I. What every physician needs to know

Osteomyelitis refers to inflammation of bone due to infection. Infection can reach bone through a number of different means, such as:

1. Contiguous spread from a nearby source (e.g., infected sacral decubitus ulcer)

2. Direct inoculation (e.g., following penetrating trauma or surgery)

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3. Hematogenous seeding (e.g., vertebral osteomyelitis in the setting of bacteremia)

The sequence of development can be divided into three phases: microbial invasion/biofilm proliferation, immune response, and bacterial invasion/destruction of bone tissue. When infection reaches bone it can cause localized suppurative inflammation which may result in increased intraosseous pressure, ischemic necrosis and separation of fragments of bone. These fragments (sequestrum) lack blood supply and may further harbor bacteria. Additionally, pus may erupt through the cortex of bone resulting in soft tissue abscesses, subperiosteal deposits, and sinus tracts.

The clinical manifestations of osteomyelitis vary depending on the location, the mechanism of infection and whether the infection is acute or chronic. Acute infection, typically measured in days to weeks, is often characterized by redness, pain and swelling of the affected bone. Systemic symptoms (such as fever and rigors) may also be present.

Chronic osteomyelitis, measured in weeks to months/years, can be more subtle and may involve chronic pain and malaise or may have relatively few symptoms at all. The first clue to the presence of chronic osteomyelitis may be a history of a nonhealing ulcer or fracture, breakdown of a surgical wound, or the development of a sinus tract. The presence of sequestra and/or sinus tracts are pathognomonic for chronic osteomyelitis.

The microbiology of osteomyelitis depends greatly on the mechanism of infection. Osteomyelitis from a hematogenous source is typically monomicrobial; that from contiguous spread of a local infection is often polymicrobial.

The presence of devascularized areas within bone make antibiotic treatment challenging (i.e., if antibiotics are unable to reach the focus of infection). Thus the optimal treatment for osteomyelitis may be both medical and surgical.

Though osteomyelitis can occur in any bone, and thus present in a myriad of ways, there are various important subtypes of osteomyelitis in the adult population. These include osteomyelitis in patients with diabetes or vascular insufficiency, infected joint prostheses, vertebral osteomyelitis and assorted other types (e.g., puncture wounds, infection in IVDU, etc). These will be discussed below.

II. Diagnostic Confirmation: Are you sure your patient has Osteomyelitis?

The gold standard for diagnosis of osteomyelitis is isolation of an organism via direct culture of the bone.

Other features suggesting the diagnosis are the presence of sinus tracts, classic findings on imaging (e.g., bone edema in early infection or the presence of sequestrum in chronic infection). Other specific subtypes of osteomyelitis may have additional diagnostic criteria. For example, a diabetic ulcer that can be probed to bone is diagnostic of osteomyelitis.

A. History Part I: Pattern Recognition

Osteomyelitis may be a challenging diagnosis to make and requires a high index of suspicion. Symptoms may vary depending on the location, the mechanism of infection and whether infection is acute or chronic.

In general features supporting a diagnosis of acute osteomyelitis include:

  • Local symptoms- erythema, swelling, tenderness, warmth over bone
  • Systemic symptoms- fever, rigors
  • Supportive history- e.g., penetrating trauma, bacteremia

Features supporting a diagnosis of chronic osteomyelitis include:

  • Local symptoms- pain, erythema. Systemic symptoms are rare.
  • Nonhealing skin ulcers- often in patients with diabetes or vascular insufficiency, particularly those that probe to bone
  • Nonhealing fractures or nonunion; prosthetic joint instability on imaging
  • Draining sinus tracts

Clinical patterns vary depending on the specific location and mechanism of osteomyelitis. For example:

  • Diabetic foot ulcer: In this setting there is commonly a triad of a nonhealing ulcer, neuropathy, and vascular insufficiency. Exam often reveals weak or insufficient pedal pulses, decreased sensation on monofilament testing and ulceration that may probe to bone.
  • Vertebral osteomyelitis: Commonly presents with back pain, particularly the lower thoracic and lumbar spine, and tenderness to spinal percussion. Fever is an inconsistent finding.
  • Infected joint prosthesis: Typically presents with pain and may have joint instability or hardware failure on imaging. Fever is uncommon.
  • Sternoclavicular septic arthritis/osteomyelitis: Swelling and pain in this region has been described in intravenous drug users and those with indwelling intravenous devices.
  • Puncture wounds: Osteomyelitis of the calcaneus, often caused by Pseudomonas aeruginosa.
  • Sacral decubitus ulcers: May present as a nonhealing ulcer with or without systemic symptoms such as fever. The presence of exposed bone (i.e., a stage 4 ulcer), purulent drainage or other infectious signs or symptoms does not accurately predict the presence of osteomyelitis.
  • Osteomyelitis/osteonecrosis of the jaw: Certain medications such as bisphosphonates predispose patients to necrosis and subsequent infection of bone tissue. Symptoms such as jaw pain, tooth mobility, gingival swelling and oral ulcers or fistulae should prompt consideration of this diagnosis.

B. History Part 2: Prevalence

Prevalence varies with the particular subtype of osteomyelitis.

  • Diabetic foot ulcers: Approximately 15% of patients with diabetes develop foot ulcers; of these up to two thirds may have osteomyelitis.
  • Vertebral osteomyelitis: This is typically a disease of adults over the age of 50. The incidence increases with age and (for unknown reasons) is more common in men.
  • Prosthetic infections: varies depending on the type of joint. In general the risk of infection is highest in the first 2 years after implantation.

C. History Part 3: Competing diagnoses that can mimic osteomyelitis

The differential diagnosis for an infected foot ulcer in a diabetic patient may include superficial wound infection or cellulitis (i.e., infection without extension to bone). A patient with fever and back pain should cause one to consider vertebral osteomyelitis, however may be due to noninfectious etiologies such as compression fracture, spinal metastases, etc. (with fever stemming from another origin). Additional differential diagnoses will be generated depending on the location, the host and whether the infection is acute or chronic.

D. Physical examination findings

In acute osteomyelitis, exam findings may include erythema, swelling, tenderness and warmth over the affected bone (though depending on the location, these signs may be absent or hard to detect). Assess for tenderness over the involved bone (e.g., point tenderness on percussion of the spine in vertebral osteomyelitis). In chronic osteomyelitis, there may be ulcers that probe to bone, sinus tracts or evidence of exposed bone. Consider probing diabetic foot ulcers using a blunt, sterile, stainless steel probe. If the ulcer probes to bone there is a high likelihood (high pretest probability) of osteomyelitis.

E. What diagnostic tests should be performed?

The gold standard for the diagnosis of osteomyelitis is isolation of bacteria from bone biopsy (open or percutaneous). Additionally, biopsy should reveal histopathologic findings of inflammation and osteonecrosis. While bone biopsy is the gold standard, imaging findings can strongly suggest the diagnosis (see below), and in certain situations bone biopsy may not be required. For example, vertebral osteomyelitis is most often from hematogenous spread and monomicrobial; positive blood cultures may obviate the need for bone biopsy. Lastly, bone biopsy may not be feasible in all settings.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Additional testing may include:

  • ESR and CRP. Both are commonly elevated in acute osteomyelitis; however, both tests suffer from a lack of specificity. The CRP in particular may be useful to demonstrate the response to treatment over time.
  • Blood cultures (especially if there is concern for hematogenous spread of infection).

The white blood cell (WBC) count is typically normal, particularly in chronic infection. Other tests such as calcium, phosphate, alkaline phosphatase are typically normal (and may help distinguish osteomyelitis from metastases or metabolic bone diseases).

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Plain films are readily available and may be useful in diagnosing osteomyelitis. However, these are likely to be negative in the setting of acute infection (in the first 10-14 days). Later findings may include evidence of bony destruction, periosteal reaction, or alterations in joint space.

The imaging modality of choice for diagnosing osteomyelitis (both acute and chronic) is magnetic resonance imaging (MRI). MRI is the particularly sensitive for bone edema, one of the earliest findings in acute infections. It is also useful for vertebral osteomyelitis and diabetic foot ulcers. Additional imaging studies may also be of benefit (e.g., computed tomography [CT] and bone scan), particularly when MRI is unavailable or contraindicated. Both have lower sensitivity and specificity.

Additional imaging considerations:

  • Both CT and ultrasound may be useful to determine extent of infection or to guide percutaneous sampling.
  • Tagged WBC scans may help distinguish infectious from non-infectious processes.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis

Bone scan (scintigraphy) is of limited value as it may be (falsely) positive due to adjacent inflammation/infection or fracture.

III. Default management

The gold standard for diagnosis is direct biopsy. As such, it is imperative to try to obtain bone cultures prior to initiating antibiotics.

A. Immediate management

  • Assess for neurologic compromise (e.g., from vertebral osteomyelitis with accompanying epidural abscess). If present, obtain immediate imaging and surgical consultation.
  • Consult radiology or surgery to obtain bone cultures: Send bone specimen for grams stain and culture.
  • Initiate empiric antibiotics* (or if patient is clinically stable, await culture data before initiating antibiotics).
  • Culture data should guide antibiotic therapy. When initiating empiric therapy consider that osteomyelitis due to direct inoculation or contiguous spread is typically polymicrobial, whereas hematogenous spread of infection is usually monomicrobial.

*The most common etiologic organisms are Staph aureus, coagulase-negative staphylococci, gram negative bacilli; followed by Strep species, enterococci, anaerobes, mycobacterium and fungi. Empiric antibiotic regimens may include nafcillin, cefazolin or benzylpenicillin for Staph or Strep infections, respectively (or vancomycin if MRSA is suspected). Gram negative coverage may be achieved with quinolones or third-generation cephalosporins. For suspected mixed infection consider ampicillin/sulbactam or imipenam.

Acute osteomyelitis may be successfully treated with antibiotics alone. A combination of antibiotics and surgery are typically required for the successful treatment of chronic osteomyelitis. The goal of surgery is to eradicate dead bone or foreign materials (e.g., infected prosthetic devices) and to restore viable tissue to facilitate wound healing. Surgery to restore vascularization may be required.

B. Physical examination tips to guide management

C. Laboratory tests to monitor response to, and adjustments in, management

CRP may be used to follow response to therapy.

D. Long-term management

Successful eradication of acute osteomyelitis may require a long course (4-6 weeks) of parenterally administered antibiotics. Long term management of chronic osteomyelitis may include surgery as well as a long course of parenteral and oral antibiotics.

E. Common pitfalls and side-effects of management

Most parenteral antibiotics will require weekly lab monitoring. The hospitalist must establish whom is going to follow these labs and with what frequency. Additionally, parenteral antibiotics will require a central venous catheter (such as a peripherally inserted central catheter [PICC]) which will require regular dressing changes and care. Lastly, some consideration must be given to the safety of sending a patient out of the hospital with a PICC (i.e., relatively contraindicated in a patient with a history of injection drug use).

IV. Management with co-morbidities

A. Renal insufficiency

Antibiotic dosing will need to be adjusted for renal insufficiency.

B. Liver insufficiency

No change in standard management.

C. Systolic and diastolic heart failure

No change in standard management.

D. Coronary artery disease or peripheral vascular disease

If vascular insufficiency is present, surgery to restore vascularization may be required for optimal treatment of osteomyelitis. Consultation with a vascular surgeon is imperative for these patients.

E. Diabetes or other endocrine issues

As noted above, patients with diabetes represent an important subclass of individuals with osteomyelitis. They have a very high rate of osteomyelitis due to foot ulcers, and are at higher risk for vascular disease. If vascular insufficiency is present, surgery to restore vascularization may be required for optimal treatment of infection. Other specific management issues are noted above.

F. Malignancy

No change in standard management.

G. Immunosuppression (HIV, chronic steroids, etc.)

Avoid fluoroquinolones due to risk of tendon rupture for those on steroid therapy and patients who are kidney, heart or lung transplant recipients.

H. Primary lung disease (COPD, asthma, ILD)

No change in standard management.

I. Gastrointestinal or nutrition issues

No change in standard management.

J. Hematologic or coagulation issues

No change in standard management.

K. Dementia or psychiatric illness/treatment

No change in standard management.

V. Transitions of care

D. Arranging for clinic follow-up

Patients discharged on parenteral antibiotics will need to have weekly labs as well as routine care for central venous catheters.

1. When should clinic follow up be arranged and with whom?

Osteomyelitis, especially chronic osteomyelitis, may be best managed by an infectious diseases specialist and appropriate surgeon (e.g., orthopedic or vascular). An appointment should occur prior to the end of the anticipated course of antibiotics (e.g., within 6 weeks) with repeat imaging (if appropriate) at that time.

2. What tests should be conducted prior to discharge to enable best clinic first visit?

For patients discharging on parenteral antibiotics, it may be useful to document a CBC with differential and complete metabolic panel to establish a baseline and facilitate monitoring for toxicity from antibiotics. A CRP may also be obtained to monitor response to treatment. A vancomycin trough should be obtained for patients on this medication. Additional testing will depend on the particular medication a patient is being discharged on (e.g., for patients discharging on daptomycin, obtain a CK as this medication can cause elevations in CK).

E. Placement considerations

Many patients may be safely discharged home with parenteral antibiotics. Considerations should include:

  • Insurance coverage for home infusion and home health care
  • Sophistication of patient/family to participate in central venous catheter care, administration of antibiotics
  • Transportation to infusion center
  • History of iv drug abuse (may be inappropriate for discharge home or to a facility with iv antibiotics)

Whether the patient is discharging home, to an infusion center, or to a skilled nursing facility, a plan for whom is going to follow labs and response to treatment will need to be established.

VII. What’s the evidence?

Beck-Broichsitter, BE, Smeets, F, Heiland, M. “Current concepts in pathogenesis of acute and chronic osteomyelitis”. Curr Opin Infect Dis. vol. 28. 2015. pp. 240-245.

Berbari, EF, Kanj, SS, Kowalski, TJ. “Infectious Diseases Society of America (IDSA) clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults”. Clin Infec Dis. vol. 61. 2015. pp. e26-46.

Boulton, AJM, Kirsner, RS, Vileikyte, L. “Neuropathic diabetic foot ulcers”. N Engl J Med. vol. 351. 2004. pp. 48-55.

Lew, DP, Waldvogel, FA. “Osteomyelitis”. Lancet. vol. 364. 2004. pp. 369-79.

Osmon, DR, Berbari, EF, Berendt, AR. “Diagnosis and management of prosthetic joint infection: Clinical practice guidelines by the Infectious Diseases Society of America”. Clin Infec Dis. vol. 56. 2013. pp. e1-25.

Ruggiero, SL, Dodson, TB, Fantasia, J. Medication-related osteonecrosis of the jaw – 2014 update. 2014.

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