Etiology of Osteomyelitis
Osteomyelitis is caused by
Contiguous spread from infected tissue or an infected prosthetic joint Prosthetic Joint Infectious Arthritis Prosthetic joints are at risk of acute and chronic infection, which can cause sepsis, morbidity, or mortality. Patients often have a history of a recent fall. Symptoms include joint pain, swelling... read more
Bloodborne organisms (hematogenous osteomyelitis)
Open wounds (from contaminated open fractures or bone surgery)
Trauma, ischemia, and foreign bodies predispose to osteomyelitis. Osteomyelitis may form under deep pressure ulcers Pressure Injuries Pressure injuries are areas of necrosis and often ulceration (also called pressure ulcers) where soft tissues are compressed between bony prominences and external hard surfaces. They are caused... read more 
.
Contiguous spread from adjacent infected tissue or open wounds
Contiguous spread from adjacent infected tissue or open wounds causes about 80% of osteomyelitis; it is often polymicrobial. Staphylococcus aureus Staphylococcal Infections Staphylococci are gram-positive aerobic organisms. Staphylococcus aureus is the most pathogenic; it typically causes skin infections and sometimes pneumonia, endocarditis, and osteomyelitis... read more 
(including both methicillin-sensitive and methicillin-resistant strains) is present in ≥ 50% of patients; other common bacteria include streptococci, gram-negative enteric organisms, and anaerobic bacteria.
Osteomyelitis that results from contiguous spread is common in the feet (in patients with diabetes Infection In patients with diabetes mellitus, years of poorly controlled hyperglycemia lead to multiple, primarily vascular, complications that affect small vessels (microvascular), large vessels (macrovascular)... read more 
or peripheral vascular disease Peripheral Arterial Disease Peripheral arterial disease (PAD) is atherosclerosis of the extremities (virtually always lower) causing ischemia. Mild PAD may be asymptomatic or cause intermittent claudication; severe PAD... read more 
), at sites where bone was penetrated during trauma or surgery, at sites damaged by radiation therapy, and in bones contiguous to pressure ulcers, such as the hips and sacrum. A sinus, gum, or tooth infection may spread to the skull.
Hematogenously spread osteomyelitis
Hematogenously spread osteomyelitis usually results from a single organism. In children, gram-positive bacteria are most common, usually affecting the metaphyses of the tibia, femur, or humerus. In adults, hematogenously spread osteomyelitis usually affects the vertebrae. Risk factors in adults are older age, debilitation, hemodialysis Hemodialysis In hemodialysis, a patient’s blood is pumped into a dialyzer containing 2 fluid compartments configured as bundles of hollow fiber capillary tubes or as parallel, sandwiched sheets of semipermeable... read more , sickle cell disease Sickle Cell Disease Sickle cell disease (a hemoglobinopathy) causes a chronic hemolytic anemia occurring almost exclusively in people with African ancestry. It is caused by homozygous inheritance of genes for hemoglobin... read more 
, and injection drug use. Common infecting organisms include the following:
In adults who are older, debilitated, or receiving hemodialysis: S. aureus (methicillin-resistant S. aureus [MRSA] is common) and enteric gram-negative bacteria
In injection drug users: S. aureus, Pseudomonas aeruginosa Pseudomonas and Related Infections Pseudomonas aeruginosa and other members of this group of gram-negative bacilli are opportunistic pathogens that frequently cause hospital-acquired infections, particularly in ventilator... read more , and Serratia Klebsiella, Enterobacter, and Serratia Infections The gram-negative bacteria Klebsiella, Enterobacter, and Serratia are closely related normal intestinal flora that rarely cause disease in normal hosts. Diagnosis is by... read more species
In patients with sickle cell disease, liver disease, or immunocompromise: Salmonella Overview of Salmonella Infections The genus Salmonella is divided into 2 species, S. enterica and S. bongori, which include > 2500 known serotypes. Some of these serotypes are named. In such cases, common... read more species
Fungi and mycobacteria can cause hematogenous osteomyelitis, usually in immunocompromised patients or in areas of endemic infection with histoplasmosis Histoplasmosis Histoplasmosis is a pulmonary and hematogenous disease caused by Histoplasma capsulatum; it is often chronic and usually follows an asymptomatic primary infection. Symptoms are those... read more 
, blastomycosis Blastomycosis Blastomycosis is a pulmonary disease caused by inhaling spores of the dimorphic fungus Blastomyces dermatitidis. Occasionally, the fungi spread hematogenously, causing extrapulmonary... read more 
, or coccidioidomycosis Coccidioidomycosis Coccidioidomycosis is caused by the fungi Coccidioides immitis and C. posadasii; it usually occurs as an acute, benign, asymptomatic or self-limited respiratory infection. The... read more 
. The vertebrae are often involved.
Pathophysiology of Osteomyelitis
Osteomyelitis tends to occlude local blood vessels, which causes bone necrosis and local spread of infection. Infection may expand through the bone cortex and spread under the periosteum, with formation of subcutaneous abscesses that may drain spontaneously through the skin.
In vertebral osteomyelitis, paravertebral or epidural abscess can develop.
If treatment of acute osteomyelitis is only partially successful, low-grade chronic osteomyelitis develops.
Symptoms and Signs of Osteomyelitis
Patients with acute osteomyelitis of peripheral bones usually experience weight loss, fatigue, fever, and localized warmth, swelling, erythema, and tenderness.
Vertebral osteomyelitis causes localized back pain and tenderness with paravertebral muscle spasm that is often continuous and unresponsive to conservative treatment. More advanced disease may cause compression of the spinal cord or nerve roots, with radicular pain and extremity weakness or numbness. Patients are often afebrile.
Chronic osteomyelitis causes intermittent (months to many years) bone pain, tenderness, and draining sinuses.
Diagnosis of Osteomyelitis
Erythrocyte sedimentation rate or C-reactive protein
X-rays, MRI, or radioisotopic bone scanning
Culture of bone, abscess, or both
Acute osteomyelitis is suspected in patients with localized peripheral bone pain, fever, and malaise or with localized refractory vertebral pain, particularly in patients with recent risk factors for bacteremia Bacteremia Bacteremia is the presence of bacteria in the bloodstream. It can occur spontaneously, during certain tissue infections, with use of indwelling genitourinary or IV catheters, or after dental... read more .
Chronic osteomyelitis is suspected in patients with persistent localized bone pain, particularly if they have risk factors.
If osteomyelitis is suspected, complete blood count and erythrocyte sedimentation rate (ESR) or C-reactive protein, as well as plain x-rays of the affected bone, are obtained. Leukocytosis and elevations of the ESR and C-reactive protein support the diagnosis of osteomyelitis. However, the ESR and C-reactive protein may be elevated in inflammatory conditions, such as rheumatoid arthritis, or normal in infection caused by indolent pathogens. Thus, the results of these tests must be considered in the context of physical examination and imaging study results.
X-rays become abnormal after 2 to 4 weeks, showing periosteal elevation, bone destruction, soft-tissue swelling, and, in the vertebrae, loss of vertebral body height or narrowing of the adjacent infected intervertebral disk space and destruction of the end plates above and below the disk.
If x-rays are equivocal or symptoms are acute, CT and MRI are the current imaging techniques of choice to define abnormalities and reveal adjacent infections, such as paravertebral or epidural abscesses, or infected facet joints.
Alternatively, a radioisotope bone scan with technetium-99m can be done. The bone scan shows abnormalities earlier than plain x-rays but does not distinguish between infection, fractures, and tumors.
A white blood cell scan using indium-111–labeled cells may help to better identify areas of infection seen on bone scan.
Bacteriologic diagnosis is necessary for optimal therapy of osteomyelitis; bone biopsy with a needle or surgical excision and aspiration or debridement of abscesses provides tissue for culture and antibiotic sensitivity testing. Culture of sinus drainage does not necessarily reveal the bone pathogen. Biopsy and culture should precede antibiotic therapy unless the patient is in shock or has neurologic dysfunction (eg, due to vertebral and spinal cord involvement).
Treatment of Osteomyelitis
Antibiotics
Surgery for abscess, constitutional symptoms, potential spinal instability, or much necrotic bone
Antibiotics
Antibiotics effective against both gram-positive and gram-negative organisms are given after cultures have been done and until culture results and sensitivities are available.
For acute hematogenous osteomyelitis, initial antibiotic treatment should include a penicillinase-resistant semisynthetic penicillin (eg, nafcillin or oxacillin 2 g IV every 4 hours) or vancomycin 1 g IV every 12 hours (when MRSA is prevalent in a community, which is common) and a 3rd- or 4th-generation cephalosporin (such as ceftazidime 2 g IV every 8 hours or cefepime 2 g IV every 12 hours).
For chronic osteomyelitis arising from a contiguous soft-tissue focus, particularly in patients with diabetes, empiric treatment must be effective against anaerobic organisms in addition to gram-positive and gram-negative aerobes. Ampicillin/sulbactam 3 g IV every 6 hours or piperacillin/tazobactam 3.375 g IV every 6 hours is commonly used; vancomycin 1 g IV every 12 hours is added when infection is severe or MRSA is prevalent. Antibiotics must be given parenterally for 4 to 8 weeks and tailored to results of appropriate cultures.
Surgery
If any constitutional findings (eg, fever, malaise, weight loss) persist or if large areas of bone are destroyed, necrotic tissue is debrided surgically. Surgery may also be needed to drain coexisting paravertebral or epidural abscesses or to stabilize the spine to prevent injury. Skin or pedicle grafts may be needed to close large surgical defects. Broad-spectrum antibiotics should be continued for > 3 weeks after surgery. Long-term antibiotic therapy may be needed.
Key Points
Most osteomyelitis results from contiguous spread or open wounds and is often polymicrobial and/or involves S. aureus.
Suspect osteomyelitis in patients with localized peripheral bone pain, fever, and malaise or with localized refractory vertebral pain and tenderness, particularly in patients with risk factors for recent bacteremia.
Do CT or MRI because evidence of osteomyelitis on x-rays typically takes > 2 weeks to develop.
Treat initially with a broad-spectrum antibiotic regimen.
Base treatment on the results of cultured bone tissue to obtain the best outcome.
More Information
The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the contents of these resources.
2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis (NVO) in Adults: Includes evidence and opinion-based recommendations for the diagnosis and management of patients with NVO treated with antimicrobial therapy, with or without surgical intervention
Schmitt SK: Osteomyelitis. Infect Dis Clin North Am 31(2):325-338, 2017. doi:10.1016/j.idc.2017.01.010
