Current Concepts In Treating Osteomyelitis

It has been estimated that a person with diabetes has a 25 percent lifetime risk of developing a foot ulceration.1 Diabetic foot ulcers commonly become infected, can involve bones and joints and may progress to amputation. Osteomyelitis frequently complicates ulcerations in people with diabetes and may be present in up to 20 percent of mild to moderate and 50 to 60 percent of severely infected wounds.2 Diagnosing osteomyelitis in people with diabetes who present with a foot ulcer is challenging and becomes a clinical conundrum. Misdiagnosis may lead to unnecessary treatment, specifically prolonged antibiotic therapy and surgery. Accordingly, let us take a closer look at osteomyelitis in the diabetic foot, the importance of early detection, the benefits and limitations of the available diagnostic tests, and the current evidence of both surgical and non-surgical treatment. Osteomyelitis is an inflammatory process caused by an infecting microorganism.3,4 This infectious process is accompanied by bone destruction and, in most cases, clinical signs of inflammation.4,5 Waldvogel classified osteomyelitis based on etiology and developed three categories: hematogenous, contiguous and osteomyelitis associated with vascular insufficiency.6 Hematogenous osteomyelitis mostly occurs among children and elderly patients, and the infected bone is caused by bacteria seeded in the blood. Most often, this form of osteomyelitis involves the metaphysis of long bones. Local (chills, fever and malaise) and systemic (pain and local swelling) signs are typical.4 In contiguous osteomyelitis, the bone becomes infected from an external contaminated source (penetrating trauma, open fracture, bone surgery or joint replacement). This can occur at any age and can affect any bone. In regard to osteomyelitis associated with vascular insufficiency, physicians will most often see this among patients with diabetic neuropathy.6 Foot ulcers serve as portals for infection and bacteria to gain access to the bone by contiguous spread. If a diabetic foot ulcer fails to heal after at least six weeks of appropriate care and offloading, one should suspect osteomyelitis.7 In almost all cases of osteomyelitis in the diabetic foot, the infection starts in the soft tissue and spreads to bone. A Primer On The Microbiology Of Osteomyelitis There have been many classification schemes devised for osteomyelitis and researchers utilized traditional staging with the Waldvogel classification system. However, the Waldvogel classification is an etiologic system and does not convey a specific treatment regimen. Buckholz described seven different types of bone infection based on pathophysiology.8 Researchers have developed other classifications to emphasize different clinical aspects of osteomyelitis.9 Cierny and Mader developed a descriptive classification for surgeons treating patients with chronic osteomyelitis. The Cierny-Mader classification is based on the anatomy of bone infection and the physiology of the host. Anatomic characteristics of the bone infection are divided into four stages: stage I, medullar; stage II, superficial; stage III, localized; and stage IV, diffuse osteomyelitis. Likewise, the physiology of the host is subdivided into different categories. An A-host has a normal systemic defense. A B-host has systemic and local compromise. A C-host is a non-surgical candidate as surgical treatment may be worse than the disease. The Cierny-Mader classification permits the development of a comprehensive treatment guideline for each stage.9 This detailed classification system applies best to long bones and is not very useful for the small bones of foot.4,10 As far as microbiology goes, eradicating infection in bone is difficult. Among the many pathogenic microorganisms, Staphylococcus aureus is the most commonly involved. Staphylococcus aureus has a range of extracellular and cell-associated factors that are reportedly crucial for its virulence.4,11,12 Although Staphylococcus aureus is the most commonly isolated microorganism, one may isolate many other microorganisms according to the type of disease and epidemiological factors.4 It is common to find Pseudomonas aeruginosa of the calcaneus after puncture wounds have occurred.4 In this climate of multi-drug resistant organisms, it is advisable to consider methicillin-resistant Staphylococcus aureus (MRSA) in the diabetic population. Imaging Studies: Are They Effective In Helping To Diagnose Osteomyelitis? Early detection of osteomyelitis is paramount. A correct diagnosis requires sound clinical judgment and a high level of suspicion. A delay in diagnosis is related to poor outcomes and can cause disabling complications.13 Patients may present with a variety of symptoms and confirming bone infection often requires several diagnostic procedures. There are many available diagnostic tests but most yield equivocal results.14 Leukocytosis is a poor indicator of acute osteomyelitis among people with diabetes.15 While clinicians may use inflammatory markers, such as the erythrocyte sedimentation rate (ESR) and C-reative protein (CRP), as screening tools, they are not specific for infection.16 Radiographs may show osseous changes associated with infection (e.g., cortical destruction and periosteal reaction), but these changes are not usually evident in the early stages after infection and radiographs have a sensitivity of only 55 percent for diagnosing osteomyelitis.17 Additionally, bone infection may precede radiographic changes by up to four weeks.5 Osteomyelitis may complicate feet with Charcot neuro-osteoarthropathy and bone infection is difficult to distinguish from this destructive, noninfectious process on plain film radiographs. Three-phase bone scans are sensitive but cannot reliably differentiate between osteomyelitis and Charcot neuro-osteoarthropathy because both undergo significant bone remodeling.18 However, the white blood cell labeled bone scan is more sensitive and specific for infection than either the three-phase bone scan or plain film radiographs.17 These scans are useful in distinguishing osteomyelitis from a soft tissue infection or Charcot-neuro-osteoarthropathy.19 However, these scans are relatively expensive, technically demanding and time-consuming.14 Magnetic resonance imaging (MRI) is the most sensitive and specific imaging study for defining bone infection but MRIs are not universally available and are expensive.14 Yet MRI does reveal bone marrow edema associated with inflammation and may aid in early detection of bone infection. Enderle, et al., reported positive and negative predictive values of 93 percent and 100 percent respectively.20 Magnetic resonance imaging is useful to determine the extent of bone infection. How Effective Is The PTB Test? In 1995, Grayson, et al., introduced a simple, inexpensive bedside technique to help diagnose osteomyelitis in an infected ulcer among people with diabetes.21 The investigators prospectively assessed infected foot ulcers for detectable bone by probing with a sterile, blunt, stainless steel probe. If a clinician could probe to bone (PTB), there was an 89 percent positive predictive value for osteomyelitis. The authors concluded that palpation of bone in an infected ulcer in patients with diabetes was strongly correlated with the presence of osteomyelitis. They also noted that specialized radiographic and radionuclide tests are unnecessary.21 However, the Grayson study was originally designed for the treatment of severe limb-threatening infections whereas the PTB test was a side study. Given the severity of infections in this study, the pre-test probability of osteomyelitis was higher than a normal cross section of diabetic foot ulcers. The overall prevalence of osteomyelitis in the Grayson study population was 66 percent.22 Additionally, the investigators did not obtain a bone specimen for analysis, the criterion standard for the diagnosis.23 Recently, Lavery, et al., assessed the accuracy of the PTB test in diagnosing foot osteomyelitis in a cohort of diabetic patients who were previously diagnosed via bone cultures.23 The researchers prospectively enrolled and tracked 1,666 patients with diabetes over an eight-month period. They saw all patients at regular intervals and instructed them to return to the foot clinic if they developed foot-related complications. Over an average of 27.2 months, 247 (14.8 percent) of the patients developed a foot wound and 151 (9.1 percent) developed a foot infection. The study authors performed the PTB test in all of the patients with a wound and it was positive in 46 patients (18.6 percent). A positive bone culture confirmed bone infection and researchers found osteomyelitis in 30 patients. The investigators assessed the value of PTB in diagnosing osteomyelitis and calculated the sensitivity, specificity and positive and negative predictive values using the results of the bone culture. For all diabetic foot wounds, the PTB was highly sensitive (0.87) and specific (0.91). The negative predictive value was 98 percent and the positive predictive value was 57 percent. Translating these study findings into plain clinical language, a negative PTB test is excellent at ruling out osteomyelitis. However, a positive PTB test cannot accurately diagnose osteomyelitis. There were many factors that contributed to the difference in outcomes between the separate studies by Lavery and Grayson. The most important disparity was the pre-test probability of osteomyelitis between the two patient populations. In the Grayson study, all of the patients were hospitalized for severe foot infections and had a 66 percent prevalence of osteomyelitis.21 In contrast, Lavery’s patients presented in a clinic setting and had a lower prevalence of osteomyelitis (20 percent).23 This difference in disease rates between the testing populations explains the difference in the positive predictive values reported in the two studies and confirms the importance of disease prevalence when assessing the PTB test to diagnose osteomyelitis.24 While the PTB test has limitations, it also has value in assisting the clinician. Although the PTB test — when one uses it in a clinically relevant population — has a relatively low positive predictive value in a setting of normal bone infection prevalence (i.e. an outpatient setting), a negative test may exclude the diagnosis of osteomyelitis. Also, when a clinician uses the PTB test for a patient with a severe, limb-threatening infection, it may be useful to diagnose bone infection. The PTB test is highly valuable and should be a routine part of an exam. Probing the wound may uncover sinus tracts or abscesses, and aids the clinician in determining the extent of the wound. However, the clinician must realize the effect that the pre-test prevalence of osteomyelitis greatly affects the usefulness of the PTB test.23 Why Bone Biopsy Remains The Gold Standard Bone biopsy remains the diagnostic criterion standard for diagnosing osteomyelitis. Bone biopsy results in a definitive diagnosis. It identifies the pathogen and its antibiotic sensitivity, and these findings guide appropriate therapy.5 If one suspects osteomyelitis, the physician can obtain bone specimens by either a percutaneous technique or as an open procedure, and send the specimen for histological and microbiological analysis.5,25 Histological analysis is sufficient to render a diagnosis and is based on the presence of osteonecrosis and infiltration with leukocytes or chronic inflammatory cells. However, microbiological analysis has the advantage and ability to identify the pathogen and guide antibiotic therapy.26 Be aware that false negative results can occur because osteomyelitis has a patchy distribution in bone or there may have been previous suppressive antibiotic therapy.4 A Guide To Current Treatment Recommendations Optimal and effective treatment of osteomyelitis requires sound clinical judgment and ensuring adequate limb perfusion. Eradicating infection in bone is difficult and traditional treatment of osteomyelitis includes surgery and antibiotics. Surgical debridement of all infected bone and soft tissue, and four to six weeks of parental antibiotic therapy have been the hallmark of treatment.27 Antibiotics should have good bioavailability and achieve suitable soft tissue and bone antimicrobial levels. However, the duration of therapy and the optimal route of antibiotic delivery have not been systematically studied.28 Early studies attempting to manage bone infection with antibiotics alone were unsuccessful.5,29 More recent published reports on non-surgical treatment with prolonged antibiotic therapy have reported clinical success.7 However, most of these studies had a large variation in the extent of surgical debridement. Embril reported an 80 percent success rate with 79 patients (93 episodes of osteomyelitis) and concluded that osteomyelitis of the foot was successfully treated with oral antibiotic therapy, with or without in-office debridement. However, there was considerable variation in the duration of antibiotic therapy (40 + 30 weeks).28 The Infectious Diseases Society of America (IDSA) guidelines list four scenarios in which one may consider non-surgical management for osteomyelitis: 1) There is no acceptable surgical target. 2) The patient has ischemia caused by non-bypassable vascular disease but desires to avoid amputation. 3) Infection is confined to the forefoot and there is minimal soft tissue loss. 4) Surgical management carries excessive risk or is otherwise not appropriate or desirable.7 Optimal management may involve a combination of antibiotics and early surgical intervention. Ha Van, et al., reported a 57 percent cure rate with antibiotics alone in comparison to a 78 percent cure rate with the addition of conservative surgery.30 If one is considering surgery, debridement of infected, necrotic bone and soft tissue is key. One should utilize adequate debridement to remove devitalized and non-viable bone, and soft tissue as they impede healing and provide an ongoing nidus for infection. Attinger, et al., recommend aggressively debriding infected bone until one notes bleeding and normal appearing marrow.31 Biomechanical considerations should not discourage the surgeon from debriding enough bone to ensure that all infection has been eliminated. One may address correction of the resultant biomechanical abnormality after the wound has healed.31 However, distal amputations are preferred and it is imperative that the surgeon evaluates the final outcome, and considers function and the risk for future complications. Obtaining appropriate bone cultures and isolating the offending organism is paramount. If one performs surgical resection and some infected soft tissue remains, continued parental or oral antibiotic therapy is recommended for two to four weeks. If dead and infected bone remains in the wound or if one does not perform surgery, the IDSA guidelines recommend initial parental antibiotic therapy followed by oral antibiotics for a total duration greater than three months.7 In Summary Diagnosing and managing osteomyelitis in the diabetic foot is challenging and requires astute clinical judgment and early intervention. Numerous diagnostic tests are available to detect bone infection but each of these tests has limitations when one uses them independently. However, combining these tests with sound clinical judgment can be beneficial in diagnosing osteomyelitis. Although some recent reports suggest successful treatment with antibiotics alone, an effective treatment of osteomyelitis is probably a combination of appropriate, culture guided antibiotics and early surgical debridement. Dr. Bevilacqua is an attending surgeon at the Foot and Ankle Clinics at Broadlawns Medical Center in Des Moines, Iowa.
 

References:

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