Osteomyelitis 78
SECTION K: Bone and Joint Infections
78 Osteomyelitis
Kathleen Gutierrez
Osteomyelitis is inflammation of bone. Bacteria are the usual etio-
logic agents, but fungal osteomyelitis occurs occasionally. Osteo-
myelitis in children primarily has hematogenous origin, occurring
less commonly as a result of trauma, surgery, or infected contigu-
ous 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.1–3 Infecting organisms enter the
bone through the nutrient artery and then travel to the metaphy-
seal 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.3–6 Bacteria prolifer-
ate, spread through vascular tunnels, and are anchored to areas of
exposed cartilaginous matrix. Large colonies of bacteria sur-
rounded 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
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.)
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 infec-
tion to the epiphysis and into the joint space. When the metaphy-
sis 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 sup-
puration 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 involu-
crum 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 socioeco-
nomic or environmental factors accounted for this difference.
Microbiology
S. aureus is the most common cause of AHO.1,13,15–21 Kingella
kingae, Streptococcus pneumoniae,22 and S. pyogenes23 are the organ-
isms 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 staphyloco-
cci (CoNS) (almost exclusively as a complication of medical inter-
vention), enteric gram-negative bacilli, and anaerobic bacteria
are uncommon causes of AHO. Bartonella henselae can cause
granulomatous infection of bone.27–29 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.33–36 Some
CA-MRSA isolates causing osteoarticular infection carry the genes
for Panton–Valentine 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 Tender-
ness out of proportion to soft-tissue findings suggests osteomyeli-
tis 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 meta-
static 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
Humerus
12%
Ulna
3%
Radius
Pelvis
4%
Hands and 9%
feet 13%
Femur
27%
Tibia Fibula
22% 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
predictive factors (temperature 38°C, hematocrit <34%, WBC
count >12,000 cells/mm3 and C-reactive protein level >1.3 mg/
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.33,35–37 Compared with
infection due to PVL-negative organisms, infection with PVL-
positive 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 (>2 mL) of purulent material are aspi-
rated.43 Diagnosis of K. kingae infection is enhanced with intraop-
erative 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 60 mm/h, but levels
>100 mm/h can occur. ESR generally peaks 3 to 5 days after initia-
tion of therapy and returns to normal in approximately 3 weeks.
CRP levels peak by the second day (mean, 8.3 mg/dL) and return
to normal (<2.0 mg/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
Radiographic abnormalities in osteomyelitis reflect inflammation,
destruction, and new formation of bone.3,48 The earliest abnor-
malities, 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 approxi-
mately 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 Scanning
Radionuclide scans are useful in the early diagnosis of osteomy-
elitis, even when plain radiographs are normal. Technetium-
labeled 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),49–53 (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.52,54–56 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 78
infarction, can result in positive scan results. Metaphyseal site of
TABLE 78-1.  Technetium Bone Scans for Osteomyelitis in Children
maximal uptake and lack of uptake in bone on both sides of a
joint support the diagnosis of AHO, rather than pyogenic arthritis.
Studya Year Patient Age Sensitivity (%)
Diaphyseal uptake suggests tumor, trauma, or infarction.
Tuson et al. 49
1994 6 months–13 years 92 In some cases of osteomyelitis, bone scans show areas of
Hamdan et al.50 1987 6 months–14 years 89 decreased technetium uptake (“cold scans”), probably reflecting
Howie et al.51 1983 6 weeks–13 years 89 compromised vascular supply to the bone from ischemia or
Sullivan et al.52 1980 3 weeks–15 years 81b
thrombosis;49,58 such findings make differentiation of osteomyeli-
tis from infarction associated with sickle-cell disease difficult.
Bressler et al.53 1984 <6 weeks 100
Patients with osteomyelitis and decreased uptake on bone scan
a
Superscript numbers indicate references. may have more complicated infection, frequently with thrombosis
b
The 2 patients younger than 6 weeks of age had normal scans. and ischemic necrosis.58

A B C

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. Christopher’s Hospital for Children,
Philadelphia, PA.)

A B C

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 fat–muscle 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. Christopher’s Hospital for Children, Philadelphia, PA.)

All references are available online at www.expertconsult.com

471
 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-111-
labeled leukocytes is positive in diseases characterized by increased
bone turnover and, thus, have limited specificity for osteomyeli-
tis.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 infec-
tion (i.e., bone versus soft tissue), decreased sensitivity in diagnos-
ing 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 bone–imaging
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 tomogra-
phy (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, sus-
pected pathogens and their susceptibility pattern, antibiotic phar-
macodynamics, and the safety and efficacy of the antibiotic.
Most β-lactam antibiotics achieve therapeutic concentrations in
bone.67,68 Clindamycin has particularly good bone penetration,
attaining a high bone-to-serum ratio.67,69–71 Vancomycin has excel-
lent penetration into the bones of experimental animals.67
Aminoglycoside agents theoretically have poor bactericidal activ-
ity 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 first-
generation 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 com-
munities 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 β-lactam antibiot-
ics. Ampicillin-sulbactam should be considered in addition to
clindamycin or vancomycin, especially in young children.
Empiric therapy for young children who have not been immu-
nized 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 immuno-
competent child.
Neonates with osteomyelitis should be treated with antibiotics
active against S. aureus, group B streptococcus (GBS), and gram-
negative 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 first-
generation 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 vancomy-
cin 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 alterna-
tive 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, thrombocy-
topenia, 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 trimethoprim-
sulfamethoxazole, 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 chil-
dren 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; for-
mation of a sinus tract; and presence of necrotic, nonviable
bone.16,84–86
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 evi-
dence 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 complica-
tions,87 including catheter malfunction, thrombosis and catheter-
associated 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 150 4

or
Clindamycinc 30–40 3–4
or
Vancomycin 45–60 3–4
<3 years S. aureus Nafcillin 150 4
Haemophilus influenzae type ba or
Kingella kingaeb Clindamycinc 30–40 3–4
or
Vancomycin 45–60 3–4
plus
Cefotaxime 100–150 4
or
Ceftriaxone 100 2
or
Cefuroxime 75–150 3
or
Ampicillin-sulbactam 300 4
Neonate S. aureus Nafcillin 100 4
Group B streptococcus
or
Enteric gram-negative bacteria
Vancomycin 30 2
plus
Gentamicin 5–7.5 3
OR
Nafcillin 100 4
or
Vancomycin 30 2
plus
Cefotaxime 150 3
a
If patient is fully immunized against Haemophilus influenzae type b, consider using only antistaphylococcal coverage.
b
If patient is treated with either clindamycin or vancomycin, consider adding an ampicillin or cephalosporin agent for Kingella kingae.
c
Clindamycin 40 mg/kg/day recommended for treatment of susceptible MRSA osteomyelitis.

Sequential parenteral–oral antibiotic regimens can be Once the change to oral therapy is made, the child should be
successful.89–94 Early transition to oral therapy was not associated monitored to ensure continued clinical improvement. The CRP
with a higher risk of treatment failure in a recent study.87 The level is expected to return to normal 7 to 10 days after initiation
change to oral antibiotics is generally made when fever, pain, and of appropriate therapy, and the ESR normalizes within 3 to 4
signs of local inflammation have resolved and laboratory values, weeks.45,93
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 β-lactam
SPECIAL CLINICAL SITUATIONS
agent is used, dosage required is generally two to three times the Neonatal Osteomyelitis
usual oral dose (Table 78-3).
Osteomyelitis is uncommon in the neonatal period. The incidence
is estimated to be approximately 1 to 3 cases for every 1000
TABLE 78-3.  Dosage of Antibiotics Commonly Used in the Oral
intensive-care nursery admissions.95
Phase of Treatment of Osteomyelitisa
Associated risk factors include prematurity, low birthweight,
preceding infection, bacteremia, exchange transfusion, and the
Dosage
presence of an intravenous or umbilical catheter.96–99 Osteomyeli-
Antibiotic mg/kg per day Doses/Day tis of the skull secondary to contiguous spread of infection has
occurred as a complication of fetal scalp electrode monitoring100–102
Dicloxacillin 75–100 4 and in association with infected cephalohematoma.103,104 Osteomy­
Cephalexin 100–150 4 elitis of the calcaneus has complicated heel lancet puncture.97,105
Clindamycin 30–40b 3–4 The diagnosis of osteomyelitis in neonates often is delayed
a
In general, the dose of β-lactam antibiotics used for osteomyelitis is 2–3 because of nonspecific symptoms.106 Signs and symptoms include
times the usual dose. fever, irritability, swelling or decreased movement of a limb
b
Clindamycin 40 mg/kg/day is recommended for treatment of susceptible
(pseudoparalysis), erythema, and tenderness over the affected
MRSA osteomyelitis.72a
bone.95–97,107 Preterm infants are more likely than term infants to
manifest symptoms of septicemia.108

All references are available online at www.expertconsult.com

473
 PART II  Clinical Syndromes and Cardinal Features of Infectious Diseases: Approach to Diagnosis and Initial Management
SECTION K  Bone and Joint Infections
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.
Christopher’s Hospital for Children, Philadelphia, PA.)
Approximately 20% to 50% of neonates with osteomyelitis have
infection of multiple bones,95,96,109and about 75% have suppura-
tive arthritis of contiguous joints96 (Figure 78-5).
S. aureus (including CA-MRSA110), GBS, and enteric gram-
negative 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 uncom-
plicated neonatal course and have infection of a single bone. There
is a predilection for involvement of long bones on the right, par-
ticularly the right proximal humerus,113,114 which may be related
to trauma during vaginal delivery.113 Misdiagnosis of bone infec-
tion 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 (fre-
quently 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 abnormali-
ties or disturbance in skeletal growth secondary to damage to the
cartilaginous growth plate, including arthritis, decreased range
TABLE 78-4.  Frequency of Organisms Causing Neonatal
Osteomyelitis (n = 128)
Single Organism % present) include a history of pelvic trauma, intravenous drug use,
Staphylococcus aureus 60.6
β-Hemolytic streptococcus
  Group B 16.5
  Group A 3.1
Enteric gram-negative bacilli 8.7
Staphylococcus epidermidis 2.4
Nonhemolytic streptococcus 2.4
Streptococcus pneumoniae 0.8
Neisseria gonorrhoeae 0.8
Multiple organisms 4.7
474
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
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 hema-
togenous 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 ten-
derness 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, Sal-
monella spp. caused 12% of cases of childhood vertebral osteomy-
elitis.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 Tuber-
culosis 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 ver-
tebral 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 considera-
tion 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 decom-
pression 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
Approximately 6% to 9% of all cases of hematogenous osteomy-
elitis involve the bones of the pelvis.40,137,138 The ilium and ischium
are most commonly involved;137 infection of the sacrum, acetabu-
lum, or pubic symphysis is rare.137–140 Risk factors (not always
and genitourinary procedures.137,140
Most patients with pelvic osteomyelitis have fever, gait abnor-
malities, and pain that is often localized to the hip, groin, or
buttock.137,140–143 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.

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,137,138,141–143 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.137–140,143 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 infec-
tion. Splenic hypofunction, impaired opsonization, impaired
macrophage function, and microembolism as well as tissue infarc-
tion 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 hemo-
globinopathies in past decades.148–151 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 multi-
focal, symmetrical bone involvement.146,152 Manifestations of
osteomyelitis are difficult to differentiate from those of acute vaso-
occlusive crisis. Fever, bone pain, and leukocytosis are common
to both conditions. Temperature >39°C, 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 dif-
ferentiate 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 pro-
tracted. 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
Osteomyelitis 78
intravenous drug users.111,154–157 Osteomyelitis caused by Candida
spp. is reported in intravenous drug users and in prematurely born
neonates.111,154–158 Aspergillus spp. cause osteomyelitis in children
with chronic granulomatous disease, often resulting from contigu-
ous spread of pulmonary infection.159 Blastomyces dermatitidis,
Coccidioides immitis, Histoplasma capsulatum, and Cryptococcus neo-
formans cause osteomyelitis in indigenous geographic regions and
in immunosuppressed hosts.160–163
Tuberculous Osteomyelitis
Skeletal lesions occur in approximately 1% of children with tuber-
culosis.130,164 Bones and joints are infected through hematogenous
or lymphatic dissemination of Mycobacterium tuberculosis. Infec-
tion 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-γ 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 radio-
graph often is normal. CT is useful for the evaluation of bone
destruction, adjacent soft-tissue abscess formation, and calcifica-
tion, and in guiding percutaneous biopsy.169,170 MRI is helpful in
determining extent of bone and soft-tissue disease.171 Biopsy speci-
mens should be obtained in an attempt to demonstrate the organ-
ism 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.173–175 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 contigu-
ous spread from aspiration lung infection; Actinomyces spp. are the
primary pathogens. Soft-tissue swelling or abscess can be the pre-
senting abnormality. Similarly, Actinomyces spp. can cause osteo-
myelitis of the maxilla or mandible, frequently without dental
pathology.
Infection usually is polymicrobial; gram-positive cocci, Bacter-
oides spp., Prevotella spp., and Fusobacterium spp. are the most
common anaerobes, and S. aureus is the most commonly associ-
ated aerobic isolate.174 Therapy consists of treatment of underlying
conditions, surgical debridement of necrotic bone, and appropri-
ate antibiotic therapy. Examples of effective antibiotics are clin-
damycin, 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
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. Christopher’s 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 β-lactamase production. Therapy is protracted, fre-
quently 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 reduc-
tion,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 destruc-
tion. 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 organ-
isms 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 ulcer-
associated osteomyelitis frequently is beneficial.185
476
PUNCTURE WOUND OSTEOCHONDRITIS
OF THE FOOT
Bacterial osteochondritis is a complication of puncture wounds of
the foot, occurring in approximately 1.5% of such injuries.182,186–188
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 micro-
biologic diagnosis is desirable.
Empiric antibiotic therapy should include coverage for
P. aeruginosa and S. aureus. Ticarcillin-clavulanate, piperacillin-
tazobactam, ceftazidime or cefepime, with or without an aminogly-
coside, 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. aeru-
ginosa,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 inflam-
matory 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 meta-
physis 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 mul-
tiple, often symmetrical lesions are present in CRMO. Bone scan-
ning and MRI are useful in determining the extent and evolution
of disease.199–201 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 anti-
biotics 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 ther-
apies utilized in small numbers of patients have included colchi-
cine, INF-γ, IFN-α, 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 speci-
mens should be performed. Histologic findings in CRMO are non-
specific 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. Infec-
tions are often polymicrobial, and the original metaphyseal infec-
tion, 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 antibiotic-
impregnated 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.210–212

REFERENCES
1. Winters JL, Cahen I. Acute hematogenous osteomyelitis:
a review of sixty-six cases. J Bone Joint Surg Am 1960;42:97.
2. Trueta J. The three types of acute haematogenous
osteomyelitis: a clinical and vascular study. J Bone Joint Surg
Br 1959;41:671.
3. Waldvogel FA, Medoff G, Swartz MN. Osteomyelitis: a review
of clinical features, therapeutic considerations and unusual
aspects (first of three parts). N Engl J Med 1970;282:198.
4. Anderson CE, Parker J. Invasion and resorption in enchondral
ossification: an electron microscope study. J Bone Joint Surg
Am 1966;48:899.
5. Howlett CR. The fine structure of the proximal growth plate
and metaphysis of the avian tibia: endochondral osteogenesis.
J Anat 1980;130:745.
6. Emslie KR, Nade S. Pathogenesis and treatment of acute
hematogenous osteomyelitis: evaluation of current views with
reference to an animal model. Rev Infect Dis 1986;8:841.
7. Mayberry-Carson KJ, Tober-Meyer B, Smith JK, et al. Bacterial
adherence and glycocalyx formation in osteomyelitis
experimentally induced with Staphylococcus aureus. Infect
Immun 1984;43:825.
8. Trueta J. The normal vascular anatomy of the human femoral
head during growth. J Bone Joint Surg Br 1957;39:358.
9. Ogden JA, Lister G. The pathology of neonatal osteomyelitis.
Pediatrics 1975;55:474.
10. Gillespie WJ. The epidemiology of acute haematogenous
osteomyelitis of childhood. Int J Epidemiol 1985;14:600.
11. Hevroni A, Koplewitz BZ. Images in medicine. Bone within
bone: chronic osteomyelitis. N Engl J Med 2007;35:e7.
12. Nelson JD. Acute osteomyelitis in children. Infect Dis Clin
North Am 1990;4:513.
13. Dich VQ, Nelson JD, Haltalin KC. Osteomyelitis in infants
and children. Am J Dis Child 1975;129:1273.
14. Rossaak M, Pitto RP. Osteomyelitis in Polynesian children.
Int Orthop 2005;29:55.
15. Lebel MH, Nelson JD. Haemophilus influenzae type b
osteomyelitis in infants and children. Pediatr Infect Dis J
1988;7:250.
16. Waldvogel FA, Papageorgiou PS. Osteomyelitis: the past
decade. N Engl J Med 1980;303:360.
17. Scott RJ, Christoferson MR, Robertson WW, et al. Acute
osteomyelitis in children: a review of 116 cases. J Pediatr
Orthop 1990;10:649.
18. Faden H, Grossi M. Acute osteomyelitis in children:
reassessment of etiologic agents and their clinical
characteristics. Am J Dis Child 1991;145:65.
19. Blyth MJG, Kincaid R, Craigen MAC, et al. The changing
epidemiology of acute and subacute haematogenous
osteomyelitis in children. J Bone Joint Surg Br
2001;83:99–102.
20. Kiang KM, Ogunmodede F, Juni BA, et al. Outbreak of
osteomyelitis/septic arthritis caused by Kingella kingae among
child care center attendees. Pediatrics 2005;116:e206.
21. Moumile K, Merckx J, Glorion JC, et al. Bacterial aetiology of
acute osteoarticular infections in children. Acta Paediatr
2005;94:419.
22. Bradley JS, Kaplan SL, Tan TQ, et al. Pediatric pneumococcal
bone and joint infections. Pediatrics 1998;102:1376.
23. Ibia Eo, Imoisili M, Pikis A. Group A beta-hemolytic
streptococcal osteomyelitis in children. Pediatrics
2003;112:e22.
24. Black S, Shinefield H, Baxter R, et al. Postlicensure
surveillance for pneumococcal invasive disease after use of
heptavalent pneumococcal conjugate vaccine in Northern
California Kaiser Permanente. Pediatr Infect Dis J
2004;23:485.
Osteomyelitis 78
25. Poehling KA, Talbot TR, Griffin MR, et al. Invasive
pneumococcal conjugate vaccine. JAMA 2006;295:1668.
26. Yagupsky P, Erlich Y, Ariela S, et al. Outbreak of Kingella
kingae skeletal system infections in children in daycare.
Pediatr Infect Dis J 2006;25:526.
27. Robson JMB, Harte GJ, Osborne DRS, et al. Cat-scratch
disease with bone involvement. Clin Infect Dis 1999;28:274.
28. Hipp SJ, O’Shields A, Fordham LA, et al. Multifocal bone-
marrow involvement in cat-scratch disease. Pediatr Infect
Dis J 2005;24:472.
29. de Kort JG, Robben SG, Schrander JJ, et al. Multifocal
osteomyelitis in a child: a rare manifestation of cat scratch
disease: a case report and systematic review of the literature.
J Pediatr Orthop B 2006;15:285.
30. Robinson JL, Vaudry WL, Dobrovolsky W. Actinomycosis
presenting as osteomyelitis in the pediatric population.
Pediatr Infect Dis J 2005;24:365.
31. Winkelstein JA, Marino MC, Johnston RB Jr, et al. Chronic
granulomatous disease: report on a national registry of 368
patients. Medicine 2000;79:155.
32. Bowerman SG, Green NE, Mencio GA. Decline of bone and
joint infections attributable to Haemophilus influenzae type b.
Clin Orthop 1997;341:128.
33. Martinez-Aguilar G, Avalos-Mishaan A, Hulten K, et al.
Community acquired, methicillin-resistant and methicillin-
susceptible Staphylococcus aureus musculoskeletal infections in
children. Pediatr Infect Dis J 2004;23:701.
34. Mishaan AM, Mason EO Jr, Martinez-Aguilar G, et al.
Emergence of a predominant clone of community-acquired
Staphylococcus aureus among children in Houston, Texas.
Pediatr Infect Dis J 2005;24:201.
35. Gonzalez BE, Hulten KG, Dishop MK, et al. Pulmonary
manifestations in children with invasive community-acquired
Staphylococcus aureus infection. Clin Infect Dis 2005;41:583.
36. Gonzalez BE, Teruya J, Mahoney DH, et al. Venous
thrombosis associated with staphylococcal osteomyelitis in
children. Pediatrics 2006;117:1673.
37. Mitchell PD, Hunt DM, Lyall H, et al. Panton-Valentine
leukocidin-secreting Staphylococcus aureus causing severe
musculoskeletal sepsis in children: a new threat. J Bone Joint
Surg Br 2007;89:1239.
38. Bocchini CE, Hulten KG, Mason EO, et al. Panton-valentine
leukocidin genes are associated with enhanced inflammatory
response and local disease in acute hematogenous
Staphylococcus aureus osteomyelitis in children. Pediatrics
2006;117:433.
39. Vaughan PA, Newman NM, Rosman MA. Acute
hematogenous osteomyelitis in children. J Pediatr Orthop
1987;7:652.
40. Morrey BF, Bianco AJ, Rhodes KH. Hematogenous
osteomyelitis at uncommon sites in children. Mayo Clin Proc
1978;53:707.
41. Kaplan SL. Osteomyelitis in children. Infect Dis Clin North
Am 2005;19:787.
42. Arnold SR, Elias D, Buckingham SC, et al. Changing patterns
of acute hematogenous osteomyelitis and septic arthritis.
Pediatr Orthop 2006;26:703.
42a. Ju KL, Zurakowski D, Kocher MS. Differentiating between
methicillin-resistant and methicillin-sensitive Staphylococcus
aureus osteomyelitis in children. J Bone Joint Surg Am
2011;93:1693.
43. Wu JS, Gorbachova T, Morrison WB, Haims AH. Imaging-
guided bone biopsy for osteomyelitis: are there factors
associated with positive or negative cultures? AJR Am J
Roentgenol 2007;188:1529.
44. Gene A, Garcia-Garcia JJ, Sala P, et al. Enhanced culture
detection of Kingella kingae, a pathogen of increasing clinical
importance in pediatrics. Pediatr Infect Dis J 2004:23;886.
477.e1
 PART II  Clinical Syndromes and Cardinal Features of Infectious Diseases: Approach to Diagnosis and Initial Management
SECTION K  Bone and Joint Infections
45. Unkila-Kallio L, Kallio MJ, Eskola J, et al. Serum C-reactive
protein, erythrocyte sedimentation rate, and white blood cell
count in acute hematogenous osteomyelitis of children.
Pediatrics 1994;93:59.
46. Roine I, Arguedas A, Faingezicht I, et al. Early detection
of sequela-prone osteomyelitis in children with use of
simple clinical and laboratory criteria. Clin Infect Dis
1997;24:849.
47. Hollmig ST, Copley LA, Browne RH, et al. Deep venous
thrombosis associated with osteomyelitis in children. J Bone
Joint Surg Am 2007;89(7):1517.
48. Capitanio MA, Kirkpatrick JA. Acute roentgen observations in
acute osteomyelitis. AJR 1970;108:488.
49. Tuson CE, Hoffman EB, Mann MD. Isotope bone scanning
for acute osteomyelitis and septic arthritis in children. J Bone
Joint Surg Br 1994;76:306–310.
50. Hamdan J, Mohassed A, Mallouh A, et al. Technetium bone
scintigraphy in the diagnosis of osteomyelitis in children.
Pediatr Infect Dis J 1987;6:529.
51. Howie DW, Savage JP, Wilson TG, et al. The technetium
phosphate bone scan in the diagnosis of osteomyelitis in
childhood. J Bone Joint Surg Am 1983;65:431.
52. Sullivan DC, Rosenfield NS, Ogden S, et al. Problems in the
scintigraphic detection of osteomyelitis in children. Radiology
1980;135:731.
53. Bressler EL, Conway JJ, Weiss SC. Neonatal osteomyelitis
examined by bone scintigraphy. Radiology 1984;152:685.
54. Wald ER, Mirro R, Gartner JC. Pitfalls on the diagnosis of
acute osteomyelitis by bone scan. Clin Pediatr 1980;19:597.
55. Berkowitz ID, Wenzel W. Normal technetium bone scans in
patients with acute osteomyelitis. Am J Dis Child
1980;134:828.
56. Fleisher GR, Paradise JE, Plotkin SA, et al. Falsely normal
radionuclide scans for osteomyelitis. Am J Dis Child
1980;134:499.
57. Connolly LP, Connolly SA, Drubach LA, et al. Acute
hematogenous osteomyelitis of children: assessment of
skeletal scintigraphy-based diagnosis in the era of MRI. J Nucl
Med 2002;43:1310.
58. Pennington WT, Mott MP, Thometz JG, et al. Photopenic
bone scan osteomyelitis: a clinical perspective. J Pediatr
Orthop 1999;19:695.
59. Tsan M. Mechanism of gallium-67 accumulation in
inflammatory lesions. J Nucl Med 1985;26:88.
60. Schauwecker DS, Park HM, Mock BH, et al. Evaluation of
complicating osteomyelitis with Tc-99m MDP, In-111
granulocytes, and Ga-67 citrate. J Nucl Med 1984;25:849.
61. Schauwecker DS. Osteomyelitis: diagnosis with In-111 labeled
leukocytes. Radiology 1989;171:141.
62. Mazur JM, Ross G, Cummings RJ, et al. Usefulness of
magnetic resonance imaging for the diagnosis of acute
musculoskeletal infections in children. J Pediatr Orthop
1995;15:144.
63. Dangman BC, Hoffer JA, Rand FF, et al. Osteomyelitis in
children: gadolinium-enhanced MR imaging. Radiology
1992;182:743.
64. Fletcher BD, Scoles PV, Nelson AD. Osteomyelitis in children:
detection by magnetic resonance. Radiology 1984;150:57.
65. Cohen D, Cory DA, Kleiman M, et al. Magnetic resonance
differentiation of acute and chronic osteomyelitis in children.
Clin Radiol 1990;41:53.
66. Averill LW, Hernandez A, Gonzalez L, et al. Diagnosis of
osteomyelitis in children: utility of fat-suppressed contrast-
enhanced MRI. AJR Am J Roentgenol 2009;192:1232.
67. Mader JT, Landon GC, Calhoun J. Antimicrobial treatment of
osteomyelitis. Clin Orthop 1993;295:87.
68. Tetzlaff TR, Howard JB, McCracken GH, et al. Antibiotic
concentrations in pus and bone of children with
osteomyelitis. J Pediatr 1978;92:135.
477.e2
69. Norden CW, Shinners E, Niederriter K. Clindamycin
treatment of experimental chronic osteomyelitis due to
Staphylococcus aureus. J Infect Dis 1986;153:956.
70. Rodriguez W, Ross S, Khan W, et al. Clindamycin in the
treatment of osteomyelitis in children. Am J Dis Child
1977;131:1088.
71. Feigin RD, Pickering LK, Anderson D, et al. Clindamycin
treatment of osteomyelitis and septic arthritis in children.
Pediatrics 1975;55:213.
72. Gentry LO, Rodriguez GG. Oral ciprofloxacin compared with
parenteral antibiotics in the treatment of osteomyelitis.
Antimicrob Agents Chemother 1990;34:40.
72a. Liu C, Bayor 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;52:1.
73. Prober CG. Current antibiotic therapy of community-acquired
bacterial infections in hospitalized children: bone and joint
infections. Pediatr Infect Dis J 1992;11:156.
73a. Peltola H, Pääkkönen M, Kallio P, Kallio MJT and The OM-SA
Study Group. Clindamycin vs. first-generation cephalosporins
for acute osteoarticular infections of childhood: a prospective
quasi-randomized controlled trial. Clin Microbiol Infect
(doi: 10.1111/j.1469-0691.2011.03643.x).
74. Siberry GK, Tekle T, Carroll K, et al. Failure of clindamycin
treatment of methicillin-resistant Staphylococcus aureus
expressing inducible clindamycin resistance in vitro. Clin
Infect Dis 2003;37:1257.
75. Lewis JS II, Jorgensen JH. Inducible clindamycin resistance in
staphylococci: should clinicians and microbiologists be
concerned? Clin Infect Dis 2005;40:280.
76. Birmingham MC, Rayner CR, Megher AK, et al. Linezolid for
the treatment of multidrug-resistant, gram-positive infections:
experience from a compassionate-use program. Clin Infect
Dis 2003;36:159.
77. Kaplan SL, Deville JG, Yogev R, et al. Linezolid versus
vancomycin for treatment of resistant gram-positive infections
in children. Pediatr Infect Dis J 2003;22:677.
78. Tan TQ. Update on the use of linezolid. Pediatr infect Dis J
2004;23:955.
79. Apodaca AA, Rakita RM. Linezolid-induced lactic acidosis.
N Engl J Med 2003;348:86.
80. Lee E, Burger S, Shah J, et al. Linezolid-associated toxic
optic neuropathy: a report of 2 cases. Clin Infect Dis
2003;37:1389.
81. Adra M, Lawrence KR. Trimethoprim-sulfamethoxazole for
treatment of severe Staphylococcus infections. Ann
Pharmacother 2004;38:338.
82. Ruhe JJ, Monson T, Bradsher RW, et al. Use of long-acting
tetracyclines for methicillin-resistant Staphylococcus aureus
infections: case series and review of the literature. Clin Infect
Dis 2005;40:11429.
83. Floyed RL, Steele RW. Culture-negative osteomyelitis. Pediatr
Infect Dis J 2003;22:731.
84. Dagan R. Management of acute hematogenous osteomyelitis
and septic arthritis in the pediatric patient. Pediatr Infect
Dis J 1993;12:88.
85. LaMont RL, Anderson PA, Dajani AS, et al. Acute
hematogenous osteomyelitis in children. J Pediatr Orthop
1987;7:579.
86. Nade S. Acute haematogenous osteomyelitis in infancy and
childhood. J Bone Joint Surg Br 1983;65:109.
87. 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;123:636.
88. Ruebner R, Keren R, Coffin S, et al. Complications of
central venous catheters used for the treatment of acute
hematogenous osteomyelitis. Pediatrics 2006;117:1210.

89. Tetzlaff TR, McCracken GH Jr, Nelson JD. Oral antibiotic
therapy for skeletal infections of children. II: Therapy of
osteomyelitis and suppurative arthritis. J Pediatr 1978;92:485.
90. Bryson YJ, Connor JD, LeClerc M, et al. High-dose oral
dicloxacillin treatment of acute staphylococcal osteomyelitis
in children. J Pediatr 1979;94:673.
91. Kolyvas E, Ahronheim G, Marks MI, et al. Oral antibiotic
therapy of skeletal infections in children. Pediatrics
1980;65:867.
92. Syrogiannopoulos GA, Nelson JD. Duration of antimicrobial
therapy for acute suppurative osteoarticular infections. Lancet
1988;1:37.
93. Peltola H, Unkila-Kallio L, Kallio MJT. Simplified treatment
of acute staphylococcal osteomyelitis of childhood. Pediatrics
1997;99:846.
94. Karwowska A, Davies D, Jadavji T. Epidemiology and
outcome of osteomyelitis in the era of sequential intravenous-
oral therapy. Pediatr Infect Dis J 1998;17:1021.
95. Asmar BI. Osteomyelitis in the neonate. Infect Dis Clin North
Am 1992;6:117.
96. Fox L, Sprunt K. Neonatal osteomyelitis. Pediatrics
1978;62:535.
97. Frederiksen B, Christiansen P, Knudsen FU. Acute
osteomyelitis and septic arthritis in the neonate: risk factors
and outcome. Eur J Pediatr 1993;152:577.
98. Lim MO, Gersham EL, Franken EA, et al. Osteomyelitis as a
complication of umbilical artery catheterization. Am J Dis
Child 1977;131:142.
99. Simmons PB, Harris LE, Bianco AJ. Complications of
exchange transfusion: Report of two cases of septic arthritis
and osteomyelitis. Mayo Clin Proc 1973;48:190.
100. Brook I. Osteomyelitis and bacteremia caused by Bacteroides
fragilis: a complication of fetal monitoring. Clin Pediatr
1980;19:639.
101. Overturf GD, Balfour G. Osteomyelitis and sepsis: severe
complications of fetal monitoring. Pediatrics 1975;55:244.
102. McGregor JA, McFarren T. Osteomyelitis: a complication of
fetal monitoring. Obstet Gynecol 1989;73:490.
103. Mohon RT, Mehalic TF, Grimes CK, et al. Infected
cephalhematoma and neonatal osteomyelitis of the skull.
Pediatr Infect Dis J 1986;5:253.
104. Brook I. Infected neonatal cephalohematomas caused by
anaerobic bacteria. J Perinat Med 2005;33:255.
105. Lilien LD, Harris VJ, Ramamurthy RS, et al. Neonatal
osteomyelitis of the calcaneus: complication of heel puncture.
J Pediatr 1976;88:478.
106. Wong M, Isaacs D, Howman-Giles R, et al. Clinical and
diagnostic features of osteomyelitis occurring in the first three
months of life. Pediatr Infect Dis J 1995;14:1047.
107. Weissberg ED, Smith AL, Smith DH. Clinical features of
neonatal osteomyelitis. Pediatrics 1974;53:505.
108. Williamson JB, Galasko CS, Robinson MJ. Outcome after
acute osteomyelitis in preterm infants. Arch Dis Child
1990;65:1060.
109. Bergdahl S, Ekengren K, Eriksson M. Neonatal hematogenous
osteomyelitis: risk factors for long-term sequelae. J Pediatr
Orthop 1985;5:564.
110. Healy CM, Hulten KG, Palazzi DL, et al. Emergence of new
strains of methicillin-resistant Staphylococcus aureus in a
neonatal intensive care unit. Clin Infect Dis 2004;39:1460.
111. Oleinik EM, Della-Latta P, Rinaldi MG, et al. Candida
lusitaniae osteomyelitis in a premature infant. Am J Perinatol
1993;10:313.
112. Gjuric G, Prislin-Muskic M, Nikolic E, et al. Ureaplasma
urealyticum osteomyelitis in a very low birth weight infant.
J Perinat Med 1994;22:79.
113. Edwards MS, Baker CJ, Wagner ML, et al. An etiologic shift in
infantile osteomyelitis: the emergence of the group B
Streptococcus. J Pediatr 1978;93:578.
Osteomyelitis 78
114. Baxter MP, Finnegan MA. Skeletal infection by group B
beta-haemolytic streptococci in neonates. J Bone Joint Surg Br
1988;70:812.
115. Schrag SJ, Zywicki S, Farley MM, et al. Group B streptococcal
disease in the era of intrapartum antibiotic prophylaxis.
N Engl J Med 2000;342:15.
116. Shortland DB, MacFayden U, Elston A, et al. Evaluation of
C reactive protein values in neonatal sepsis. J Perinatol Med
1990;18:157.
117. Morrissy RT. Bone and joint infection in the neonate. Pediatr
Ann 1989;18:33.
118. Mok P, Reilly B, Ash J. Osteomyelitis in the neonate.
Radiology 1982;145:677.
119. Peters W, Irving J, Letts M. Long-term effects of neonatal bone
and joint infection on adjacent growth plates. J Pediatr
Orthop 1992;12:806.
120. Correa AG, Edwards MS, Baker CJ. Vertebral osteomyelitis in
children. Pediatr Infect Dis J 1993;12:228.
121. Le CT. Salmonella vertebral osteomyelitis: a case report with
literature review. Am J Dis Child 1982;136:722.
122. Sapico FL, Montgomerie JZ. Pyogenic vertebral osteomyelitis:
report of nine cases and review of the literature. Rev Infect
Dis 1979;1:754.
123. Musher DM, Thorsteinsson SB, Minuth JN, et al. Vertebral
osteomyelitis: still a diagnostic pitfall. Arch Intern Med
1976;136:105.
124. Eismont FJ, Bohlman HH, Soni PL, et al. Vertebral
osteomyelitis in infants. J Bone Joint Surg Br 1982;64:32.
125. Bolivar R, Kohl S, Pickering LK. Vertebral osteomyelitis in
children: report of four cases. Pediatrics 1978;62:549.
126. Bartels JW, Brammer RE. Cervical osteomyelitis with
prevertebral abscess formation. Otolaryngol Head Neck Surg
1990 ;102:180.
127. Silverthorn KG, Gillespie WJ. Pyogenic spinal osteomyelitis:
a review of 61 cases. N Z Med J 1986;99:62.
128. Sapico FL, Montgomerie JZ. Vertebral osteomyelitis in
intravenous drug abusers: report of three cases and review of
the literature. Rev Infect Dis 1980;2:196.
129. Lafont A, Olive A, Gelman M, et al. Candida albicans
spondylodiscitis and vertebral osteomyelitis in patients
with intravenous heroin drug addiction. J Rheumatol
1994;21:953.
130. Colmenero JD, Jimenez-Mejias ME, Reguera JM, et al.
Tuberculous vertebral osteomyelitis in the new millennium:
still a diagnostic and therapeutic challenge. Eur J Clin
Microbiol Infect Dis 2004;23:477.
131. Pourbagher A, Pourbagher MA, Savas L, et al. Epidemiologic,
clinical and imaging findings in brucellosis patients with
osteoarticular involvement. AJR 2006;187:873.
132. Meyers SP, Weiner SN. Diagnosis of hematogenous pyogenic
vertebral osteomyelitis by magnetic resonance imaging. Arch
Intern Med 1991;151:683.
133. Modic MT, Feiglin DH, Piraino DW, et al. Vertebral
osteomyelitis: assessment using MR. Radiology 1985;
157:157.
134. Fischer EG, Greene CS, Winston KR. Spinal epidural abscess
in children. Neurosurgery 1981;9:257.
135. Faidas A, Ferguson JV Jr, Nelson JE, et al. Cervical vertebral
osteomyelitis presenting as a retropharyngeal abscess. Clin
Infect Dis 1994;18:992.
136. McHenry MC, Rehm SJ, Krajewski LP, et al. Vertebral
osteomyelitis and aortic lesions: case report and review.
Rev Infect Dis 1991;13:1184.
137. Mustafa MM, Saez-Llorens X, McCracken GH, et al. Acute
hematogenous pelvic osteomyelitis in infants and children.
Pediatr Infect Dis J 1990;9:416.
138. Weber-Chrysochoou C, Corti N, Goetschel P, et al. Pelvic
osteomyelitis: a diagnostic challenge in children. J Pediatr
Surg 2007;42:553.
477.e3
 PART II  Clinical Syndromes and Cardinal Features of Infectious Diseases: Approach to Diagnosis and Initial Management
SECTION K  Bone and Joint Infections
139. Ukwu HN, Graham BS, Latham RH. Acute pubic
osteomyelitis in athletes. Clin Infect Dis 1992;15:636.
140. Busto RD, Quinn EL, Fisher EJ, et al. Osteomyelitis of the
pubis. JAMA 1982;248:1498.
141. Farley T, Conway J, Shulman ST. Hematogenous pelvic
osteomyelitis in children. Am J Dis Child 1985;139:946.
142. Highland TR, LaMont RL. Osteomyelitis of the pelvis in
children. J Bone Joint Surg Am 1983;65:230.
143. Edwards MS, Baker CJ, Granberry WM, et al. Pelvic
osteomyelitis in children. Pediatrics 1978;61:62.
144. Connolly SA, Connolly LP, Drubach LA, et al. MRI for
detection of abscess in acute osteomyelitis of the pelvis in
children. AJR Am J Roentgenol 2007;189:867.
145. Piehl FC, Davis RJ, Prugh SI. Osteomyelitis in sickle cell
disease. J Pediatr Orthop 1993;13:225.
146. Epps CH, Bryant DD, Coles MJ, et al. Osteomyelitis in
patients who have sickle-cell disease. J Bone Joint Surg Am
1991;73:1281.
147. Johnston RB. Increased susceptibility to infection in sickle cell
disease: review of its occurrence and possible causes. South
Med J 1974;67:1324.
148. Syrogiannopoulos GA, McCracken GH, Nelson JD.
Osteoarticular infections in children with sickle cell disease.
Pediatrics 1986;78:1090.
149. Givner LB, Luddy RE, Schwartz AD. Etiology of osteomyelitis
in patients with major sickle hemoglobinopathies. J Pediatr
1981;99:411.
150. Mallouh A, Talab Y. Bone and joint infection in patients with
sickle cell disease. J Pediatr Orthop 1985;5:158.
151. Burnett MW, Bass JW, Cook BA. Etiology of osteomyelitis
complicating sickle cell disease. Pediatrics 1998;101:296.
152. Reynolds J. Radiologic manifestations of sickle cell
hemoglobinopathy. JAMA 1977;238:247.
153. Bonnerot V, Sebag G, de Montalembert M, et al. Gadolinium-
DOTA enhanced MRI of painful osseous crises in children
with sickle cell anemia. Pediatr Radiol 1994;24:92.
154. Glick C, Graves GR, Feldman S. Neonatal fungemia and
amphotericin B. South Med J 1993;86:1368.
155. Ward RM, Sattler FR, Dalton SA. Assessment of antifungal
therapy in an 800-gram infant with candidal arthritis and
osteomyelitis. Pediatrics 1983;72:234.
156. Dato VM, Dajani AS. Candidemia in children with central
venous catheters: role of catheter removal and amphotericin
B therapy. Pediatr Infect Dis J 1990;9:309.
157. Collignon PJ, Sorrell TC. Disseminated candidiasis: evidence
of a distinctive syndrome in heroin abusers. Br Med J
1983;287:861.
158. Hendrickx L, Wijngaerden EV, Samson I, et al. Candidal
vertebral osteomyelitis: report of 6 patients, and a review.
Clin Infect Dis 2001;32:527-533.
159. Sponseller PD, Malech HL, McCarthy EF, et al. Skeletal
involvement in children who have chronic granulomatous
disease. J Bone Joint Surg Am 1991;73:37.
160. Leggiadro RJ, Barrett FF, Hughes WT. Disseminated
histoplasmosis of infancy. Pediatr Infect Dis J 1988;7:799.
161. Rhangos WC, Chick EW. Mycotic infections of bone. South
Med J 1964;57:664.
162. MacDonald PB, Black GB, MacKenzie R. Orthopaedic
manifestations of blastomycosis. J Bone Joint Surg Am
1990;72:860.
163. Zerbe CS, Holland SM. Disseminated histoplasmosis in
persons with interferon-gamma receptor 1 deficiency. Clin
Infect Dis 2005;41:e38.
164. Snider D, Rieder H, Combs D, et al. Tuberculosis in children.
Pediatr Infect Dis J 1988;7:271.
165. Waldvogel F, Medoff G, Swartz MN. Osteomyelitis: a review
of clinical features, therapeutic considerations and unusual
aspects (third of three parts). N Engl J Med 1970;282:316.
477.e4
166. Lachenauer CS, Cosentino S, Wood RS, et al. Multifocal
skeletal tuberculosis presenting as osteomyelitis of the jaw.
Pediatr Infect Dis J 1991;10:940.
167. Muradali D, Gold WL, Vellend H, et al. Multifocal
osteoarticular tuberculosis: report of four cases and review of
management. Clin Infect Dis 1993;17:204.
168. Haygood TM, Williamson SL. Radiographic findings of
extremity tuberculosis in childhood: back to the future?
Radiographics 1994;14:561.
169. Coppola J, Muller NL, Connell DG. Computed tomography
of musculoskeletal tuberculosis. J Can Assoc Radiol
1987;38:199.
170. Jain R, Sawhney S, Berry M. Computed tomography of
vertebral tuberculosis: patterns of bone destruction. Clin
Radiol 1993;47:196.
171. Thrush A, Enzmann D. MR imaging of infectious spondylitis.
Am J Neuroradiol 1990;11:1171.
172. American Academy of Pediatrics. Tuberculosis. In: Pickering
LK, Baker CJ, Kimberlin DW, Long SS (eds) Red Book: 2009
Report of the Committee on Infectious Diseases, 28th ed. Elk
Grove Village, IL, American Academy of Pediatrics, 2009, p 680.
173. Brook I. Anaerobic osteomyelitis in children. Pediatr Infect
Dis J 1986;5:550.
174. Brook I, Frazier EH. Anaerobic osteomyelitis and arthritis
in a military hospital: a 10 year experience. Am J Med
1993;94:21.
175. Pichichero ME, Friesen HA. Polymicrobial osteomyelitis:
report of three cases and review of the literature. Rev Infect
Dis 1982;4:86.
176. Lewallen RP, Peterson HA. Nonunion of long bone fractures
in children: a review of 30 cases. J Pediatr Orthop
1985;5:135.
177. Waldvogel FA, Medoff G, Swartz MN. Osteomyelitis: a review
of clinical features, therapeutic considerations and unusual
aspects (second of three parts). N Engl J Med 1970;282:260.
178. Caputo GM, Cavanagh PR, Ulbrecht JS, et al. Assessment and
management of foot disease in patients with diabetes. N Engl
J Med 1994;331:854.
179. Sapico FL, Witte JL, Canawati HN, et al. The infected foot of
the diabetic patient: quantitative microbiology and analysis
of clinical features. Rev Infect Dis 1984;6:S171.
180. Jarvis WR. Pasteurella multocida osteomyelitis following dog
bites. Am J Dis Child 1981;135:625.
181. Gonzalez MH, Papierski P, Hall RF. Osteomyelitis of the hand
after a human bite. J Hand Surg 1993;18:520.
182. Imoisili MA, Bonwit AM, Bulas DI. Toothpick puncture
injuries of the foot in children. Pediatr Infect Dis J
2004;23:80.
183. Dubey L, Krasinski K, Hernanz-Schulman M. Osteomyelitis
secondary to trauma or infected contiguous soft tissue.
Pediatr Infect Dis J 1988;7:26.
184. Mackowiak PA, Jones SR, Smith JW. Diagnostic value of
sinus-tract cultures in chronic osteomyelitis. JAMA
1978;239:2772.
185. Smith IM, Austin OM, Batchelor AG. The treatment of
chronic osteomyelitis: a 10 year audit. J Plast Reconstr Aesthet
Surg 2006;59:11.
186. Johanson PH. Pseudomonas infections of the foot following
puncture wounds. JAMA 1968;204:262.
187. Brand RA, Black H. Pseudomonas osteomyelitis following
puncture wounds in children. J Bone Joint Surg Am
1974;56:1637.
188. Miller EH, Semian DW. Gram-negative osteomyelitis
following puncture wounds of the foot. J Bone Joint Surg Am
1975;57:535.
189. Jacobs RF, McCarthy RE, Elser JM. Pseudomonas
osteochondritis complicating puncture wounds of the foot in
children: a 10-year evaluation. J Infect Dis 1989;160:657.

190. Fisher MC, Goldsmith JF, Gilligan PH. Sneakers as a source of
Pseudomonas aeruginosa in children with osteomyelitis
following puncture wounds. J Pediatr 1985;106:607.
191. Jacobs RF, Adelman L, Sack CM, et al. Management of
Pseudomonas osteochondritis complicating puncture wounds
of the foot. Pediatrics 1982;69:432.
192. Raz R, Miron D. Oral ciprofloxacin for treatment of infection
following nail puncture wounds of the foot. Clin Infect Dis
1995;21:194.
193. Schultz C, Holterhus PM, Seidel A, et al. Chronic recurrent
multifocal osteomyelitis in children. Pediatr Infect Dis J
1999;18:1008.
194. Chun CS. Chronic recurrent multifocal osteomyelitis of the
spine and mandible: case report and review of the literature.
Pediatrics 2004;113:380.
195. King SM, Laxer RM, Manson D, et al. Chronic recurrent
multifocal osteomyelitis: a noninfectious inflammatory
process. Pediatr Infect Dis J 1987;6:907.
196. Bjorksten B, Gustavson KH, Eriksson B, et al. Chronic
recurrent multifocal osteomyelitis and pustulosis
palmoplantaris. J Pediatr 1978;93:227.
197. Huber AM, Lam P-Y, Duffy CM, et al. Chronic
recurrent multifocal osteomyelitis: clinical outcome
after more than five years of follow-up. J Pediatr
2002;141:198.
198. Probst F, Bjorksten B, Gustavson K-H. Radiological aspect of
chronic recurrent multifocal osteomyelitis. Ann Radiol
1978;21:115.
199. Mortensson W, Edeburn G, Fries M, et al. Chronic
recurrent multifocal osteomyelitis in children: a
roentgenologic and scintigraphic investigation. Acta Radiol
1988;29:565.
200. Machiels F, Seynaeve P, Lagey C, et al. Chronic recurrent
multifocal osteomyelitis with MR correlation: a case report.
Pediatr Radiol 1992;22:535.
Osteomyelitis 78
201. Dawson JS, Webb JK, Preston BJ. Case report: chronic
recurrent multifocal osteomyelitis with magnetic resonance
imaging. Clin Radiol 1994;49:133.
202. Solheim LF, Paus B, Liverud K, et al. Chronic recurrent
multifocal osteomyelitis. Acta Orthop Scand 1980;51:37.
203. Catalano-Pons C, Comte A, Wipff J, et al. Clinical outcome in
children with chronic recurrent multifocal osteomyelitis.
Rheumatology (Oxford) 2008;47(9):1397.
204. Gallagher KT, Roberts RL, MacFarlane JA, et al. Treatment of
chronic recurrent multifocal osteomyelitis with interferon
gamma. J Pediatr 1997;131:470.
205. Bjorksten B, Boquist L. Histopathological aspects of chronic
recurrent multifocal osteomyelitis. J Bone Joint Surg Br
1980;62:376.
206. Gillespie WJ, Mayo KM. The management of acute
haematogenous osteomyelitis in the antibiotic era: a study of
the outcome. J Bone Joint Surg Br 1981;63:126.
207. Mader JT, Shirtliff ME, Bergquist SC, et al. Antimicrobial
treatment of chronic osteomyelitis. Clin Orthop
1999;360:47–65.
208. Henry SL, Hood GA, Seligson D. Long term implantation of
gentamicin polymethyl-methacrylate antibiotic beads. Clin
Orthop 1993;295:47.
209. Perry CR, Pearson RL. Local antibiotic delivery in the
treatment of bone and joint infections. Clin Orthop
1991;263:215.
210. Fitzgerald RH, Ruttle PE, Arnold PG, et al. Local muscle flaps
in the treatment of chronic osteomyelitis. J Bone Joint Surg
Am 1985;67:175.
211. Patzakis MJ, Abdollahi K, Sherman R, et al. Treatment of
chronic osteomyelitis with muscle flaps. Orthop Clin North
Am 1993;24:505.
212. Anthony JP, Mathes SJ, Alpert BS. The muscle flap in the
treatment of lower extremity osteomyelitis: results in patients
over 5 years of treatment. Plast Reconstr Surg 1991;88:311.
477.e5