Background

Osteomyelitis is inflammation of the bone caused by an infecting organism.

Although bone is normally resistant to bacterial colonization, events such as trauma,
surgery, the presence of foreign bodies, or the placement of prostheses may disrupt
bony integrity and lead to the onset of bone infection. Osteomyelitis can also result
from hematogenous spread after bacteremia. When prosthetic joints are associated
with infection, microorganisms typically grow in biofilm, which protects bacteria from
antimicrobial treatment and the host immune response.
Early and specific treatment is important in osteomyelitis, and identification of
the causative microorganisms is essential for antibiotic therapy. [1] The major cause of
bone infections is Staphylococcus aureus. Infections with an open fracture or
associated with joint prostheses and trauma often must be treated with a combination
of antimicrobial agents and surgery. When biofilm microorganisms are involved, as in
joint prostheses, a combination of rifampin with other antibiotics might be necessary
for treatment.

Anatomy
The bony skeleton is divided into two parts: the axial skeleton and the
appendicular skeleton. The axial skeleton is the central core unit, consisting of the
skull, vertebrae, ribs, and sternum; the appendicular skeleton comprises the bones of
the extremities. The human skeleton consists of 213 bones, of which 126 are part of
the appendicular skeleton, 74 are part of the axial skeleton, and six are part of the
auditory ossicles.
Hematogenous osteomyelitis most commonly involves the vertebrae, but
infection may also occur in the metaphysis of the long bones, pelvis, and clavicle.
Vertebral osteomyelitis involves two adjacent vertebrae with the corresponding
intervertebral disk. (See the image below.) The lumbar spine is most commonly
affected, followed by the thoracic and cervical regions.
 Osteomyelitis of T10 secondary to streptococcal disease. Photography by David
Effron MD, FACEP.

Posttraumatic osteomyelitis begins outside the bony cortex and works its way
in toward the medullary canal, typically found in the tibia. Contiguous-focus
osteomyelitis often occurs in the bones of the feet in patients with diabetes mellitus
and vascular compromise.

Pathophysiology
Bone is normally resistant to infection. However, when microorganisms are
introduced into bone hematogenously from surrounding structures or from direct
inoculation related to surgery or trauma, osteomyelitis can occur. Bone infection may
result from the treatment of trauma, which allows pathogens to enter bone and
proliferate in the traumatized tissue. When bone infection persists for months, the
resulting infection is referred to as chronic osteomyelitis and may be polymicrobial.
Although all bones are subject to infection, the lower extremity is most commonly
involved. [1, 2]
Some important factors in the pathogenesis of osteomyelitis include the
virulence of the infecting organism, underlying disease, immune status of the host,
and the type, location, and vascularity of the bone. Bacteria may possess various
factors that may contribute to the development of osteomyelitis. For example, factors
promoted by S aureus may promote bacterial adherence, resistance to host defense
mechanism, and proteolytic activity. [3]

Hematogenous osteomyelitis
In adults, the vertebrae are the most common site of hematogenous
osteomyelitis, but infection may also occur in the long bones, pelvis, and clavicle. [4]
Primary hematogenous osteomyelitis is more common in infants and children,
usually occurring in the long bone metaphysis. However, it may spread to the
medullary canal or into the joint. When infection extends into soft tissue, sinus tracts
may eventually form. Secondary hematogenous osteomyelitis is more common and
occurs when a childhood infection is reactivated. In adults, the location is also usually
metaphyseal. [4]
S aureus is the most common pathogenic organism recovered from bone,
followed by Pseudomonas and Enterobacteriaceae. Less common organisms
involved include anaerobe gram-negative bacilli. Intravenous drug users may acquire
pseudomonal infections. Gastrointestinal or genitourinary infections may lead to
osteomyelitis involving gram-negative organisms. Dental extraction has been
associated with viridans streptococcal infections. In adults, infections often recur and
usually present with minimal constitutional symptoms and pain. Acutely, patients may
present with fever, chills, swelling, and erythema over the affected area. [2, 5]

Contiguous-focus and posttraumatic osteomyelitis

The initiating factor in contiguous-focus osteomyelitis often consists of direct
inoculation of bacteria via trauma, surgical reduction and internal fixation of fractures,
prosthetic devices, spread from soft-tissue infection, spread from adjacent septic
arthritis, or nosocomial contamination. Infection usually results approximately one
month after inoculation.
Posttraumatic osteomyelitis more commonly affects adults and typically
occurs in the tibia. The most commonly isolated organism is S aureus. At the same
time, local soft-tissue vascularity may be compromised, leading to interference with
healing. Compared with hematogenous infection, posttraumatic infection begins
outside the bony cortex and works its way in toward the medullary canal. Low-grade
fever, drainage, and pain may be present. Loss of bone stability, necrosis, and soft
tissue damage may lead to a greater risk of recurrence. [4, 5]
Septic arthritis may lead to osteomyelitis. Abnormalities at the joint margins or
centrally, which may arise from overgrowth and hypertrophy of the synovial pannus
and granulation tissue, may eventually extend into the underlying bone, leading to
erosions and osteomyelitis. One study demonstrated that septic arthritis in elderly
persons most commonly involves the knee and that, despite most of the patients
having a history of surgery, 38% developed osteomyelitis. Septic arthritis is more
common in neonates than in older children and is often associated with metaphyseal
osteomyelitis. Although rare, gonococcal osteomyelitis may arise in a bone adjacent
to a chronically infected joint. [6, 7]
Patients with vascular compromise, as in diabetes mellitus, are predisposed
to osteomyelitis owing to an inadequate local tissue response. [4]
Infection is most often caused by minor trauma to the feet with multiple
organisms isolated from bone,
including Streptococcus species, Enterococcus species, coagulase-positive and -
negative staphylococci, gram-negative bacilli, and anaerobic organisms. Foot ulcers
allow bacteria to reach the bone. Patients may not experience any resulting pain,
because of peripheral neuropathy, and may present with a perforating foot ulcer,
cellulitis, or an ingrown toenail.
Physical examination may reveal decreased sensation, poor capillary refill,
and decreased dorsalis pedis and posterior tibial pulses. Treatment is aimed at
suppressing infection and improving vascularity. However, most patients develop
recurrent or new bone infections. Resection or amputation of the affected tissue is
sometimes necessary. Debridement, incision and drainage, and tendon lengthening
are attempted first.

Vertebral osteomyelitis
The incidence of vertebral osteomyelitis generally increases progressively
with age, with most affected patients being older than 50 years. Although devastating
complications may result from a delay in diagnosis, vertebral osteomyelitis is rarely
fatal since the development of antibiotics. The infection usually originates
hematogenously and involves two adjacent vertebrae with the corresponding
intervertebral disk. The lumbar spine is most commonly affected, followed by the
thoracic and cervical regions. [4, 1]
Potential sources of infection include skin, soft tissue, respiratory tract,
genitourinary tract, infected intravenous sites, and dental infections. S aureus is the
most common isolated organism. However, Pseudomonas aeruginosa is more
common in intravenous drug users.
Most patients with vertebral osteomyelitis present with localized pain and
tenderness of the involved vertebrae with a slow progression over 3 weeks to 3
months. Fever may be present in approximately 50% of patients. Fifteen percent of
patients may have motor and sensory deficits. Laboratory studies may reveal
peripheral leukocytosis and an elevated erythrocyte sedimentation rate. Extension of
the infection may lead to abscess formation. [4]

Osteomyelitis in children
Acute hematogenous osteomyelitis usually occurs after an episode of
bacteremia in which the organisms inoculate the bone. The most common organisms
isolated in these cases include S aureus, Streptococcus pneumoniae,
and Haemophilus influenza type b (less common since the use of vaccine for H
influenza type b).
Acute hematogenous S aureus osteomyelitis in children can lead to
pathologic fractures. This can occur in about 5% of cases with a 72-day mean time
from disease onset to fracture. [8]
In children with subacute focal osteomyelitis (see the image below), S
aureus is the most commonly isolated organism.

Rarefaction and periosteal new-bone formation

around the left upper fibula in a 12-year-old
patient. This was caused by subacute
osteomyelitis.
 Gram-negative bacteria such as Pseudomonas species or Escherichia
coli are common causes of infection after puncture wounds of the feet or open injuries
to bone. Anaerobes can also cause bone infection after human or animal bites.
Osteomyelitis in the neonate results from hematogenous spread, especially in
patients with indwelling central venous catheters. The common organisms in
osteomyelitis of the neonate include those that frequently cause neonatal sepsis,
namely group B Streptococcus species, and E coli. Infections in the neonate can
involve multiple osseous sites, and approximately half of the cases also involve
eventual development of septic arthritis in the adjacent joint.
Children with sickle cell disease are at an increased risk for bacterial
infections, and osteomyelitis is the second most common infection in these patients.
The most common organisms involved in osteomyelitis in children with sickle cell
anemia include Salmonella species, S aureus, Serratia species, and Proteus
mirabilis.

Etiology
Posttraumatic osteomyelitis accounts for as many as 47% of cases of
osteomyelitis. Other major causes of osteomyelitis include vascular insufficiency
(mostly occurring in persons with diabetes; 34%) and hematogenous seeding (19%).
Motor vehicle accidents, sports injuries, and the use of orthopedic hardware to
manage trauma also contribute to the apparent increase in prevalence of
posttraumatic osteomyelitis. Osteomyelitis may complicate puncture wounds of the
foot, occurring in 1.8%-6.4% of patients following injury. [9, 10, 11, 12, 13]

Epidemiology
Approximately 20% of adult cases of osteomyelitis are hematogenous, which
is more common in males for unknown reasons. [4]
The incidence of spinal osteomyelitis was estimated to be 1 in 450,000 in
2001. In subsequent years, however, the overall incidence of vertebral osteomyelitis
is believed to have increased as a consequence of intravenous drug use, increasing
age of the population, and higher rates of nosocomial infection due to intravascular
devices and other instrumentation. [14, 15] The overall incidence of osteomyelitis is
higher in developing countries.
Prognosis
Inadequate therapy may lead to relapsing infection and progression to chronic
infection. Because of the avascularity of bone, chronic osteomyelitis is curable only
with radical resection or amputation. These chronic infections may recur as acute
exacerbations, which can be suppressed by debridement followed by parenteral and
oral antimicrobial therapy. Rare complications of bone infection include pathologic
fractures, secondary amyloidosis, and squamous cell carcinoma at the sinus tract
cutaneous orifice.

History
Osteomyelitis is often diagnosed clinically with nonspecific symptoms such as
fever, chills, fatigue, lethargy, or irritability. The classic signs of inflammation, including
local pain, swelling, or redness, may also occur and normally disappear within 5-7
days. [1]
Chronic posttraumatic osteomyelitis requires a detailed history for diagnosis,
including information regarding the initial injury and previous antibiotic and surgical
treatment. Weightbearing and function of the involved extremity are typically disturbed.
Local pain, swelling, erythema, and edema may also be reported. [2]

Physical Examination
On physical examination, scars or local disturbance of wound healing may be
noted along with the cardinal signs of inflammation. [2] Range of motion, deformity, and
local signs of impaired vascularity are also sought in the involved extremity. If
periosteal tissues are involved, point tenderness may be present. [5]
In children, the clinical presentation of osteomyelitis can be challenging for
physicians because it can present with only nonspecific signs and symptoms and
because the clinical findings are extremely variable. Children may present with
decreased movement and pain in the affected limb and adjacent joint, as well as
edema and erythema over the involved area. In addition, children may also present
with fever, malaise, and irritability. Newborns with osteomyelitis may demonstrate
decreased movement of a limb without any other signs or symptoms.
Complications
The most common complication in children with osteomyelitis is recurrence of
bone infection. Although adverse outcomes are common with delays in treatment,
chronic infection may still develop in 5-10% of patients treated appropriately. Common
complications in children younger than 18 months include bone destruction, chronic
osteomyelitis, and impaired bone growth, especially when the growth plate is affected.
Although rare, extreme bone destruction or thinning of the cortex can lead to
pathologic fractures. When centrally placed intravenous catheters are used in cases
that require prolonged antibiotic treatment intravenously, catheter-associated
complications can occur. However, the use of peripherally inserted central venous
catheters has decreased this complication.
In a study of 17,238 Taiwanese patients newly diagnosed with chronic
osteomyelitis from 2000 to 2008 who were identified on the basis of Taiwanese
National Health Insurance (NHI) inpatient claims, Tseng et al found chronic
osteomyelitis to be associated with an increased risk of dementia, particularly among
the younger patients studied. [16]

Laboratory Studies
A complete blood count (CBC) is useful for
evaluating leukocytosis and anemia. Leukocytosis is common in acute osteomyelitis
before therapy. The leukocyte count rarely exceeds 15,000/µL acutely and is usually
normal in chronic osteomyelitis. Erythrocyte sedimentation rate and C-reactive protein
levels are usually increased.[17, 2, 18]
Blood cultures are positive in only 50% of cases of osteomyelitis. [5] They
should be obtained before or at least 48 hours after antibiotic treatment. Although
sinus tract cultures do not predict the presence of gram-negative organisms, they are
helpful for confirming S aureus.
Bone biopsy leads to a definitive diagnosis by isolation of pathogens directly
from the bone lesion. [5] Bone biopsy should be performed through uninfected tissue
and either before the initiation of antibiotics or more than 48 hours after
discontinuance.
Imaging Studies
Radiography
Conventional radiography is the initial imaging study at presentation of acute
osteomyelitis. It is helpful to interpret current and old radiographs together. (See the
image below.)

Osteomyelitis, chronic. Image in a 56-year-old man with diabetes shows chronic

osteomyelitis of the calcaneum. Note air in the soft tissues.

Radiographic findings include periosteal thickening or elevation, as well as

cortical thickening, sclerosis, and irregularity. Other changes include loss of trabecular
architecture, osteolysis, and new bone formation. These changes may not be evident
until 5-7 days in children and 10-14 days in adults. Plain films show lytic changes after
at least 50%-75% of the bone matrix is destroyed. Therefore, negative radiographic
studies do not exclude the diagnosis of acute osteomyelitis.
Healing fractures, cancers, and benign tumors may appear similarly on plain
film. Subtle changes may indicate contiguous-focus or chronic osteomyelitis. [4, 2, 5]
Computed tomography
Computed tomography (CT) is useful for guiding needle biopsies in closed
infections and for preoperative planning to detect osseous abnormalities, foreign
bodies, or necrotic bone and soft tissue. It may assist in the assessment of bony
integrity, cortical disruption, and soft-tissue involvement. It may also reveal edema.
Intraosseous fistula and cortical defects that lead to soft tissue sinus tracts are also
demonstrated on CT.
Although CT may play a role in diagnosis of osteomyelitis, the scatter
phenomenon may result in significant loss of image resolution when metal is near the
area of inflammation. [4, 2, 5]

Magnetic resonance imaging

Magnetic resonance imaging (MRI) is a very useful modality in detecting
osteomyelitis and gauging the success of therapy because of high sensitivity and
excellent spatial resolution. The extent and location of osteomyelitis is demonstrated
along with pathologic changes of bone marrow and soft tissue. [4](See the image
below.)

Osteomyelitis, chronic. T1- and T2-weighted sagittal MRIs show bone marrow
edema in L1 and obliteration of the disk space between L1 and L2.

MRI shows a localized marrow abnormality in osteomyelitis. T1-weighted

images typically show decreased signal intensity, whereas T2-weighted images
produce increased signal intensity. [4] Increased intensity on T2-weighted images may
indicate sinus tracts, which extend from marrow and bone to skin through soft tissue.
A decreased intensity on T1-weighted images with no change on T2-weighted images
may indicate surgical or posttraumatic scarring of bone marrow.
Ultrasonography
The presence of fluid collection adjacent to the bone without intervening soft
tissue usually suggests osteomyelitis. Other findings on ultrasonography include
elevation and thickening of the periosteum. [19, 20, 21]

Nuclear medicine imaging

Three-phase bone scanning is helpful in evaluating acute osteomyelitic and
doubtful diskitis. However, the specificity of this procedure is decreased in secondary
osteomyelitis. The bone scan may reveal increased metabolic activity in osteomyelitis,
but this finding is indistinguishable from posttraumatic injury or following surgery or
cancer. [4, 1] (See the image below.)

Osteomyelitis, chronic. Three-phase technetium-99m diphosphonate bone scans

(static component) show increased activity in the heel and in the first and second
toes and in the fifth tarsometatarsal joint.

One approach makes use of white blood cells (WBCs) labeled with
technetium-99m (99mTc) hexamethylpropylene amine oxime (99mTc-HMPAO) or
indium-111 (111In) oxime. This method, when used in the combination of 111In-oxime

WBC scan with 99mTc-sulfur colloid bone marrow scan, is helpful for evaluating
infections of hip prostheses. Isotope accumulates in areas of increased blood flow and
new bone formation in the 99mTc polyphosphate scan. A negative test result may
indicate an impaired blood supply to the affected area. When red marrow is present
(ie, axial skeleton and spine), WBC scanning is less sensitive for imaging. [4, 1]
 Gallium citrate attaches to transferrin, which then leaks into inflamed areas
from the bloodstream. Increased uptake may occur in infection, cancer, and sterile
inflammatory conditions. Performing a technetium-99m scan along with the gallium-67
(67Ga) citrate scan may help distinguish bone and soft-tissue inflammation and show
bone detail. [4, 1]
In the assessment of inflammation of spinal lesions, 2-[18F]fluoro-2-deoxy-D-
glucose (18F-FDG) positron emission tomography (PET) may provide high-resolution
tomographic images and may represent an alternative to 67Ga citrate scanning.
However, comparison with CT or MRI is essential. [1]

Diagnostic Procedures
Open bone biopsy with histopathologic examination and culture is the criterion
standard for the microbiologic diagnosis of osteomyelitis. This procedure may not be
necessary if blood cultures are positive with consistent radiologic findings. Needle
biopsy may also be used to obtain bone for analysis.
When clinical suspicion is high but blood cultures and needle biopsy have
yielded negative results, a repeat needle biopsy or an open biopsy should be
performed. A bone sample can be collected at the time of debridement for
histopathologic diagnosis in patients with compromised vasculature. To obtain
accurate cultures, bone biopsy must be performed through uninvolved tissue. Cultures
of the sinus tract may be useful if S aureus and Salmonella species are isolated. [22, 23]

Histologic Findings
Acute osteomyelitis presents with acute inflammatory cells, edema, vascular
congestion, and small-vessel thrombosis. In early disease, infection extends into the
surrounding soft tissue, which compromises the vascular supply to the bone, as well
as host response, surgery, and/or antibiotic therapy.
Large areas of dead bone may form if both medullary and periosteal blood
supplies are compromised. Necrotic bone shows extensive resorption and
inflammatory exudates on bone biopsy and appears whiter than living bone owing to
the loss of blood supply. The development of granulation tissue occurs at the surface
of dead bone, which is broken down by proteolytic enzymes, including
polymorphonuclear leukocytes, macrophages, and osteoclasts. This occurs most
rapidly at the junction of living and necrotic bone. A sequestrum is formed when dead
cortical bone is gradually detached from living bone.
Chronic osteomyelitis presents with pathologic findings of necrotic bone,
formation of new bone, and polymorphonuclear leukocyte exudation, which is joined
by large numbers of lymphocytes, histiocytes, and occasional plasma cells.
The formation of new bone occurs over weeks or months as a vascular
reaction to the infection. New bone arises from the surviving fragments of periosteum,
endosteum, and cortex in the region of infection along the intact periosteal and
endosteal surfaces. It may also occur when periosteum forms an involucrum, which is
dead bone surrounded by a sheath of living bone. Involucrum may lead to sinus tracts
due to perforations that allow pus to enter surrounding soft tissues and ultimately skin
surface. A new shaft forms as the density and thickness of involucrum increases.
As a result of inflammatory reaction and atrophy disuse during the active period of
osteomyelitis, surviving bone in the area of infection usually becomes osteoporotic.
Bone density increases partially from reuse as the infection subsides and extensive
transformation of bone may occur to conform to areas of new mechanical stresses.
Over time, old living bone and newly formed bone may appear similar and might be
indistinguishable, especially in children.

Staging
Two classification systems are commonly used for osteomyelitis.
In 1970, Waldvogel et al classified bone infections on the basis of
pathogenesis and proposed the original osteomyelitis staging system. This system
classifies bone infections as either hematogenous or osteomyelitis secondary to a
contiguous focus of infection. Contiguous-focus osteomyelitis is further classified
according to the presence or absence of vascular insufficiency. Both hematogenous
and contiguous-focus osteomyelitis may then be classified as either acute or
chronic.[24]
 In 2003, Cierny-Mader et al developed their staging system, which at present
is more commonly used. This system considers host immunocompetence in addition
to anatomic osseous involvement and histologic features of osteomyelitis. [25, 1] The
first part of the system specifies four stages, as follows:
 Stage 1 disease involves medullary bone and is usually caused by a single
organism
 Stage 2 disease involves the surfaces of bones and may occur with deep soft-
tissue wounds or ulcers
 Stage 3 disease is an advanced local infection of bone and soft tissue that often
results from a polymicrobially infected intramedullary rod or open fracture; stage
3 osteomyelitis often responds well to limited surgical intervention that preserves
bony stability
 Stage 4 osteomyelitis represents extensive disease involving multiple bony and
soft tissue layers; stage 4 disease is complex and requires a combination of
medical and surgical therapies, with postsurgical stabilization as an essential part
of therapy
The second part of the Cierny-Mader classification system describes the physiologic
status of the host, as follows:
 Class A hosts have normal physiologic, metabolic, and immune functions
 Class B hosts are systemically (Bs) or locally (Bl) immunocompromised;
individuals with local and systemic immune deficiencies are labeled as ‘‘Bls’’
 In Class C hosts, treatment poses a greater risk of harm than osteomyelitis itself;
the state of the host is the strongest predictor of osteomyelitis treatment failure,
and thus the physiologic class of the infected individual is often more important
than the anatomic stage [5]
Other classification systems have been proposed for long-bone osteomyelitis. The
Gordon classification classifies long-bone osteomyelitis on the basis of osseous
defects, using infected tibial nonunions and segmental defects, as follows [26] :
 Type A includes tibial defects and nonunions without significant segmental loss
 Type B includes tibial defects greater than 3 cm with an intact fibula
 Type C includes tibial defects of greater than 3 cm in patients without an intact
fibula
The Ger classification is used to address the physiology of the wound in osteomyelitis,
which is categorized as follows [27, 28] :
  Simple sinus
 Chronic superficial ulcer
 Multiple sinuses
 Multiple skin-lined sinuses

Bone infection persists if appropriate wound management is not undertaken.

It is important to cover open tibial fractures with soft tissue early in the disease to
prevent infection and ulceration.
The Weiland classification categorizes chronic osteomyelitis as a wound with
exposed bone, positive bone culture results, and drainage for more than 6
months.[29] This system also considers soft tissue and location of affected bone. It does
not recognize chronic infection if wound drainage lasts less than 6 months. Weiland et
al specified the following three types:
 Type I osteomyelitis was defined as open exposed bone without evidence of
osseous infection but with evidence of soft-tissue infection
 Type II osteomyelitis showed circumferential, cortical, and endosteal infection,
demonstrated on radiographs as a diffuse inflammatory response, increased
bone density, and spindle-shaped sclerotic thickening of the cortex; other
radiographic findings included areas of bony resorption and often a sequestrum
with a surrounding involucrum
 Type III osteomyelitis revealed cortical and endosteal infection associated with a
segmental bone defect
The Kelly classification considers the following types of osteomyelitis in adults:
 Hematogenous osteomyelitis
 Osteomyelitis in a fracture with union
 Osteomyelitis in a fracture with nonunion
 Postoperative osteomyelitis without fracture
This system emphasizes the etiology of the infection along with its relation to fracture
healing. [30, 27]
Approach Considerations
Surgery is indicated for osteomyelitis if the patient has not responded to
specific antimicrobial treatment, if there is evidence of a persistent soft tissue abscess
or subperiosteal collection, or if concomitant joint infection is suspected. Debridement
of necrotic tissues, removal of foreign materials, and sometimes skin closure of chronic
unhealed wounds are necessary in some cases.
Although vertebral osteomyelitis does not usually necessitate surgical
treatment, indications include failure to respond to antimicrobial therapy, neural
compression, spinal instability, or drainage of epidural or paravertebral abscesses.
The Infectious Diseases Society of America has published clinical practice guidelines
for the diagnosis and treatment of native vertebral osteomyelitis in adults, including
recommendations regarding antibiotic therapy and surgical intervention (see
Guidelines). [31]

Medical Therapy
Antibiotic treatment should be based on the identification of pathogens from
bone cultures at the time of bone biopsy or debridement. [1, 4] Bone cultures are
obtained first, and suspected pathogens are then covered by initiation of a parenteral
antimicrobial treatment. However, treatment may be modified once the organism is
identified. Parenteral and oral antibiotics may be used alone or in combination
depending on microorganism sensitivity results, patient compliance, and infectious
disease consultation.
Prophylactic treatment with the bead pouch technique has been suggested in
open fractures to reduce the risk of infection, with systemic antibiotics supplemented
with antibiotic beads compared to using systemic antibiotics alone.
Local antibiotic therapy with gentamicin-impregnated Septopal beads,
though available in Europe, is controversial. [32] Factors involved in the debate include
the length of implantation, the need for removal, and the choice of nonabsorbable
versus bioabsorbable delivery vehicles. Prolonged implantation of antibiotic beads and
spacers remains controversial owing to the risk of secondary infection and
development of resistant organisms. Secondary infection stems from the beads, which
may serve as a foreign body upon complete elution of antibiotic.
 Traditionally, antibiotic treatment of osteomyelitis consists of a 4- to 6-week
course.[4] Animal studies and observations show that bone revascularization after
debridement takes about 4 weeks.
Oral antibiotics that have been proven to be effective include clindamycin,
rifampin, trimethoprim-sulfamethoxazole, and fluoroquinolones. Clindamycin is given
orally after initial intravenous treatment for 1-2 weeks and has excellent bioavailability.
It is active against most gram-positive bacteria, including staphylococci. Linezolid is
active against methicillin-resistant staphylococci and vancomycin-
resistant Enterococcus. It inhibits bacterial protein synthesis, has excellent bone
penetration, and is administered intravenously or orally.
Oral quinolones are often used in adults for gram-negative organisms.
Quinolones have excellent oral absorption and may be used as soon as patient is able
to take them. Rifampin has an optimal intercellular concentration and a good sensitivity
profile for methicillin-resistant staphylococci. It is used in combination with cell wall
active antibiotics to achieve synergistic killing and to avoid rapid emergence of
resistant strains.
Empiric therapy is necessary when it is not possible to isolate organisms from
the infection site. [1] Hospital-acquired infections are usually derived from methicillin-
resistant staphylococci. Infections contracted outside the hospital are often
polymicrobial with the presence of gram-negative bacteria.
Parenteral antibiotics should be administered for several weeks, often requiring
patients to remain in the hospital for an extended duration. At this time, oral therapy is
indicated only in children whose compliance is certain. Infection may fail to improve
owing to the ability of bacteria to resist antibiotics. Some bacteria, such as S
epidermidis in prosthesis infections, adhere to a biofilm that protects the organism
from phagocytosis and impedes delivery of the antibiotic.
Rifampin must always be used in combination with other antibiotics for
prosthesis infections because it acts on the biofilm and avoids recurrence. Infection
may recur if rifampin is not used within a few weeks to a month of treatment.
Suppressive antibiotic therapy should also be directed by bone culture and is given
orally when surgery is contraindicated. [4] Good bioavailability, low toxicity, and
adequate bone penetration are important factors in treatment. If the infection recurs
after 6 months of suppressive antibiotic treatment, a new, lifelong regimen of
suppressive therapy may be tried.
Extensive studies of suppressive therapy with administration of rifampin, ofloxacin,
fusidic acid, and trimethoprim-sulfamethoxazole for 6-9 months have been performed
in patients with infected orthopedic implants. Studies have shown that, after
discontinuation of antibiotics, no recurrence of infection occurred in 67% of patients
treated with trimethoprim-sulfamethoxazole, 55% of patients treated with rifampin and
fusidic acid, and 50% of patients treated with rifampin and ofloxacin. [4]

Surgical Therapy
Preoperative planning
The Cierny-Mader classification system (see Workup) plays an important role
in guiding treatment. As described above, stage 1 and 2 disease usually do not require
surgical treatment, whereas stage 3 and 4 respond well to surgical treatment. In
Cierny-Mader class C hosts, treatment may be more harmful than the osteomyelitis
itself. [5]
Operative treatment consists of adequate drainage, extensive debridement of
necrotic tissue, management of dead space, adequate soft-tissue coverage, and
restoration of blood supply. [4] When a fracture and stable hardware are involved,
surgery is used to treat a residual infection after suppressing the infection until the
fracture heals. Techniques involve second-stage hardware removal followed by
treatment of an infected nonunion, often with an external fixator. External fixators,
plates, screws, and rods may be used to restore skeletal stability at the infection
site. [4] Since hardware tends to become secondarily infected, external fixation is
preferred over internal fixation.
Remission or cure is most likely with extensive debridement, obliteration of
dead space, removal of any hardware, and appropriate antibiotic therapy.
Debridement of all nonviable or infected tissue is critical because retained necrotic or
infected debris can result in osteomyelitis recurrence. Bone debridement is performed
until punctuate bleeding is noted. [4] The remaining tissue is still considered
contaminated even after adequate debridement of necrotic tissue. Studies have shown
that marginal resection may be sufficient in normal hosts. However, in compromised
hosts, extensive resection seems to be much more important.
“Dead space” refers to the soft tissue and bony defect left behind after
debridement. [4] Appropriate management of this space is necessary to reduce the risk
of persistent infection from poor vascularization of the area and to maintain the
integrity of the skeletal part. Dead space must be filled with durable vascularized
tissue, sometimes from the fibula or ilium. Antibiotic-impregnated beads may be used
for temporary sterilization of dead space. Vancomycin, tobramycin, and gentamicin
are some of the common antibiotics used in these beads. Within 2-4 weeks, the beads
may be replaced with cancellous bone graft.
Because two major aims of surgical treatment include resection of necrotic
bone and thorough debridement of intraosseous and soft tissue fistula, CT scanning
is sometimes performed when planning a surgical intervention and for guiding surgery.
Preoperatively, CT scanning is helpful to characterize bone quality, demonstrate
intraosseous fistula, and detect devitalized bone areas, or cortical defects that lead to
soft tissue sinus tracts. [2]
When osteomyelitis involves a fracture, it is also important to include a workup
to be sure the fracture has healed. Antibiotic-impregnated beads may be used as an
effective measure to maintain sterile dead space until a definitive surgical procedure
can be performed.
In order to apply the Ilizarov method successfully and to prevent damage to
vital nerves and blood vessels, preoperative planning is helpful with careful attention
to "safe zones" during wire insertion. It is important to adjust the skin to prevent tension
on the skin-wire interface. Correction of the deformity or lengthening is better achieved
by appropriately constructing the Ilizarov frame. [33]

Ilizarov method
The Ilizarov method, developed by G. A. Ilizarov in 1951, promotes bone
growth through distraction osteogenesis using a specialized device and systematic
approach. This technique has facilitated limb lengthening, decreased the incidence of
many complications, and decreased the level of surgical intervention necessary.
The Ilizarov method involves the use of a tissue-sparing, cortical osteotomy-
osteoclasis technique that preserves the osteogenic elements in the limb. To create a
preliminary callus that can be lengthened, Ilizarov advocated a delay of several days
before initiating distraction. A high-frequency, small-step distraction rhythm permits
regeneration of good-quality bone and less soft-tissue complications such as nerve
and vessel injury. An advantage of using this procedure is that it minimizes the
prevalence of nonunion and thus further bone grafting by producing good-quality bone
formation.
 The risk of repeat osteotomy and osteoclasis is also decreased owing to less-
premature consolidation of the lengthened segment. [34] However, Ilizarov techniques
are often not tolerated well by patients, and other options, including amputation, may
be preferred.
The Ilizarov external fixator is a popular device that is composed of wires,
fixation bolts, rings, threaded rods, hinges, and plates, together allowing customized
assemblies. Although this apparatus is stiff for bending and torsion, it is less stiff for
axial loading. This feature is thought to help promote osteogenesis. [33]
The Ilizarov method is based on the concept of "tension stress," in which
gradual distraction stimulates bone production and neogenesis. The Ilizarov device is
attached to the distal or proximal portion of the affected bone. Bone regenerates as
the screw and wire mechanism moves the healthy bone fragment at a maximal rate of
approximately 0.25 mm 4 times per day for an overall rate of 1 mm per day. Gentle
distraction allows bone formation and decreases the need for supplemental bone
grafting and internal fixation. The distraction force permits tissue fibers and cells to
become oriented in the same direction as the distraction vector, which is thought to
mimic the process of natural bone growth. [33]
Nonunions, malunions, or defects of any length can be treated and may also
be corrected using the Ilizarov method. At the same time, the Ilizarov technique is
labor-intensive and may require at least 8 months of treatment. In addition, the fixator
pins can be uncomfortable and often become infected. Amputation is an option if
reconstruction is not suitable.
Wound closure
To arrest infection, it is necessary to provide adequate soft-tissue
coverage. [4] Over small soft-tissue defects, a split-thickness skin graft may be placed,
whereas large soft-tissue defects may be covered with local muscle flaps and free
vascularized muscle flaps. Rotation of a local muscle with its neurovascular supply
must be possible anatomically for that procedure to be successful.
These flaps bring in a blood supply, which is important for host defense
mechanisms, new bone regeneration, delivery of antibiotics, and healing. They also
may be used in combination with antibiotics and surgical debridement of necrotic and
infected tissues. The fibula and iliac crest are common donor sites for free flaps.
Adjunctive hyperbaric oxygen therapy
Adjunctive hyperbaric oxygen therapy can promote collagen production,
angiogenesis, and healing in an ischemic or infected wound. [4]

Complications
The Ilizarov technique is usually well tolerated by the patient, with little
associated pain. A few complications that have been reported include pin-tract
infections and cellulitis, flexion contractures above and below the frame, limb edema,
and bone fragment rotation with malunion. [35]
The complication rate may be decreased by future trends to improve the
Ilizarov method. [34] Some goals include improving the technique to prevent pin-track
infections and osteomyelitis, premature or delayed consolidation of bone, angular or
axial deviation of the new bone, joint contracture or instability, neurovascular
compromise, and psychological adjustment reactions.

Long-Term Monitoring
After a corticotomy is made for bone lengthening, a latency period is required
before distraction. Once distraction has begun using the Ilizarov technique, new bone
should be apparent within 3-4 weeks. After obtaining the appropriate length or
correcting the angular deformity, the apparatus remains in place until completion of
the consolidation phase. During the postoperative period, it is necessary to adjust or
modify the assembly, and the apparatus is removed when the goal is achieved. [33]
Because the apparatus may be in place for an extended period, even up to a
year, special postoperative considerations are important. [33] Pain management may
be a challenge because of the duration of mild to moderate postoperative pain. To
prevent flexion contractures of the surrounding joints, a key element is intensive
physical therapy and splinting techniques. Successful treatment also requires
psychological support and family counseling. Some problems to be cautious of during
the postoperative period include pin-track infections, premature or delayed
consolidation, joint contractures, and pin breakage that may require replacement.
Imaging studies in the follow-up period are most useful in patients who have
equivocal or worse clinical status at the end of therapy.
1. [Guideline] Concia E, Prandini N, Massari L, Ghisellini F, Consoli V, Menichetti
F. Osteomyelitis: clinical update for practical guidelines. Nucl Med Commun.
2006 Aug. 27(8):645-60. [Medline].
2. Gross T, Kaim AH, Regazzoni P, Widmer AF. Current concepts in posttraumatic
osteomyelitis: a diagnostic challenge with new imaging options. J Trauma.
2002 Jun. 52(6):1210-9. [Medline].
3. Newman LG, Waller J, Palestro CJ, Schwartz M, Klein MJ, Hermann G.
Unsuspected osteomyelitis in diabetic foot ulcers. Diagnosis and monitoring by
leukocyte scanning with indium in 111 oxyquinoline. JAMA. 1991 Sep 4.
266(9):1246-51. [Medline].
4. Calhoun JH, Manring MM. Adult osteomyelitis. Infect Dis Clin North Am. 2005
Dec. 19(4):765-86. [Medline].
5. Paluska SA. Osteomyelitis. Clinics in Family Practice. 2004. 6:127-56.
6. Shaw B A, Kasser J R. Acute septic arthritis in infancy and childhood. Clinical
Orthopaedics & Related Research. August 1990. 257:212-225. [Medline].
7. Vincent GM, Amirault JD. Septic Arthritis in the Elderly. Clinical Orthopaedics
and related research. February/1990. 251:241-245. [Medline].
8. Belthur MV, Birchansky SB, Verdugo AA, et al. Pathologic Fractures in Children
with Acute Staphylococcus aureus Osteomyelitis. J Bone Joint Surg Am. 2012
Jan 4. 94(1):34-42. [Medline].
9. Böhm E, Josten C. What's new in exogenous osteomyelitis?. Pathol Res Pract.
1992 Feb. 188(1-2):254-8. [Medline].
10. Laughlin RT, Reeve F, Wright DG, Mader JT, Calhoun JH. Calcaneal
osteomyelitis caused by nail puncture wounds. Foot Ankle Int. 1997 Sep.
18(9):575-7. [Medline].
11. Mader JT, Cripps MW, Calhoun JH. Adult posttraumatic osteomyelitis of the
tibia. Clin Orthop Relat Res. 1999 Mar. (360):14-21. [Medline].
12. Roesgen M, Hierholzer G, Hax PM. Post-traumatic osteomyelitis.
Pathophysiology and management. Arch Orthop Trauma Surg. 1989. 108(1):1-
9. [Medline].
13. Weber EJ. Plantar puncture wounds: a survey to determine the incidence of
infection. J Accid Emerg Med. 1996 Jul. 13(4):274-7. [Medline].
14. Beronius M, Bergman B, Andersson R. Vertebral osteomyelitis in Göteborg,
Sweden: a retrospective study of patients during 1990-95. Scand J Infect Dis.
2001. 33(7):527-32. [Medline].
15. Digby JM, Kersley JB. Pyogenic non-tuberculous spinal infection: an analysis
of thirty cases. J Bone Joint Surg Br. 1979 Feb. 61(1):47-55. [Medline].
16. Tseng CH, Huang WS, Muo CH, Kao CH. Increased risk of dementia among
chronic osteomyelitis patients. Eur J Clin Microbiol Infect Dis. 2014 Aug
7. [Medline].
17. Bernard L, Lübbeke A, Stern R, Bru JP, Feron JM, Peyramond D. Value of
preoperative investigations in diagnosing prosthetic joint infection: retrospective
cohort study and literature review. Scand J Infect Dis. 2004. 36(6-7):410-
6. [Medline].
18. Spangehl MJ, Masri BA, O'Connell JX, Duncan CP. Prospective analysis of
preoperative and intraoperative investigations for the diagnosis of infection at
the sites of two hundred and two revision total hip arthroplasties. J Bone Joint
Surg Am. 1999 May. 81(5):672-83. [Medline].
19. Abiri MM, Kirpekar M, Ablow RC. Osteomyelitis: detection with US. Radiology.
1989 Aug. 172(2):509-11. [Medline].
20. Howard CB, Einhorn M, Dagan R, Nyska M. Ultrasound in diagnosis and
management of acute haematogenous osteomyelitis in children. J Bone Joint
Surg Br. 1993 Jan. 75(1):79-82. [Medline].
21. Wheat J. Diagnostic strategies in osteomyelitis. Am J Med. 1985 Jun 28.
78(6B):218-24. [Medline].
22. Howard CB, Einhorn M, Dagan R, Yagupski P, Porat S. Fine-needle bone
biopsy to diagnose osteomyelitis. J Bone Joint Surg Br. 1994 Mar. 76(2):311-
4. [Medline].
23. Perry CR, Pearson RL, Miller GA. Accuracy of cultures of material from
swabbing of the superficial aspect of the wound and needle biopsy in the
preoperative assessment of osteomyelitis. J Bone Joint Surg Am. 1991 Jun.
73(5):745-9. [Medline].
24. Waldvogel FA, Medoff G, Swartz MN. Osteomyelitis: a review of clinical
features, therapeutic considerations and unusual aspects. 3. Osteomyelitis
associated with vascular insufficiency. N Engl J Med. 1970 Feb 5. 282(6):316-
22. [Medline].
25. Cierny G 3rd, Mader JT, Penninck JJ. A clinical staging system for adult
osteomyelitis. Clin Orthop Relat Res. 2003 Sep. (414):7-24. [Medline].
26. Gordon L, Chiu EJ. Treatment of infected non-unions and segmental defects of
the tibia with staged microvascular muscle transplantation and bone-grafting. J
Bone Joint Surg Am. 1988 Mar. 70(3):377-86. [Medline].
27. Mader JT, Shirtliff M, Calhoun JH. Staging and staging application in
osteomyelitis. Clin Infect Dis. 1997 Dec. 25(6):1303-9. [Medline].
28. Ger R. Muscle transposition for treatment and prevention of chronic post-
traumatic osteomyelitis of the tibia. J Bone Joint Surg Am. 1977 Sep. 59(6):784-
91. [Medline].
29. Weiland AJ, Moore JR, Daniel RK. The efficacy of free tissue transfer in the
treatment of osteomyelitis. J Bone Joint Surg Am. 1984 Feb. 66(2):181-
93. [Medline].
30. Kelly PJ. Infected nonunion of the femur and tibia. Orthop Clin North Am. 1984
Jul. 15(3):481-90. [Medline].
31. [Guideline] Berbari EF, Kanj SS, Kowalski TJ, Darouiche RO, Widmer AF,
Schmitt SK, et al. 2015 Infectious Diseases Society of America (IDSA) Clinical
Practice Guidelines for the Diagnosis and Treatment of Native Vertebral
Osteomyelitis in Adultsa. Clin Infect Dis. 2015 Sep 15. 61 (6):e26-46. [Medline].
32. Zalavras CG, Patzakis MJ, Holtom P. Local antibiotic therapy in the treatment
of open fractures and osteomyelitis. Clin Orthop Relat Res. 2004 Oct. (427):86-
93. [Medline].
33. Louie KW. Ilizarov method. West J Med. 1991 Aug. 155(2):170. [Medline].
34. Rosenfeld SR. The Ilizarov method. West J Med. 1995 Dec.
163(6):568. [Medline].
35. Gateley DR, Irby SJ, Martin DL, Simonis RB. Ilizarov bone transport for the
treatment of chronic osteomyelitis: a rare complication. J R Soc Med. 1996 Jun.
89(6):348P-50P. [Medline]. [Full Text].
36. May JW Jr, Jupiter JB, Weiland AJ, Byrd HS. Clinical classification of post-
traumatic tibial osteomyelitis. J Bone Joint Surg Am. 1989 Oct. 71(9):1422-
8. [Medline].