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Journal of the American Academy of Orthopaedic Surgeons
166
The annual rate of acute hematog-
enous osteomyelitis in children
under the age of 13 in the United
States is estimated to be approxi-
mately 1:5,000.
1
Population studies
show a worldwide incidence rang-
ing from 1:1,000 to 1:20,000,
2
making
this an uncommon, but not a rare,
problem. Half of all cases of acute
hematogenous osteomyelitis occur
in children under the age of 5.
3
Neo-
natal osteomyelitis is estimated to
occur in 1 to 3 infants per 1,000
intensive-care-nursery admissions.
3
Before the advent of antibiotics,
bacterial osteomyelitis in children
carried mortality rates of 20% to
50%.
2,4
Advances in antibiotic
treatment, diagnostic modalities,
and surgical management have

made death uncommon, but mor-
bidity due to delays in diagnosis
and inadequate treatment continue
to result in permanent sequelae
and poor outcomes in as many as
6% of affected children.
4,5
Failure
of cultures to demonstrate patho-
genic bacteria in many patients,
poor understanding of the patho-
physiology of bone infections, and
emerging antibiotic resistance have
led to the development of many
different empirical treatments.
However, recent advances in the
evaluation and management of
acute hematogenous osteomyelitis
and a thorough understanding of
this disease entity will help to
ensure accurate diagnosis and
prompt treatment.
Basic Science
The etiology and pathophysiology
of bone infections are still incomplete-
ly defined. Introduction of bacteria
into bone can occur by direct inocu-
lation, hematogenous spread from
bacteremia, or local invasion from a
contiguous focus of infection. A his-

tory of trauma is common. Most
long-bone infections occur in the
metaphyseal portions of tubular
bones of the lower extremities (Fig. 1).
The majority of infections involve
only a single bone; involvement at
two or more sites is very uncommon
except in neonatal infections.
Infection spreads via Volkmann’s
canals or the haversian bone system
through the metaphyseal bone to
the subperiosteal space. Elevation
of the periosteum can result in ab-
scess formation. In severe cases,
infarction of cortical bone may lead
to the formation of a sequestrum
and chronic osteomyelitis.
Septic arthritis can occur in joints
in which the metaphysis is intra-
Dr. Song is Assistant Director of Orthopedic
Surgery, Children’s Hospital and Regional
Medical Center of Seattle, Seattle, Wash. Dr.
Sloboda is Resident in Orthopaedic Surgery,
Madigan Army Medical Center, Tacoma, Wash.
Reprint requests: Dr. Song, Department of
Orthopedic Surgery, Children’s Hospital and
Regional Medical Center of Seattle, 4800 Sand
Point Way NE, Seattle WA 98105.
Copyright 2001 by the American Academy of
Orthopaedic Surgeons.

Abstract
Acute hematogenous osteomyelitis in children is a relatively uncommon but
potentially serious disease. Improvements in radiologic imaging, most notably
magnetic resonance imaging, and a heightened awareness of this condition have
led to earlier detection and resultant marked decreases in morbidity and mortal-
ity. Staphylococcus aureus, which has the ability to bind to cartilage, pro-
duce a protective glycocalyx, and stimulate the release of endotoxins, accounts
for 90% of infections in all age groups. Infections with Haemophilus influen-
zae have become rare in immunized children. A careful history and a thorough
physical examination remain important. Positive cultures are obtained in only
50% to 80% of cases; the yield is improved by the use of blood cultures and
evolving molecular techniques. Improvements in antibiotic treatment have
lessened the role of surgery in managing these infections. Sequential intra-
venous and high-dose oral antibiotic therapy is now an accepted modality.
Evaluation of response to treatment by monitoring C-reactive protein levels has
decreased the average duration of therapy to 3 to 4 weeks with few relapses.
The emergence of antibiotic resistance, particularly resistance to methicillin
and vancomycin by S aureus organisms, is of increasing concern. Long-term
sequelae and morbidity are primarily due to delays in diagnosis and inadequate
treatment.
J Am Acad Orthop Surg 2001;9:166-175
Acute Hematogenous Osteomyelitis in Children
Kit M. Song, MD, and John F. Sloboda, MD
Kit M. Song, MD, and John F. Sloboda, MD
Vol 9, No 3, May/June 2001
167
articular (e.g., hip, shoulder, and
ankle). It has been estimated that
10% to 16% of cases of septic arthri-
tis are secondary to bacterial osteo-

myelitis. The avascular physis gen-
erally limits extension of infection
into the epiphysis except in neo-
nates and infants. Blood vessels
cross the physis until approximately
15 to 18 months of age, with the
potential for concomitant septic ar-
thritis. This may be present in as
many as 75% of cases of neonatal
osteomyelitis.
3
Fewer than 20% of infections
occur in nontubular bones. The cal-
caneus and pelvis are the most com-
mon sites. Infections in the flat
bones (e.g., the skull, scapula, ribs,
and sternum) and the spine are rare.
2
Staphylococcus aureus is by far
the most common pathogen causing
acute hematogenous osteomyelitis
in all age categories. It has been im-
plicated in as many as 89% of all in-
fections. Streptococcus pneumoniae,
group A Streptococcus, and coagulase-
negative staphylococci are more age-
and disease-specific. Group B strepto-
cocci have been found with greater
frequency in neonates, but account
for only 3% of infections in this age

group.
3
Infections with these patho-
gens generally result in a single focus
of infection, unlike neonatal infec-
tions with group A streptococci and
S aureus. The introduction of a vac-
cine against Haemophilus influenzae
type b has led to a marked decline in
the incidence of infections by this
organism from 2% to 5% of all bone
infections to nearly 0% in immu-
nized children.
1-3,5-7
Avian models of bone infection
most closely mimic what is observed
in humans and have provided infor-
mation about the pathophysiology
of bone infections. Gaps in the en-
dothelium of growing metaphyseal
vessels allow the passage of bacteria
that then adhere to type I collagen in
the hypertrophic zone of the growth
plate. Staphylococcus aureus surface
antigens appear to play a key role in
this local adherence, while endotox-
ins suppress local immune response.
An extensive glycocalyx surround-
ing each bacterium enhances adhe-
sion of other bacteria and may be

protective against antibiotic treat-
ment. Bacterial proliferation then
occurs, occluding vascular tunnels
within 24 hours. Abscesses appear
after 48 hours, with local tissue
necrosis and extension beyond the
calcifying area of the growth plate.
Four to eight days after infection,
localized sequestra of dead cartilage
are formed, and infection extends
beyond the metaphysis. Further
bone destruction may be mediated
by prostaglandin production as a
result of S aureus infection.
8,9
Diagnosis
Bacterial osteomyelitis in children
must be differentiated from the
wide range of conditions that may
present with clinical symptoms and
signs mimicking infection (Table 1).
Figure 1 Sites of acute osteomyelitis in 657
children with single-site involvement.
(Adapted with permission from Gutierrez
KM: Osteomyelitis, in Long SS, Pickering
LK, Prober CG [eds]: Principles and Practice
of Pediatric Infectious Diseases. New York:
Churchill Livingstone, 1997, p 529.)
Ulna 3%
Pelvis 9%

Radius
4%
Humerus 12%
Tibia 22%
Fibula 5%
Femur
27%
Hands and
feet 13%
Table 1
Differential Diagnosis of a
Painful, Swollen Extremity
in a Child
Systemic conditions
Acute rheumatic fever
Chronic recurrent multifocal
osteomyelitis
Fungal arthritis
Gaucher’s disease
Henoch-Schönlein purpura
Histiocytosis
Leukemia
Primary bone malignant tumors
Reactive arthritis
Reiter’s syndrome
Round cell tumors
Sarcoidosis
Septic arthritis
Sickle cell disease
Systemic juvenile rheumatoid

arthritis
Tuberculosis
Nonsystemic conditions
Cellulitis
Fracture/nonaccidental trauma
Hemangioma/lymphangioma
Histiocytosis
Legg-Perthes disease
Osteochondrosis
Overuse syndromes
Reactive arthritis
Reflex neurovascular dystrophy
Slipped capital femoral epiphysis
Stress fracture/toddler’s fracture
Subacute osteomyelitis
Transient synovitis
Acute Hematogenous Osteomyelitis in Children
Journal of the American Academy of Orthopaedic Surgeons
168
The history and physical examina-
tion findings associated with acute
hematogenous osteomyelitis are sen-
sitive but rarely specific. The most
frequent clinical findings are fever,
pain at the site of infection, and lim-
ited use of the affected extremity.
Constitutional symptoms, such as
lethargy and anorexia, are less com-
mon. The degree of abnormality
does not correlate with the extent of

infection, and older children will
often have more subtle symptoms.
Most patients will have had symp-
toms for less than 2 weeks.
On physical examination, signs
are often age-dependent. Neonates
have a thin periosteum that is easi-
ly penetrated by infection and as a
result frequently have swelling at
the affected site and irritability on
movement of the limb. Infants and
young children will have point ten-
derness with limited ability to bear
weight or use the extremity. Older
children, with their thicker metaph-
yseal cortex and densely adherent
periosteum, will generally have
point tenderness and a mild limp.
Cellulitis is occasionally present
and may be a manifestation of an
underlying abscess.
1-4,6,10
Serologic Studies
Serologic studies that should be
ordered when evaluating a child
with possible acute hematogenous
osteomyelitis include a complete
blood cell (CBC) count with differ-
ential and peripheral smear, eryth-
rocyte sedimentation rate (ESR), C-

reactive protein (CRP) determina-
tion, and blood cultures. As most
blood counts are automated, in-
spection of the peripheral smear
can be helpful in eliminating the
possibility of leukemia. The white
blood cell (WBC) count will be ele-
vated in 31% to 40% of patients with
acute hematogenous osteomyeli-
tis
6,11,12
; the ESR, in up to 91%.
6,11-13
Several authors have reported
on the usefulness of the CRP level
in making the diagnosis and fol-
lowing response to treatment of
acute hematogenous osteomye-
litis.
12-14
On presentation, it is ele-
vated in as many as 97% of pa-
tients. The degree of rise of the
CRP has not been correlated with
severity of infection. The CRP rises
more rapidly than the ESR after
onset of infection, with synthesis
beginning within 4 to 6 hours after
injury and peaking after 24 to 72
hours (Fig. 2). Failure of the CRP

level to fall rapidly after initiation
of treatment has been predictive of
long-term sequelae.
15
Unlike the
ESR, the CRP concentration is inde-
pendent of the physical properties
of cells and is a direct quantitative
measurement. Similar to the ESR,
it will rise and fall after surgery,
trauma, or systemic illnesses, as
well as in patients with benign and
malignant tumors, thereby limiting
its usefulness in some situations.
16,17
Both the ESR and CRP are frequently
elevated in neonatal infections,
18
but the response to treatment of
these indices has not yet been doc-
umented.
Radiologic Evaluation
Radiography remains an essential
tool for diagnosing and managing
osteomyelitis in children and should
be performed in every case of sus-
pected infection. The sensitivity and
specificity of radiographs range
from 43% to 75% and from 75% to
83%,

19
respectively (Fig. 3). Soft-
tissue swelling will be evident with-
in 48 hours of the onset of infection.
Periosteal new-bone formation may
be evident by 5 to 7 days. Osteolytic
changes require bone mineral loss of
at least 30% to 50% and may take 10
days to 2 weeks after the onset of
symptoms to develop.
19,20
Technetium-99m bone scintigra-
phy is useful in the setting of nor-
mal radiographs and clinical suspi-
cion of osteomyelitis (Figs. 4, A; 5,
B). It can be positive within 24 to 48
hours of the onset of symptoms.
The reported sensitivity ranges
from 84% to 100% for detection of
osteomyelitis; the specificity, from
70% to 96%.
19
Aspiration of bone
has not been shown to create a
false-positive result if bone scintig-
100
160
140
120
80

60
40
20
0
0
Days Days
Osteomyelitis alone
Osteomyelitis with
adjacent arthritis
CRP, mg/L
ESR, mm/hr
CRP, mg/L
ESR, mm/hr
5 10 15 20 25 30
100
160
140
120
80
60
40
20
0
0 5 10 15 20 25 30
CRP
ESR
CRP
ESR
Figure 2 Rise and fall of erythrocyte sedimentation rate (ESR) and C-reactive protein
(CRP) level in 50 patients with osteomyelitis with and without associated septic arthritis.

Shaded areas indicate the normal range of values. Bars indicate 1 SD. (Reproduced with
permission from Unkila-Kallio L, Kallio MJT, Peltola H: The usefulness of C-reactive pro-
tein levels in the identification of concurrent septic arthritis in children who have acute
hematogenous osteomyelitis: A comparison with the usefulness of the erythrocyte sedi-
mentation rate and the white blood-cell count. J Bone Joint Surg Am 1994;76:848-853.)
Kit M. Song, MD, and John F. Sloboda, MD
Vol 9, No 3, May/June 2001
169
raphy is carried out within 24 hours
of aspiration. The use of pinhole-
collimated views and single-photon-
emission computed tomography
(SPECT) (Fig. 5, C) can increase both
sensitivity and specificity.
21
In the
early stages of an infection, scintig-
raphy may show decreased uptake
because of the relative ischemia
caused by the increased pressure
from the presence of purulent mate-
rial (Fig. 3). Such “cold” scans have
been reported to have a positive pre-
dictive value of 100%, compared
with a positive predictive value of
83% for “hot” scans.
21,22
Scintigraphy
is of more limited use in neonatal in-
fections, with reported sensitivity

ranging from 30% to 86%; radiogra-
phy may be more sensitive in this
setting.
2,3,10
Gallium scanning, although more
sensitive for infection than Tc-99m
scanning, delivers a higher amount
of radiation, may take up to 48
hours to perform, and is not specific
for infection. Scanning with indium-
111–tagged WBCs can be helpful
in those rare situations in which
osteomyelitis is suspected but the
Tc-99m scan appears normal.
2,19
It
requires preparation time and can
take as long as 24 hours to perform.
Monoclonal antibody scans have
been investigated, but are as yet of
unproven benefit.
2
Magnetic resonance imaging has
a reported sensitivity of 88% to
100% and a specificity of 75% to
100% in the detection of osteomye-
litis. The positive-predictive values
for MR imaging and Tc-99m scin-
tigraphy are comparable (85% and
83%).

20
However, MR imaging can
provide biplanar images of the in-
fected site and is superior to scintig-
raphy and CT for depicting the
marrow cavities of long bones and
adjacent soft tissues. It is most use-
ful for detecting spinal and pelvic
infections (Fig. 5, D) and for plan-
ning surgical approaches for de-
bridement when a subperiosteal or
soft-tissue abscess may be pres-
ent.
19-21,23,24
Characteristic T1- and
T2-weighted images can be used to
differentiate acute, subacute, and
chronic osteomyelitis.
24
T1-weighted
and short-tau inversion recovery
(STIR) images are most useful for
the detection of acute osteomyelitis
(Fig. 4). The use of gadolinium en-
hancement can aid in identifying
sinus tracts and distinguishing cel-
lulitis from abscess.
19
Like scintig-
raphy, MR imaging is limited by a

lack of specificity; the signal pat-
terns seen with fractures, bone
infarction, tumors, postsurgical
changes, bone contusions, and sym-
pathetic edema are similar.
24
Computed tomography has been
most useful in the detection of gas
in soft-tissue infections and in the
identification of sequestra in cases
of chronic osteomyelitis.
19,21
It is
also useful in diagnosing and accu-
rately defining the location of pelvic
and spinal infections after localiza-
tion with scintigraphy (Fig. 5). For
deep infections, needle localization
prior to biopsy or debridement can
be helpful.
Ultrasonography is attractive for
evaluating the possibility of bone
and joint infections in children
because of its low cost, relative avail-
ability, and noninvasive nature, as
well as because there is no ionizing
radiation involved and no need for
Figure 3 A, Radiograph of a child with a swollen forearm, elevated temperature, and elevated CRP value. B, Technetium bone scan per-
formed on day of presentation was interpreted as normal, although it shows a “cold” left radius (i.e., area of decreased radionuclide uptake).
C, Follow-up radiograph at 6 weeks shows periosteal elevation of the entire radius. D, Follow-up radiograph at 3 months demonstrates seg-

mental bone loss in the radius.
A B C D
Acute Hematogenous Osteomyelitis in Children
Journal of the American Academy of Orthopaedic Surgeons
170
sedation. It has been used to detect
intra-articular, soft-tissue, and sub-
periosteal fluid collections prior to
their appearance on plain radio-
graphs. However, the lack of speci-
ficity, dependence on operator skill,
and inability to image marrow or
show cortical detail of bone have
limited the usefulness of ultrasound
compared with MR imaging or CT.
An algorithm for radiologic
evaluation of suspected bone infec-
tions is shown in Figure 6. Radiog-
raphy should be the initial study.
If positive, MR imaging, CT, or
ultrasonography can be used to de-
fine the infected area and to plan
surgical approaches if needed. If
the results of any of those studies
are negative, scintigraphy can be
very helpful in isolating the infected
area, after which one of the other
modalities can be used to provide
additional information for treat-
ment planning.

Bacterial Cultures
Obtaining cultures of organisms
directly from sites of bone infection
in order to focus antibiotic treat-
ment is critical to effective manage-
ment.
2,3,25
However, direct culture
of the affected bone results in isola-
tion of the bacterial agent in only
48% to 85% of cases.
5,6,26,27
Given
the potentially low yield from cul-
tures and the reluctance to perform
invasive procedures on distressed
children, it may be tempting not to
perform bone aspiration. Neverthe-
less, concerns about emerging anti-
biotic resistance by bacteria make
the identification of pathogens and
the use of organism-specific treat-
ment desirable.
Aspiration is easily performed
through thin metaphyseal bone
with an 18-gauge spinal needle, and
the central trocar can be used to dis-
engage any bone plugs created by
passage through the cortex. Local
infiltration of lidocaine into the tis-

sues combined with intravenous
sedation is generally effective. The
aspiration of bone through an over-
lying area of cellulitis has not been
shown to cause osteomyelitis. Direct
culture of cellulitic areas yields a
positive culture in fewer than 10%
of cases,
28
with Staphylococcus and
Streptococcus species being most
commonly isolated.
Blood cultures are positive in 30%
to 60% of cases of acute osteomye-
litis in children.
1,4,6,27
The use of
multiple blood cultures has not been
shown to increase the likelihood of
having a positive culture, especially
if the samples were drawn after the
initiation of antibiotic treatment.
The combination of blood and direct
cultures provides the highest yield,
but in many cases treatment of pre-
sumed infections will be empirical,
based on clinical and radiographic
criteria.
Most bacterial cultures will be
positive within 48 hours of speci-

men collection. However, fastidi-
ous organisms may take as long as 7
days to become positive. A survey
of hospitals in one area showed that
cultures are held an average of 5
days before being discarded.
A B
C D
Figure 4 A, Technetium bone scan shows acute osteomyelitis in the distal left femur.
B, T1-weighted MR image also demonstrates acute osteomyelitis, which was confirmed by
biopsy and treated with intravenous antibiotics. C, A STIR MR image further demon-
strates acute osteomyelitis. D, Gradient-echo MR image illustrates growth arrest due to
the infection.
Kit M. Song, MD, and John F. Sloboda, MD
Vol 9, No 3, May/June 2001
171
The relatively low yield of stan-
dard bacterial cultures has stimulated
interest in using molecular tecniques
for detection and speciation of bacte-
rial and viral infections. Molecular
methods have been shown to be
more sensitive than standard culture
techniques for detecting pathogens
and can do so even in the absence of
viable organisms. These techniques
fall into two broad categories: non-
amplified and amplified. With non-
amplified techniques, direct binding
of a target molecule is done with a

labeled oligonucleotide probe or
monoclonal antibody, followed by
detection of the probe agent with
radiolabeling, enzyme-linked immu-
nosorbent assay, or chemolumines-
cence. These methods are specific
and applicable when looking for a
particular organism.
With amplified techniques, geo-
metric amplification of the target
molecule is achieved by using
enzyme-driven reactions. The most
common of these techniques is the
polymerase chain reaction (PCR).
The basis of these methods is to tar-
get a portion of bacterial DNA or
RNA that is not present in human
cells. A probe or primer specific to
that region of DNA or RNA is in-
troduced, which on binding pro-
motes binding of a polymerase that
replicates the target region in a
series of temperature-dependent
cycles. The amplified products are
then identified by gel electrophoresis.
Much recent work has focused on the
highly conserved area of DNA that
codes for the 16s ribosomal RNA
subunit. There is enough gene se-
quence variation within this area to

allow differentiation among bacterial
species and from human DNA.
29,30
Polymerase chain reaction has
produced some promising results
in diagnosing periprosthetic infec-
tions and septic arthritis, but a high
false-positive rate has been ob-
served.
31
The PCR method has been
found to be very sensitive for the
detection of infection when a primer
for a specific organism is used. In
cases of polymicrobial infection or
infection due to an unknown bacter-
ial strain, the use of universal prim-
ers that amplify all bacterial species
present is being developed. Identi-
fication of the amplified genetic ma-
terial remains difficult.
Treatment
The management of acute hematog-
enous osteomyelitis is largely non-
operative. The role of surgery is to
improve the local environment by
removing infected devitalized bone
and soft tissue, decompressing a
Acetabular
roof

Proximal
femur
A B
C D E
Figure 5 A, AP radiograph of a 15-year-old girl with right hip pain. B, Technetium bone scan of hips with pinhole collimation.
C, SPECT images of the right hip show lesion in the supra-acetabular area. D, MR image depicts pelvic osteomyelitis. E, Brodie’s abscess
of the acetabulum was localized on this CT scan prior to biopsy.
large abscess cavity, and facilitating
antibiotic delivery. If antibiotic
treatment is initiated before signifi-
cant bone and soft-tissue necrosis
has occurred, it is more likely to be
successful without the need for sur-
gical treatment.
Antibiotic Therapy
Most recent studies of antibiotic
treatment of acute hematogenous
osteomyelitis have emphasized a
sequential parenteral-oral antibiotic
regimen.
2,3,5,12,13
Due to the low
yield of culture techniques, empirical
treatment based on known epidemi-
ologic trends in different age groups
and at-risk populations will often be
necessary (Table 2).
Empirical antibiotic coverage
should always include coverage for S
aureus, as this is the most common

pathogen in all age groups. For neo-
natal osteomyelitis, treatment tar-
geting group B streptococci and
Gram-negative rods should be
added. Children less than 4 years of
age need antibiotic coverage for H in-
fluenzae type b if the immunization
program has not been completed or
the history is uncertain. For fully
immunized children, the most likely
pathogens are S aureus, Streptococcus
pyogenes, and S pneumoniae. For im-
munocompromised children with
sickle cell disease, broad-spectrum
coverage to include Salmonella spe-
cies should be included.
Children with human immuno-
deficiency virus (HIV) infection
have a propensity for infection by S
pneumoniae. However, to date, there
is no evidence to suggest that pre-
senting signs and symptoms or re-
covery from infection are affected by
coinfection by HIV. Broad-spectrum
coverage is suggested for HIV-
positive children due to the wide
range of organisms reported.
2
Antibiotic selection should sub-
sequently be altered according to

the results of culture and sensitivity
testing. There are concerns about
emerging antibiotic resistance.
Methicillin- and cephalosporin-
resistant S aureus organisms have
been reported in as many as 20% of
community-acquired bone and joint
infections.
32,33
Recently, emergence
of vancomycin-resistant S aureus in
Japan and parts of the United States
has raised the specter of emerging
bacterial strains for which there are
no known antibiotic treatments.
34
The duration and route of ad-
ministration of antibiotic treatment
have previously been empirical, with
the length of intravenous therapy
ranging from 4 to 8 weeks. The du-
Acute Hematogenous Osteomyelitis in Children
Journal of the American Academy of Orthopaedic Surgeons
172
Negative
Bone scan
Positive
Negative Positive
Negative Positive
Positive Negative

Radiographic
evaluation
Antibiotic
therapy
Antibiotic
therapy
Antibiotic
therapy
Biopsy, surgical
debridement
Biopsy, surgical
debridement
Consider
aspiration
Suspicion of osteomyelitis
(clinical/serologic evidence)
No clinical
improvement
in 48 hr
MR imaging,
CT, or ultrasound;
reassess diagnosis
MR imaging, CT,
or ultrasound for
abscess/sequestrum
Figure 6 Algorithm for radiologic evaluation and treatment when acute hematogenous osteomyelitis is suspected.
Kit M. Song, MD, and John F. Sloboda, MD
Vol 9, No 3, May/June 2001
173
ration of antibiotic treatment has

not been related to the presence or
absence of positive blood or direct
cultures; antibiotic sensitivity or
resistance of the bacteria; degree of
elevation of the WBC count, CRP, or
ESR; presence or absence of puru-
lent material; or symptoms at pre-
sentation. Authors of earlier studies
suggested that a total duration of
treatment of less than 3 weeks is
associated with a higher rate of re-
lapse.
35
Although previously con-
troversial, the need to complete at
least a 3-week oral antibiotic regi-
men has become accepted.
5,6,12-14,25
Success of treatment correlates
most closely with an adequate
serum level of the antibiotic, rather
than the route of administration.
25
Doses that are two to three times
the package recommendation are
generally necessary to ensure a
peak serum titer greater than or
equal to 1:8.
2,25
Inability to reliably

take oral medications, poor oral
absorption, poor response to intra-
venous therapy, inadequate moni-
toring of antibiotic levels, and inad-
equate improvement of the local
environment by surgery have been
implicated in treatment failures
using this approach.
2,6,25
Early treat-
ment protocols suggested transition
to oral antibiotics once clinical im-
provement was observed, with treat-
ment continuing until normalization
of the ESR.
25
Peltola et al
12
documented suc-
cessful treatment of acute hematog-
enous osteomyelitis in children
from 3 months to 14 years old with
a very short course of intravenous
antibiotics followed by oral therapy.
The authors utilized changes in the
CRP level to guide treatment. Ini-
tiation of oral treatment resulted in
a rapid fall in the CRP and an im-
provement in the clinical course.
Treatment was discontinued when

the CRP level and ESR normalized.
The average length of intravenous
treatment was 5 days, and the total
duration of treatment averaged 23
days. A more controversial issue in
this study was the absence of serum
monitoring of antibiotic levels. The
authors used very high doses of
cefadroxil (150 mg per kilogram of
body weight per day in four doses)
or clindamycin, which is readily
absorbed. No failures of treatment
were seen in this study with a mini-
mum follow-up period of 1 year.
In our institution over the past 5
years, we have utilized a protocol
whereby empirical treatment is started
with high-dose intravenous cefazolin
after obtaining local and/or blood
cultures for all bone and joint infec-
tions. A regimen of 100 to 150 mg/
kg/day is started, with doses admin-
istered every 8 hours. Serial values
for CRP are checked. Once clinical
improvement is seen and the CRP
level approaches normal, oral cepha-
lexin therapy is started at a dosage of
150 mg/kg/day, with doses every 6
hours. Peak serum levels are checked
after the fourth dose. If the response

is adequate, the patient is discharged,
and antibiotic treatment is continued
until the ESR normalizes. A weekly
outpatient CBC count with differential
is obtained to monitor for the develop-
ment of antibiotic-induced neutrope-
nia. In our series of 40 consecutive
patients treated in this manner, the
average length of antibiotic treatment
was 21 days. There were no relapses.
There are no reports of neonates
with osteomyelitis being treated by
intravenous-oral regimens. Serious
permanent sequelae occur in 6% to
50% of affected children due to the
multiple sites of involvement (in
Table 2
Common Pathogens and Recommended Antibiotic Therapy
Age Likely Organisms Intravenous Antibiotic Treatment Oral Antibiotic Therapy (in 4 doses)
Neonate Staphylococcus aureus Nafcillin, 150-200 mg/kg/day and Dicloxacillin, 75-100 mg/kg/day or
Beta-hemolytic Streptococcus Gentamicin, 5.0-7.5 mg/kg/day or Cephalexin, 100-150 mg/kg/day or
(group A, group B) Cefotaxime, 150 mg/kg/day Clindamycin, 30 mg/kg/day
Gram-negative rods
Infant/ S aureus Non-Hib-immunized: Dicloxacillin, 75-100 mg/kg/day or
toddler Haemophilus influenzae Nafcillin, 150 mg/kg/day and Cephalexin, 100-150 mg/kg/day or
<3 yr old type b (Hib) Cefotaxime, 100-150 mg/kg/day Clindamycin, 30 mg/kg/day
Pneumococci Single-agent treatment:
Streptococci Cefuroxime, 150-200 mg/kg/day
Child S aureus Hib-immunized: Dicloxacillin, 75-100 mg/kg/day or
≥3 yr old Cefazolin, 100-150 mg/kg/day or Cephalexin, 100-150 mg/kg/day or

Nafcillin, 150-200 mg/kg/day or Clindamycin, 30 mg/kg/day
Clindamycin, 30-40 mg/kg/day
Acute Hematogenous Osteomyelitis in Children
Journal of the American Academy of Orthopaedic Surgeons
174
20% to 50% of cases) and the high
rate of concomitant septic arthritis.
Because neonates are more prone to
generalized sepsis, have less consis-
tent oral antibiotic absorption, and
have a less predictable radiographic
and serologic response to treatment,
it has generally been recommended
that the entire course of treatment
be intravenous.
3,4,10
Uncomplicated pelvic and verte-
bral osteomyelitis or diskitis
2-4,36
and calcaneal osteomyelitis
37
in chil-
dren have been successfully treated
with antibiotics without surgical in-
tervention. The necessary duration
of antibiotic treatment regimens is
frequently longer than for osteomy-
elitis in an extremity, although the
surgical indications are the same.
Surgical Treatment

The indications for surgical inter-
vention have been controversial.
38,39
The primary aim of surgery is to im-
prove the local environment for anti-
biotic delivery. A “hole-in-bone” ap-
pearance has not been shown to
mandate surgical intervention un-
less there is aspiration of purulent
material. Rates of surgical interven-
tion have decreased with the advent
of better antibiotic treatment for os-
teomyelitis, the heightened aware-
ness that has led to earlier detection
of infections, and a shift toward more
subacute forms of osteomyelitis,
which do not routinely require sur-
gical debridement.
40
The cited rates
of surgical intervention in earlier
studies ranged from 22%
39
to as
high as 83%,
25
compared with 8% to
45% in more recent series.
6,12,38
The

presence of subperiosteal, associated
soft-tissue, or bone abscess on aspi-
ration; an obvious osseous seques-
trum; failure to respond to antibiotic
therapy; and concomitant septic
arthritis in a deep joint are generally
recognized indications for surgical
intervention.
2,4,6,12,25,38,39
Complications
Major complications related to os-
teomyelitis are becoming less com-
mon. Recurrent infection, chronic
osteomyelitis, pathologic fracture,
and growth disturbance have been
linked to late recognition and inad-
equate treatment of acute hematog-
enous osteomyelitis.
5
Children who
present with combined osteomye-
litis and septic arthritis have been
observed to have a more prolonged
course of recovery
13
and a greater
potential for growth disturbance
and long-term sequelae.
2,3
Excessive surgical debridement

can also cause pathologic fracture and
growth arrest with subsequent limb-
length discrepancy or angular defor-
mity.
4
Complications associated with
antibiotic treatment have been few.
Diarrhea, nausea, rash, thrombocyto-
sis, transient changes in liver en-
zymes, and antibiotic-induced neu-
tropenia have been observed with
high-dose oral antibiotic therapy.
25
Summary
The management of acute hematog-
enous osteomyelitis has been greatly
improved by enhanced imaging
capabilities and advances in antibi-
otic therapy. Early recognition and
prompt intervention will decrease
the morbidity associated with this
condition. Initial evaluation should
include plain radiography; serologic
studies, including ESR, CRP, CBC
count with differential and smear;
blood cultures; and, when possible,
aspiration of the suspected site.
Empirical intravenous treatment
based on the known epidemiology
of age-specific pathogens should be

started, with antibiotic selection
modified on the basis of the culture
results. Sequential intravenous-oral
therapy is now accepted, with tran-
sition based on the clinical and/or
CRP response to treatment. Moni-
toring of serum antibiotic levels is
controversial, but may be helpful to
ensure adequate treatment.
Surgical treatment is warranted
if there is aspiration of purulent
material from the suspected site, an
obvious area of necrotic bone, or
failure to rapidly respond to antibi-
otic therapy. Generally good out-
comes with few long-term compli-
cations can be expected.
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