Hyperbaric Treatment of Chronic Refractory Osteomyelitis

Etiology

Staphylococcus and Streptococcus species are the most common organisms isolated in infants and children after hematogenous spread. In adults, Staphylococcus aureus is usually isolated. Infection can be caused by hematogenous spread or by direct inoculation of microorganisms into bone. Intravenous drug abuse has been linked to hematogenous osteomyelitis involving the long bones or the vertebrae.[3][4]

Chronic refractory osteomyelitis is a subset of osteomyelitis that does not respond to standard antibiotic courses and surgical debridement. To be considered "chronic" and "refractory," most sources state that the infection must have been under appropriate culture-directed antibiotic therapy and surgical debridement as warranted for at least 6 weeks without improvement or healing. One problem commonly seen in wound clinics is the patient who, due to nonadherence with medical treatment or a lack of awareness on the part of the treating clinician, receives an insufficient course of antibiotic therapy or lacks follow-up imaging and laboratory work to assess the response to treatment. These patients invariably return months later with a reopened wound or a draining sinus, as the body attempts to rid itself of the indolent infection in the bone.

Epidemiology

Approximately 1 in 675 United States hospital admissions annually (approximately 50,000 cases annually) are due to osteomyelitis. Patients with diabetes, intravenous drug abusers, and other immunocompromised individuals are at increased risk for osteomyelitis. Post-traumatic osteomyelitis accounts for almost 50% of cases. Other major causes include neuropathy (mostly in diabetics) and hematogenous seeding (primarily seen in children).[5][6]

Overall, resolution and healing rates for primary osteomyelitis treated with surgery and antibiotics range between 35% and 100%. Therefore, 70% and 80% of patients treated for primary osteomyelitis are cured. Long-term recurrence rates of osteomyelitis can vary between 20% and 30%. When appropriate medical and surgical interventions fail (or are contraindicated), the infection progresses or recurs, or the infection is associated with high morbidity and mortality, adjunctive hyperbaric oxygen treatments should be considered.[7]

Pathophysiology

S aureus is the most common pathogen cultured in osteomyelitis. Osteomyelitis is classified according to the Cierny-Mader classification:

• Stage 1: Medullary osteomyelitis (confined to the medullary cavity of the bone)
• Stage 2: Superficial cortical bone infection (most often results from direct inoculation or contiguous wound infection)
• Stage 3: Localized osteomyelitis (usually involves both cortical and medullary bone)
• Stage 4: Diffuse osteomyelitis (involves the entire thickness of the bone and results in structural instability, such as with an infected nonunion fracture)

Histopathology

Most infectious disease specialists advocate obtaining a bone culture from the site of the infection to treat with culture-directed therapy. Bone is sometimes visible or palpable in chronic wounds and can easily be obtained in the clinic using a rongeur. For deeper wounds or when bone cannot be obtained in the clinic, patients require referral to either surgery or interventional radiology to obtain a specimen for Gram stain, acid-fast bacillus culture, and sensitivity testing.

History and Physical

Many patients treated for chronic nonhealing wounds have underlying osteomyelitis as a contributing factor to impaired healing. Wounds that fail to close, close but reopen, have draining sinuses, or occur over areas where patients may have implanted hardware warrant a high index of suspicion for osteomyelitis. Bone infection in and around total joint prostheses can have catastrophic outcomes.

Evaluation

Laboratory tests, such as the erythrocyte sedimentation rate and C-reactive protein, should be obtained. If these levels are elevated, the patient is likely to have osteomyelitis. Magnetic resonance imaging is the gold standard for imaging osteomyelitis, as osteomyelitis often does not appear on plain film radiographs. A bone biopsy should be obtained to facilitate culture-directed antibiotics. An interprofessional team consisting of a surgeon, infectious disease specialist, and wound and hyperbaric medicine specialist is often needed to manage these cases effectively.

Treatment / Management

Surgical debridement and culture-directed antibiotics are the mainstays of treatment for chronic osteomyelitis. For patients who do not respond to appropriate therapy for 4 to 6 weeks, the diagnosis of chronic refractory osteomyelitis becomes appropriate. These patients should be referred for adjunctive hyperbaric oxygen therapy. Hyperbaric oxygen improves the penetration of certain antibiotics (cephalosporins and aminoglycosides) into bone and stimulates osteogenesis.

Mader and Niinikoski showed that infected bone has a decreased oxygen content. During treatment, hyperbaric oxygen therapy increases the oxygen content to normal or above-normal levels. Leukocyte-mediated killing of gram-positive organisms such as S aureus and certain gram-negative bacteria is enhanced by increasing the oxygen content of infected bone through hyperbaric oxygen therapy. The transport of antibiotics such as aminoglycosides and cephalosporins into the infected bone is improved and increased with adjunctive hyperbaric oxygen treatment.[8][9] In patients for whom hardware removal or surgical debridement is not feasible, a trial of hyperbaric oxygen therapy combined with antibiotics should be considered before pursuing more aggressive surgical intervention.[1](A1)

Treatment is typically performed once a day for 90 to 120 minutes, using 100% oxygen at 2 to 3 atmospheres absolute pressure, along with appropriate antibiotic therapy. Usually, 20 to 40 HBO₂ sessions are needed to resolve the infection. During cases where improvement or recurrence is seen, modification of antibiotics and surgical intervention should be considered. Hyperbaric oxygen may still be used after additional interventions, particularly if the infection remains refractory.[1]

Differential Diagnosis

The differential diagnoses for hyperbaric treatment of chronic refractory osteomyelitis include the following:

• Charcot joint
• Cellulitis
• Ewing sarcoma
• Giant cell tumour
• Gout and pseudogout
• Infectious arthritis
• Rheumatoid arthritis
• Septic arthritis
• Sickle cell anemia

Prognosis

Patients diagnosed promptly can be treated with appropriate culture-directed antibiotic therapy, surgical debridement (if indicated), and regular local wound care. Most patients can be treated entirely to the point of wound closure. Those with uncontrolled diabetes or other comorbidities tend to have poorer outcomes. Long-term treatment and follow-up care must be emphasized to the patient, as a multidisciplinary treatment protocol is essential.[10]

Patients who complete hyperbaric oxygen therapy have a significantly greater likelihood of improvement in chronic osteomyelitis compared with those who initiate but do not complete therapy. Diabetes and congestive heart failure increase the probability of amputation.[11]

Complications

The most significant complication is failure to have a high index of suspicion and not making the diagnosis promptly. This can lead to the patient developing serious wound problems and can lead to major amputation when a foot or lower limb is involved.