Donna M. DeFreitas, MD, University of California, Davis, Sacramento
Published Online: May 17, 2007 - 11:48:21 PM (CDT)
Donna M. DeFreitas, MD, MPH
Assistant Professor Division of Infectious Diseases and Immunology Department of Internal Medicine University of California, Davis Sacramento
Osteomyelitis encompasses a spectrum of bone infections in which treatment, diagnosis, and associated morbidities depend on the characteristics of the patient, the organism involved, and the site of infection. The organism responsible for most types of osteomyelitis is Staphylococcus aureus. Osteomyelitis affects thousands of Americans every year and is a source of morbidity and mortality in young and old patients. The 3 major forms of osteomyelitis are acute or hematogenously spread osteomyelitis; contiguously spread osteomyelitis without vascular insufficiency; and contiguously spread, often leading to chronic, osteomyelitis with vascular insufficiency. Among the wide array of diagnostic tools available, some methods have stronger empiric support. Culture-driven therapy is the best treatment option. Relapse is relatively common and often requires consultation with an infectious diseases specialist.
Osteomyelitis is an infection of the bone that encompasses a wide assortment of clinical syndromes, depending on how it is classified. For the sake of simplicity, osteomyelitis can be divided into 3 major types: (1) acute or hematogenously spread disease; (2) contiguously spread disease in those without vascular compromise, such as trauma victims; and (3) contiguously spread disease in those with vascular disease, such as diabetes or peripheral vascular disease.
Acute Hematogenous Osteomyelitis Acute osteomyelitis, also known as hematogenously spread osteomyelitis, should be thought of as secondary to hematogenous spread from an infected focus to damaged bone (Figure 1). Acute osteomyelitis most often occurs in children, although it is quite common in specific adult populations, including patients on hemodialysis, individuals who use intravenous (IV) drugs, and patients with sickle-cell anemia.
In the IV drug user, acute osteomyelitis often follows bacteremia. Typically, such patients present with acute vertebral osteomyelitis. In patients with Staphylococcus aureus bacteremia, acute osteomyelitis often occurs 2 to 3 weeks after the bacteremia has resolved. These patients present with hot, acutely inflamed joints, and the sternomanubrial joint is typically involved.
In adults with sickle-cell crisis, osteomyelitis usually follows partial devascularization of the bone. Patients tend to present with pain that is out of proportion to what is expected with such an attack. Fever, leukocytosis, pain, and poor limb function continue even after the sickling episode has resolved. Salmonella species are the classic pathogens associated with osteomyelitis in patients with sickle-cell disease.1 Diagnosing such patients can be difficult, because they often present with avascular necrosis, which can mimic deep-bone infections.
Signs of acute osteomyelitis can be difficult to recognize, as they often mimic other illnesses. Acute osteomyelitis frequently involves only 1 organism responsible for the infection.2 Thus, aspiration of the source of the infection and guided antibiotic therapy are important strategies for successful treatment.
Contiguous Osteomyelitis without Vascular Compromise Unlike acute osteomyelitis, which often involves previously injured bone that is infected through bacteremia, contiguous osteomyelitis tends to develop from nearby infection that has spread to the bone. Contiguous disease can occur in 2 types of hosts?patients with or without vascular insufficiency. Bone is naturally resistant to infection, so younger patients (≤45 years old) tend to develop contiguous osteomyelitis without vascular insufficiency after bone trauma or surgery. Coagulase-negative Staphylococcus and S aureus are usually the causative pathogens. Most patients have symptoms of joint prosthesis failure, bone instability, tissue necrosis, nonunions of fractures, and draining sinus tracts.
Less common, contiguous osteomyelitis without vascular compromise can present as acute disease, often occurring within a short distance from the site of the bone trauma. The trauma that usually leads to this type of osteomyelitis is blunt force trauma, such as a motor vehicle accident or a fall leading to an injury. Such patients are normally otherwise healthy. In contrast to hematogenous osteomyelitis, the symptoms in this type of infection are caused by direct inoculation of bacteria into the bone. Patients often present with cryptic symptoms of pain and fever that can be difficult to differentiate from symptoms of trauma. In bone trauma, the infection is often discovered when the patient undergoes early surgery to treat the bone. But experience shows that many of these patients still progress to chronic osteomyelitis, with symptoms of prosthesis failure despite early and aggressive antibiotic therapy and surgery.2
Contiguous (Chronic) Osteomyelitis with Vascular Compromise Patients with diabetes, peripheral vascular disease, or neuropathy are at greatest risk for contiguous (or chronic) osteomyelitis with vascular insufficiency. Staphylococcus species, Streptococcus species, and gram-negative or anaerobic organisms are the most common pathogens responsible for osteomyelitis in these patient populations.
In patients with vascular compromise, the disease often begins with an overlying cellulitis or wound that gradually affects the underlying bone. As vascular supply becomes compromised, soft-tissue wound healing becomes extremely poor and bone death may occur over time. Often, these patients are trapped in cycles of chronic bone disease.
In chronic disease, a nidus (also called a sequestrum) of infected bone is surrounded by a soft-tissue envelope of inflammation that becomes refractory to treatment. Symptoms and signs are usually nonspecific, often accompanied by nonspecific pain in the affected bone, constitutional symptoms (eg, fever, fatigue), elevated erythrocyte sedimentation rate (ESR), and moderately elevated white blood cell (WBC) count. These features provide early clues that osteomyelitis should be included in the differential diagnosis.
Although the 3 types of osteomyelitis are distinctive in their etiology and progression, the diagnosis and treatment overlap considerably.
Diagnosis The diagnostic modalities for osteomyelitis have evolved considerably over the past 30 years. Bone biopsy is the gold standard modality used to confirm the diagnosis. Biopsy may be performed with an open procedure or by fine-needle aspiration. Fine-needle biopsy can differentiate tumors from infection but is not as accurate as open biopsy in diagnosing osteomyelitis. Open biopsy is often the best technique for determining culture-based therapy and debridement of necrotic bone, but this procedure requires surgery, with its inherent risks. Sinus tract cultures are very inaccurate compared with bone cultures, unless S aureus is recovered.3,4
Laboratory tests can be useful in the diagnosis. A recent prospective study showed that the ESR was elevated in 92% of children presenting with osteomyelitis, C-reactive protein (CRP) level was elevated in 98%, and the WBC count was elevated in 35%.5 These tests have a high positive (but not negative) predictive value. Therefore, normal values of WBC count, CRP level, or ESR cannot be used to rule out the diagnosis of osteomyelitis in adults. Elevated values should increase suspicion of osteomyelitis. Generally, it is believed that CRP levels may be a better early indicator of osteomyelitis than ESR.5,6
A standard x-ray is often the initial screening test for osteomyelitis, because of its ease of use, availability, and low cost. Radiographic findings classically lag 7 to 10 days behind the infection. Findings include soft-tissue swelling, loss of fascial planes, periosteal thickening and elevation, and osteopenia, followed by a cortical punched out lesion, which can coalesce to cause cortical destruction (Figure 2). The sensitivity of plain film radiographs is thought to be 70%.7
Bone scans (Figure 3) use technetium (Tc) 99m (99mTc), a radiolabeled technetium that binds to phosphorus in bone, to mark osteoblastic activities, usually called ?hot spots.? Bone scans historically are thought to have high sensitivity (range, 82%-100%) and relatively low specificity.8,9
Indium 111 (111In)-labeled WBC scans use the body?s own WBCs to detect bone infections. WBCs are harvested from patients, tagged with 111In, and returned to the patients by IV infusion. A certain portion of the WBCs will localize to an area of presumed osteomyelitis and/or infection. The sensitivity range for WBC scans is between 60% and 100% for osteomyelitis; lower specificities have been noted.10 In patients with arthritis, WBC scans often yield false-positive results. For peripheral lesions, both WBC and bone scans have a relatively high false-negative rate.8 Many radiology departments use a combination of 111In-tagged WBC scanning and 99mTc bone scanning to increase diagnostic accuracy for this disease.
Ultrasound is used for diagnosis in children and can also be used as an inexpensive screening method to guide computed tomography (CT), magnetic resonance imaging (MRI), or biopsy. MRI, along with CT, are considered the best radiologic methods for diagnosing osteomyelitis.
CT can be used to visualize intramedullary gas and cortical bone destruction. These scans have high sensitivity and specificity, although it is difficult to scan patients with large amounts of arthritis and metal hardware. Spiral CT is proving to be a useful modality for diagnosing osteomyelitis of the sternum, vertebrae, and the cranium. CT is also useful in the patient with chronic osteomyelitis who might have a sequestrum or areas of dead bone and abscess.
MRI sensitivity ranges from 84% to 100% for the diagnosis of osteomyelitis (Figure 4), in different patient groups, with caveats regarding its use in patients with sickle-cell disease, recurrent surgeries, hardware in place, and/or acute versus quiescent disease.9,11 MRI has excellent resolution for deep-bone or Brodie?s abscesses. Osteomyelitis usually has low signal intensity on T1-weighted images and high signal intensity on T2-weighted images.
The diagnosis of osteomyelitis is best accomplished within the context of understanding the microbiology of the disease.
The Microbiology of Osteomyelitis The pathogenic organisms in osteomyelitis are numerous. The organism responsible for most types of osteomyelitis is S aureus,12 which has long been known to have special molecules called adhesins. These molecules allow S aureus to adhere to the bone matrix and to collagen-binding proteins, and enable the organism to bind to cartilage as well.
In the IV-drug?using population, S aureus is the most likely cause of infection, followed by Pseudomonas species. Pseudomonas aeruginosa is also an important cause of osteomyelitis in puncture wounds, postsurgical wounds, and in patients with sickle-cell anemia.13 In patients with freshwater exposure, Aeromonas hydrophilia can cause cellulitis, leading to osteomyelitis. Osteomyelitis after a dog or a cat bite might involve Pasteurella species,14 and those evolving from human bites may be more prone to involve Streptococcus anginosus, Fusobacterium nucleatum, S aureus, and Eikenella species.15
Special Considerations Diabetic patients Patients with diabetes are prone to foot infections because of vascular compromise, impaired neutrophil killing, impaired wound healing, and neuropathy associated with the disease. In this patient population, large wounds that can be probed to the bone have an 89% positive predictive value for involving osteomyelitis.16 Diabetes often involves changes in bone secondary to neuropathy that render most imaging studies confusing and unreliable. Therefore, bone biopsy is the best diagnostic option in the diabetic patient with accessible tissue; the reported sensitivity is 94%.4 Diabetic patients with osteomyelitis appear to do better with a longer treatment course for osteomyelitis, about 8 to 10 weeks.17
Vertebral osteomyelitis Vertebral osteomyelitis is a rare infection that can be catastrophic and is considered to be the type of acute osteomyelitis to which adults are prone. S aureus is the most common causative agent. Spinal osteomyelitis or discitis often occurs in those with back injury and secondary unrelated bacteremia. It is usually caused by an infection that travels through the arterial system rather than Batson?s plexus. Direct spread through the genitourinary tract is also a common route of infection. Associated infections include urinary tract infections, IV-line infections, endocarditis, and bacteremia secondary to dental sources. Signs of vertebral osteomyelitis include elevated ESR and nonspecific back pain.
In most patients, physical examination will reveal back pain and tenderness over the spinal process. Neurologic sequelae are often an indication of an epidural abscess. Up to 50% of patients with these abscesses present without fever or leukocytosis.18,19 The areas most prone to vertebral infections include the lumbar, thoracic, and cervical spine, in that order. Most patients require prolonged antibiotic therapy, and conservative surgical therapy may also be necessary.20
Prosthetic joint infection As populations age, prosthetic joint infections become more common. Generally, these infections occur after hip or knee replacement. Most patients present with constant severe pain in the joint, prosthesis failure, and a draining sinus tract. On rare occasions, fever or elevated ESR can be the presenting symptoms. Patients are usually infected at the time of surgery either by the procedure or by a concomitant bacteremia. S aureus and coagulase-negative staphylococci are the major culprits, but skin flora, Pseudomonas species, and Candida species have all been implicated. The best therapy for this type of infection is a 2-step surgical debridement with prosthesis removal at that time, followed by 4 to 6 weeks of antibiotics, and a new prosthesis implanted at the end of that period. An antibiotic-laden spacer is often used after the initial prosthesis removal.21 There are many variations of this basic protocol, including prosthesis debridement with cultures, followed by 6 weeks of IV antibiotic therapy; or 2 weeks of IV therapy and 3 to 6 months of oral combination therapy, with the prosthesis being left in place.22
Treatment Because bone tends to wall off bacterial infection with dead bone, it can be extremely difficult to cure osteomyelitis. For many patients with the disease, containment of the infection is a more reasonable goal. In this author?s experience, conventional treatment with 6 weeks of IV antibiotic therapy directed against the pathogen(s) isolated from cultures is generally recommended.2
Treatment of most patients with osteomyelitis is best guided by culture results. However, in this age of multidrug-resistant organisms, empiric therapy may well prove gravely detrimental to both patient and provider. Generally speaking, beta-lactam agents, such as nafcillin, are the treatment of choice for methicillin-sensitive S aureus. Gram-negative bacteria are usually well treated with oral fluoroquinolones.2,22,23 Combinations of a fluoroquinolone and another antibiotic, such as rifampin (Rifadin), have been used with great success and provide an oral option for gram-positive osteomyelitis.24Candida species osteomyelitis may respond to fluconazole (Diflucan) but may also require surgery.25,26 Other atypical bacteria that can cause osteomyelitis, such as methicillin-resistant S aureus (MRSA), may require the consultation of an infectious diseases specialist.
Suppressive therapy for osteomyelitis remains controversial. A good rule of thumb is that in patients with a foreign body (eg, joint prosthesis) in place, suppressive therapy may play a role. Such therapy should be discussed with an experienced infectious diseases specialist.23,24
Surgery is often the last option, but an important adjunct, for osteomyelitis. Most surgeons screen patients based on the potential for wound healing, comorbidities, extent of areas involved, and risk for amputation. The goals of surgery are the removal of soft-tissue scars and necrotic tissue, while preserving the underlying bony structures.
Conclusion Osteomyelitis involves a wide spectrum of bone infections. Reasonable guidelines include the use of culture-driven therapy, an understanding of predisposing circumstances for the individual patient, and considerable patience in light of disease recurrence. Consultation with an infectious diseases specialist is recommended for complicated cases, especially those involving prostheses or fixation devices.
Acknowledgements The author wishes to thank Edward J. Callahan, PhD, Gregory P. Melcher, MD, and Anne Knowlton, MD, of the University of California, Davis, for their comments.
Self-assessment test 1. Which of the following organisms is the most common cause of osteomyelitis? A. Streptococcus species B. S aureus C. Eikenella species D. Candida species
2. Of the following options, which is the best imaging modality for osteomyelitis? A. MRI scan or CT scan B. Plain x-ray C. Ultrasound D. Bone scan
3. Which of the following statements explains why diabetic patients are prone to foot infections and osteomyelitis? A. Patients are often bacteremic B. They have impaired wound healing C. They tend to have hyperfunctional neutrophils, which lead to abscess formation D. None of the above
4. Which of the following options is the recommended treatment for osteomyelitis? A. 3 weeks of oral antibiotics, such as a fluoroquinolone B. Surgery C. Empiric therapy D. 6 weeks of culture-directed antibiotics, usually IV
5. Which of the following statements about cultures in suspected osteomyelitis is true? A. Cultures are worthless for most patients with diabetes B. They are best obtained with an open biopsy procedure C. They are difficult to interpret because of the large amount of organism usually obtained D. They are not helpful in vertebral disease, which is almost always caused by Streptococcus species
(Answers at end of references list)
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