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-nurs
Trang 1The 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 1:20,000,2making
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
Kit M Song, MD, and John F Sloboda, MD
Trang 2articular (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
Trang 3The 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-tis6,11,12; 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 with-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
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.)
Trang 4raphy 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.
Trang 5sedation 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
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 illudemon-strates growth arrest due to
the infection.
Trang 6The 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:
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
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.
Trang 7large 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 psenting 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-Negative
Bone scan
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.
Trang 8ration 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 al12 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
Trang 920% 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 diskitis2-4,36
and calcaneal osteomyelitis37in
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%39to as high as 83%,25compared 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 recovery13 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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