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Hyperbaric Treatment of Chronic Refractory Osteomyelitis
Introduction
Osteomyelitis is an infection of the bone or marrow caused by bacteria or mycobacteria. It is difficult to treat due to the relative paucity of blood vessels in bone and many antimicrobials do not penetrate bone well. Refractory osteomyelitis is a chronic osteomyelitis that does not respond or return 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 chronic and refractory osteomyelitis treatment includes surgical debridement and culture-directed antibiotics. Hyperbaric oxygen treatments can be considered an American Heart Association (AHA) Class II recommendation for treating 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 postulated 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 1 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.
Etiology
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Etiology
Staphylococcus and Streptococcus are the most common organisms isolated in infants and children 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 lacks 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.
Epidemiology
Approximately 1 in 675 United States hospital admissions yearly (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 are between 35% and 100%. It can be inferred that 70% and 80% of patients treated for primary osteomyelitis are 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.
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 if bone cannot be obtained in the clinic, patients need referral either to surgery or interventional radiology to obtain a specimen for gram stain, AFB culture, and sensitivity.
History and Physical
Many patients who are treated for chronic non-healing wounds have underlying osteomyelitis as the cause of their failure to heal the wound. 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
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. an interprofessional 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. During treatment, hyperbaric oxygen treatment increases the oxygen content to normal or above normal levels. The leukocyte-mediated killing of gram-positive organisms like S aureus and 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.[1][2](A1)
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 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. Long-term treatment and follow-up care must be emphasized to the patient, as a multidisciplinary treatment protocol is important.[3]
Complications
The greatest 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.
Deterrence and Patient Education
Diabetic patients should be taught to seek care for any wound as soon as it is discovered, to see a podiatrist regularly for diabetic foot care, and to have 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. Adding adjunctive hyperbaric oxygen treatment to the regimen is appropriate at that point. 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.
Enhancing Healthcare Team Outcomes
An interprofessional team must manage the patient with osteomyelitis. This team should include a wound and hyperbaric medicine specialist, podiatric, general or vascular Surgeons, interventional radiologists, and infectious disease specialists. Osteomyelitis is usually treated with IV antibiotics, but chronic or recalcitrant cases may be managed with HBO therapy. It should be understood that HBO therapy is not a substitute treatment but an adjunct treatment to antibiotics. The limited cases indicate that HBO therapy can help improve healing.
References
Savvidou OD, Kaspiris A, Bolia IK, Chloros GD, Goumenos SD, Papagelopoulos PJ, Tsiodras S. Effectiveness of Hyperbaric Oxygen Therapy for the Management of Chronic Osteomyelitis: A Systematic Review of the Literature. Orthopedics. 2018 Jul 1:41(4):193-199. doi: 10.3928/01477447-20180628-02. Epub [PubMed PMID: 30035798]
Level 1 (high-level) evidenceLam G, Fontaine R, Ross FL, Chiu ES. Hyperbaric Oxygen Therapy: Exploring the Clinical Evidence. Advances in skin & wound care. 2017 Apr:30(4):181-190. doi: 10.1097/01.ASW.0000513089.75457.22. Epub [PubMed PMID: 28301358]
Level 3 (low-level) evidenceSkeik N, Porten BR, Isaacson E, Seong J, Klosterman DL, Garberich RF, Alexander JQ, Rizvi A, Manunga JM Jr, Cragg A, Graber J, Alden P, Sullivan T. Hyperbaric oxygen treatment outcome for different indications from a single center. Annals of vascular surgery. 2015 Feb:29(2):206-14. doi: 10.1016/j.avsg.2014.07.034. Epub 2014 Oct 13 [PubMed PMID: 25308240]
Level 2 (mid-level) evidence