Introduction Background Osteomyelitis is an acute or chronic inflammatory process of the bone and its structures secondary to infection with

pyogenic organisms. Pathophysiology The infection associated with osteomyelitis may be localized or it may spread through the periosteum, cortex, marrow, and cancellous tissue. The bacterial pathogen varies on the basis of the patient's age and the mechanism of infection. The following are the 2 primary categories of acute osteomyelitis: hematogenous osteomyelitis and direct or contiguous inoculation osteomyelitis. Hematogenous osteomyelitis is an infection caused by bacterial seeding from the blood. Acute hematogenous osteomyelitis is characterized by an acute infection of the bone caused by the seeding of the bacteria within the bone from a remote source. This condition primarily occurs in children. The most common site is the rapidly growing and highly vascular metaphysis of growing bones. The apparent slowing or sludging of blood flow as the vessels make sharp angles at the distal metaphysis predisposes the vessels to thrombosis and the bone itself to localized necrosis and bacterial seeding. Acute hematogenous osteomyelitis, despite its name, may have a slow clinical development and insidious onset. Direct or contiguous inoculation osteomyelitis is caused by direct contact of the tissue and bacteria during trauma or surgery. Direct inoculation (contiguous-focus) osteomyelitis is an infection in the bone secondary to the inoculation of organisms from direct trauma, spread from a contiguous focus of infection, or sepsis after a surgical procedure. Clinical manifestations of direct inoculation osteomyelitis are more localized than those of hematogenous osteomyelitis and tend to involve multiple organisms. Additional categories include chronic osteomyelitis and osteomyelitis secondary to peripheral vascular disease. Chronic osteomyelitis persists or recurs, regardless of its initial cause and/or mechanism and despite aggressive intervention. Although listed as an etiology, peripheral vascular disease is actually a predisposing factor rather than a true cause of infection. Disease states known to predispose patients to osteomyelitis include diabetes mellitus,1 sickle cell disease, acquired immune deficiency syndrome (AIDS), intravenous (IV) drug abuse, alcoholism, chronic steroid use, immunosuppression, and chronic joint disease. In addition, the presence of a prosthetic orthopedic device is an independent risk factor, as is any recent orthopedic surgery or open fracture.

For the radiologic perspective, see Osteomyelitis, Acute Pyogenic and Osteomyelitis, Chronic. Frequency United States The overall prevalence is 1 per 5,000 children. Neonatal prevalence is approximately 1 per 1,000. The annual incidence in patients with sickle cell anemia is approximately 0.36%. The prevalence of osteomyelitis after foot puncture (as is seen in the image below) may be as high as 16% (3040% in patients with diabetes).

Osteomyelitis of diabetic foot. Photography by David Effron MD, FACEP. International The overall incidence is higher in developing countries. Mortality/Morbidity Morbidity can be significant and can include localized spread of infection to associated soft tissues or joints; evolution to chronic infection, with pain and disability; amputation of the involved extremity; generalized infection; or sepsis. As many as 10-15% of patients with vertebral osteomyelitis develop neurologic findings or frank spinal-cord compression. As many as 30% of pediatric patients with long-bone osteomyelitis may develop deep venous thrombosis (DVT). The development of DVT may also be a marker for disseminated infection.2 Mortality rates are low, unless associated sepsis or an underlying serious medical condition is present. Race No increased incidence of osteomyelitis is noted based on race. Sex Male-to-female ratio is approximately 2:1. Age

In general, osteomyelitis has a bimodal age distribution. Acute hematogenous osteomyelitis is primarily a disease in children. Direct trauma and contiguous focus osteomyelitis are more common among adults and adolescents than in children. Spinal osteomyelitis is more common in persons older than 45 years. Clinical History Hematogenous osteomyelitis usually presents with a slow insidious progression of symptoms. Direct osteomyelitis generally is more localized, with prominent signs and symptoms. General symptoms of osteomyelitis include the following:

Hematogenous long-bone osteomyelitis o Abrupt onset of high fever (fever is present in only 50% of neonates with osteomyelitis) o Fatigue o Irritability o Malaise o Restriction of movement (pseudoparalysis of limb in neonates) o Local edema, erythema, and tenderness Hematogenous vertebral osteomyelitis o Insidious onset o History of an acute bacteremic episode o May be associated with contiguous vascular insufficiency o Local edema, erythema, and tenderness o Failure of a young child to sit up normally3 Chronic osteomyelitis o Nonhealing ulcer o Sinus tract drainage o Chronic fatigue o Malaise

Physical Findings at physical examination may include the following:

Fever (present in only 50% of neonates) Edema Warmth Fluctuance Tenderness to palpation Reduction in the use of the extremity (eg, reluctance to ambulate, if the lower extremity is involved or pseudoparalysis of limb in neonates) Failure of a young child to sit up normally Sinus tract drainage (usually a late finding or one that occurs with chronic infection)

Causes Note that responsible pathogens may be isolated in only 35-40% of infections. Bacterial causes of acute and direct osteomyelitis include the following:

Acute hematogenous osteomyelitis (Note increasing reports of other pathogens in bone and joint infections including communityassociated methicillin-resistant Staphylococcus aureus [MRSA],4 Kingella kingae,5 and others.) o Newborns (younger than 4 mo): S aureus, Enterobacter species, and group A and B Streptococcus species o Children (aged 4 mo to 4 y): S aureus, group A Streptococcus species, Haemophilus influenzae, and Enterobacter species o Children, adolescents (aged 4 y to adult): S aureus (80%), group A Streptococcus species, H influenzae, and Enterobacter species o Adult - S aureus and occasionally Enterobacter or Streptococcus species Direct osteomyelitis o General - S aureus, Enterobacter species, and Pseudomonas species o Puncture wound through an athletic shoe - S aureus and Pseudomonas species o Sickle cell disease -S aureus and Salmonellae species

Differential Diagnoses Bites, Animal Cellulitis Deep Venous Thrombophlebitis Gas Gangrene Gout and Pseudogout Hand Infections Juvenile Rheumatoid Arthritis Lumbar (Intervertebral) Disk Disorders Other Problems to Be Considered Fractures Aseptic Neuropathic joint disease Workup Laboratory Studies The following studies are indicated in patients with osteomyelitis: bone infarction Thrombosis Neoplasms, Spinal Cord Pediatrics, Limp and Pediatrics, Disease Septic Arthritis Septic Arthritis, Pediatrics Spinal Cord Infections Transient Synovitis Sickle Cell

Plantar Fasciitis

CBC count: The WBC count may be elevated, but it is frequently normal. o A leftward shift is common with increased polymorphonuclear leukocyte counts. o The C-reactive protein level is usually elevated and nonspecific; this study may be more useful than the erythrocyte sedimentation rate (ESR) because it reveals elevation earlier. o The ESR is usually elevated (90%); however, this finding is clinically nonspecific. Culture: With osteomyelitis, culture or aspiration findings in samples of the infected site are normal in 25% of cases. Blood culture results are positive in only 50% of patients with hematogenous osteomyelitis.

Imaging Studies

Radiography o Radiographic evidence of acute osteomyelitis is first suggested by overlying soft-tissue edema at 3-5 days after infection. Examples of radiographic evidence of osteomyelitis are presented in the images below.
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Osteomyelitis of the elbow. Photography by David Effron MD, FACEP.

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Osteomyelitis of index finger metacarpal head secondary to clenched fist injury. Photography by David Effron MD, FACEP.
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Osteomyelitis of the great toe. Photography by David Effron MD, FACEP.

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Osteomyelitis of T10 secondary to streptococcal disease. Photography by David Effron MD, FACEP.

Osteomyelitis. Radiography of diabetic foot showing osteomyelitis with gas. Photography by David Effron MD, FACEP.
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Bony changes are not evident for 14-21 days and initially manifest as periosteal elevation followed by cortical or medullary lucencies. By 28 days, 90% of patients demonstrate some abnormality. Approximately 40-50% focal bone loss is necessary to cause detectable lucency on plain films.

MRI

The MRI is effective in the early detection and surgical localization of osteomyelitis.6,7 o Studies have shown its superiority compared with plain radiography, CT, and radionuclide scanning in selected anatomic locations. o Sensitivity ranges from 90-100%. Radionuclide bone scanning o A 3-phase bone scan with technetium 99m is probably the initial imaging modality of choice. o In special circumstances, additional information can be obtained from further scanning with leukocytes labeled with gallium 67 and/or indium 111. CT scanning o CT scans can depict abnormal calcification, ossification, and intracortical abnormalities. o It is probably most useful in the evaluation of spinal vertebral lesions. It may also be superior in areas with complex anatomy: pelvis, sternum, and calcaneus. Ultrasonography o This simple and inexpensive technique has shown promise, particularly in children with acute osteomyelitis. o Ultrasonography may demonstrate changes as early as 1-2 days after onset of symptoms. o Abnormalities include soft tissue abscess or fluid collection and periosteal elevation.
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o o

Ultrasonography allows for ultrasound-guided aspiration. It does not allow for evaluation of bone cortex.

Treatment Emergency Department Care Osteomyelitis rarely requires emergent stabilization or resuscitation. The primary challenge for ED physicians is considering the appropriate diagnosis in the face of subtle signs or symptoms. Treatment for osteomyelitis involves the following:

Initiation of intravenous antibiotics that penetrate bone and joint cavities Referral of the patient to an orthopedist or general surgeon Possible medical infectious disease consultation

Select the appropriate antibiotics using direct culture results in samples from the infected site, whenever possible. Empiric therapy is often initiated on the basis of the patient's age and the clinical presentation. Further surgical management may involve removal of the nidus of infection, implantation of antibiotic beads or pumps, hyperbaric oxygen therapy,8,9 or other modalities. Diagnosis requires 2 of the 4 following criteria:

Purulent material on aspiration of affected bone Positive findings of bone tissue or blood culture Localized classic physical findings of bony overlying soft-tissue erythema or edema Positive radiological imaging study

tenderness,

with

Consultations Order an orthopedics, general surgery, or infectious disease consultation, as needed. Patients with diabetic foot osteomyelitis are best cared for by a multidisciplinary team.10 Medication The primary treatment for osteomyelitis is parenteral antibiotics that penetrate bone and joint cavities. Treatment is required for at least 4-6 weeks. After intravenous antibiotics are initiated on an inpatient basis, therapy may be continued with intravenous or oral antibiotics, depending on the type and location of the infection, on an outpatient basis. The following are recommendations for the initiation of empiric antibiotic treatment based on the age of the patient and mechanism of infection:

With hematogenous osteomyelitis (newborn to adult), the infectious agents include S aureus, Enterobacteriaceae organisms, group A and B Streptococcus species, and H influenzae. Primary treatment

is a combination of penicillinase-resistant synthetic penicillin and a third-generation cephalosporin. Alternate therapy is vancomycin or clindamycin and a third-generation cephalosporin, particularly if methicillin-resistant S aureus (MRSA) is considered likely. Linezolid is also used in these circumstances. In addition to these abovementioned antibacterials, ciprofloxacin and rifampin may be an appropriate combination therapy for adult patients. If evidence of infection with gram-negative bacilli is observed, include a thirdgeneration cephalosporin. In patients with sickle cell anemia and osteomyelitis, the primary bacterial causes are S aureus and Salmonellae species. Thus, the primary choice for treatment is a fluoroquinolone antibiotic (not in children). A third-generation cephalosporin (eg, ceftriaxone) is an alternative choice. When a nail puncture occurs through an athletic shoe, the infecting agents may include S aureus and Pseudomonas aeruginosa. The primary antibiotics in this scenario include ceftazidime or cefepime. Ciprofloxacin is an alternative treatment. For patients with osteomyelitis due to trauma, the infecting agents include S aureus, coliform bacilli, and Pseudomonas aeruginosa. Primary antibiotics include nafcillin and ciprofloxacin. Alternatives include vancomycin and a third-generation cephalosporin with antipseudomonal activity.

Antibiotics Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Nafcillin (Nafcil, Unipen) Initial therapy for suspected penicillin Gresistant streptococcal or staphylococcal infections. Use parenteral therapy initially in severe infections. Change to oral therapy as condition warrants. Because of thrombophlebitis, particularly in elderly patients, administer parenterally for only the short term (1-2 d). Change to PO route as clinically indicated. Note: Administer in combination with a third-generation cephalosporin to treat osteomyelitis. Do not admix with aminoglycosides for IV administration.

Dosing Interactions Contraindications Precautions

Adult 1-2 g IV/IM q4h; reduce dose 35-50% in severe renal or hepatic impairment; change to PO as clinically indicated Pediatric 100-200 mg/kg/d IV/IM divided q6h; maximum 12 g/d; change to PO as clinically indicated

Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions

Ceftriaxone (Rocephin) Third-generation cephalosporin with broad-spectrum gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms; arrests bacterial growth by binding to one or more penicillin-binding proteins. Note: Administer with a penicillinaseresistant synthetic penicillin, when treating osteomyelitis.

Dosing Interactions Contraindications Precautions

Adult 2 g IV qd Pediatric 75 mg/kg/d IV qd

Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions

Cefazolin (Ancef) First-generation semisynthetic cephalosporin that arrests bacterial cell wall synthesis, inhibiting bacterial growth; primarily active against skin flora, including S aureus; typically used alone for skin and skin-structure coverage.

Dosing

Adult 2 g IV/IM q8h; not to exceed 12 g/d Pediatric 20 mg/kg/d IV/IM divided q8h depending on severity of infection; not to exceed 6 g/d

Interactions Contraindications Precautions

Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions

Ciprofloxacin (Cipro) Fluoroquinolone with activity against pseudomonads, streptococci, MRSA, Staphylococcus epidermidis, and most gram-negative organisms, but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth. Continue treatment for at least 2 d (typical treatment, 7-14 d) after signs and symptoms disappear.

Dosing Interactions Contraindications Precautions

Adult 200-400 mg IV q12h Pediatric <18 years: >18 years: Administer as in adults

Not

recommended

Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions Dosing

Interactions Contraindications Precautions

Ceftazidime (Fortaz, Ceptaz) Third-generation cephalosporin with broad-spectrum gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms; arrests bacterial growth by binding to one or more penicillin-binding proteins.

Dosing Interactions Contraindications Precautions

Adult 2 g IV q8h Pediatric 150 mg/kg/d IV divided q8h; not to exceed 6 g/d

Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions

Clindamycin (Cleocin) Lincosamide for the treatment of serious skin and soft-tissue staphylococcal infections; also effective against aerobic and anaerobic streptococci (except enterococci); inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, arresting RNAdependent protein synthesis.

Dosing Interactions Contraindications Precautions

Adult 600-1200 mg/d IV/IM divided q6-8h, depending on the degree of infection Pediatric

20-40 mg/kg/d IV/IM divided tid/qid Severe infections: May increase dose to 16-20 mg/kg/d IV/IM divided tid/qid

Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions

Vancomycin (Vancocin) Potent antibiotic directed against gram-positive organisms and active against Enterococcus species. Useful in the treatment of septicemia and skin structure infections. Indicated for patients who can not receive or have failed to respond to penicillins and cephalosporins or have infections with resistant staphylococci. For abdominal penetrating injuries, it is combined with an agent active against enteric flora and/or anaerobes. To avoid toxicity, current recommendation is to assay vancomycin trough levels after third dose drawn 0.5 h prior to next dosing. Use creatinine clearance to adjust dose in patients with renal impairment. Used in conjunction with gentamicin for prophylaxis in penicillin-allergic patients undergoing gastrointestinal or genitourinary procedures.

Dosing Interactions Contraindications Precautions

Adult 500 mg to 2 g/d IV divided tid/qid 7-10 d Pediatric 40 mg/kg/d IV divided tid/qid 7-10 d

Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications

Precautions

Linezolid (Zyvox) Prevents formation of functional 70S initiation complex, which is essential for bacterial translation process. Bacteriostatic against staphylococci.

Dosing Interactions Contraindications Precautions

Adult 400-600 mg PO/IV q12h Pediatric Preterm neonate <7 days: 10 mg/kg Term neonates to 12 years: 10 mg/kg >12 years: Administer as in adults Follow-up Deterrence/Prevention

PO/IV PO/IV

q12h q8h

Acute hematogenous osteomyelitis can potentially be avoided by preventing bacterial seeding of bone from a remote site. This involves the appropriate diagnosis and treatment of primary bacterial infections. Direct inoculation osteomyelitis can best be prevented with appropriate wound management and consideration of prophylactic antibiotic use at the time of injury.

Complications Complications of osteomyelitis may include the following:

Bone abscess Bacteremia Fracture Loosening of the prosthetic implant Overlying soft-tissue cellulitis Draining soft-tissue sinus tracts

Prognosis

The prognosis varies but is markedly improved with timely diagnosis and aggressive therapeutic intervention.