INTRODUCTION

Section 2 of 10  

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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 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 occurs primarily 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, sickle cell disease, acquired immune deficiency syndrome (AIDS), 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.

Frequency

United States

The overall prevalence is 1 per 5,000 children. Neonatal prevalence is approximately 1 per 1,000. The annual incidence in sickle cell patients is approximately 0.36%. The prevalence of osteomyelitis after foot puncture may be as high as 16% (30-40% in patients with diabetes).

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. Up to 10-15% of patients with vertebral osteomyelitis will develop neurologic findings or frank spinal-cord compression.
• Mortality rates are low, unless associated sepsis or an underlying serious medical condition is present.

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

Section 3 of 10  

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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
• • Abrupt onset of high fever (fever is present in only 50% of neonates with osteomyelitis)
  • Fatigue
  • Irritability
  • Malaise
  • Restriction of movement (pseudoparalysis of limb in neonates)
  • Local edema, erythema, and tenderness
• Hematogenous vertebral osteomyelitis
• • Insidious onset
  • History of an acute bacteremic episode
  • May be associated with contiguous vascular insufficiency
  • Local edema, erythema, and tenderness
• Chronic osteomyelitis
• • Nonhealing ulcer
  • Sinus tract drainage
  • Chronic fatigue
  • 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)
• Sinus tract drainage (usually a late finding or one that occurs with chronic infection)

Causes

Bacterial causes of acute and direct osteomyelitis include the following:

• Acute hematogenous osteomyelitis
• • Newborns (younger than 4 mo): S aureus, Enterobacter species, and group A and B Streptococcus species
  • Children (aged 4 mo to 4 y): S aureus, group A Streptococcus species, Haemophilus influenzae, and Enterobacter species
  • Children, adolescents (aged 4 y to adult): S aureus (80%), group A Streptococcus species, H influenzae, and Enterobacter species
  • Adult: S aureus and occasionally Enterobacter or Streptococcus species
• Direct osteomyelitis
• • Generally: S aureus, Enterobacter species, and Pseudomonas species
  • Puncture wound through an athletic shoe: S aureus and Pseudomonas species
  • Sickle cell disease - S aureus and Salmonellae species

DIFFERENTIALS

Section 4 of 10  

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Other Problems to be Considered

Fractures
Aseptic bone infarction
Neuropathic joint disease

WORKUP

Section 5 of 10  

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• Follow-up
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Lab Studies

• CBC: The WBC count may be elevated, but it frequently is normal.
• • A leftward shift is common with increased polymorphonuclear leukocyte counts.
  • The C-reactive protein level usually is elevated and nonspecific; it may be more useful than the erythrocyte sedimentation rate. It will show elevation earlier than the erythrocyte sedimentation rate (ESR).
  • The erythrocyte sedimentation rate usually is elevated (90%); this finding is clinically nonspecific.
• 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
• • Radiographic evidence of acute osteomyelitis is first suggested by overlying soft-tissue edema at 3-5 days after infection.
  • 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.
  • Studies have shown its superiority compared with plain radiography, CT, and radionuclide scanning in selected anatomic locations.
  • Sensitivity ranges from 90-100%.
• Radionuclide bone scanning
• • A 3-phase bone scan with technetium 99m is probably the initial imaging modality of choice.
  • In special circumstances, additional information can be obtained from further scanning with leukocytes labeled with gallium 67 and/or indium 111.
• CT scanning
• • CT scans can depict abnormal calcification, ossification, and intracortical abnormalities.
  • It probably is most useful in the evaluation of spinal vertebral lesions. It may also be superior in areas with complex anatomy: pelvis, sternum, and calcaneus.
• Ultrasonography
• • This simple and inexpensive technique has shown promise, particularly in children with acute osteomyelitis.
  • Ultrasonography may demonstrate changes as early as 1-2 days after onset of symptoms.
  • Abnormalities include soft tissue abscess or fluid collection and periosteal elevation.
  • Ultrasonography allows for ultrasound-guided aspiration.
  • It does not allow for evaluation of bone cortex.

TREATMENT

Section 6 of 10  

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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, 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 tenderness, with overlying soft-tissue erythema or edema
• Positive radiological imaging study

Consultations

Order an orthopedics, general surgery, or infectious disease consultation, as needed.

MEDICATION

Section 7 of 10  

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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 MRSA is considered likely. Linezolid is also used in these circumstances. In addition to these above-mentioned antibacterials, ciprofloxacin and rifampin may be an appropriate combination therapy for adult patients. If there is evidence of infection with gram-negative bacilli, include a third-generation 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 are nafcillin and ciprofloxacin. Alternatives include vancomycin and a third-generation cephalosporin with antipseudomonal activity.

Drug Category: Antibiotics

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

Drug Name	Ceftriaxone (Rocephin)
Description	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 penicillinase-resistant synthetic penicillin, when treating osteomyelitis.
Adult Dose	2 g IV qd
Pediatric Dose	75 mg/kg/d IV qd
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment; caution in women who are breastfeeding and in patients with an allergy to penicillin

Drug Name	Cefazolin (Ancef)
Description	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.
Adult Dose	2 g IV/IM q8h; not to exceed 12 g/d
Pediatric Dose	20 mg/kg/d IV/IM divided q8h depending on severity of infection; not to exceed 6 g/d
Contraindications	Documented hypersensitivity
Interactions	Probenecid prolongs effect; coadministration with aminoglycosides may increase renal toxicity; may yield false-positive results for glucose at urine-dip testing
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment; superinfections, promotion of nonsusceptible organisms, and pancytopenia may occur with prolonged use or repeated therapy; complications are usually reversible

Drug Name	Ciprofloxacin (Cipro)
Description	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.
Adult Dose	200-400 mg IV q12h
Pediatric Dose	<18 years: Not recommended >18 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Antacids, iron salts, and zinc salts may reduce serum levels; if used, administer antacids no sooner than 2-4 h before or after administration; cimetidine may interfere with metabolism of fluoroquinolones; ciprofloxacin reduces therapeutic effects of phenytoin; probenecid may increase ciprofloxacin serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	In prolonged therapy, periodically evaluate organ system (eg, renal, hepatic, hematopoietic) functions; adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy

Drug Name	Ceftazidime (Fortaz, Ceptaz)
Description	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.
Adult Dose	2 g IV q8h
Pediatric Dose	150 mg/kg/d IV divided q8h; not to exceed 6 g/d
Contraindications	Documented hypersensitivity
Interactions	Nephrotoxicity may increase with aminoglycosides, furosemide, and ethacrynic acid use; probenecid may increase ceftazidime levels
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment

Drug Name	Clindamycin (Cleocin)
Description	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 RNA-dependent protein synthesis.
Adult Dose	600-1200 mg/d IV/IM divided q6-8h, depending on the degree of infection
Pediatric Dose	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
Contraindications	Documented hypersensitivity; regional enteritis, ulcerative colitis; hepatic impairment; antibiotic-associated colitis
Interactions	Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects; antidiarrheals may delay absorption
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis

Drug Name	Vancomycin (Vancocin)
Description	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.
Adult Dose	500 mg to 2 g/d IV divided tid/qid 7-10 d
Pediatric Dose	40 mg/kg/d IV divided tid/qid 7-10 d
Contraindications	Documented hypersensitivity
Interactions	Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; taken concurrently with aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; effects in neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in renal failure, neutropenia; red man syndrome is caused by too rapid IV infusion (dose given over a few min) but rarely happens when dose given IV over 2 h administration or as PO or IP administration; red man syndrome is not an allergic reaction

Drug Name	Linezolid (Zyvox)
Description	Prevents formation of functional 70S initiation complex, which is essential for bacterial translation process. Bacteriostatic against staphylococci.
Adult Dose	400-600 mg PO/IV q12h
Pediatric Dose	Preterm neonate <7 days: 10 mg/kg PO/IV q12h Term neonates-12 years: 10 mg/kg PO/IV q8h >12 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	May cause hypertension when used concomitantly with adrenergic agents including pseudoephedrine, sympathomimetic agents, vasopressor or dopaminergic agents (reduce dose of dopamine or epinephrine if concurrent use required); serotonin syndrome may occur if used concomitantly with serotonergic agents including tricyclic antidepressants, meperidine, dextromethorphan, trazodone, venlafaxine, and selective serotonin reuptake; may cause myelosuppression or pseudomembranous colitis inhibitors
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Has mild MAO inhibitor properties and has potential to have same interactions as other MAO inhibitors; caution in uncontrolled hypertension, pheochromocytoma, carcinoid syndrome, or untreated hyperthyroidism, and patients who are at increased risk for bleeding, have preexisting thrombocytopenia, receive concomitant medications that may decrease platelet count or function, or who may require > 2 wk of therapy (monitor platelet counts); unnecessary use may lead to development of resistance to drug; may cause peripheral or optic neuropathy

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Deterrence/Prevention

• 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

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

Prognosis

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

MULTIMEDIA

Section 9 of 10  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
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• Follow-up
• Multimedia
• References

Media file 1:  Osteomyelitis of the elbow. Photography by David Effron MD, FACEP.
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Media file 2:  Osteomyelitis of index finger metacarpal head secondary to clenched fist injury. Photography by David Effron MD, FACEP.
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Media file 3:  Osteomyelitis of index finger metacarpal head secondary to clenched fist injury. Photography by David Effron MD, FACEP.
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Media file 4:  Osteomyelitis of the great toe. Photography by David Effron MD, FACEP.
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Media file 5:  Osteomyelitis of T10 secondary to streptococcal disease. Photography by David Effron MD, FACEP.
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Media file 6:  Osteomyelitis of diabetic foot. Photography by David Effron MD, FACEP.
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Media file 7:  Osteomyelitis. Radiography of diabetic foot showing osteomyelitis with gas. Photography by David Effron MD, FACEP.
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Media type:  X-RAY

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

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Article Last Updated: Jul 13, 2006