Chronic Refractory Osteomyelitis

Hyperbaric Oxygen Therapy – Chronic Refractory Osteomyelitis

What is Osteomyelitis?

Osteomyelitis is infection of the bone or marrow caused by bacteria or mycobacteria. It is difficult to treat due to the relative insufficient amount of blood vessels in bone and the fact that many antimicrobials do not penetrate bone well. Refractory osteomyelitis is a chronic osteomyelitis that does not respond or that returns after appropriate treatment. Patients presenting with osteomyelitis to the spine, skull, or sternum have a high risk for morbidity and mortality from this infection. The standard treatment for chronic and refractory osteomyelitis include surgical debridement and culture directed antibiotics.

Hyperbaric oxygen treatments (HBOT) can be considered an American Heart Association (AHA) Class II recommendation for the treatment of chronic, refractory osteomyelitis. In patients with Wagner grade 3 or 4 diabetic foot ulcers (DFU) with osteomyelitis, adjunctive hyperbaric oxygen therapy is an AHA Class I intervention.

Recent studies have suggested that up to 20% of patients presenting to Wound Care Centers for treatment of Wagner 3 Diabetic foot ulcers already have Osteomyelitis. Infection in bone is one of the causes of a nonhealing wound, and should be suspected and tested for sooner rather than later when a patient presents with a chronic, nonhealing wound.

Causes of Osteomyelitis

In Infants and children, Staphylococcus and Streptococcus are the most common organisms isolated after hematogenous spread. In adults, it is usually S. aureus.

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.

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.

A problem commonly seen in the wound clinic is the patient who whether through nonadherence with medical treatment, or lack of awareness on the part of the treating physician receives too short a course of antibiotic therapy, or lack of follow up imaging and lab work to assess the response to treatment. These patients invariably return months later with a re-opened wound or draining sinus as the body tries to rid itself of the indolent infection in the bone.


Approximately one in 675 United States hospital admissions each year (50,000 cases annually) is due to osteomyelitis. Patients with diabetes, intravenous (IV) drug abusers and other immunocompromised individuals are at increased risk for osteomyelitis.

Post-traumatic osteomyelitis accounts for almost 50% of cases. Other major causes are neuropathy (mostly in diabetics) and hematogenous seeding (primarily seen in children).

Overall, resolution and healing rates for primary osteomyelitis treated with surgery and antibiotics is between 35% and 100%. It can be inferred that between 70% and 80% of patients treated for primary osteomyelitis will be cured. Long-term osteomyelitis recurrence rates can range between 20% and 30 %. When appropriate medical and surgical interventions fail, the infection progresses or recurs, or the infection is in an area associated with high morbidity and mortality, adjunctive hyperbaric oxygen treatments should be considered.


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)

History of Osteomylitis

Most infectious disease specialists advocate obtaining bone culture from the site of the infection in order 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 if there is no way to obtain bone in the clinic, patients will need referral either to surgery or interventional radiology to obtain a specimen for gram stain, AFB and culture and sensitivity.

Many patients who are treated for chronic non-healing wounds will have an underlying osteomyelitis as the cause of their failure to heal the wound. Wounds which 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 prosthesis can have catastrophic outcomes.


Lab tests such as erythrocyte sedimentation rate and C-reactive protein should be checked. If these are elevated, there is a high likelihood that the patient has osteomyelitis. MRI is the gold standard for imaging osteomyelitis. Osteomyelitis often does not show up on plain film radiographs.

A bone biopsy should be obtained for culture-directed antibiotics to be ordered. A multidisciplinary team consisting of a surgeon, infectious disease specialist, and wound and hyperbaric medicine specialist is often needed to manage these patients effectively.

Treatment & Management

Surgical debridement and culture-directed antibiotics are the mainstays of treatment. For patients who do not respond to appropriate therapy for 4 to 6 weeks, the diagnosis of chronic refractory osteomyelitis (CRO) 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.

Hyperbaric oxygen treatment increases the oxygen content to normal or above normal levels during treatment. The leukocyte-mediated killing of gram-positive organisms like S. aureus as well as some gram-negative microbes is restored when the oxygen content of the infected bone is increased with hyperbaric oxygen treatment.

The transport of antibiotics such as aminoglycosides and cephalosporins into the infected bone is improved and increased with adjunctive hyperbaric oxygen treatment.


Patients who are diagnosed in a timely fashion, have appropriate culture directed antibiotic therapy, surgical debridement if indicated and regular local wound care can do very well and be completely treated to the point of wound closure. Those with uncontrolled diabetes or other comorbidities tend not to do as well. Longterm treatment and follow up care must be emphasized to the patient as well as the importance of a multidisciplinary treatment protocol.


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


It is crucial that the patient with Osteomyelitis be managed by a multidisciplary team

This team should consist of a Wound & Hyperbaric Medicine Specialist, Podiatric, General or Vascular Surgeons, Interventional Radiologists and Infectious Disease specialists.

Deterrence and Patient Education

Diabetic patients should be taught to seek care for any wound as soon as it is discovered and to see a Podiatrist for diabetic foot care regularly as well as regular visits with their Primary Care Physician and Endocrinologist. Good glycemic control prevents infection and the loss of function of the White blood cells that lead to infections in poorly controlled diabetic patients.

Pearls and Other Issues

Osteomyelitis is a common and potentially devastating complication of postoperative, traumatic or chronic wounds. Patients with diabetes mellitus, peripheral neuropathy, and foot ulcers are at high risk for osteomyelitis as are those who abuse IV drugs, and children.

Clinicians must have a high index of suspicion and order appropriate lab tests and diagnostic imaging studies as soon as a wound does not respond to standard treatment in a timely fashion. Any diabetic foot wound that does not improve with 4 weeks of standard wound care including debridement and appropriate dressings should be checked for osteomyelitis.

Chronic refractory osteomyelitis is diagnosed after an infection has not shown improvement or resolution after 4 to 6 weeks of adequate and appropriate surgical debridement and culture-directed antibiotics. At that point, it is appropriate to add adjunctive hyperbaric oxygen treatment to the regimen.

Patients are usually treated at 2.4 atmospheres absolute for 90 minutes with 5-minute air breaks every 30 minutes for 40 to 60 treatment sessions. The Erythrocyte sedimentation rate and C-reactive protein should be measured every 4 to 6 weeks during treatment to assess response.

These levels should fall to normal with adequate culture-directed antibiotic therapy. IV antibiotics are often needed for 6 weeks or more.

from ncbi
by Mary E. Hanley; Jeffrey S. Cooper.
Update: June 26, 2018.