MISE AU POINT / IN-DEPTH REVIEW

OSTEOMYELITIS : REVIEW OF PATHOPHYSIOLOGY, DIAGNOSTIC MODALITIES

AND THERAPEUTIC OPTIONS
http://www.lebanesemedicaljournal.org/articles/60-1/review1.pdf

Albert J. EID1, Elie F. BERBARI2

Eid AJ, Berbari EF. Osteomyelitis : Review of pathophysiology,

diagnostic modalities and therapeutic options. J Med Liban
2012 ; 60 (1) : 51-60.

ABSTRACT : Osteomyelitis can affect every bone

and is heterogeneous in its pathophysiology and presentation. When the diagnosis is clinically suspected,
further studies such as serum inflammatory markers
and imaging studies should be performed. Magnetic
resonance imaging can be very useful in establishing
the diagnosis and determining the extent of infection.
When possible, bone specimens should be obtained
and cultured prior to the initiation of antimicrobial
therapy. Surgical debridement is often required for
chronic or contiguous osteomyelitis for successful
eradication of the infection. The ultimate test-of-cure
is the lack of clinical relapse after the discontinuation
of antimicrobials.
INTRODUCTION

Osteomyelitis is an infection of the bone and bone marrow. It can involve any bone of the human body and can
occur through a variety of mechanisms. The difference in
pathophysiology of various types of osteomyelitis mandates specific therapeutic strategies aimed at the eradication of the infection while preserving bone integrity and
function. Osteomyelitis can be acute or chronic and may
result from hematogenous seeding of the bone, extension
of the infection from adjacent soft tissue, or direct inoculation of the bone through skin and soft tissue defects following trauma or surgery. Once established, osteomyelitis
leads to progressive softening and necrosis of the bone
resulting into the formation of sequestra. At this stage of
the disease, surgical debridement becomes a requirement
for cure. The presence of hardware at the site of infection
is a complicating factor that could compromise treatment
success. Despite adequate treatment, failure is not uncommon. Therefore, in order to improve the outcome, clinicians should understand the disease process and gain
experience manipulating the treatment tools. Hence, the
importance of this review.

Division of Infectious Diseases, University of Kansas Medical

Center, Kansas City, Kansas; 2Division of Infectious Diseases,
College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Correspondence: Albert J. Eid, MD. Division of Infectious
Diseases. University of Kansas Medical Center, 2067 Delp.
3901 Rainbow Blvd. Kansas City. KS 66160 USA.
e-mail: aeid@kumc.edu
Tel.: +1 913 588 6035

Eid AJ, Berbari EF. Lostomylite : tude approfondie de la

pathophysiologie, des modalits diagnostiques et des options
thrapeutiques. J Med Liban 2012 ; 60 (1) : 51-60.

RSUM : Lostomylite peut atteindre tous les os du

squelette humain et possde une pathophysiologie et
une prsentation clinique trs htrognes. Lorsque le
diagnostic est considr, certains examens doivent tre
obtenus, notamment les marqueurs dinflammation et
des examens radiologiques. Limagerie par rsonance
magntique peut tre trs utile pour confirmer le diagnostic et dterminer ltendue de linfection. Lorsque
cela savre possible, des chantillons osseux doivent
tre obtenus et cultivs avant le dbut de lantibiothrapie. Un dbridement chirurgical est souvent ncessaire pour lradication complte de lostomylite
chronique ou contigu. Le test ultime de gurison est
labsence de rechute clinique aprs larrt des antibiotiques.

Herein, we will address the pathogenesis of osteomyelitis, the available diagnostic modalities, and various
therapeutic strategies. Due to the difference in pathophysiology, microbiology, and management, we will separately discuss different entities including osteomyelitis due to
open fractures, vertebral osteomyelitis, acute hematogenous osteomyelitis, osteomyelitis in patients with diabetes
mellitus and osteomyelitis associated with prosthetic joint
infection. A brief overview of osteomyelitis due to some
specific pathogens such as Brucella species, Salmonella
species, mycobacteria and fungi will also be reviewed.
PATHOGENESIS OF OSTEOMYELITIS

Experimental animal model of bone infection has revealed that bone is resistant to infection [1]. Osteomyelitis
occurs only when a large inoculum of bacteria is introduced into the bone in conjunction with trauma, necrosis,
or presence of foreign bodies [2]. Bacteria (i.e. Staphylococcus aureus) adhere to bone matrix via receptors to
fibronectin, laminin, collagen and other structural proteins.
Microorganisms elude the host defenses and antibiotics
through a variety of mechanisms including surviving in a
dormant state inside osteoblasts, developing a biofilm, and
acquiring a very slow metabolic rate [3-4]. Furthermore,
studies in a guinea pig model of post-traumatic osteomyelitis showed significant reduction of leukocyte locomotion after trauma and infection with S. aureus for up to
90 days [5]. The presence of prosthetic material contiguous to bone can lead to specific polymorphonuclear leuLebanese Medical Journal 2012 Volume 60 (1) 51

kocytes defect and therefore protects bacteria from phagocytosis. Inflammation, resulting from the interaction between bacteria and leukocytes, results in the release of
cytokines and the development of osteolysis [3-4].
In patients with acute osteomyelitis of the long bones,
it is believed that the metaphysis is the site of predilection
due to slow blood flow in the metaphyseal vascular loops
and the lack of phagocytic lining cells [6]. Once the infection is established in the metaphysis, the inflammatory
exudate leads to increased pressure in the bone and intramedullary canal. Subsequently, the extension of this exudate into the cortex will eventually lead to periosteal elevation or rupture, disrupting the blood flow and causing
bone infarction and the formation of an abscess or sequestrum. In chronic osteomyelitis, the inflammation is mild to
moderate and little or no ischemic necrosis occurs [4].
The type and site of osteomyelitis is largely determined
by the mechanism of infection, the virulence of the infecting organism, and the immune status and comorbid conditions of the patient [6-7] (Table I). Osteomyelitis could
develop through hematogenous seeding of the bone from a
remote source of infection, extension of the infection from
adjacent soft tissue overlying the involved bone; or directly via inoculation of the bone following trauma or surgery.

S. aureus is the most commonly isolated organism in

osteomyelitis. Other microorganisms such as coagulasenegative staphylococci, aerobic gram-negative bacilli, and
anaerobes are frequently encountered as well (Table II).
Patients with certain conditions such as immunosuppression, immune diseases (i.e. rheumatoid arthritis), diabetes
mellitus, smoking, malnutrition, malignancy, extremes of
age, chronic hypoxia, and renal or hepatic failure are at
increased risk for osteomyelitis. Other local factors are
equally important. Those include chronic edema, peripheral vascular disease, neuropathy, prior surgery, extensive
scarring, and radiation fibrosis [6-8].
DIAGNOSIS AND DIAGNOSTIC MODALITIES

Osteomyelitis should be suspected when patients present

with pain, swelling, erythema or warmth of the skin and
soft tissue overlying bone. Subacute or chronic pain is
commonly the only manifestation. Systemic symptoms
(i.e. fever and chills) are present in patients with acute
osteomyelitis but seldom present in patients with chronic
osteomyelitis. Draining sinuses are typically seen in cases
of chronic osteomyelitis. The presence of exposed bone
or prosthetic material for a period of time is highly sug-

TABLE I
ETIOLOGY OF OSTEOMYELITIS AND UNDERLYING CONDITIONS

Mechanism

Hematogenous osteomyelitis

Vertebral osteomyelitis

Special groups

Common in children and adults

Neonates
Infants and children*
Injection drug users
Most common in adults
Urinary tract infection
Injection drug users
Following spine surgery

Contiguous focus osteomyelitis

Infections of intravascular devices

In endemic regions
Diabetes mellitus, vascular insufficiency,
or following a contaminated open fracture
Soil contamination
Orthopedic fixation devices
Cat bites
Following puncture injuries on the foot
by nails or other sharp objects
Following periodontal infection

Etiology

Staphylococcus aureus
Enterobacteriaceae, Group B streptococci
Haemophilus influenzae group B
Staphylococcus aureus, Pseudomonas aeruginosa,
Candida spp.

Staphylococcus aureus
Aerobic gram-negative bacilli, Enterococcus spp.
Pseudomonas aeruginosa, Staphylococcus aureus,
Candida spp.
Coagulase-negative staphylococci, Staphylococcus
aureus, aerobic gram-negative bacilli
Candida spp.
Mycobacterium tuberculosis, Brucella spp.
Polymicrobial: Staphylococcus aureus, beta-hemolytic
streptococci, Enterococcus spp., aerobic gram-negative
bacilli
Clostridium spp., Bacillus spp., Stenotrophomonas
maltophilia, Nocardia spp., atypical mycobacteria,
Aspergillus spp., Rhizopus spp., Mucor spp.
Staphylococcus aureus, coagulase-negative staphylococci
Pasteurella multocida
Pseudomonas aeruginosa
Actinomyces spp.

*The incidence of osteomyelitis due to Haemophilus influenza type B significantly decreased due to the routine vaccination of children.
52 Lebanese Medical Journal 2012 Volume 60 (1)

A.J. EID, E.F. BERBARI Osteomyelitis

TABLE II

Common

MICROBIOLOGY OF OSTEOMYELITIS

Staphylococcus aureus
Coagulase-negative staphylococci
Streptococci
Enterococci
Pseudomonas spp.
Enterobacter spp.
Proteus spp.
Escherischia coli
Serratia spp.
Anaerobes (Peptostreptococcus spp.,

Less common

Mycobacterium tuberculosis
Rapidly growing mycobacteria
Mycobacterium avium complex
Endemic fungi
Candida spp.
Aspergillus spp.
Mycoplasma spp.
Brucella spp.
Salmonella spp.

Clostridium spp., B. fragilis group.)

Actinomycetes

Tropheryma whipplei

gestive of osteomyelitis. In fact, the probe-to-bone test is

widely used to diagnose osteomyelitis in patients with diabetic foot ulcers and contiguous osteomyelitis. Grayson
et al. found that this test has a sensitivity of 66% and a
positive predictive value of 89% [9].
The confirmation of osteomyelitis requires the use of
a variety of laboratory, microbiologic, radiographic and
pathologic tests. Erythrocyte sedimentation rate (ESR)
and C-reactive protein (CRP) are usually abnormal. The
white blood cell count is occasionally elevated. The
platelet count can be elevated (inflammatory marker)
while the hemoglobin concentration can be low (anemia
of chronic disease). Blood cultures may be positive in
acute hematogenous and vertebral osteomyelitis. Cultures
of superficial wounds or sinus tracts should be cautiously
interpreted and should not be used to guide antimicrobial
therapy unless S. aureus is isolated from those cultures
[10-11]. In one study, only 44% of the sinus tract cultures
grew the same operative pathogen. The isolation of S. aureus from the sinus tract correlated with the presence of
S. aureus in the operative specimen. However, less than
half of the sinus tract cultures obtained from patients with
S. aureus osteomyelitis contained this organism [11]. Bone
tissue sampling via needle aspiration under radiologic
guidance or surgical procedure allow the identification of
the infectious organism and the determination of its in vitro
susceptibility profile [6]. The latter information is crucial
for the initiation of appropriate and effective antimicrobial
therapy (Table III). The bone tissue collected from the
infected site can also be submitted for histopathologic
examination which is considered the gold standard for the
diagnosis of osteomyelitis.
Conventional radiography has little value in diagnosing
acute osteomyelitis but it might be helpful in cases of
chronic osteomyelitis. At least 10-14 days are needed before abnormalities consistent with osteomyelitis are seen.
In one study, the sensitivity of plain radiographs in cases
of diabetic foot osteomyelitis was found to be 54%, while
the specificity was 68%. The radiographic signs that were
considered diagnostic included focal or geographic areas
of marrow lucency, loss of cortex with bony erosion, new
A.J. EID, E.F. BERBARI Osteomyelitis

bone formation, bone sclerosis with or without erosion,

sequestration, involucrum, and periosteal elevation [12].
Nuclear bone scans using a variety of radiotracers
(Technetium 99m methylene diphosphonate, Galliumcitrate 67, and Indium 111-labeled white blood cells) are
commonly used to diagnose osteomyelitis. The performance of those scans varies depending upon the clinical
situation [13]. In adults with normal radiographs (no
lesions that cause increased bone turnover), the threephase bone scan has higher accuracy than the other scans
with 94% sensitivity and 95% specificity. However, when
bone remodeling is increased, the specificity of the test
decreases to 33% [13]. In presence of osteomyelitis, significant uptake is seen in all three phases of the study
(immediately after injection, at 15 minutes and 4 hours) as
opposed to increased uptake only in the first two phases in
patients with cellulitis. Gallium scans detect the areas of
inflammation due to the affinity of gallium-67 to acute
phase reactants (i.e. lactoferrin and transferrin) [14]. The
results of studies evaluating their sensitivity and specificity are not consistent. When studies are combined together, the overall sensitivity is approximately 81% and the
specificity is 69% [13]. Some authors believe that gallium
scans have better performance for the evaluation of vertebral osteomyelitis. This is supported by data from one
study showing high sensitivity, specificity and accuracy
[15]. Tagged white blood cell scans show accumulation of
tagged white cells in the bone marrow and at the site of
inflammation or infection [14]. In a meta-analysis, the sensitivity of Indium 111-labeled white blood cells scan was
84% for extra-axial chronic osteomyelitis as opposed to
only 21% for the axial skeleton. Similarly, the specificity
was 80% in the peripheral skeleton and 60% in the axial
skeleton [16].
Positron emission tomography (PET) using 18-fluorodeoxyglucose is increasingly being utilized in the diagnosis of osteomyelitis. In a systematic review and metaanalysis, Termaat et al. found PET scans to have a sensitivity of 96% and a specificity of 91% for the diagnosis of
osteomyelitis. [16]. PET scanning is a cheaper modality
when compared with other nuclear bone scanning techniques and is typically performed in one day. Unfortunately, however, false positive results can be seen with
bone healing. Computed tomography (CT) provides
excellent cortical bony details showing cortical bone erosion or destruction and periosteal reaction. It could also
show small foci of air within the medullary canal, tiny foreign bodies serving as a nidus for infection and sequestrum formation [17]. Magnetic resonance imaging (MRI)
is more sensitive than CT in detecting osteomyelitis and
as sensitive as nuclear studies. The sensitivity and specificity of MRI ranged from 82% to 100% and 75% to 96%,
respectively. MRI is considered the imaging modality of
choice in cases of established osteomyelitis because it
allows accurate determination of the extent of the infection, especially in case of vertebral osteomyelitis (identifies epidural abscess, phlegmon, and cord compression)
[17].
Lebanese Medical Journal 2012 Volume 60 (1) 53

Aqueous crystalline penicillin G, 20 x 106 U/24 hr IV, either continuously or

in 6 equally divided daily doses for 4-6 wks
OR Ceftriaxone 1-2 g IV or IM q 24 hr for 4-6 wks
OR Cefazolin 1-2 g IV every 8 hr for 4-6 wks
Enterococci or streptococci with
Aqueous crystalline penicillin G, 20 x 106 U/24 hr IV, either continuously or
Vancomycin*, 20 mg/kg IV q 12 hr for 4-6 wks
penicillin MIC 0.5 g/mL or
in 6 equally divided daily doses for 4-6 wks
Optional: Add Gentamicin sulfate, 1 mg/kg IV or IM every 8 hr for 1-2 wks
Abiotrophia defectiva,
OR Ampicillin sodium 12 g/24 hr IV either continuously or in 6 equally divided
Granulicatella spp., Gemella spp.
daily doses for 4-6 wks
Optional: Add Gentamicin sulfate, 1 mg/kg IV or IM every 8 hr for 1-2 wks
Ciprofloxacin** 500-750 mg PO q 24 hr for 4-6 wks
Enterobacteriaceae
Ceftriaxone 2 g IV q 24 hr for 4-6 wks
Pseudomonas aeruginosa or
Cefepime 2 g IV q 12 hr for 4-6 wks
Ciprofloxacin** 750 mg PO q 12 hr for 4-6 wks
Enterobacter spp.
OR Meropenem 1 g IV q 8 hr for 4-6 wks
OR Ceftazidime 2 g IV q 8 hr for 4-6 wks
hr: hour IM: intramuscular IV: intravenous wks: weeks PO: per os *Dose based on normal creatinine clearance; vancomycin trough level should be 15-20.
**Should be avoided if possible, in the pediatric population and in osteomyelitis associated with fractures.

Linezolid 600 mg PO/IV q 12 hr for 6 wks

Levofloxacin** 500-750 mg PO/IV daily and rifampin 600 mg PO daily for 6 wks
Vancomycin*, 20 mg/kg IV q 12 hr for 4-6 wks
Penicillin-sensitive streptococci

Staphylococci, oxacillin-resistant

Microorganisms

Staphylococci, oxacillin-sensitive

OR

First choice

Nafcillin sodium or oxacillin sodium, 1.5-2.0 g IV q 4 hr for 4-6 wks

Cefazolin 1-2 g IV q 8 hr for 4-6 wks
Vancomycin*, 15 mg/kg IV q 12 hr for 4-6 wks

OR

Alternative Choice

Vancomycin*, 20 mg/kg IV q 12 hr for 4-6 wks

ANTIMICROBIAL THERAPY FOR OSTEOMYELITIS DUE TO SPECIFIC MICROORGANISMS

TABLE III

THERAPEUTIC STRATEGIES

The optimal treatment of osteomyelitis is still not well

defined due to the lack of prospective randomized controlled clinical trials. Most of the data supporting treatment guidelines derive from studies in animal models,
expert opinions, and retrospective studies in humans. In
general, treatment consists of a combination of surgical
debridement and antimicrobial therapy [6]. Both treatment components should be tailored to manage various
forms of osteomyelitis. The details of treatment will be
discussed in the following sections addressing specific
osteomyelitis entities.

Medical management
In order to establish a microbiological diagnosis and
unless the patient is hemodynamically unstable, every
effort should be directed at obtaining bone specimens prior
to the initiation of empiric antimicrobial therapy. The optimal duration of antimicrobial therapy for osteomyelitis is
not known. In an animal model, S. aureus grew from 78%
of specimens after 14 days of therapy with clindamycin but
only from 16% of specimens after 28 days of therapy. In
this model, surgical debridement was not part of the treatment, however [18]. In the clinical setting, relapse is not
uncommon even after 4 weeks of antibiotic therapy. Therefore, many experts recommend 4 to 6 weeks of therapy [6].
In some instances, when surgical debridement is suboptimal or lacking, treatment is extended to 8-10 weeks.
During treatment, the inflammatory markers (ESR and
CRP) are expected to go down when compared to baseline
values. In one study of vertebral osteomyelitis, the rate of
clinical failure when ESR fell or failed to fall by more than
25% of the baseline value during the first month of treatment was 12% and 50%, respectively [19].
Parenteral antimicrobial therapy is commonly used;
however, oral antimicrobials with good bioavailability and
bone penetration (e.g. trimethoprim-sulfamethoxazole,
clindamycin, tetracyclines, fluoroquinolones, metronidazole, and linezolid) can be used if compliance is ascertained. Betalactams (i.e. intravenous penicillins and cephalosporins) are commonly used to treat osteomyelitis due
to their efficacy and relative safety when given for a prolonged period of time [6] (Table III). Vancomycin is used
to treat methicillin-resistant S. aureus (MRSA) and ampicillin-resistant Enterococcus species; however, vancomycin use is associated with higher treatment failure rate
when compared with betalactams [20]. Data regarding the
use of newer drugs such as linezolid and daptomycin for
the treatment of osteomyelitis due to MRSA and vancomycin-resistant Enterococcus (VRE) are limited [21-23].
In recent years, osteomyelitis due to resistant Gramnegative bacilli (i.e. multidrug resistant Pseudomonas
aeruginosa, extended-spectrum -lactamase producing
Klebsiella pneumonia and Escherichia coli) has become a
serious therapeutic challenge. In those cases, antimicrobial therapy should always be guided by in vitro susceptibility studies. Intravenous colistin and carbapenems (i.e.
doripenem) are frequently used and synergy studies could
also be considered in difficult cases.
The data from animal models suggest that fluoro-

quinolones significantly impair fracture healing [24];

therefore, experts recommend caution when using fluoroquinolones for the treatment of osteomyelitis in the context
of fractured bone [6]. The use of rifampin for the treatment
of staphylococcal osteomyelitis could be beneficial due to
biofilm penetration and increased bactericidal activity
when co-administered with other antibiotics [25-26], especially in case of hardware-associated osteomyelitis [2728]. Hyperbaric oxygen therapy (HBOT) can be used in
cases of chronic and refractory osteomyelitis but its use
remains highly controversial [29].

Surgical treatment
The goal of surgery in patients with osteomyelitis is to
drain all infected fluid at the site of infection, completely
debride all infected and devitalized soft tissue and bone,
and achieve good wound coverage. Ideally all infected
hardware should be removed; however, this is not possible when the fractured bone is not stable enough. When
significant soft tissue defect is present, musculocutaneous
flaps can be used to eliminate the dead-space and provide
adequate coverage of the wound. Patients presenting with
severe and recurrent osteomyelitis might require multiple
surgical debridements in order to insure complete removal
of the infected tissue. In those situations, antibiotic impregnated polymethyl metacrylate (PMMA) beads can be
placed deep into the wound around the infected bone.
Those beads allow the local delivery of higher concentrations of antibiotics; however, they should be ultimately
removed from the wound.
MANAGEMENT OF PATIENTS WITH VARIOUS TYPES
OF OSTEOMYELITIS

Osteomyelitis in patients with contaminated open

fracture
Osteomyelitis can develop at the site of an open fracture
in 3% to 25% of cases [30-31]. Factors determining the
rate of infection include the type of fracture, degree of
contamination of the wound (fracture type IIIB), extent of
soft tissue injury, the timing of surgical debridement, the
use of systemic, and local antimicrobials (i.e. PMMA
beads) [30-35]. Patients are usually young men presenting
with fractures of the lower extremities, mainly the tibia
and fibula. Short course of systemic antibiotic therapy
(24 hours) in addition to the use of antibiotic-impregnated
PMMA beads is recommended [6] in order to minimize
the risk of subsequent osteomyelitis. Antibiotic-impregnated intramedullary nails are being used as well and
the preliminary data from retrospective studies showed
promise [36-37]. The impact of osteomyelitis in those
cases could be devastating due to nonunion of the infected bone and the need for amputation.
Patients typically present several months after the accident with nonunion at the fracture site and poor wound
healing or draining sinuses. Local signs and systemic
symptoms are not common. Imaging studies are not helpful in establishing the diagnosis of osteomyelitis due to
A.J. EID, E.F. BERBARI Osteomyelitis

bony changes secondary to trauma and surgery and artifacts due to prosthetic material. Following a course of parenteral antimicrobial therapy, oral suppressive therapy
should be considered and continued until the fracture
heals. In case of relapse of the infection after bone healing, the hardware should be removed and another course
of parenteral antimicrobial therapy should be given [6].

Vertebral osteomyelitis and spondylodiskitis

Vertebral osteomyelitis and intervertebral disk infection
commonly result from hematogenous seeding via the segmental artery supplying two adjacent end plates of contiguous vertebrae [38]. Less frequently, vertebral osteomyelitis and disk space infection complicates spinal
surgery. The routine use of preoperative antibiotic prophylaxis further reduced the incidence of postoperative
spinal infection. In one study, the rates of infection with
and without antimicrobial prophylaxis were 0.2% and
2.8%, respectively [39]. The infection involves most commonly the lumbar spine followed by the thoracic and cervical spine [40-41]. Vertebral osteomyelitis and disk space
infection can be complicated with paravertebral and epidural abscesses. The latter could lead to spinal cord or
nerve root compression and require urgent surgical intervention.
The majority of patients with vertebral osteomyelitis
present with back pain while less than half have fever.
Neurological symptoms such as motor or sensory deficits,
bladder and bowel incontinence are not uncommon and
should receive urgent attention. S. aureus is the most commonly isolated organism while coagulase-negative staphylococcus and gram-negative bacilli are less commonly
encountered. Pseudomonas aeruginosa and Candida spp.
are typically seen in intravenous drug users. Vertebral
osteomyelitis due to Brucella spp. and Mycobacterium
tuberculosis is common in endemic areas. When bacteremia is present, endocarditis should be ruled out [41-43].
Spine MRI is the test of choice when vertebral osteomyelitis is suspected. Gallium or PET scans are alternatives when MRI cannot be performed (i.e. patients with
claustrophobia or patients with implantable cardiovascular
devices). If the diagnosis is supported by imaging studies,
a microbiological diagnosis should be established. CTguided percutaneous biopsies are easy to perform but have
limited sensitivity (52%) [44]. When the results of the first
percutaneous biopsy are inconclusive, a second CT-guided
biopsy should be attempted before resorting to an open
biopsy. Tissue should be submitted for pathology as well as
bacterial, fungal and mycobacterial stains and cultures.
When the patient has concomitant bacteremia, it is safe to
assume that his vertebral osteomyelitis is caused by the
same organism isolated from the blood. Surgical debridement is necessary when patients present with an epidural
abscess compressing the spinal cord, large paravertebral
abscess, spine instability or failing medical treatment [6].
Effective antimicrobial therapy should be given for at
least four to six weeks. When vertebral osteomyelitis is
treated with surgical debridement and instrumented spine
Lebanese Medical Journal 2012 Volume 60 (1) 55

fusion or when hardware-associated osteomyelitis develops following spinal surgery, some experts recommend
parenteral antibiotic therapy followed by oral suppressive
antibiotic therapy for up to two years to allow bone healing [6].

Acute hematogenous osteomyelitis

Acute hematogenous osteomyelitis occurs mainly in prepubertal children. Long tubular bones (i.e. femur, tibia, and
fibula) are more commonly affected than flat bones and
spine [45]. Multiple bones could be infected concomitantly. The infection originates in the metaphyseal region and
can extend to the cortex or the epiphysis and joint space.
S. aureus and Streptococcus pneumoniae are responsible
for most cases. Children present with pain in the metaphyseal region of a long bone. Blood cultures are typically
positive. Radiological findings such as periosteal new
bone formation (periosteal elevation) or bone destruction
support the diagnosis. If plain radiographs are not conclusive, MRI may establish the diagnosis. Blood cultures
should be obtained before administering antimicrobials.
Bone, subperiosteal exudate, and synovial fluid should be
obtained if possible in order to identify the infecting microorganism. Acute hematogenous osteomyelitis in children is
frequently treated with antimicrobial therapy alone. Antibiotics are typically given for three weeks. Sequential therapy with intravenous followed by oral antibiotics is commonly used. Surgical treatment is considered in case of
no clinical response after 48 hours of antibiotic therapy,
septic arthritis, or failure to cure the infection despite adequate antibiotic therapy. Adequate and prompt treatment
leads to excellent outcome in newborns, infants and children; however, in cases associated with septic arthritis or
complicated with the destruction of the growth plate, the
prognosis is more reserved. In those situations, abnormal
growth of the affected bone is likely to occur and significant damage of the infected joint might be irreversible
[46].
Osteomyelitis in patients with diabetes mellitus
Patients with diabetes mellitus are at increased risk of
developing foot infections due to hyperglycemia, neuropathy, and peripheral vascular disease. During their lifetime, 15% of diabetic patients develop foot ulcers and 6%
are hospitalized because of those ulcers [47].
The infectious process usually originates at the site of an
ulcer and commonly progresses to reach contiguous bone.
When the size of an ulcer is > 2 x 2 cm and when ESR is
> 70 mm/hour, osteomyelitis is more likely to be present
[48]. The presence of exposed bone or the ability to probe
the bone is strongly suggestive of underlying osteomyelitis
(positive predictive value of 89%) [9, 48-49]. Further testing is not required when the probe-to-bone test is positive.
In other situations, plain radiographs, nuclear bone scans,
or MRI could be helpful to establish the diagnosis. ESR
and CRP should always be measured at baseline and monitored during therapy to assess response.
Chronic osteomyelitis in patients with diabetes mellitus
56 Lebanese Medical Journal 2012 Volume 60 (1)

is usually polymicrobial. Multiple aerobic and anaerobic

bacteria can be involved. When possible, bone tissue
should be submitted for cultures prior to the initiation of
antimicrobial therapy. When hemodynamically significant
stenosis is present, revascularization should be considered
before surgical debridement of the infected foot. Intravenous antimicrobials such as piperacillin-tazobactam,
ticarcillin-clavulanate, ampicillin-sulbactam, Ertapenem,
or other -lactams in combination with metronidazole are
commonly used. An oral regimen consisting of levofloxacin or moxifloxacin with metronidazole or clindamycin
can also be used [50]. HBOT might be beneficial in this
context due to limited oxygenation of the infected tissue
and the likelihood of anaerobic infection; however, data
from randomized, controlled studies are lacking. Limited amputation of the limb should be considered in cases
with persistent or recurrent osteomyelitis despite optimal
therapy.

Osteomyelitis associated with prosthetic joint infection

Joint arthroplasty represent a true success story due to its
ability to restore function. The projected number of patients who will undergo arthroplasty in the United States in
2030 is 3-4 millions [51]. It is estimated that 0.8 to 1.9% of
knee arthroplasties and 0.3 to 1.7% of hip arthroplasties get
infected [52]. The treatment also consists of a combination
of surgical and antimicrobial therapy. Three different therapeutic strategies are available:
1. Surgical debridement and retention of the prosthesis is
an option when certain criteria are met. Those include
duration of symptoms < 3 weeks, infection developing within 3 months of arthroplasty or presentation
consistent with hematogenous seeding, well-fixed
prosthesis, adequate soft tissue envelop, absence of
sinus tract, and established microbiologic diagnosis
and favorable susceptibility profile [52-53].
2. One-stage exchange entails resection of the infected
prosthesis, debridement of the infected tissue and immediate implantation of a new prosthesis. Antibioticimpregnated PMMA cement is frequently used during reimplantation. This strategy is not advisable
when the infection is caused by virulent organisms
(i.e. S. aureus, Gram-negative bacteria) or in presence
of draining sinus or significant purulence.
3. Two-stage exchange consists of resection of the infected prosthesis followed by parenteral antimicrobial therapy for 4-6 weeks and reimplantation of a
new prosthesis 2-6 weeks after finishing antimicrobial therapy. The use of a spacer impregnated with antimicrobial(s) (i.e. vancomycin, gentamicin or tobramycin) is a common practice currently and was
shown to reduce the rate of recurrent infection [54].
Antimicrobial therapy should be guided by in vitro susceptibilities (Table III). Following debridement and retention of the prosthesis, Rifampin was successfully used in
combination with fluoroquinolones. The duration of treatment was 3-6 months for prosthetic knee infection and
6 months for prosthetic hip infection [27, 55]. Shorter
A.J. EID, E.F. BERBARI Osteomyelitis

course (4 weeks) of parenteral antibiotic therapy can be

given followed by suppressive oral antibiotic therapy [56].
Rifampin-based regimen is also recommended after onestage exchange.

Osteomyelitis in injection drug users

Intravenous drug use is associated with hematogenous
osteomyelitis due to the introduction of bacteria and fungi
into the bloodstream. However, direct inoculation or contiguous spread is also possible [6]. Multifocal infections
may occur. The spine, sterno-clavicular, sterno-chondral,
and sacro-iliac joints are commonly involved [57-58]. The
most common organisms responsible for osteomyelitis in
injection drug users (IDU) are S. aureus, Pseudomonas
species, and Candida species. Eikenella corrodens, which
is part of the normal oral flora, is seen in IDU who lick
their needles or skin prior to injection (needle lickers
osteomyelitis) [59]. M. tuberculosis can cause skeletal
infection in IDU and most cases involve the spine [60].
Treatment of osteomyelitis in IDU is similar to treatment
of other patients; however, an oral regimen should be
used, if at all possible, to avoid using long-term intravenous access (e.g. peripherally inserted intravenous
catheter).

Osteomyelitis due to Brucella species

Brucellosis is endemic in the Mediterranean basin and the
Arabian Gulf; therefore, osteomyelitis due to Brucella
species should be considered in this setting. Brucellosis is
commonly transmitted via ingestion of contaminated food
such as raw milk, cheese made from unpasteurized milk, or
raw meat. Infection could also result from direct skin inoculation through skin abrasions or cuts during contact with
animal carcasses, placentas, and animal vaginal secretions.
Patients present with fever, night sweats, arthralgias,
anorexia and fatigue. When the diagnosis is delayed, localized infection occurs. Osteoarticular infections, mainly sacroiliitis, represent 20-30% of those localized infections [61-62]. Specific cultures (Ruiz-Castaneda or lysis
centrifugation) or prolonged incubation of cultures can
be used to establish a diagnosis. Serological studies using
serum agglutination (standard tube agglutination) and
enzyme-linked immunosorbent assay (ELISA) can be
very helpful, especially in case of negative cultures. The
combination of doxycycline-streptomycin or doxycyclinestreptomycin-rifampin seem to be more effective than
doxycycline-rifampim [63-64]. Ciprofloxacin-rifampin
can be considered as an alternative regimen for doxycycline-streptomycin when patients experience drug toxicity [65]. Osteoarticular disease, similar to other localizing
manifestations, carries with it higher risk of relapse compared to brucellosis without localizing disease. Therefore,
antibiotic therapy should be administered for 3-6 months
[61, 64] in order to minimize the risk of relapse.

Osteomyelitis due to Salmonella species

Osteomyelitis due to Salmonella species is uncommon
accounting for 0.45% of all osteomyelitis cases and is seen
A.J. EID, E.F. BERBARI Osteomyelitis

in only 0.8% of all Salmonella infections [66]. Patients

with sickle cell disease, however, have much higher risk
of developing this infection. Other risk factors include
comorbidities such as diabetes mellitus, systemic lupus
erythematosus, lymphoma, liver disease, previous surgery
or trauma, treatment with steroids, and extremes of age
[66]. Patients are usually treated with third-generation
cephalosporins or fluoroquinolones. In anecdotal reports,
the duration of successful antibiotic therapy ranged from
6-12 weeks [66-69].

Osteomyelitis due to mycobacteria

Osteomyelitis can result from infection due to M. tuberculosis or non-tuberculous mycobacteria (NTBM). Mycobacterial osteomyelitis should be suspected when bacterial
cultures remain negative or when granulomatous inflammation is identified in bone tissue [70]. Tuberculosis (TB)
of the musculoskeletal system represents 1-5% of all TB
cases [6]. Osteomyelitis is attributed to hematogenous
seeding of the bone at the time of primary infection and
should be considered in patients with history of treated or
untreated tuberculosis, known exposure to M. tuberculosis,
positive tuberculin skin test, and evidence of old or active
TB on chest X-ray. Potts disease or vertebral osteomyelitis due to M. tuberculosis represents around 50% of all
musculoskeletal TB cases [71]. The lumbar and lower
thoracic spine is more commonly involved than the upper
thoracic and cervical spine [72-73]. In 50% of cases, spine
MRI shows evidence of paravertebral abscesses and those
are frequently bilateral. Extraspinal tuberculosis presents
with swelling, pain, and mild erythema. A cold abscess
is usually present and spontaneous drainage through a
sinus tract could occur. The most common manifestations
of spinal osteomyelitis are pain and stiffness. Due to delayed diagnosis, neurological deficit due to spinal cord
compression is present in 42-76% of patients [74-75].
Treatment of tuberculous osteomyelitis is for the most
part medical. The regimens of antituberculous medications
used to treat osteoarticular TB are similar to those used to
treat other forms of TB, but treatment should be given for
a longer period of time (12-18 months) [76]. Surgical therapy might be necessary for abscess drainage, cord decompression, and spinal stabilization [74].
Musculoskeletal infections due to NTBM seem to have
increased in frequency over the past few years, possibly
due to better recognition of this infection [77]. Multiple
species can be responsible for osteomyelitis and those
include M. abscessus, M. chelonae, M. fortuitum, M. marinum, M. avium-intracellulare, M. kansasii, M. xenopi
and M. terrae complex [78-81]. The infection develops in bones, joints, bursae, or tendon sheaths following
direct inoculation at the time of surgery, trauma, puncture
wounds, or injections (intraarticular or extraarticular).
Patients present with non-healing wounds associated with
chronic drainage and sinus formation. Axial bone or
extremities could also be infected through hematogenous
seeding. Mycobacterial cultures of tissue specimens are
required to establish a diagnosis; however, rapidly-growLebanese Medical Journal 2012 Volume 60 (1) 57

ing mycobacteria grow on routine cultures as well. The

identification of the infecting species and its susceptibility
profile are crucial to guide antimicrobial therapy. A combination of two or three antibiotics (depending upon the
degree of severity of the infection) should be used to treat
the infection. The antibiotics should be determined based
on the susceptibility profile. Osteomyelitis due to rapidlygrowing mycobacteria is treated for six months while
osteomyelitis due to other mycobacteria is treated for at
least 12 months [82].

Osteomyelitis due to fungi

Fungal osteomyelitis is more likely to result from disseminated fungal infection than direct inoculation of the bone.
Osteomyelitis is commonly seen with disseminated endemic fungal infections such as blastomycosis, coccidioidomycosis and sporotrichosis. Up to 25% of patients with
disseminated blastomycosis develop osteomyelitis [83].
Candida osteomyelitis can complicate candidemia or result
from surgical site infection. Even though uncommon, disseminated Aspergillus and Cryptococcus infections in immunocompromised patients can lead to osteomyelitis.
Fungal osteomyelitis due to molds such as Pseudollascheria boydii, Scedosporium prolificans, and Fusarium
species is usually seen with open contaminated fractures.
The clinical context is often helpful to identify the fungus
responsible for osteomyelitis. The role of surgical treatment is relatively limited and the medical treatment
depends on the etiology.

Recurrent osteomyelitis
Patients presenting with recurrent osteomyelitis should
undergo comprehensive evaluation in order to determine
the underlying etiology. Recurrence of osteomyelitis
could be attributed to a variety of factors. Those include
incorrect microbiological diagnosis, inability to culture
the true pathogen (e.g. Mycobacteria, Coxiella, Mycoplasma, and Chlamydia species), use of inappropriate or
suboptimal dose of antimicrobial(s), development of
resistance of the infecting organism, and inadequate surgical debridement of the infected bone. Occasionally, failure of treatment is attributed solely to the virulence of the
infecting bacteria (e.g. Brucella species, MRSA). Antibiotic therapy should be held for at least two weeks prior
to repeat surgical debridement. Tissue specimens must be
submitted for aerobic and anaerobic bacterial, as well as
fungal and mycobacterial cultures. Following surgery,
antimicrobial therapy should be guided by culture results
and in vitro susceptibilities.
CONCLUSION

Osteomyelitis continues to be a serious infection associated with high relapse rate and significant morbidity and loss
of function. Preventive strategies should be emphasized
and widely implemented in order to reduce the incidence,
especially in high risk patients such as those with diabetes
mellitus. When osteomyelitis develops, the patient should
58 Lebanese Medical Journal 2012 Volume 60 (1)

be treated by a multidisciplinary team including an orthopedic surgeon, vascular surgeon, plastic surgeon, interventional radiologist, endocrinologist and an infectious diseases specialist. Such an approach provides the best chance
for cure and restoration of function.
REFERENCES

1. Belmatoug N, Cremieux AC, Bleton R et al. A new model

of experimental prosthetic joint infection due to methicillin-resistant Staphylococcus aureus : a microbiologic,
histopathologic, and magnetic resonance imaging characterization. J Infect Dis 1996 Aug ; 174 (2) : 414-17.
2. Lew DP, Waldvogel FA. Osteomyelitis. N Engl J Med
1997 Apr 3 ; 336 (14) : 999-1007.
3. Norden CW. Lessons learned from animal models of
osteomyelitis. Rev Infect Dis 1988 Jan-Feb ; 10 (1) :
103-10.
4. Ciampolini J, Harding KG. Pathophysiology of chronic
bacterial osteomyelitis. Why do antibiotics fail so often ?
Postgrad Med J 2000 Aug ; 76 (898) : 479-83.
5. Muller C, Zielinski CC, Passl R, Eibl MM. Divergent
patterns of leucocyte locomotion in experimental posttraumatic osteomyelitis. Br J Exp Pathol 1984 Jun ; 65
(3) : 299-303.
6. Berbari EF, Steckelberg JM, Osmon DR. Osteomyelitis.
In : Mandell, Douglas and Bennetts Principles and Practice of Infectious Diseases, 7th edition, Volume 1. Edinburgh, UK : Churchill Livingstone, 2009.
7. Chihara S, Segreti J. Osteomyelitis. Dis Mon 2010 Jan ;
56 (1) : 5-31.
8. Mader JT, Shirtliff M, Calhoun JH. Staging and staging
application in osteomyelitis. Clin Infect Dis 1997 Dec ;
25 (6) : 1303-9.
9. Grayson ML, Gibbons GW, Balogh K, Levin E,
Karchmer AW. Probing to bone in infected pedal ulcers.
A clinical sign of underlying osteomyelitis in diabetic
patients. JAMA 1995 Mar 1 ; 273 (9) : 721-3.
10. 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.
11. Mackowiak PA, Jones SR, Smith JW. Diagnostic value of
sinus-tract cultures in chronic osteomyelitis. JAMA 1978
Jun 30 ; 239 (26) : 2772-5.
12. Dinh MT, Abad CL, Safdar N. Diagnostic accuracy of the
physical examination and imaging tests for osteomyelitis
underlying diabetic foot ulcers : meta-analysis. Clin Infect
Dis 2008 Aug 15 ; 47 (4) : 519-27.
13. Schauwecker DS. The scintigraphic diagnosis of osteomyelitis. Am J Roentgenol 1992 Jan ; 158 (1) : 9-18.
14. Gotthardt M, Bleeker-Rovers CP, Boerman OC, Oyen WJ.
Imaging of inflammation by PET, conventional scintigraphy, and other imaging techniques. J Nucl Med Dec ; 51
(12) : 1937-49.
15. Hadjipavlou AG, Cesani-Vazquez F, Villaneuva-Meyer J,
et al. The effectiveness of gallium citrate Ga 67 radionuclide imaging in vertebral osteomyelitis revisited. Am J
Orthop (Belle Mead NJ) 1998 Mar ; 27 (3) : 179-83.
16. Termaat MF, Raijmakers PG, Scholten HJ, Bakker FC,
Patka P, Haarman HJ. The accuracy of diagnostic imaging for the assessment of chronic osteomyelitis : a sysA.J. EID, E.F. BERBARI Osteomyelitis

17.
18.

19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.

33.

tematic review and meta-analysis. J Bone Joint Surg Am

2005 Nov ; 87 (11) : 2464-71.
Pineda C, Vargas A, Rodriguez AV. Imaging of osteomyelitis : current concepts. Infect Dis Clin North Am
2006 Dec ; 20 (4) : 789-825.
Norden CW, Shinners E, Niederriter K. Clindamycin treatment of experimental chronic osteomyelitis due to Staphylococcus aureus. J Infect Dis 1986 May ; 153 (5) : 956-9.
Carragee EJ, Kim D, van der Vlugt T, Vittum D. The
clinical use of erythrocyte sedimentation rate in pyogenic
vertebral osteomyelitis. Spine (Phila Pa 1976) 1997 Sep
15 ; 22 (18) : 2089-93.
Tice AD, Hoaglund PA, Shoultz DA. Outcomes of osteomyelitis among patients treated with outpatient parenteral antimicrobial therapy. Am J Med 2003 Jun 15 ; 114
(9) : 723-8.
Razonable RR, Osmon DR, Steckelberg JM. Linezolid
therapy for orthopedic infections. Mayo Clin Proc 2004
Sep ; 79 (9) : 1137-44.
Rao N, Hamilton CW. Efficacy and safety of linezolid for
Gram-positive orthopedic infections : a prospective case
series. Diagn Microbiol Infect Dis 2007 Oct ; 59 (2) :
173-9.
Rao N, Regalla DM. Uncertain efficacy of daptomycin
for prosthetic joint infections : a prospective case series.
Clin Orthop Relat Res 2006 Oct ; 451 : 34-7.
Huddleston PM, Steckelberg JM, Hanssen AD, Rouse MS,
Bolander ME, Patel R. Ciprofloxacin inhibition of experimental fracture healing. J Bone Joint Surg Am 2000 Feb ;
82 (2) : 161-73.
Norden CW. Experimental chronic staphylococcal
osteomyelitis in rabbits : treatment with rifampin alone
and in combination with other antimicrobial agents. Rev
Infect Dis 1983 Jul-Aug ; 5 (Suppl 3) : S491-S494.
Shirtliff ME, Mader JT, Calhoun J. Oral rifampin plus
azithromycin or clarithromycin to treat osteomyelitis
in rabbits. Clin Orthop Relat Res 1999 Feb (359) : 22936.
Zimmerli W, Widmer AF, Blatter M, Frei R, Ochsner PE.
Role of rifampin for treatment of orthopedic implantrelated staphylococcal infections : a randomized controlled trial. Foreign-Body Infection (FBI) Study Group.
JAMA 1998 May 20 ; 279 (19) : 1537-41.
Perlroth J, Kuo M, Tan J, Bayer AS, Miller LG.
Adjunctive use of rifampin for the treatment of Staphylococcus aureus infections : a systematic review of the literature. Arch Intern Med 2008 Apr 28 ; 168 (8) : 805-19.
Kranke P, Bennett M, Roeckl-Wiedmann I, Debus S.
Hyperbaric oxygen therapy for chronic wounds. Cochrane
Database Syst Rev 2004 (2) : CD004123.
Ostermann PA, Seligson D, Henry SL. Local antibiotic
therapy for severe open fractures. A review of 1085 consecutive cases. J Bone Joint Surg Br 1995 Jan ; 77 (1) :
93-7.
Sterett WI, Ertl JP, Chapman MW, Moehring HD. Open
tibia fractures in the splenectomized trauma patient :
results of treatment with locking, intramedullary fixation. J Trauma 1995 Apr ; 38 (4) : 639-41.
DeLong WG Jr., Born CT, Wei SY, Petrik ME, Ponzio R,
Schwab CW. Aggressive treatment of 119 open fracture
wounds. J Trauma 1999 Jun ; 46 (6) : 1049-54.
Holcombe SJ, Schneider RK, Bramlage LR, Embertson
RM. Use of antibiotic-impregnated polymethyl methacrylate in horses with open or infected fractures or joints :

A.J. EID, E.F. BERBARI Osteomyelitis

34.
35.

36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.

47.

48.
49.

50.
51.
52.
53.

19 cases (1987-1995). J Am Vet Med Assoc 1997 Oct 1 ;

211 (7) : 889-93.
Henry SL, Ostermann PA, Seligson D. The prophylactic
use of antibiotic impregnated beads in open fractures.
J Trauma 1990 Oct ; 30 (10) : 1231-8.
Kindsfater K, Jonassen EA. Osteomyelitis in grade II and
III open tibia fractures with late debridement. J Orthop
Trauma 1995 Apr ; 9 (2) : 121-7.
Shyam AK, Sancheti PK, Patel SK, Rocha S, Pradhan C,
Patil A. Use of antibiotic cement-impregnated intramedullary nail in treatment of infected non-union of long
bones. Indian J Orthop 2009 Oct ; 43 (4) : 396-402.
Qiang Z, Jun PZ, Jie XJ, Hang L, Bing LJ, Cai LF. Use
of antibiotic cement rod to treat intramedullary infection
after nailing : preliminary study in 19 patients. Arch
Orthop Trauma Surg 2007 Dec ; 127 (10) : 945-51.
Wiley AM, Trueta J. The vascular anatomy of the spine
and its relationship to pyogenic vertebral osteomyelitis.
J Bone Joint Surg Br 1959 Nov ; 41-B : 796-809.
Schnoring M, Brock M. [Prophylactic antibiotics in lumbar disc surgery : analysis of 1,030 procedures]. Zentralbl
Neurochir 2003 ; 64 (1) : 24-9.
Torda AJ, Gottlieb T, Bradbury R. Pyogenic vertebral
osteomyelitis : analysis of 20 cases and review. Clin
Infect Dis 1995 Feb ; 20 (2) : 320-8.
Hopkinson N, Stevenson J, Benjamin S. A case ascertainment study of septic discitis : clinical, microbiological and radiological features. QJM 2001 Sep ; 94 (9) :
465-70.
Pigrau C, Almirante B, Flores X et al. Spontaneous pyogenic vertebral osteomyelitis and endocarditis : incidence, risk factors, and outcome. Am J Med 2005 Nov ;
118 (11) : 1287.
Vlahakis NE, Temesgen Z, Berbari EF, Steckelberg JM.
Osteoarticular infection complicating enterococcal endocarditis. Mayo Clin Proc 2003 May ; 78 (5) : 623-8.
Nolla JM, Ariza J, Gomez-Vaquero C et al. Spontaneous
pyogenic vertebral osteomyelitis in nondrug users.
Semin Arthritis Rheum 2002 Feb ; 31 (4) : 271-8.
Vazquez M. Osteomyelitis in children. Curr Opin Pediatr
2002 Feb ; 14 (1) : 112-15.
De Boeck H. Osteomyelitis and septic arthritis in children. Acta Orthop Belg 2005 Oct ; 71 (5) : 505-15.
Ramsey SD, Newton K, Blough D et al. Incidence, outcomes, and cost of foot ulcers in patients with diabetes.
Diabetes Care 1999 Mar ; 22 (3) : 382-7.
Butalia S, Palda VA, Sargeant RJ, Detsky AS, Mourad O.
Does this patient with diabetes have osteomyelitis of the
lower extremity ? JAMA 2008 Feb 20 ; 299 (7) : 806-13.
Newman LG, Waller J, Palestro CJ et al. 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.
Lipsky BA, Berendt AR, Deery HG et al. Diagnosis and
treatment of diabetic foot infections. Clin Infect Dis 2004
Oct 1 ; 39 (7) : 885-910.
Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections
of primary and revision hip and knee arthroplasty in the
United States from 2005 to 2030. J Bone Joint Surg Am
2007 Apr ; 89 (4) : 780-5.
Del Pozo JL, Patel R. Clinical practice. Infection associated with prosthetic joints. N Engl J Med 2009 Aug 20 ;
361 (8) : 787-94.
Brause B. Infections with prostheses in bones and joints.
Lebanese Medical Journal 2012 Volume 60 (1) 59

54.
55.
56.
57.
58.
59.

60.
61.
62.
63.
64.

65.
66.

67.

In : Mandell, Douglas and Bennetts Principles and Practice of Infectious Diseases, 7th edition, Volume 1. Churchill
Livingstone, 2009.
Cabrita HB, Croci AT, Camargo OP, Lima AL. Prospective
study of the treatment of infected hip arthroplasties with
or without the use of an antibiotic-loaded cement spacer.
Clinics (Sao Paulo) 2007 Apr ; 62 (2) : 99-108.
Barberan J, Aguilar L, Carroquino G et al. Conservative
treatment of staphylococcal prosthetic joint infections in
elderly patients. Am J Med 2006 Nov ; 119 (11) : 993.
e7-10.
Marculescu CE, Berbari EF, Hanssen AD et al. Outcome
of prosthetic joint infections treated with debridement
and retention of components. Clin Infect Dis 2006 Feb
15 ; 42 (4) : 471-8.
Kak V, Chandrasekar PH. Bone and joint infections in
injection drug users. Infect Dis Clin North Am 2002 Sep ;
16 (3) : 681-95.
Chandrasekar PH, Narula AP. Bone and joint infections
in intravenous drug abusers. Rev Infect Dis 1986 NovDec ; 8 (6) : 904-11.
Swisher LA, Roberts JR, Glynn MJ. Needle lickers osteomyelitis. Am J Emerg Med 1994 May ; 12 (3) : 343-6.
Firooznia H, Seliger G, Abrams RM, Valensi V, Shamoun
J. Disseminated extrapulmonary tuberculosis in association with heroin addiction. Radiology 1973 Nov ; 109
(2) : 291-6.
Colmenero JD, Reguera JM, Martos F et al. Complications associated with Brucella melitensis infection : a
study of 530 cases. Medicine (Baltimore) 1996 Jul ; 75
(4) : 195-211.
Ariza J, Pujol M, Valverde J et al. Brucellar sacroiliitis:
findings in 63 episodes and current relevance. Clin Infect
Dis 1993 Jun ; 16 (6) : 761-5.
Ariza J, Gudiol F, Pallares R et al. Treatment of human
brucellosis with doxycycline plus rifampin or doxycycline plus streptomycin. A randomized, double-blind
study. Ann Intern Med 1992 Jul 1 ; 117 (1) : 25-30.
El Miedany YM, El Gaafary M, Baddour M, Ahmed I.
Human brucellosis : do we need to revise our therapeutic
policy ? J Rheumatol 2003 Dec ; 30 (12) : 2666-72.
Alp E, Koc RK, Durak AC et al. Doxycycline plus streptomycin versus ciprofloxacin plus rifampicin in spinal
brucellosis [ISRCTN31053647]. BMC Infect Dis 2006 ;
6 : 72.
Arora A, Singh S, Aggarwal A, Aggarwal PK.
Salmonella osteomyelitis in an otherwise healthy adult
male successful management with conservative treatment : a case report. J Orthop Surg (Hong Kong) 2003
Dec ; 11 (2) : 217-20.
van Cappelle HG, Veenendaal D, de Vogel PL. Salmonella panama osteomyelitis in an otherwise healthy
patient. A case report. Clin Orthop Relat Res 1995 Dec
(321) : 235-8.

60 Lebanese Medical Journal 2012 Volume 60 (1)

68.
69.
70.

71.
72.
73.
74.
75.
76.
77.
78.

79.

80.

81.
82.
83.

Santos EM, Sapico FL. Vertebral osteomyelitis due to

salmonellae : report of two cases and review. Clin Infect
Dis 1998 Aug ; 27 (2) : 287-95.
Agustsson AI, Olafsson K, Thorisdottir AS. Salmonella
osteomyelitis in pregnancy. Acta Obstet Gynecol Scand
2009 ; 88 (10) : 1171-3.
Ikem IC, Bamgboye EA, Olasinde AA. Spinal tuberculosis : a 15-year review at OAUTHC Ile-Ife. Niger Postgrad Med J 2001 Mar ; 8 (1) : 22-5.
Pertuiset E, Beaudreuil J, Liote F et al. Spinal tuberculosis in adults. A study of 103 cases in a developed country, 1980-1994. Medicine (Baltimore) 1999 Sep ; 78 (5) :
309-20.
Lifeso RM, Weaver P, Harder EH. Tuberculous spondylitis in adults. J Bone Joint Surg Am 1985 Dec ; 67 (9) :
1405-13.
Weaver P, Lifeso RM. The radiological diagnosis of
tuberculosis of the adult spine. Skeletal Radiol 1984 ; 12
(3) : 178-86.
Nussbaum ES, Rockswold GL, Bergman TA, Erickson DL,
Seljeskog EL. Spinal tuberculosis : a diagnostic and management challenge. J Neurosurg 1995 Aug ; 83 (2) : 243-7.
Hsu LC, Leong JC. Tuberculosis of the lower cervical
spine (C2 to C7). A report on 40 cases. J Bone Joint Surg
Br 1984 Jan ; 66 (1) : 1-5.
Treatment of tuberculosis. MMWR Recomm Rep 2003
Jun 20 ; 52 (RR-11) : 1-77.
Eid AJ, Berbari EF, Sia IG, Wengenack NL, Osmon DR,
Razonable RR. Prosthetic joint infection due to rapidly
growing mycobacteria : report of 8 cases and review of the
literature. Clin Infect Dis 2007 Sep 15 ; 45 (6) : 687-94.
Falkinham JO 3rd. Epidemiology of infection by nontuberculous mycobacteria. Clin Microbiol Rev 1996 Apr ;
9 (2) : 177-215.
Lahey T. Invasive Mycobacterium marinum infections.
Emerg Infect Dis 2003 Nov ; 9 (11) : 1496-8.
Chan ED, Kong PM, Fennelly K, Dwyer AP, Iseman
MD. Vertebral osteomyelitis due to infection with nontuberculous Mycobacterium species after blunt trauma to
the back : 3 examples of the principle of locus minoris
resistentiae. Clin Infect Dis 2001 May 15 ; 32 (10) :
1506-10.
Hellinger WC, Smilack JD, Greider JL Jr et al. Localized
soft-tissue infections with Mycobacterium avium/Mycobacterium intracellulare complex in immunocompetent
patients : granulomatous tenosynovitis of the hand or
wrist. Clin Infect Dis 1995 Jul ; 21 (1) : 65-9.
Griffith DE, Aksamit T, Brown-Elliott BA et al. An official ATS/IDSA statement : diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J
Respir Crit Care Med 2007 Feb 15 ; 175 (4) : 367-416.
Moore RM, Green NE. Blastomycosis of bone. A report
of six cases. J Bone Joint Surg Am 1982 Sep ; 64 (7) :
1097-101.

A.J. EID, E.F. BERBARI Osteomyelitis