E. Geller and S.S. Long, St. Christophers Hospital for Children,
Philadelphia, PA.)

Figure 78-4. Plain film and technetium-99 bone scan of acute osteomyelitis and pyogenic arthritis in a 7-month-old boy who had a 3-day history of high fever,
fussiness and redness, and swelling of the lateral right leg from the thigh to the lower leg, with limitation of motion of the knee. Aspiration of the knee revealed
169,000 white blood cells/mm2 and gram-positive cocci. Plain film shows obscuration of right lateral subcutaneous fatmuscle plane, from the thigh to the lower
leg (A). Triple-phase bone scan shows increased tracer activity in the region of the right knee in the angiographic phase (B) and in the periarticular soft tissues
in the blood pool phase (C), as well as localization of tracer in the distal femur (arrow) but not in the proximal tibia in the delayed phase (D). Diagnosis of
osteomyelitis of the femur was confirmed at surgery. Methicillin-susceptible Staphylococcus aureus was isolated from blood, joint and bone specimens.
(Courtesy of E. Geller and S.S. Long, St. Christophers Hospital for Children, Philadelphia, PA.)

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PART II Clinical Syndromes and Cardinal Features of Infectious Diseases: Approach to Diagnosis and Initial Management
SECTION K Bone and Joint Infections

Nuclear scanning using gallium-67 citrate or indium-111labeled leukocytes is positive in diseases characterized by increased
bone turnover and, thus, have limited specificity for osteomyelitis.59 Indium scanning, which reflects migration of white blood
cells into areas of inflammation, can be useful in the diagnosis of
osteomyelitis associated with trauma, surgery, chronic ulcers, or
prosthetic devices,60 but is limited by poor localization of infection (i.e., bone versus soft tissue), decreased sensitivity in diagnosing infection in the central skeleton, and relatively high radiation
exposure. Simultaneous performance of a technetium bone scan
sometimes increases specificity.61

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is a sensitive boneimaging
test.62,63 Its reported sensitivity for detection of osteomyelitis
ranges from 92% to 100%. Normal red and fatty portions of the
bone marrow have a characteristic appearance on MRI. Fatty
marrow produces a bright signal on T1-weighted images.64 Changes
in marrow caused by infection and inflammation produce an area
of low signal intensity within the bright fatty marrow. Areas of low
signal intensity in infected marrow seen on a T1-weighted image
change to bright signal intensity on a T2-weighted image. These
changes are not specific for osteomyelitis and can be seen with
malignancy, fracture, and bone infarction.
MRI can detect signal alterations in soft tissue and is particularly
useful in differentiating cellulitis from osteomyelitis. MRI also
may differentiate acute from chronic osteomyelitis.65
Gadolinium-enhanced MRI can be particularly useful in the
diagnosis of soft-tissue, muscle, or bone abscesses associated with
infection.41 The use of contrast agents can increase confidence in
the diagnosis of osteomyelitis in cases which bone and soft-tissue
edema are seen on unenhanced images.66 MRI has been used to
identify bone marrow infection in cases of Bartonella henselae
infection, particularly when plain films and computed tomography (CT) of the affected bones appear normal.28

TREATMENT
Antibiotic Choice
Considerations in choosing a specific antimicrobial regimen
include the age of the child, underlying medical conditions, suspected pathogens and their susceptibility pattern, antibiotic pharmacodynamics, and the safety and efficacy of the antibiotic.
Most -lactam antibiotics achieve therapeutic concentrations in
bone.67,68 Clindamycin has particularly good bone penetration,
attaining a high bone-to-serum ratio.67,6971 Vancomycin has excellent penetration into the bones of experimental animals.67
Aminoglycoside agents theoretically have poor bactericidal activity in bone because of local tissue hypoxia and acidosis. Although
ciprofloxacin penetrates well into bone, fluoroquinolones are not
recommended routinely for use in young children.72
Most cases of AHO in any age group are caused by S. aureus.
Empiric therapy should include coverage for this organism.
Parenterally administered nafcillin, clindamycin, or a firstgeneration cephalosporin historically have been the usual choices
for empiric therapy; however, the increase in CA-MRSA infections
has made the choice of initial antibiotic therapy challenging.
Direct sampling of bone for culture is increasingly important.
Clindamycin remains a good choice for empiric therapy in communities where resistance (both constitutive and inducible) occurs
in fewer than 10% of S. aureus isolates.41 In communities where
CA-MRSA resistance to clindamycin and methicillin is greater than
10% to 15%, vancomycin is the drug of choice for empiric
therapy.72a Clindamycin and vancomycin are active against most
isolates of S. pyogenes and S. pneumoniae. Neither offers coverage for
K. kingae infection, which is susceptible to most -lactam antibiotics. Ampicillin-sulbactam should be considered in addition to
clindamycin or vancomycin, especially in young children.
Empiric therapy for young children who have not been immunized against Haemophilus influenzae type b should include a

472

third-generation cephalosporin in addition to antistaphylococcal

coverage. A second-generation cephalosporin such as cefuroxime
alone is a reasonable alternative if suspicion for MRSA is low.73
However, with the dramatic reduction of cases of Hib disease in
the United States, it is reasonable to use only an antistaphylococcal
antistreptococcal antibiotic in the fully immunized and immunocompetent child.
Neonates with osteomyelitis should be treated with antibiotics
active against S. aureus, group B streptococcus (GBS), and gramnegative enteric organisms. Suggested initial empiric parenteral
antibiotic therapy for neonates and children with AHO is outlined
in Table 78-2.
Antibiotic therapy should be modified according to results of
culture and susceptibility testing. Nafcillin, oxacillin, a firstgeneration cephalosporin, or clindamycin (if susceptible) are the
drugs of choice for infections caused by MSSA. Clindamycin is a
good definitive choice for susceptible MRSA and MSSA73a but
should not be used if inducible resistance is detected because of
reports of treatment failure under this circumstance.74,75
There are few antibiotic choices for clindamycin-resistant
CA-MRSA infection in children. Recently published guidelines
by the Infectious Disease Society of America (IDSA) recommend
vancomycin plus/minus rifampin for the treatment of MRSA
osteomyelitis in children. Linezolid is suggested as an alternative
choice.72a Limited data support efficacy of linezolid.76,77 In one
group of pediatric patients, linezolid was as effective as vancomycin in treating infections caused by MRSA, although efficacy in
treating bone or joint infections was not specifically evaluated.77
Linezolid has excellent oral bioavailability and offers an alternative to prolonged intravenous therapy. However, it is expensive
and many children object to the taste of the oral suspension.
Long-term use has been associated with neutropenia, thrombocytopenia, and elevated serum transaminase levels.78 There are rare
reports of lactic acidosis and optic neuropathy associated with
linezolid therapy.79,80
Most CA-MRSA isolates are susceptible to trimethoprimsulfamethoxazole, tetracyclines, and rifampin. Clinical experience
with these drugs for osteoarticular infections is limited.81,82
Rifampin should not be used as a single agent because of rapid
development of resistance. Although daptomycin and tigecycline
have activity against MRSA, neither is approved for use in children.
The IDSA guidelines suggest that daptomycin may used in children in selected circumstances.72a If no organism is isolated, and
the symptoms are resolving, initial empiric therapy should be
continued. Most cases of culture-negative osteomyelitis respond
to therapy with antistaphylococcal antibiotics.83
Management of children with osteomyelitis should include
concurrent care by an orthopedic surgeon. Indications for surgery
include desirability of specific pathogen diagnosis; prolonged
fever, erythema, pain, and swelling; persistent bacteremia despite
adequate antibiotic therapy; soft-tissue or periosteal abscess; formation of a sinus tract; and presence of necrotic, nonviable
bone.16,8486

Duration of Therapy
Duration of antibiotic therapy depends on the cause and extent
of infection as well as the clinical course. The usual duration
ranges from 3 to 6 weeks and should be individualized on the
basis of severity of illness and clinical response. Historical evidence suggests that <3 weeks of treatment is associated with higher
rates of relapse or recurrence than longer duration of therapy.13
Plain radiographs obtained at the end of therapy may be useful
as a marker of maximal anticipated destruction, a baseline for
further studies, and a guide to possible complications.
Peripherally inserted or tunneled central venous catheter (PICC/
CVC) often is placed to continue intravenous antibiotics at home.
Use of PICC or CVC for >2 weeks in children with osteomyelitis
can be associated with an increase in catheter-related complications,87 including catheter malfunction, thrombosis and catheterassociated bloodstream infections.88

Osteomyelitis

78

TABLE 78-2. Antibiotic Selection for Initial Treatment of Osteomyelitis

Dosage
Patient Age

Likely Pathogen

Antibiotic Selection

mg/kg per day

Doses/Day

>3 years

Staphylococcus aureus

Nafcillin
or

150

Clindamycinc
or
Vancomycin
<3 years

Neonate

S. aureus
Haemophilus influenzae type ba
Kingella kingaeb

S. aureus
Group B streptococcus
Enteric gram-negative bacteria

3040

34

4560

34

Nafcillin
or
Clindamycinc
or
Vancomycin
plus
Cefotaxime
or
Ceftriaxone
or
Cefuroxime
or
Ampicillin-sulbactam

150

300

Nafcillin

100

30

or
Vancomycin
plus
Gentamicin
OR
Nafcillin
or
Vancomycin
plus
Cefotaxime

3040

34

4560

34

100150

100

75150

57.5

100

30

150

If patient is fully immunized against Haemophilus influenzae type b, consider using only antistaphylococcal coverage.

If patient is treated with either clindamycin or vancomycin, consider adding an ampicillin or cephalosporin agent for Kingella kingae.

Clindamycin 40 mg/kg/day recommended for treatment of susceptible MRSA osteomyelitis.

Sequential parenteraloral antibiotic regimens can be

successful.8994 Early transition to oral therapy was not associated
with a higher risk of treatment failure in a recent study.87 The
change to oral antibiotics is generally made when fever, pain, and
signs of local inflammation have resolved and laboratory values,
especially CRP, are normalizing. The willingness of the child to
take oral medication and the likelihood of adherence to the
regimen also must be assessed. The oral antibiotic should have
the same spectrum of coverage as the parenteral drug. If a -lactam
agent is used, dosage required is generally two to three times the
usual oral dose (Table 78-3).
TABLE 78-3. Dosage of Antibiotics Commonly Used in the Oral
Phase of Treatment of Osteomyelitisa
Dosage
Antibiotic

mg/kg per day

Doses/Day

Dicloxacillin
Cephalexin
Clindamycin

75100
100150
3040b

4
4
34

In general, the dose of -lactam antibiotics used for osteomyelitis is 23

times the usual dose.
a

Clindamycin 40mg/kg/day is recommended for treatment of susceptible

MRSA osteomyelitis.72a

Once the change to oral therapy is made, the child should be

monitored to ensure continued clinical improvement. The CRP
level is expected to return to normal 7 to 10 days after initiation
of appropriate therapy, and the ESR normalizes within 3 to 4
weeks.45,93

SPECIAL CLINICAL SITUATIONS

Neonatal Osteomyelitis
Osteomyelitis is uncommon in the neonatal period. The incidence
is estimated to be approximately 1 to 3 cases for every 1000
intensive-care nursery admissions.95
Associated risk factors include prematurity, low birthweight,
preceding infection, bacteremia, exchange transfusion, and the
presence of an intravenous or umbilical catheter.9699 Osteomyelitis of the skull secondary to contiguous spread of infection has
occurred as a complication of fetal scalp electrode monitoring100102
and in association with infected cephalohematoma.103,104 Osteomy
elitis of the calcaneus has complicated heel lancet puncture.97,105
The diagnosis of osteomyelitis in neonates often is delayed
because of nonspecific symptoms.106 Signs and symptoms include
fever, irritability, swelling or decreased movement of a limb
(pseudoparalysis), erythema, and tenderness over the affected
bone.9597,107 Preterm infants are more likely than term infants to
manifest symptoms of septicemia.108
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PART II Clinical Syndromes and Cardinal Features of Infectious Diseases: Approach to Diagnosis and Initial Management
SECTION K Bone and Joint Infections

of motion, limb length discrepancy, and gait abnormalities.119

The reported incidence of permanent sequelae varies from 6%
to 50%.96,97,108,113

Vertebral Osteomyelitis

Figure 78-5. Plain radiograph of an infant at 2 months of age who had

Staphylococcus aureus bloodstream infection during a stay in the neonatal
intensive care unit in the first month of life. He had multiple sites of infection,
including the proximal and distal femur and hip joint. Note widespread
destruction of femur, acetabulum, and joint. (Courtesy of S.S. Long, St.
Christophers Hospital for Children, Philadelphia, PA.)

Approximately 20% to 50% of neonates with osteomyelitis have

infection of multiple bones,95,96,109and about 75% have suppurative arthritis of contiguous joints96 (Figure 78-5).
S. aureus (including CA-MRSA110), GBS, and enteric gramnegative bacilli are the most common causes (Table 78-4); fungi,111
Ureaplasma urealyticum,112 CoNS,113 Neisseria gonorrhoeae,107 and
anaerobic100 bacteria are unusual causes.
Infants with GBS bone infection usually have had an uncomplicated neonatal course and have infection of a single bone. There
is a predilection for involvement of long bones on the right, particularly the right proximal humerus,113,114 which may be related
to trauma during vaginal delivery.113 Misdiagnosis of bone infection as trauma in these mildly ill infants is common. Since the
release of the 1996 consensus guidelines for prevention of GBS
disease, the incidence of early-onset perinatal GBS disease but not
late-onset disease has declined in the U.S.115
The white blood cell count commonly is normal; ESR and CRP
often are elevated.116 In most infants, an osteolytic lesion is visible
on plain radiograph 10 to 12 days after onset of symptoms (frequently the time of diagnosis).86,96,97,107,117,118 Radionuclide bone
scans can be positive53,95,106 but sometimes are less sensitive than
plain radiographs.97
Neonatal osteomyelitis can lead to permanent joint abnormalities or disturbance in skeletal growth secondary to damage to the
cartilaginous growth plate, including arthritis, decreased range

Vertebral osteomyelitis accounts for approximately 1% to 3% of

cases of osteomyelitis in children.13,18,120,121 Boys are affected twice
as frequently as girls.122 Infection usually occurs as a result of hematogenous seeding of the vertebral bodies by arterial or venous
vessels. Osteomyelitis also can result from extension of soft-tissue
infection or as a complication of a surgical procedure.16,123
Clinical manifestations can be indolent and nonspecific, leading
to delayed diagnosis. Young infants can have nonspecific signs of
septicemia.124 Symptoms in older children include back, chest,
abdominal, or leg pain as well as loss of normal curvatures.120,125
Rarely, children manifest dysphagia secondary to a paravertebral
or retropharyngeal abscess or acute spinal cord paresis/paralysis
due to paraspinal compression.120,126 Fever is common, and tenderness over the involved vertebrae is expected. Neurologic deficits
are found in 15% to 20% of cases.120,122
S. aureus is isolated in most cases.16,120,122,127 In one review, Salmonella spp. caused 12% of cases of childhood vertebral osteomyelitis.120 Gram-negative bacilli such as Escherichia coli cause
vertebral osteomyelitis in adults, particularly those with a history
of recent urinary tract infection or instrumentation. Vertebral
osteomyelitis in intravenous drug users is commonly caused by
Pseudomonas aeruginosa and less commonly by S. aureus, Serratia
spp., Klebsiella spp., Enterobacter spp., or Candida spp.128,129 Tuberculosis and brucellosis should be considered if symptoms and
radiographs suggest chronic infection.130,131
Characteristic findings on plain radiograph consist of narrowing
of the involved disk space, lucency of the adjacent vertebral bodies,
and, eventually, reactive sclerosis of the bone with fusion of vertebral bodies.16,120,127 Vertebral osteomyelitis is differentiated from
diskitis radiographically by the minimal vertebral endplate
involvement associated with diskitis (see Chapter 80, Diskitis).
MRI is reported to be highly sensitive (96%) and specific (92%)
for diagnosis of vertebral osteomyelitis.132,133
Blood culture results are positive in only about 30% of acute
cases. When blood culture results are negative, strong consideration should be given to obtaining a biopsy specimen from the
vertebral body for culture and histologic examination.133
Children with uncomplicated vertebral osteomyelitis and no
evidence of abscess formation should be treated with at least 4
weeks of antibiotic administered parenterally.120 Surgical decompression or debridement or both are indicated in the presence of
spinal epidural abscess, signs of spinal cord compression, or
extensive bony destruction.
Complications of vertebral osteomyelitis include neurologic
deficits secondary to epidural abscess,134 paravertebral abscess,135
and infected aneurysms of the aorta.136

Pelvic Osteomyelitis
TABLE 78-4. Frequency of Organisms Causing Neonatal
Osteomyelitis (n = 128)

474

Single Organism

Staphylococcus aureus
-Hemolytic streptococcus
Group B
Group A
Enteric gram-negative bacilli
Staphylococcus epidermidis
Nonhemolytic streptococcus
Streptococcus pneumoniae
Neisseria gonorrhoeae
Multiple organisms

60.6
16.5
3.1
8.7
2.4
2.4
0.8
0.8
4.7

Approximately 6% to 9% of all cases of hematogenous osteomyelitis involve the bones of the pelvis.40,137,138 The ilium and ischium
are most commonly involved;137 infection of the sacrum, acetabulum, or pubic symphysis is rare.137140 Risk factors (not always
present) include a history of pelvic trauma, intravenous drug use,
and genitourinary procedures.137,140
Most patients with pelvic osteomyelitis have fever, gait abnormalities, and pain that is often localized to the hip, groin, or
buttock.137,140143 Pain with hip movement and point tenderness
over the affected bone often is observed. Clinical features can
mimic those of pyogenic arthritis of the hip;137 however, in pelvic
osteomyelitis there is more likely to be near-normal range of
motion of the hip, absence of referred pain to the knee, specific
point tenderness over the affected bone (or pain on rocking of
the pelvic girdle), and abnormal rectal findings.143 Responsible
pathogens are similar to those that cause osteomyelitis of long
bones.

Osteomyelitis

BOX 78-1. Bacterial Causes of Osteomyelitis in Children with

Sickle-Cell Disease
COMMON
Salmonella spp.
Staphylococcus aureus
LESS COMMON
Escherichia coli
Haemophilus influenzae type b
Shigella spp.
Streptococcus pneumoniae

Plain radiographs of the pelvis often are normal. Technetium

scanning,137,138,141143 MRI, or CT can suggest the correct diagnosis
and may be useful for differentiating osteomyelitis from bacterial
infection of the muscles of the pelvic girdle. MRI has the advantage
of identifying abscesses associated with pelvic osteomyelitis and
is the imaging technique of choice.144
Patients should be treated for at least 4 weeks with antibiotics
parenterally.137140,143 Surgical drainage or debridement should be
considered in cases of extraosseous abscess formation or in
patients whose symptoms do not respond to intravenous anti
biotic therapy.

Children with Sickle Hemoglobinopathies

Children with sickle-cell disease have increased susceptibility to
bacterial infections, including osteomyelitis.145 The suspected
pathogenesis is primary microscopic infarction in the intestinal
mucosa and bone, resulting in bacteremia and focal bone infection. Splenic hypofunction, impaired opsonization, impaired
macrophage function, and microembolism as well as tissue infarction are likely contributing factors in osteomyelitis.146,147
Salmonella spp. plus other gram-negative enteric bacilli were the
cause of >70% of cases of osteomyelitis in children with hemoglobinopathies in past decades.148151 S. aureus currently is an
important/dominant cause of osteomyelitis in this population.
Other organisms causing osteomyelitis in children with sickle
hemoglobinopathies are listed in Box 78-1.
Distinctive features of osteomyelitis in children with sickle-cell
disease are frequent involvement of the diaphyses of long bones,
flat bones, and small bones of the hands and feet as well as multifocal, symmetrical bone involvement.146,152 Manifestations of
osteomyelitis are difficult to differentiate from those of acute vasoocclusive crisis. Fever, bone pain, and leukocytosis are common
to both conditions. Temperature >39C, toxic appearance, and an
absolute band count >500 cells/mm3 are more consistent with
infection; however, there is considerable clinical and laboratory
overlap.148
Plain radiograph, technetium scanning, and MRI cannot differentiate infarction from infection.152,153 Therefore, if fever and
bone pain have not improved after supportive care has been given
for vaso-occlusive crisis, needle aspiration of the affected area of
bone for Gram stain and culture should be performed.
A prolonged course of parenteral antibiotic therapy (6 to 8
weeks) may be necessary for treatment of osteomyelitis in patients
with sickle hemoglobinopathy. Oral therapy can be substituted for
parenteral treatment once a pathogen has been confirmed and
there is clinical improvement; therapy may need to be very protracted. Relapses especially when due to Salmonella are not
infrequent.146,148

OSTEOMYELITIS DUE TO UNUSUAL ORGANISMS

Fungal Osteomyelitis
Fungal osteomyelitis is unusual in healthy children, occurring
occasionally in neonates, immunocompromised patients, and

78

intravenous drug users.111,154157 Osteomyelitis caused by Candida

spp. is reported in intravenous drug users and in prematurely born
neonates.111,154158 Aspergillus spp. cause osteomyelitis in children
with chronic granulomatous disease, often resulting from contiguous spread of pulmonary infection.159 Blastomyces dermatitidis,
Coccidioides immitis, Histoplasma capsulatum, and Cryptococcus neoformans cause osteomyelitis in indigenous geographic regions and
in immunosuppressed hosts.160163

Tuberculous Osteomyelitis
Skeletal lesions occur in approximately 1% of children with tuberculosis.130,164 Bones and joints are infected through hematogenous
or lymphatic dissemination of Mycobacterium tuberculosis. Infection can smolder for years before clinical signs are apparent. The
most commonly involved bones are the vertebrae (tuberculous
spondylitis), femur, long bones around knees and ankles, and
small bones of the hands and feet.165 Other sites less frequently
infected are the ribs, mandible, sternum, clavicle, and other long
bones. Multifocal osteomyelitis is reported in 10% to 15% of
cases.166,167
Clinical signs and symptoms of skeletal tuberculosis include
low-grade fever, weight loss, pain, and soft-tissue swelling at the
site of infection. Vertebral involvement begins in the anterior
vertebral body, eventually causing disk space collapse and anterior
wedging of vertebral bodies, and sometimes gibbus deformity. The
lower thoracic spine is the usual site of involvement (Pott disease),
followed by the lumbar spine.
The Mantoux tuberculin skin reaction is usually positive. The
role of interferon- release assays in the diagnosis of Pott disease
is currently being evaluated. Plain radiographic findings include
periarticular osteopenia, lytic lesions in the body of the vertebra,
joint space narrowing, and soft-tissue swelling.168 The chest radiograph often is normal. CT is useful for the evaluation of bone
destruction, adjacent soft-tissue abscess formation, and calcification, and in guiding percutaneous biopsy.169,170 MRI is helpful in
determining extent of bone and soft-tissue disease.171 Biopsy specimens should be obtained in an attempt to demonstrate the organism with stains and culture.
Antituberculous therapy includes 2 months of therapy with four
drugs, followed by 7 to 10 months of isoniazid and rifampin
(for susceptible organisms) daily or twice weekly (see Chapter
134, Mycobacterium tuberculosis).172 Surgical intervention is
indicated in cases of spinal instability and neurologic impairment
secondary to paravertebral abscess formation and for drainage
of soft-tissue abscesses. Nontuberculous Mycobacterium spp.
infrequently cause osteomyelitis in immunocompromised
individuals.

Anaerobic Bacterial Osteomyelitis

Anaerobic bacteria are associated with chronic and nonhemato
genously acquired osteomyelitis.173175 Risk factors include surgery,
trauma, diabetes mellitus, human bites, chronic otitis media or
sinusitis, dental infection, fibrous dysplasia of bone, presence of
a prosthesis, and decubitus ulcers (Figure 78-6). Children are
more likely than adults to experience anaerobic osteomyelitis of
the skull and facial bones.173 Osteomyelitis of ribs follows contiguous spread from aspiration lung infection; Actinomyces spp. are the
primary pathogens. Soft-tissue swelling or abscess can be the presenting abnormality. Similarly, Actinomyces spp. can cause osteomyelitis of the maxilla or mandible, frequently without dental
pathology.
Infection usually is polymicrobial; gram-positive cocci, Bacteroides spp., Prevotella spp., and Fusobacterium spp. are the most
common anaerobes, and S. aureus is the most commonly associated aerobic isolate.174 Therapy consists of treatment of underlying
conditions, surgical debridement of necrotic bone, and appropriate antibiotic therapy. Examples of effective antibiotics are clindamycin, metronidazole, imipenem, and amoxicillin-clavulanate.
All references are available online at www.expertconsult.com

475

PART II Clinical Syndromes and Cardinal Features of Infectious Diseases: Approach to Diagnosis and Initial Management
SECTION K Bone and Joint Infections

PUNCTURE WOUND OSTEOCHONDRITIS

OF THE FOOT

Figure 78-6. Actinomycosis of the mandible in a 9-year-old girl with history of

painless expansion of the jaw over several months. Reconstructed spiral
computed tomography shows expansion of bone with complex lytic and
sclerotic mass (arrow). Surgical biopsy confirmed Actinomyces osteomyelitis
and fibrous dysplasia of bone. (Courtesy of L. Kaban and M. Pasternack,
Massachusetts General Hospital; and S.S. Long, St. Christophers Hospital for
Children, Philadelphia, PA.)

Many anaerobic isolates are susceptible to penicillin. The choice

of antibiotic depends on the specific organisms isolated and their
potential for -lactamase production. Therapy is protracted, frequently exceeding 1 year of oral penicillin or amoxicillin plus
probenecid for actinomycosis.

NONHEMATOGENOUS OSTEOMYELITIS
Contiguous Infection
Factors associated with the development of nonhematogenous
osteomyelitis include open fractures requiring surgical reduction,176,177 implanted orthopedic devices, decubitus ulcers,173 and
neuropathic ulcers.178,179 Facial osteomyelitis usually is secondary
to untreated mastoiditis, sinusitis, or periodontal abscess.173,177
Osteomyelitis can occur after local soft-tissue infection or direct
inoculation of bone from human and animal bites.180,181 Puncture
wounds can lead to osteomyelitis of the foot (e.g., stepping on a
nail or toothpick182) or the patella (e.g., kneeling on a needle).
Indolent presentation is common among children with non
hematogenous osteomyelitis. Fever is present in less than half of
patients.183 Persistent drainage or ulceration of the soft tissue over
the affected bone is typical. Plain radiograph shows bony destruction. Peripheral white blood cell count often is normal, and ESR
and CRP can be normal.
Nonhematogenous osteomyelitis often is caused by S. aureus,
although coinfection with gram-negative and anaerobic organisms occurs.174 Examination of specimens from an associated sinus
tract is unreliable in defining the etiology of osteomyelitis.184
Biopsy with culture of the affected bone is the best method of
determining appropriate antibiotic therapy. Therapy should be
prolonged if infection is chronic, sometimes with parenteral
therapy followed by oral therapy for a total of 4 to 6 months.
The rate of recurrence in nonhematogenous osteomyelitis is as
high as 40%, even with prolonged courses of antibiotic therapy.183
Aggressive surgical debridement or other interventions are required
in addition to antibiotic therapy. Implanted devices commonly
must be removed for cure. Debridement followed by muscle flap
procedure to re-establish the blood supply in decubitus ulcerassociated osteomyelitis frequently is beneficial.185

476

Bacterial osteochondritis is a complication of puncture wounds of

the foot, occurring in approximately 1.5% of such injuries.182,186188
Symptoms of osteochondritis, which appear several days to weeks
after the initial injury, include increasing tenderness, erythema,
and swelling at the site of the puncture.
Infection usually is caused by Pseudomonas aeruginosa,189often as
a result of inoculation from the colonized moist soles of tennis
shoes.190 S. aureus is the usual pathogen if symptoms began within
3 to 5 days of injury. Obtaining specimens from bone for microbiologic diagnosis is desirable.
Empiric antibiotic therapy should include coverage for
P. aeruginosa and S. aureus. Ticarcillin-clavulanate, piperacillintazobactam, ceftazidime or cefepime, with or without an aminoglycoside, would be appropriate empiric therapy if MRSA is not likely.
With appropriate surgical debridement, short-duration (7 to 10
days) parenteral antibiotic therapy has been effective for P. aeruginosa,189,191 as has 3 to 4 weeks of antibiotic therapy without
debridement.190 Treatment with oral ciprofloxacin in conjunction
with surgical debridement also is successful192 (see Chapter 292,
Antimicrobial Agents).

CHRONIC RECURRENT MULTIFOCAL

OSTEOMYELITIS
Chronic recurrent multifocal osteomyelitis (CRMO) is an inflammatory disease of children and young adults characterized by
recurring episodes of low-grade fever, swelling, and pain over
affected bones and by radiologic abnormalities suggestive of
osteomyelitis.193,194 Females are more frequently affected than
males.195 The median age of onset of illness is 10 years. CRMO
sometimes is associated with palmoplantar pustulosis,196psoriasis,
arthritis, sacroiliitis, inflammatory bowel disease,197 and Sweet
syndrome.
Radiographic abnormalities occur most commonly in the metaphysis of long bones and are characterized by radiolucent bone
lesions with reactive sclerosis and soft-tissue swelling.195,198,199 The
sternal end of the clavicle, the vertebral bodies, and the smaller
bones of the hands and feet often are involved. Radiographic
changes are similar to those seen in acute osteomyelitis, but multiple, often symmetrical lesions are present in CRMO. Bone scanning and MRI are useful in determining the extent and evolution
of disease.199201 An infectious cause of CRMO has not been
determined.
The course of CRMO consists of prolonged bone pain with
remissions and relapses over several years; the mean duration of
disease is 6 years.202 In a long-term follow-up study of 23 patients
with CRMO, 26% had active disease at a median of 13 years after
diagnosis.197Although the clinical outcome in most patients is
good, approximately 20% of patients have a prolonged and severe
course. Young age at onset and multiple sites of involvement
predict less favorable outcome.203 Treatment with a variety of antibiotics has no apparent effect on the course or outcome. Some
experts have advocated the use of corticosteroids or nonsteroidal
anti-inflammatory agents for relief of symptoms.195,198 Other therapies utilized in small numbers of patients have included colchicine, INF-, IFN-, and infliximab.197,203,204
Because multifocal bone lesions in childhood can occur with
neuroblastoma, histiocytosis X, leukemia, and staphylococcal
osteomyelitis, histologic examination and culture of bone specimens should be performed. Histologic findings in CRMO are nonspecific acute and chronic inflammatory changes; in the chronic
phase of the disease, granulomatous changes can be seen.205

CHRONIC OSTEOMYELITIS
Chronic osteomyelitis develops in fewer than 5% of cases
of AHO;12,206 it more often follows nonhematogenous
osteomyelitis.183

Chronic osteomyelitis is characterized by alternating periods of

quiescence and recurrent pain, swelling, and sinus tract drainage,
persisting for years despite prolonged antibiotic therapy. Infections are often polymicrobial, and the original metaphyseal infection, with skeletal growth, moves to become a lytic lesion in the
diaphysis.175,185

Surgical debridement of necrotic bone is primary management.

Alternative therapeutic approaches include the use of antibioticimpregnated polymethyl methacrylate beads,207,208 local antibiotic
delivery via implantable pumps,209 and suction vacuum devices or
bone grafts, skin grafts, and muscle flaps to eliminate dead space
and improve vascularity.210212

Osteomyelitis

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PART II Clinical Syndromes and Cardinal Features of Infectious Diseases: Approach to Diagnosis and Initial Management
SECTION K Bone and Joint Infections
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166. Lachenauer CS, Cosentino S, Wood RS, et al. Multifocal

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206. Gillespie WJ, Mayo KM. The management of acute
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209. Perry CR, Pearson RL. Local antibiotic delivery in the
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