PT CASE: OSTEOMYELITIS

(INSTRUCTOR VERSION)

By Dan Waldman, MD
Department of Family and Community Medicine

GOALS FOR SESSION

At the end of the session, the residents should:

1. Know the basic presentation of osteomyelitis

2. Know which lab tests may be helpful in suspected osteomyelitis, and their
limitations
3. Have a basic understanding of which imaging modalities to use in the
evaluation of osteomyelitis
4. Have a basic understanding of treatment options in osteomyelitis

CASE PRESENTATION WITH QUESTIONS

You are working in clinic, mostly seeing a mix of other providers patients, and acute
care visits. Youve seen 3 URIs and a few young people with mechanical back pain,
when in walks another patient with back pain. This patient is an 85 year old man
with a history of only arthritis in his knees and back. He states that he has had the
new onset of back pain in his mid to low back for the last 3 weeks. He was seen 2
weeks ago, and prescribed Tylenol with codeine and told to follow up in a few weeks.
There was no specific trauma or injury, and the pain does not radiate. He has taken
ibuprofen with only mild improvement. The pain is not relieved by any positional
changes. His pain has been worsening for the last couple weeks.

Q. What are some of the specific questions you would want to ask
this patient about his back pain?

A. There are many questions at this point since the history was so brief. The
key here is to begin to identify possible red flags. Potential red flags in a
back pain history are: age more than 50 years, history of cancer, fever,
unexplained weight loss, pain that is worse at rest, a history of IV drug
use, symptoms of an underlying infection (such as dysuria), incontinence,
or pain that lasts more than 6 weeks.

The patient has no fevers, chills, night sweats or pain anywhere besides his back, He
denies new bowel or bladder symptoms, though he did have dysuria a few weeks ago
that resolved on its own. The patient has a history of skin cancer for which he sees
dermatology at the VA and has only needed superficial treatments, such as biopsies
and freezing with liquid nitrogen. He also has a history of BPH, and chronic
symptoms of urinary hesitancy.

1
 Q. What are some potential causes of this patients back pain on your
differential?

A. Given the patients age, osteoporosis with a resulting compression fracture

would be high on the differential. Mechanical back pain from an
unperceived strain is also possible. The patients age though puts him at
risk for some more serious causes of back pain, such as metastatic
disease, spinal stenosis, and infection.

The patient has a normal temperature, and otherwise normal vital signs. The
patients back exam is notable for tenderness of the paraspinal muscles at about T5.
Straight leg raising does not worsen the patients pain. Reflexes, strength and
sensation testing are normal. Your prostate exam reveals a diffusely enlarged
prostate without nodules. You notice a recent PSA of 6.0 ng/ml.

Q. What would be a couple basic tests you could order for the
beginning of the workup?

A. An ESR and X-Ray would be a good place to start. The X-ray shows
degenerative changes in the T1-T6 vertebra, but nothing more specific.
The ESR is elevated at 104 mm/hr. You also obtain a CBC which shows a
white count of 9400 with 70% neutrophils. Hemoglobin is 12.5.

Q. How do you interpret these findings and the overall picture so far?

A. The X-ray is helpful, but non-diagnostic in this case. Compression

fractures, if present, are usually seen on plain films. Additionally,
metastatic lesions from prostate cancer are usually blastic and visible on
X-ray. The patients mildly elevated PSA may not be meaningful. The
elevated ESR, however, is concerning for chronic infection, metastatic
tumor, vasculitis or multiple myeloma.

You arrange from admission from your clinic, to facilitate continued workup.

Q. What are the next steps in the workup?

A. Further imaging is probably the next step. A serum and urine protein
electrophoresis should be ordered as well. Other basic tests, such as
chemistry panels and LFTs could also be helpful, as well as blood and
urine cultures.

In this case, the results of the electrophoresis tests are normal, and the
chem.-7 and LFT results are normal. A CT is obtained and shows an
abnormal soft tissue density extending from the midbody of the L3 to L4
vertebra. The radiologist gives a differential for the density that includes
disc herniation, metastatic disease or infection.

Q. What are some other imaging modalities that can be attempted

for further evaluation?

2
 A. Bone scans can be helpful in the diagnosis of many conditions that have
increased bone metabolic activity, but may not be able to differentiate
between soft tissue infection, degenerative joint disease, healing fractures
or stress fractures. MRI can be helpful in unclear situations, especially
involving the spine, and can give help delineate the extension of anatomic
abnormalities caused by the disease process.

An MRI is obtained, and shows destruction of the endplates of the L3 and

L4 vertebral bodies, with destruction of the disc space between them. The
differential remains infectious or metastatic.

Q. What would be the best next step in diagnosis?

A. A guided biopsy performed by interventional radiology should be

performed next. A fine-needle aspiration biopsy of the L3-L4 disc space
reveals blood-tinged, slightly cloudy fluid. Gram staining shows numerous
white cells, but no organisms. Cytology is negative for malignant cells.
Cultures obtained of the fluid are pending.

Q. What should you do next?

A. The combination of the MRI findings and the negative cytology suggest
vertebral infection, which typically involves two adjacent vertebras and the
disc space between them. Cultures can be negative, so multiple
specimens should be obtained on biopsy. If the cultures from the first
biopsy are negative another biopsy can be performed. If the second
attempt yields no organism, the options are then empiric treatment or
open surgical biopsy.

Q. What are the most likely organisms to gear empiric therapy

towards?

A. In this case, most likely staph aureus. The specific organisms encountered
vary depending on the clinical scenario and the age of the patient. S. aureus
and streptococci are typical in neonates; S. aureus is found later in life; and
gram-negative rods are found in the elderly. Fungal osteomyelitis is a
complication of catheter-related fungemia, the use of illicit drugs
contaminated by candida species and prolonged neutropenia. Pseudomonas
can be isolated from injection-drug addicts, and from patients with urinary
catheters in place (Lew DP W. F., 1997).

Q. How long should antibiotics be given for?

Traditionally, 4-6 weeks of antimicrobial therapy are used for treatment of

osteomyelitis. The rationale for this duration is based on the results of animal
studies and the observation that revascularization of bone after debridement
takes about four weeks (Lazzarini L MD, 2004).

Q. What about using oral antibiotics?

A. Oral treatment of acute osteomyelitis in children has been accepted for

many years, though the treatment in adults has traditionally been
3
 intravenous for most acute and chronic cases. Sequential treatment
involves starting a patient with intravenous antibiotics for a week or two,
and then switching to oral antibiotics for completion of treatment. This
has been best studied in the use of quinolone antibiotics (Mader JT, 1990),
though in one review the success rates may differ by organism, with cure
rates of 92% being seen for enterobacter, 72% for pseudomonas and 75%
for staph. aureus (Lew DP W. F., 1995).

Osteomyelitis and diskitis are rare causes for back pain presenting to a primary care
physicians office. The important points with this case are recognizing that this
patient had some warning signs (age, worsening over a few weeks, and presence of
pain in all positions) for further workup. Additionally, the lack of fever and white
count is not uncommon for vertebral osteomyelitis. One study estimated that fever
was present in only 52% of patients with pyogenic osteomyelitis and only 4% of
patients with diskitis (Deyo, 1986). Leukocytosis is present in only about 43% of
patients with spinal infection, and 6% of patients with nonspecific mechanical low
back pain who do not have a spinal infection (Deyo, 1986). Thus the presence of
elevated white count and fever increase the odds of spinal infection significantly, but
the absence does not substantially decrease the odds.

Likewise an ESR greater than 100 is also significantly associated with a serious
underlying cause of back pain, which when combined with the patients age and
symptoms, warranted an aggressive workup.

OSTEOMYELITIS REVIEW

Introduction

Osteomyelitis is a difficult disease to diagnose. This is not helped by the lack of

good quality studies that evaluate different clinical criteria for the diagnosis of
osteomyelitis. Diagnostic tests must be tailored to the specific clinical scenario, as
many factors can affect the accuracy of tests, including the chronicity of the infection
and the amount of inflammation present.

Classification

There are a few different ways to classify osteomyelitis. In general, it should be

categorized by 1) the chronicity of the infection, and 2) the underlying pathogenesis.

Chronicity: Acute vs. chronic. There are many differences of opinion, some state that
more than 10 days of symptoms means chronic, as signs for more than 10 days can
correlate roughly with the development of necrotic bone (Lew DP, 1997). Most
consider acute to be evolving over several days to weeks, and chronic to be
evolving over weeks to months, or even years. The hallmark of chronic osteomyelitis
is the presence of dead bone. Subacute osteomyelitis is often used for the middle
ground of a few weeks of mild symptoms (see below).

Pathogenesis: hematogenous spread of bacteria, contiguous spread from soft tissue

infection, or local inoculation following surgery or trauma. Hematogenous spread is
more common in children and elderly patients. Osteomyelitis after injury is the most
prevalent type and is usually associated with open fractures or after orthopedic
surgery to repair injured bones.

4
Symptoms

Typical acute osteomyelitis presents with bone pain, tenderness, warmth and
swelling developing over several days to a week. The pain occurs with and
without movement. Many patients are febrile, and rigors are occasionally
present, though patients often have no constitutional symptoms.

Osteomyelitis of the hip, vertebrae and pelvis are known for presenting with
very few symptoms

Chronic osteomyelitis is easy to diagnose in patients with previously

diagnosed and treated osteomyelitis who then have the recurrence of pain or
inflammation in the same place. The difficulty arises in the unfortunately not
uncommon cases of suspected osteomyelitis associated with orthopedic
prosthesis, decubitus ulcers and foot ulcers from diabetes and/or vascular
insufficiency.

Labs

Routine labs are non-specific. These include elevated ESR and elevated
white counts. As an example, in patients with a foot ulcer and diabetes (in
the absence of end stage renal disease), ESR greater than 100 mm/hr is highly
sensitive, but non-specific for diagnosing osteomyelitis (Newman, 1991).
Blood cultures are positive in 50% of cases in acute osteomyelitis. A
positive blood culture and radiologic evidence of osteomyelitis obviates the
need for a bone biopsy.

Radiologic Evaluation

Plain films: inexpensive but insensitive. May help diagnose or choose further
studies, or exclude other conditions. Soft tissue swelling + bone destruction
+ periosteal reaction is fairly specific for osteomyelitis, but bone changes take
2-3 weeks to be evident. Some situations may be complicated by bone
changes from other processes. Osteomyelitis cannot be excluded if plain
films are negative. Chronic osteo can be seen on plain films with bone
sclerosis, periosteal new bone formation and sequestra (piece of dead bone
separated from the bone in the process of necrosis).

CT (with and without contrast): Can detect cortical destruction,

intraosseous gas, periosteal reaction and soft tissue extension.

MRI: Especially useful in imaging the vertebra and the infected foot. Also
helps in providing pre-op detail for surgical debridement. In fact, MRI may be
the best modality for evaluating the foot for osteomyelitis, including diabetic
feet. MRI can have false positive results in fractures, bone infarcts or healed
osteomyelitis.

Ultrasound: Can reveal fluid collections adjacent to bone, significant

elevation of the periosteum and thickening of the periosteum, but the
sensitivity and specificity of this modality needs further evaluation.

Bone Scan: Three phase bone scan can differentiate cellulitis from
osteomyelitis. The three phase technetium bone scan is considered by
many the test of choice in evaluating for acute osteomyelitis in cases
5
 of normal plain films, with a sensitivity and specificity near 95%
(Schauwecker, 1996). False positive results though can be seen in any
situation that causes increased bone turnover, such as after a traumatic
injury, following surgery, diabetic feet, septic arthritis, inflammatory bone
diseases, cancer, healed osteo and Pagets disease (Schauwecker, 1996).

Indium labeled leukocyte scan: Useful at evaluating for osteo at sites of

fracture nonunion. Better than bone scans in evaluation of diabetic feet, but
still relatively unspecific. This test is time consuming as it takes time to
obtain the tracer and tag the patients cells. (the whole process can take 2-3
days from the time ordered).

Dual Tracer Scans: Combine an inflammation imaging tracer (indium or

gallium) with an anatomic tracer (a technetium labeled bone scan or
marrow scan). The bone scan portion provides good sensitivity, while the
indium labeled cell scan helps localize infection to bone or soft tissue (Ghiorzi,
2006).

PET Scan: Recent meta-analysis shows PET scanning to be the most accurate
single test to diagnose chronic osteomyelitis. Similar results were seen in the
combination of bone scans and white cell scans (dual tracer scans). The
quality of the studies available for the meta-analysis was generally variable
(Termaat MF, 2005).

Bone Biopsy

Gold standard for the diagnosis of osteomyelitis. Note that open biopsy, is the
gold standard, though needle biopsy is commonly used for practical reasons.
Sampling error reduces the sensitivity and specificity of needle biopsy
somewhat, so if the clinical suspicion is high and the needle biopsy is
negative, repeating the needle biopsy, or performing an open biopsy should
be done. Bone biopsy may be warranted as well in patients with decubitus
ulcers and clinical suspicion of osteomyelitis, even with normal labs and
imaging.

Osteomyelitis associated with infected overlying wounds can present a

challenge for biopsy. Correlation of the microbiology of the overlying wound
and that of the causative organism of the osteomyelitis is generally poor, so
biopsy of the bone should still be attempted (Khatri G, 2001), avoiding the
wounded tissue.

Diabetic Foot Ulcers Associated with Osteomyelitis

Patients with diabetes and soft tissue infections for more than two weeks, especially
if they are located over bony prominences, are at high risk for osteomyelitis. The
following clinical findings were noted in a review of 35 patients with limb-threatening
diabetic foot ulcers (Newman, 1991):

6
 Lesions larger than 2 cm x 2 cm had a sensitivity of 56 percent and specificity
of 92 percent for osteomyelitis.
Ulcers deeper than 3 mm were significantly more likely to overlie infected
(osteomyelitic) bone than shallower ulcers (82 versus 33 percent).

All patients with ulcers that exposed bone were associated with underlying
osteomyelitis.

An erythrocyte sedimentation rate greater than 70 mm/h had a sensitivity of

28 percent and specificity of 100 percent for diagnosing osteomyelitis.

In another report of 76 patients with infected diabetic foot ulcers, 50 had contiguous
osteomyelitis (Grayson, 1995). A probe could be passed directly to bone in 33 of
these patients (66 percent), compared to four of 26 (15 percent) without
osteomyelitis.

As mentioned above, MRI is the best imaging choice in cases of suspected

osteomyelitis in cases of diabetic foot infections.

Treatment of Osteomyelitis

Few studies have investigated the optimal treatment for osteomyelitis. In order to
measure treatment success, patients would need to be followed for years. Also,
debridement complicates the utility of antibiotics, and clinical situations and
pathogens are heterogeneous. Most recommendations are therefore based on expert
opinion.

Obtaining a biopsy sample is essential for proper antibiotic selection. After the
biopsy is obtained, empiric antibiotics should be started. In the past this meant
nafcillin plus cefotaxime or ceftriaxone, but nafcillin is being replaced more and more
with vancomycin with increasing MRSA prevalence.

Early antibiotics limit the development of bone destruction or necrosis, and must be
parenterally administered for at least 4, but often 6 weeks. These can be completed
as an outpatient as appropriate. If antibiotics fail, or in cases complicated by poor
vascular supply or chronic infection, debridement may be necessary as well,
removing the devitalized bone and soft tissue.

In the absence of good oxygen delivery to a limb with chronic osteomyelitis,

especially in cases where the pathogen has not been adequately identified,
amputation of the limb may be required. A clear discussion regarding the pros and
cons of antibiotics versus surgical debridement should be undertaken with the
patient, especially when the chances for success with antibiotics alone are slim.

Imaging of choice in suspected osteomyelitis, by situation (in addition to

plain films):
Clinical Scenario Radiologic test of choice

Diabetic foot infection MRI

Evaluation of acute Three phase technetium bone scan

7
osteomyelitis in
uncomplicated* cases
Ferromagnetic material is Nuclear study: indium scan or dual tracer exam. Note,
present that may degrade most materials used in orthopedics, such as titanium,
CT or MRI images do not interfere with MRI.
Evaluation of the spine for MRI
ostei
Chronic osteomyelitis PET scan if available, or combination of bone scan and
white cell scan
Diabetic ulcer where there Consider no further imaging, proceed to biopsy
is either an ulcer larger than
2x2cm or bone is palpable
on probing

x
complicated = complicating a fracture, postop, patients with neuropathy,
vasculopathy

B IB LI O GRAPHY

Carek PJ, Dickerson L, Sack J (2001). Diagnosis and Management of Osteomyelitis. Am Fam Phys,
63(12):2413-2420.

Deyo, R. (1986). Early diagnostic evaluation of low back pain. J Gen Intern Med , 1:328-38.

Ghiorzi, T. M. (2006). Diagnosis of Osteomyelitis in Adults. UpToDate .

Grayson, M. G. (1995). Probing to bone in infected pedal ulcers. A clinical sign of underlying osteomyelitis
in diabetic patients. JAMA , 273:721.

Khatri G, W. D. (2001). Effect of bone biopsy in guiding antimicrobial therapy for osteomyletis complicating
open wounds. AM J Med Sci , 321(6):367-71.

Lazzarini L MD, M. J. (2004). Osteomyelitis in Long Bones. The Journal of Bone and Joint Surgery , 86:2305-
2318 .

Lew DP, W. F. (1997). Osteomyelitis. NEJM , 336: 16, 999-10073.

Lew DP, W. F. (1995). Quinolones and osteomyelitis: state-of-the-art. Drugs , Suppl 2:100-101.

Lurie JD, Gerber PD, Sox H (2000). A pain in the back. NEJM, 343(10):723-726.

Mader JT, C. J. (1990). Oral ciprofloxacin compared with standard parenteral antibiotic therapy for chronic
osteomyelitis in adults. J Bone Joint Surg Am , 72:104 -10.

Newman, L. W. (1991). Unsuspected osteomyelitis in diabetic foot ulcers. Diagnosis and monitring by
leukocyte scanning with indium In-111 oxyquinoline. JAMA , 266:1246.

Schauwecker, D. (1996). The role of nuclear imaging in osteomyelitis. In D. Collier, Skeletal Nuclear
Medicine. St Louis: Mosby.

Termaat MF, R. P. (2005). The accuracy of diagnostic imaging for the assessment of chronic osteomyelitis: a
systemic review and meta-analysis. J Bone Joint Surg Am , 87:2464-71.

Post Module Evaluation

Please place completed evaluation in an interdepartmental mail envelope and

address to Dr. Wendy Gerstein, Department of Medicine, VAMC (111).
8
1) Topic of module:__________________________

2) On a scale of 1-5, how effective was this module for learning this topic?
_________

(1= not effective at all, 5 = extremely effective)

3) Were there any obvious errors, confusing data, or omissions? Please

list/comment below:

______________________________________________________________________________
______________________________________________________________________________
______________________________________________________________________________
______________________________________________________

4) Was the attending involved in the teaching of this module? Yes/no (please
circle).

5) Please provide any further comments/feedback about this module, or the

inpatient curriculum in general:

6) Please circle one:

Attending Resident (R2/R3) Intern Medical student