Introduction

Osteomyelitis is a progressive infection of the bone marrow and cortex resulting in inflammatory destruction of the bone, bone necrosis and ultimately the formation of new bone, resulting in bone remodelling and often deformity. Before antibiotics, mortality and amputation rates were high. Antibiotic therapy has virtually eliminated mortality but osteomyelitis is still a serious infection with potentially severe consequences. Certain patients are at particular risk from osteomyelitis.

High-risk patients include:

• The immunocompromised
• Diabetics
• Drug addicts
• Patients with a catheter-related bloodstream infection. Haematogenous spread can result in deep-seated infection with virulent organisms such as Staphylococcus aureus (including MRSA).

Pathogenesis of osteomyelitis

Aetiology of osteomyelitis

Osteomyelitis can be caused by many organisms, including:

• Staphylococcus aureus including strains of MRSA
• Haemophilus influenzae
• Streptococcus spp.
• Escherichia coli
• Proteus spp.
• Pseudomonas spp.
• Coagulase-negative Staphylococcus spp.
• Mycobacteria
• Fungi.

Polymicrobial infections are uncommon (approximately 5% of cases).

The aetiology of osteomyelitis may be indicated by the clinical features, which are also used to define the main categories of osteomyelitis.

Diagnosis of osteomyelitis

Clinical

Clinical manifestations vary depending on the type of osteomyelitis and the location of the infection. There may be a recent history of infection (eg. respiratory tract, urinary tract, skin/soft tissue) or of blunt trauma to the affected area. The presentation can range from insidious onset with localised signs and symptoms to acute systemic toxicity. Acute haematogenous osteomyelitis is primarily a disease of children. Signs and symptoms can include:

Acute osteomyelitis

• Abrupt onset of high fever and systemic toxicity.
• Local signs of infection including inflammation of the affected part.
• Sympathetic effusion in neighbouring joints.

Chronic osteomyelitis

• Patients commonly present with sinus formation and drainage of pus, but there may be just local pain and swelling in an otherwise asymptomatic patient.
• Relapse or persistence of acute osteomyelitis after treatment is classed as chronic.

Early diagnosis of osteomyelitis is essential.

Osteomyelitis can be classified by duration, pathogenesis, location, extent and host status. The Cierny-Mader staging system is based on the anatomy of the bone infection and the physiology of the host.

Microbiology

Microbiology is the key to the diagnosis and effective treatment of osteomyelitis.

Identification of the organism(s) from blood, bone biopsy tissues or pus is the key to selecting the correct antibiotic(s) and avoiding the potentially serious consequences of inadequate treatment.

Acute osteomyelitis

• Bone culture is the definitive test.  Open bone biopsy has the highest detection rate (90% of cultures are positive) but culture can be performed on samples obtained by needle aspiration (60–70% of cultures are positive).  Any pus obtained should be collected in a sterile syringe or container and sent to the laboratory for urgent Gram staining. Joint fluid can also be collected for culture.
• Blood cultures are positive in about 60% of acute haematogenous osteomyelitis cases, but are rarely positive in osteomyelitis resulting from vascular insufficiency or secondary to a contiguous focus of infection. Failure to identify an organism in the blood increases the importance of biopsy specimens.
• Samples from the potential primary source of infection (eg. urine samples or swabs from any skin lesions) should be sent to the laboratory if appropriate.
• The laboratory should be informed if mycobacteria or fungi are suspected, as these organisms do not grow on standard culture media.

Chronic osteomyelitis

• Bone biopsy performed through non-infected soft tissue provides the best specimen.
• Sinus tract cultures do not reliably indicate the pathogen.
• Blood cultures are rarely positive.

Laboratory tests

Acute osteomyelitis

• ESR and CRP are elevated.
• The white cell count is increased, but the count rarely rises above 15,000/mm³.

Chronic osteomyelitis

• Raised ESR/CRP may be the only alteration in laboratory values in chronic osteomyelitis.

Imaging

Supporting evidence may be obtained from x-rays and various other radiological techniques.

Management of osteomyelitis

Acute osteomyelitis

Treatment will vary according to the bones involved, the severity of the infection and the immune status of the patient.

Treatment usually requires open surgery for debridement, drainage of abscesses and removal of sequestra. The chances of success are greatly reduced without adequate surgical cleaning of the bone. Acute haematogenous osteomyelitis in children may respond to antibiotic treatment alone provided that the treatment is started early (before ischaemic necrosis occurs), which in practice means within about 72 hours of the first onset of symptoms. If there is no clinical improvement within 24 hours, surgical drainage/debridement is indicated.

If the patient is immunocompromised/immunosuppressed, steps should be taken to improve host defences, eg. stopping corticosteroid treatment if possible.

Antibiotic rationale

Empirical high-dose intravenous antibiotic therapy should be started before all sensitivities are known; the outcome is best if treatment is started within three to five days of onset of infection.

Initial treatment should normally be targeted against the most common pathogen, Staphylococcus aureus and, unless there are reasons to suspect MRSA , high-dose flucloxacillin is the foundation of antibiotic treatment.

If there is a risk of MRSA consult your microbiologist.

The choice of additional antibiotics (including fusidic acid, aminoglycosides, quinolones or rifampicin) depends on the severity of the infection and the presence of any risk factors. In high-risk patients, anaerobes and common enteric Gram-negative bacilli should be covered. Patients fitted with prosthetic devices (prosthetic joint or fracture fixators) are at increased risk of infection with coagulase-negative Staphylococcus spp.

If the patient is fitted with prosthetic devices consult your microbiologist.

Recently, combination therapy with flucloxacillin and rifampicin has been shown to be effective and, although not widely used at present, this therapy may become more common over the next few years for treating persistent and relapsing infections.

Rifampicin should NEVER be used alone, as resistance will develop rapidly.

Empirical therapy

Because of the type of pathogens and the potential complications, treatment should be discussed with your microbiologist.

The following are suitable empirical antibiotic regimens:

• Non high-risk patients:
• High-dose, IV flucloxacillin plus benzylpenicillin (plus either fusidic acid or rifampicin depending on the severity of infection).
• If the patient is in a high-risk group or Gram-negative organisms were identified on Gram stain, treatment can be modified as follows:
  • High-dose, IV flucloxacillin plus either an aminoglycoside such as gentamicin or a quinolone such as ciprofloxacin (plus either fusidic acid or rifampicin depending on severity)
  or
  • A second-generation cephalosporin such as cefuroxime (plus either fusidic acid or rifampicin depending on severity).
• In penicillin-allergic patients:
  • Clindamycin plus a quinolone such as ciprofloxacin
  or
• Vancomycin plus a quinolone such as ciprofloxacin.
• If MRSA is suspected, consult your microbiologist, as treatment will depend on local antibiotic susceptibilities. The following general principles usually apply:
  • IV vancomycin should be used instead of flucloxacillin
  • Gentamicin or a quinolone such as ciprofloxacin can be added to vancomycin subject to local policies and the advice of your microbiologist.

Definitive therapy

Once bacterial sensitivities are known, antibiotic therapy can be adjusted if necessary in consultation with your microbiologist.

Duration of treatment

There are few data to define the optimal duration of therapy, but treatment should normally last for a total of six weeks.

• Treatment should be initiated with high-dose intravenous antibiotics, which should be continued to cover the period of any surgical intervention and at least the first two weeks after surgical treatment.
• The patient can be switched to oral therapy after that time if they have shown a good clinical response to IV therapy, their CRP is falling and good information on the pathogen and its antibiotic sensitivities has been obtained from microbiology results.
• Suitable oral therapy should be continued for a further two to four weeks subject to the patient’s clinical condition and the type of pathogen (the total duration of treatment for Staphylococcus aureus osteomyelitis should not normally be less than four weeks).
• If a switch to oral therapy is not appropriate, IV antibiotics should be continued until 4–6 weeks of therapy have been completed.
• If a two-stage surgical strategy of debridement and reconstruction is adopted, antibiotic-impregnated acrylic beads (usually gentamicin) inserted in the dead space after debridement for two to four weeks can help sterilise and maintain the dead space before placement of a cancellous bone graft, and may improve the chances of success of the graft.

CRP decreases with appropriate antibiotic therapy, but x-ray improvement lags at least two weeks behind the achievement of normal CRP levels. It is important not to halt antibiotics because CRP levels have normalised because early cessation of treatment may risk relapse.  A persistently raised CRP in the absence of inflammation or trauma in other sites suggests poor microbiological response to treatment.

Summary of the management of acute osteomyelitis.

Chronic osteomyelitis

Surgical debridement is the mainstay of treatment.

Long-term antibiotic therapy without surgery has been advocated but is generally accepted to be less effective. Surgery removes the necrotic tissue, providing both a clean platform for future healing and samples for microbiology to guide the subsequent long-term antibiotic therapy. If surgery is not possible, or unsuccessful, indefinite suppressive antibiotic therapy may be required.

Treatment can normally be delayed until culture and sensitivity results are available from biopsy. In severe infections, if immediate debridement is required, empirical therapy should be initiated after specimens have been taken at surgery and adapted once culture and sensitivity results are known.

Antibiotic rationale

Prolonged parenteral therapy with maximum doses is required to achieve high antibiotic concentrations in necrotic avascular bone.

Therapy should be targeted at the organisms isolated from the samples. But if anaerobes are found in a polymicrobial infection they may be harmless commensals, or cause infection only in complex synergistic relationships, and therapy may be targeted against the primary pathogen with anti-anaerobe therapy employed only if the infection fails to resolve. Consult your microbiologist.

There is no good evidence to suggest that regional antibiotic perfusion of an extremity or wound irrigation with antibiotics confer any advantage, and irrigation may introduce superinfecting resistant organisms.

Definitive therapy

This will be indicated by culture and sensitivity results and local policies. Consult your microbiologist.

Inadequate treatment can lead to the development of chronic low-grade infection.