P T C AS E : O ST E O M Y E L I T I S

(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.

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

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 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?

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.
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 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 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

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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.

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
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 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 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

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 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):

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

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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 osteomyelitis Three phase technetium bone scan

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

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

BIBL IOGRAP H Y

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.

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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).

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