osteomyelitis in adults: medical topics: first consult

7/31/2019 Osteomyelitis in Adults: Medical Topics: First Consult

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10/10/12 5:54 AMOsteomyelitis in adults: Medical Topics: First Consult

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May occur on both sides of a nonunion or a jointInvolves the entire thickness of the bone, with loss of stability

The second part of the system describes the patient's physiologic status, as deficiencies of leukocyte recruitment, phagocytosis, or vascular supplies may promote osteomyelitis andcontribute to its chronicity. The physiologic class of the infected patient is often more important than the anatomic type because the state of the host is the strongest predictor of treatment failure.

Class A: normal hostNormal physiologic, metabolic, and immune functionsAssociated with a much better prognosis

Class B: host factors l imit normal immune response and healingImmunocompromised, either locally (Bl), systemical ly (Bs), or both (Bls)Local factors include problems of perfusion (peripheral vascular disease, vasculitis, venous stasis, lymphedema)Systemic factors include hypoxemia, illnesses associated with impaired immune function (chronic renal or hepatic insufficiency, malignancy, diabetes), or use of immunosuppressive medication (steroids)The goal of treatment is to remove the factors that lead to the development of osteomyelitis

Class C: health of host does not allow full treatmentTreatment poses a greater risk than the infection itself Surgery may not be possible because of the patient's debilitated or immunocompromised status

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Epidemiology

There are several recent trends in the epidemiology of osteomyelitis. Acute hematogenous osteomyelitis is decreasing in incidence, whereas the incidence of osteomyelitisdue to direct inoculation or contiguous focus of infection is increasing. This is attributed to the increase in both trauma (due to motor vehicle accidents) and orthopedicsurgical proceduresOsteomyelitis secondary to open fractures occurs in 3% to 25% of cases, usually in young men in their twenties and thirties

Foot ulcers occur in 2% of patients with diabetes every year, 15% of whom will develop osteomyelitis. Recurrent infection occurs in up to 36% of patients with diabetesVertebral osteomyelitis is responsible for 2% to 4% of all cases of osteomyelitis, with an annual incidence of 5.3 cases per million persons. Men are more commonlyaffected than women, with a mean age at presentation of 61 years

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Causes and risk factors

Causes:

The focus for hematogenous osteomyelitis may vary from a mild skin infection to bacterial endocarditis; it is also a complication among intravenous drug usersOsteomyelitis secondary to a contiguous focus of infection may be caused by the direct inoculation of bacteria through trauma, from spread of adjacent soft tissue infection,or introduction of infection during preoperative or intraoperative procedures. Predisposing factors include surgical reduction and internal fixation of fractures, prostheticdevices, open fractures, and chronic soft tissue infectionsOsteomyelitis secondary to vascular insufficiency is often associated with diabetes mellitus. Infection often results from minor t rauma to the feet, such as infected nail bedsor skin ulceration. Inadequate tissue perfusion limits local tissue response to injuryMultiple organisms are responsible for osteomyelitis in different populations. The causative organism is related to the age, cl inical history, and immune status of the patient

(see Table 1). S. aureus is the most common cause in all casesTable 1. Organisms Commonly Implicated in Osteomyelitis in Different Patient Populations

Category of Osteomyelitis Population Causative Organism(s)Hematogenous osteomyelitis Patients of all ages S. aureus

Neonates Enterobacteriaceae , group B streptococciInfants and children Haemophilus influenzae type BIntravenous drug users S. aureus , Pseudomonas aeruginosa , Candida speciesPatients with sickle cell disease Streptococcus pneumoniae , Salmonella speciesHIV-infected patients Bartonella henselaePatients with nosocomial infections S. aureus , Enterobacteriaceae , Candida species,

Aspergillus (in immunocompromised patients)Vertebral osteomyelitis (hematogenous andcontiguous focus)

Adults (most commonly) S. aureusPatients with urinary tract infections Aerobic gram-negative bacilli, Enterococcus speciesIntravenous drug users S. aureus , P. aeruginosaPatients undergoing spinal surgery Coagulase-negative staphylococci, S. aureus , aerobic

gram-negative bacilliPatients with infections of intravascular devices

Candida species, staphylococci

Patients living in endemic regions M. tuberculosis , Brucella species, regional fungi(coccidioidomycosis, blastomycosis, histoplasmosis),Coxiella burnetii (Q fever)

Contiguous-focus osteomyelitis Patients exposed to contaminated soil Clostridium species, Bacillus species,Stenotrophomonas maltophilia , Nocardia species,atypical mycobacteria, Aspergillus species, Rhizopusspecies, Mucor species

Patients with orthopedic devices S. aureus , coagulase-negative staphylococci,Propionibacterium species

Patients with decubitus ulcers Enterobacteriaceae , P. aeruginosa , enterococci,
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anaerobes, Candida speciesPatients with a history of cat bites Pasteurella multocidaPatients with a history of human bites(including clenched-fist injury)

Eikenella corrodens , Moraxella species

Patients with puncture injuries on thefoot

P. aeruginosa

Patients with periodontal infection Actinomyces speciesOsteomyelitis associated with vascularinsufficiency

Patients with diabetes Polymicrobial: S. aureus , -hemolytic streptococci, Enterococcus faecalis , aerobic gram-negative bacilli

HIV = human immunodeficiency virus

Risk factors:

Diabetes mellitusImmunocompromiseNeuropathyVascular insufficiencyIntravenous drug useOpen fracturesLocal traumaOrthopedic hardware (including prosthetic joints)HemodialysisSickle cell diseaseDental infectionsUrinary tract infectionsCatheter-related bloodstream infection

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Associated disorders

Occurs more frequently in patients with diabetes mell itus, vascular insufficiency, or immunosuppressionRecent history of surgical procedure or joint or bone trauma

ScreeningNot applicable.

Primary preventionBack to Top

Summary approach

Patients with diabetes should have a complete examination of the lower extremities annually and inspection of the feet for wounds at interim routine follow-up visits.Measures to prevent diabetic foot ulcers should be emphasized. A high index of suspicion should be maintained for the contiguous spread of local diabetic foot infections tothe bone, with continuous evaluation for signs and symptoms of the development of osteomyelitisPatients with open fractures who are able to receive antibiotics within 6 hours of injury and prompt surgical treatment have a reduced risk of developing osteomyelitisThe use of prophylactic antibiotics prior to bone surgery has been shown to prevent wound infectionsScrupulous care should be taken to avoid health careassociated osteomyelitis, with careful attention to intravascular and urinary catheters, surgical incisions, and otherwounds

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Population at risk

Patients with diabetes mellitusPatients undergoing orthopedic surgery, including placement of prostheses and other clean surgery and management of open fractures

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Preventive measures [EBM]

In patients with diabetes mellitus:

Measures to prevent diabetic foot include excellent foot hygiene, glycemic control, and use of protective footwearPatients should be instructed to examine their feet daily and to seek prompt medical care for new wounds or other injuries to the feetA complete evaluation of the lower extremiti es should be done annually, and the feet should be inspected for wounds at periodic follow-up visits in the interimPatients with Charcot joints or other abnormalities that result in friction with shoes may require specially adapted shoesIn patients undergoing foot surgery or amputation, the use of protective footwear postoperatively is helpful in preventing subsequent ulceration and infection

In patients with open fractures:

Administration of antibiotics within 6 hours of injury and prompt surgical treatment are associated with a reduced risk of developing osteomyelitisA continued 24-hour regimen of penicillin or first-generation or second-generation cephalosporins is also beneficial

In patients undergoing bone surgery:

Administration of prophylactic antibiotics has proven to be successful in the prevention of infection following surgery, particularly in patients with noncompound hip
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fractures and those receiving total hip and knee prosthesesIn patients undergoing clean bone surgery, intravenous antibiotics are administered 30 minutes before skin incision and up to 24 hours following the procedure. Afirst-generation or second-generation cephalosporin is appropriate in many cases; vancomycin may be used in patients who are allergic to cephalosporin and insettings with a high prevalence of methicil lin-resistant staphylococciIn patients undergoing surgery for closed fractures, the use of penicillin, first-generation cephalosporins ( eg , cefazolin), or second-generation cephalosporins ( eg ,cefamandole, cefuroxime) has led to a reduction in postsurgical infection

Standard preoperative procedures, such as the use of antimicrobial shower, shaving, and topical disinfectants, should be followed. Observation of such procedures, togetherwith the use of surgical rooms with laminar airflow and prophylactic antibiotic therapy, has led to a reduction in the postsurgical rate of infection to 0.5% to 2%, dependingon the type of joint replacement

Evidence

An observational study of 2,847 patients receiving antibiotic prophylaxis for elective surgical procedures showed that surgical wound infections occurred in 0.6% of thosewho received antibiotics preoperatively, 1.4% of those who received antibiotics perioperatively (relative risk [RR], 2.4 compared to the preoperative group), 3.3% of thosewho received antibiotics postoperatively (RR, 5.8), and 3.8% of those who received early antibiotic treatment (RR, 6.7). Administration of antibiotics during thepreoperative period was associated with the lowest risk of surgical wound infection.[1] Level of evidence: 1

Learn about evidence grading system

DiagnosisBack to Top

Summary approach

Osteomyelitis is diagnosed on the basis of data obtained from the history, physical examination, and laboratory tests. The diagnosis is confirmed by needle aspiration orbone biopsy, with subsequent demonstration of infectious microorganism by culture or histology

Patients with osteomyelitis typically present with localized pain and swelling accompanied by nonspecific symptoms, including chills, fever, and malaiseLaboratory tests and imaging techniques, including magnetic resonance imaging (MRI), computed tomography (CT) scan, positron emission tomography (PET) scan, andradionuclide studies, are important tools in establishing the diagnosis of osteomyelitis

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Clinical presentation

History

Symptoms:

Patients with osteomyelitis often present with nonspecific constitutional symptoms, including chills, fever, malaise, irritability, fatigue, and lethargy; localized pain,swelling, and redness may also be presentPatients with diabetes and others with peripheral neuropathy may not experience painCompared to younger patients, adults with osteomyelitis present less frequently with typical systemic symptomsHematogenous osteomyelitis:

Vague symptoms (nonspecific pain and low-grade fever, chills)Symptoms of vertebral osteomyelitis include axial skeletal pain; constant, dull back or neck pain that worsens upon straining; regional paraspinal muscle spasms;and limping

Osteomyelitis secondary to a contiguous focus of infection:Localized bone painLow-grade fever

Osteomyelitis associated with vascular insufficiency:Systemic symptoms of infection, including fever, chills, and malaise, may be absent in patients with osteomyelitis associated with a diabetic foot

Other historical factors:

Presence of diabetes mellitusHistory of trauma, especially open fracturesHistory of skin and soft tissue infectionsPrevious surgical procedures, including placement of prosthetic devicesPrevious diagnosis of refractory infections ( eg , methicillin-resistant S. aureus [MRSA], fungal infections)Presence of embedded foreign bodies ( eg , gunshot wounds)

Presence of other risk factors ( eg , intravenous drug abuse, hemodialysis, vascular disease)Physical examination

Neurologic function should be assessed in patients with vertebral osteomyelitisExamination of patients with diabetes should include inspection of the entire surface of both ankles and feet, assessment of neuropathy by monofilament testing, andexamination of the vascular status of the lower extremities; osteomyelitis usually occurs at the base of chronic, nonhealing wounds in these patients

Signs:

Acute osteomyelitis:Tenderness, erythema, and calor over the affected areaLimited range of motion

Subacute and chronic osteomyelitis:Draining sinus tractsSequestrum formationDeformity

InstabilityLocal signs of impaired vascularity, range of motion, and neurologic functionVertebral osteomyelitis

There may be tenderness on palpation of the involved spinal segment, sustained paraspinal spasms, and limitation of motion
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Neurologic deficit or meningitis may be seen as a result of spread of the infection into the epidural space; paralysis is associated with epidural abscessesOsteomyelitis secondary to a contiguous focus of infection:

Patients with an infected prosthesis may have pain and instability of the jointProbing a wound may show softened bone at the base

Osteomyelitis secondary to vascular insufficiency:Patients with diabetes usually have purulent drainage from the wound, surrounding erythema, and exposed or palpable necrotic bone; there is sometimes a deceptivelack of inflammation because of poor perfusion

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Diagnostic testing

A leukocyte count and erythrocyte sedimentation rate (ESR) should be obtained, as leukocytosis (leukocyte count >10,000/mL) and ESR elevation occur early in the courseof acute osteomyelitis. Leukocytosis may not be seen in patients with chronic infectionsC-reactive protein (CRP) is also a useful diagnostic tool but is not specific for osteomyelitis. CRP i s synthesized by the liver whenever infection occurs. CRP levelsincrease within hours of infection; return to normal levels signifies improvement. Because of its short half-life, CRP can be used to gauge the response to treatmentBlood cultures to identify the causative organism are critical to guide the selection of appropriate antibiotic therapy. In patients with hematogenous osteomyelitis, bloodculture results may be positive at the time of diagnosis; in patients with health careassociated hematogenous infection, recent positive blood culture results also mayprovide a clue to the diagnosisBone biopsy for histopathology and culture is the gold standard for the diagnosis of osteomyelitis and is often required to confirm the presence of osteomyelitis whileexcluding another inflammatory process and to identify the causative pathogen. A biopsy should be obtained before antibiotic therapy is initiated or, if not possible, at least48 hours after treatment has been discontinued. Fine-needle aspiration bone biopsies have a sensitivity of 87% and a specificity of 93%. Specimens taken from drainingsinus tracts or the wound surface often yield inaccurate results due to nonpathogenic microorganisms that often colonize the site. Isolates obtained from bone biopsy shouldbe tested for both aerobic and anaerobic organisms, and cultures for mycobacterial and fungal infections also should be obtainedThe following imaging modalities have been used for the detection of osteomyelitis:

Conventional radiography is the initial imaging study obtained in all patients in whom musculoskeletal infection is suspectedIn patients with negative or unequivocal radiographic findings, magnetic resonance imaging (MRI) has been used widely due to its excellent resolution, whichshows inflammation and edema in bone tissue. Changes are evident much earlier than on plain radiographs, and MRI is more specific than bone scan

Computed tomography (CT) scan is less sensitive than MRI but provides images of good resolution and may be helpful in patients who cannot undergo MRI; CTsinography and conventional tomography also may be doneRadionuclide studies:

Three-phase bone scan is readily available and very sensitive in unviolated bone, although uptake reflects increased metabolic activity and is not specific forinfectionRadiolabeled leukocyte scan may be helpful in pati ents with prosthetic joint infectionsRadiolabeled antibiotic scintigraphy can differentiate infection from a sterile inflammatory lesionStreptavidin/indium In 111 biotin complex scintigraphy has been shown to be very sensitive in identifying vertebral osteomyelitis within the first 2 weeks of infectionFludeoxyglucose F 18 (FDG)PET is a relatively new technique that has been shown to be accurate in establishing the diagnosis of osteomyelitisThe combination of single-photon emission CT (SPECT) and CT can facil itate accurate diagnosis of osteomyelitis

Transcutaneous oximetry and measurement of pulse pressure by Doppler ultrasonography are used to assess vascular compromise in patients with osteomyelitissecondary to vascular insufficiency

Leukocyte count

DescriptionA venous blood sample is obtained, and the total leukocyte count and differential count are measured

Normal ranges

Total leukocyte count: 4,500 to 11,000/ LDifferential count (with percentage of the total count):

Neutrophilssegmented: 1,800 to 7,800/ L (56%)Neutrophilsbands: 0 to 700/ L (3%)Lymphocytes: 1,000 to 4,800/ L (34%)Monocytes: 0 to 800/ L (4%)Eosinophils: 0 to 450/ L (2.7%)Basophils: 0 to 200/ L (0.3%)

Comments

The infective nature of osteomyelitis is responsible for elevations in markers of systemic infection, such as the leukocyte countNot specific for osteomyelitis; other infections, inflammatory conditions, and hematologic malignancies al l can increase the leukocyte countLess specific and of less predictive value than CRP or ESRShould be used in conjunction with CRP and ESR to establish the diagnosis in patients in whom osteomyelitis is suspectedMay be normal in patients with chronic osteomyelitis or directly spread osteomyelitisNot widely used for monitoring or treatment of osteomyelitis

ESR

Description

A venous blood sample is obtained, and the ESR (how rapidly erythrocytes settle in a tube of blood) is measured

Normal range

0 to 20 mm/h

CommentsA useful screening method for differentiating mechanical from infective or inflammatory bone symptomsCan be used in conjunction with CRP for both diagnosis of osteomyelitis and monitoring of treatment
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Elevation suggests inflammation, with the increase in ESR approximately proportional to the degree of inflammationNot specific for osteomyelitis; other conditions, including cancers (particularly hematologic cancers, such as multiple myeloma), systemic infection ( eg , sepsis in therespiratory or urinary tract, skin or soft tissue infection), and inflammatory conditions ( eg , connective tissue disease, arteritis) may result in elevation of the ESRLess specific and has a lower predictive value than CRPAlthough an elevated ESR does not confirm the diagnosis of osteomyelitis, it can serve to alert the physician of the need for urgent orthopedic referral in patients in whomosteomyelitis is suspectedMay be falsely low in patients with conditions in which erythrocytes do not undergo rouleaux formation ( eg , sickle cell anemia, hereditary spherocytosis)

CRP [EBM]

Description

A venous blood sample is obtained, and the CRP level is measured

Normal range

0.08 to 3.1 mg/L

Comments

A useful screening method in patients with bone symptomsCan be used in conjunction with CRP for both diagnosis of osteomyelitis and monitoring of treatmentElevation suggests inflammation, with the increase in CRP approximately proportional to the degree of inflammationElevation in a patient with bony symptoms should raise the possibility of infection and prompt urgent referral to the hospitalNot specific for osteomyelitis; other conditions, including cancers, systemic infection ( eg , sepsis in the respiratory or urinary tract, skin or soft tissue infection), andinflammatory conditions ( eg , connective tissue disease, arteritis) may result in elevation of the CRP levelAlthough an elevated CRP level does not confirm the diagnosis of osteomyelitis, it can serve to alert the physician of the need for urgent orthopedic referral in patients inwhom osteomyelitis is suspected

In patients with hematogenous osteomyelitis, the CRP level increases and decreases significantly faster than the ESR, reflecting the effectiveness of therapy and predictingrecovery more sensitively than the ESR or l eukocyte count

Evidence

An observational study was conducted to determine the value of CRP in predicting healing versus infection or other complications in 52 patients undergoing soft tissuereconstructions following open fractures of the lower limbs, chronic infection, osteomyelitis, and nonunion. Of 41 patients whose CRP level peaked 4 or fewer days aftersurgery, 15% developed infection or required further surgery. Of 11 patients whose CRP level peaked more than 4 days postoperatively, 82% developed infection orrequired further surgery. Of 25 patients who achieved complete healing of a fracture, al l had CRP levels 8 mg/L. The investigators concluded that persistent elevation of CRP after the fourth postoperative day predicts complications in this sett ing.[2] Level of evidence: 2


Blood cultures

Description

Venous blood samples are obtained in specific bottles under scrupulous aseptic technique and set up for culturesUsually done in a laboratory but may involve the primary care physician, especially in rural sett ings

Normal result

No growth on culture

Comments

Results can effectively guide therapyA positive result is indicative of bacteremia, although contamination of the specimen is possible; positive results are also more likely if the patient has a fever when thesample is obtained. Microbiologic expertise is required in the interpretation of resultsNot specific for osteomyelitis; bacteremia occurs as a result of most other bacterial infectionsRecent or ongoing use of antibiotics may substantially reduce sensitivity

Bone biopsy [EBM]

Description

Fine-needle aspiration or open biopsy with subsequent histopathologic and microbiologic examination of the boneDone by an orthopedic surgeon with the patient under local anesthesia

Normal result

Marrow cellularity appropriate to the patient's age

Comments

The gold standard for the diagnosis of osteomyelitisShould be done before antibiotic therapy is started or, i f not possible, at least 48 hours after it has been discontinuedFine-needle aspiration has a sensitivity of 87% and a specificity of 93%Specimens taken from draining sinus tracts or the wound surface often yield inaccurate results due to nonpathogenic microorganisms that often colonize the siteInvasive, with attendant risks (albeit low) of hemorrhage, infection, and wrong positioning of the needle, and unpleasant for the patient

Evidence


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A prospective study evaluated the sensitivity and specificity of fine-needle bone biopsy in 30 patients in whom osteomyelitis was suspected. The diagnosis of osteomyelitiswas confirmed by conventional means in 15 patients. The sensitivity of fine-needle bone biopsy for diagnosing osteomyelitis was 87%, and the specificity was93%.[3] Level of evidence: 2


Conventional radiography

Description

Plain radiographs of the affected area are obtained to screen for osteomyelitis

Normal result

No abnormality seen

Comments

Findings in patients with osteomyelitis include soft tissue swelling (earliest change seen); swelling of the muscles with obliteration of the soft tissues; and bone destructionand periosteal reaction, signifying that infection has been present for at least 1 to 2 weeks. Brodie abscesses, circumscribed lesions favoring the ends of long bones that maybe formed during the subacute or chronic stages of osteomyelitis, also may be seenIt takes 10 to 21 days after the onset of infection for the lesion to become visible, as bone density must be reduced by 30% to 50% to produce the radiographic changenecessary for visualizationSensitivity is 43% to 75%, and specificity is 75% to 83%

MRI [EBM]

Description

Magnetic and radio energy is used to create cross-sectional images or 'slices' of the body

Normal result

No abnormality detected

Comments

Useful in distinguishing between soft tissue infections and bone infections and in diagnosing early osteomyelitis; also aids in optimal surgical management by establishingthe extent of disease and detect ing abscesses and other anatomic features that may determine the surgical approachWidely used in the diagnosis of osteomyelitis associated with a diabetic footIn patients with acute osteomyelitis, the earliest finding is an alteration of the normal marrow signal density, which is present within 1 to 2 days of onset of infection (lowsignal intensity on T1-weighted images and high signal intensity on T2-weighted, short T1 inversion recovery, or fat-saturated sequences)In patients with subacute or chronic osteomyelitis, findings include Brodie abscess, which is a characteristic abscess surrounded by granulation tissue, an outer ring of fibrotic reaction, and a peripheral rim of endosteal reaction that creates a target appearanceIn patients with chronic osteomyelitis, low signal intensity on both T1-weighted and T2-weighted images reflects areas of devascularized fibrotic scarring. Bone sclerosiswith cortical thickening from periosteal apposition can be observed, along with a focally reduced cavity of the bone marrow. Sinus tracts also can be seen. Normal andabnormal bone marrows are well delineated by a sharp interfaceSensitivity is 82% to 100% (90%-100% in patients with diabetes), and specificity is 75% to 96% (80%-100% in patients with diabetes)Advantages include provision of excellent anatomic detail, lack of radiation exposure, and rapid completionDisadvantages include occasional inability to differentiate infectious inflammation from reactive inflammation, limitations in patients with prosthetic devices, high cost($400-$3,500), and lack of availability in some areas

Evidence

A meta-analysis conducted to determine the diagnostic test performance of MRI for osteomyelitis of the foot identified 16 studies that met the inclusion criteria. Thecombined diagnostic odds ratio (OR) for MRI was 42.1, and the specificity at a 90% sensitivity cutoff was 82.5%. Diagnostic ORs for MRI compared with those for otherdiagnostic tests were as follows: 149.9 versus 3.6 for bone scan, 81.5 versus 3.3 for plain radiography, and 120.3 versus 3.4 for radiolabeled leukocyte scan.[4] Level of evidence: 2


CT scan

Description

Produces images with high spatial and contrast resolution of bone and tissue and excellent cortical bony detailReliably identifies cortical destruction, periosteal proliferation, and soft tissue extension

Normal result


Comments

Findings in patients with acute osteomyelitis include increased density of the normal fatty medullary canal as it is replaced by infectious edema and the blurring of fatplanes, eventual periosteal reaction, and loss of cortexFindings in patients with chronic osteomyelitis may include abnormal thickening of the affected cortical bone with sclerotic changes, encroachment of the medullary cavity,and sometimes a chronic draining sinusSensitivity and specificity have not been fully established, although sensitivity is certainly lower than that of MRIAdvantages are as follows:

Assesses bone integrity and cortical destruction in patients in whom osteomyelitis is suspectedAssists in preoperative planning by detecting necrotic debris, foreign bodies, etc.


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Detects sequestra, cloacae, involucra, and intraosseous gas (superior to MRI in this regard)Guides fine-needle biopsiesAssists in optimizing surgical debridement by defining surgical boundariesDelineates abscess cavities

Disadvantages include high cost, radiation exposure, and lack of availability

CT sinography

Uses contrast medium to opacify a sinus tractA small flexible catheter is inserted into a cutaneous opening, and a contrast medium is introduced, which charts the course and extent of the sinus tract and determines if there is communication with neighboring structures

Conventional tomography

Description

Provides images of a series of sections or slices of the t issues at varying depths from the skin surface

Normal result


Comments

Helpful in evaluating abnormalities within high-contrast tissues, such as boneAble to detect sequestra (pieces of necrotic bone that are separated from l iving bone by granulation tissue) in patients with chronic osteomyelitis

Bone scan

Description

Scintigraphy with triple-phase technetium Tc99m methylene diphosphonateConsists of the following three phases:

Flow phase: immediately after injection, at a rate of 2 seconds per frameBlood-pool phase: 5 to 15 minutes after injectionDelayed phase: 2 to 3 hours after injection

A fourth phase may be taken after 24 hours if the results of the first three phases are ambiguous

Normal result

No bone lesions detected

Comments

Most useful radionuclide study for the diagnosis of osteomyelitisPositive results are seen within 24 to 48 hours of the onset of symptomsClassic findings in patients with osteomyelitis are focal hyperperfusion, focal hyperemia, and focal bone uptakeA positive result on all three phases indicates a high sensitivity (69%-100%) for osteomyelitis but with a low specificity (38%-96%)Advantages include high sensitivity for osteomyelitis (can differentiate between cel lulitis and osteomyelitis reliably when no complicating conditions are present), wideavailability, relatively low cost, ease of performance, and rapid completionThe main disadvantage is that abnormalities reflect the rate of new bone formation in general and not infection specifically. Thus, the specificity for osteomyelitis decreaseswhen other conditions are present ( eg , recent trauma, surgery, placement of orthopedic devices, or diabetes)

Radiolabeled leukocyte scan

Description

The patient's leukocytes, which tend to accumulate in areas of acute infection, are isolated and labeled with indium In 111 before being administered back to the patientThe majority of the labeled l eukocytes are neutrophils; thus, the procedure is most practical for recognizing neutrophil-mediated inflammatory processes (bacterialinfections)

Comments

Sensitivity is 88% to 89%, and specificity is 85%; the high specificity is the main advantage over technetium scansCannot distinguish well between osteomyelitis and soft ti ssue infectionsInfrequently used when diagnostic urgency is present because the procedure is time intensive and requires 40 to 60 mL of whole blood

Radiolabeled antibiotic scintigraphy [EBM]

Description

Ciprofloxacin labeled with technetium Tc 99m is administered, and uptake is observed

Normal result

High uptake of technetium Tc 99m by the kidneys, moderate uptake by the liver and spleen, and absence of uptake by the bone or bone marrow

Comments

Antibiotics tend to localize a t the focus of infection, where they are taken up and metabolized by microorganismsAble to differentiate infection from a st erile inflammatory lesionOne study showed a sensitivity of 97.2% and a specificity of 80%, with positive and negative predictive values of 94.6% and 88.9%, respectively


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Administration of antibiotics before bone biopsy may alter culture results

Evidence

A clinical trial in 45 patients with known or suspected bone infection who underwent 50 scans using scintigraphy with technetium Tc 99mradiolabeled ciprofloxacin(Infecton) found that the sensitivity and specificity of Infecton scintigraphy for detecting osteomyelitis were 97.2% and 80%, respectively, and the positive and negativepredictive values were 94.6% and 88.9%, respectively.[5] Level of evidence: 2


Streptavidin/indium In 111 biotin complex scintigraphy [EBM]

Description

Streptavidin, a 65-kDA protein that builds up at sites of infection due to the locally increased vascularity and vascular permeability, is administered followed byadministration of indium In 111 biotin, which has a high affinity to streptavidin and accumulates at the focus of infection

Comments

Has been shown to be very sensitive in the recognition of vertebral osteomyelitis within the first 2 weeks of infection; this is clinically significant because conventionalradiography often yields negative results in the first 4 to 5 weeks after the onset of symptomsA potential disadvantage is the occurrence of immunogenic reactions that may develop in response to subsequent administration of the agent

Evidence

A clinical trial evaluated the diagnostic performance of streptavidin/indium In 111 biotin scintigraphy within 2 weeks of the onset of clinical symptoms in 55 consecutivepatients in whom vertebral osteomyelitis was suspected. In addition to two-step streptavidin/indium In 111 biotin scintigraphy, patients underwent MRI and CT scan.

Sensitivity and specificity were 94.12% and 95.24%, respectively, for streptavidin/indium In 111 biotin scintigraphy; 54.17% and 75%, respectively, for MRI; and 35.29%and 57.14%, respectively, for CT scan.[6] Level of evidence: 2


FDG-PET [EBM]

Description

FDG, a nonspecific indicator of increased intracellular glucose metabolism, builds up in sites of infection and inflammation

Comments

A relatively new modality used in the investigation of osteomyelitisProvides results within 30 to 60 minutes of administration, can distinguish between inflammatory cellular infiltrates and hematopoietic marrow, and can be used in patientswith metallic implant artifacts

Early bone healing also involves a short inflammatory phase, which could be mistaken for osteomyelitisExpensive ($3,000-$6,000) and not widely availableCombination with CT provides the sensitivity of PET and the resolution of CT to establish a diagnosis and clearly define the extent of involvement, which is important forsurgical planning

Evidence

A systematic review and meta-analysis conducted to determine the sensitivity and specificity of various imaging techniques in the diagnosis of chronic osteomyelitisidentified 23 clinical studies. Techniques evaluated included radiography, MRI, CT scan, bone scintigraphy, leukocyte scintigraphy, gallium scintigraphy, combined boneand leukocyte scintigraphy, combined bone and gallium scintigraphy, and FDG-PET. Because there was only 1 study each on CT, gallium scintigraphy, and radiography,no meta-analysis was done on data evaluating those modalities. Results showed that FDG-PET is the most accurate for confirming or excluding the diagnosis of chronicosteomyelitis. Sensitivity and specificity were as follows: 96% and 91%, respectively, for FDG-PET; 82% and 25%, respectively, for bone scintigraphy; 61% and 77%,respectively, for leukocyte scintigraphy; 78% and 84%, respectively, for combined bone and leukocyte scintigraphy; and 84% and 60%, respectively, for MRI.[7] Level of evidence: 1A prospective study compared the results of FDG-PET imaging with diagnosis established through surgical findings or long-term follow-up in 22 patients in whom chronicosteomyelitis was suspected. FDG-PET findings were consistent with the final diagnosis in 20 of 22 patients, resulting in a sensitivity of 100%, a specificity of 87.5%, andan accuracy of 90.9%.[8] Level of evidence: 2Another prospective study evaluating the use of FDG-PET in the detection of chronic osteomyelitis found that FDG-PET identified 17 of 18 patients with osteomyelitis and12 of 13 patients without osteomyelitis. Overall, sensitivity and specificity were 100% and 92%, respectively.[9] Level of evidence: 2A retrospective study was conducted to evaluate the accuracy of combined FDG-PET/CT in trauma patients in whom chronic osteomyelitis was suspected. Of 33 PET/CTscans, 30 were accurate, including 17 that were positive and 13 that were negative; there were two false-positive results and one false-negative result. Sensitivity,specificity, and accuracy for FDG-PET/CT were 94%, 87%, and 91%, respectively, for the whole group; 88%, 100%, and 90%, respectively, for patients with lesions in theaxial skeleton; and 100%, 85%, and 91%, respectively, for patients with lesions in the appendicular skeleton.[10] Level of evidence: 2


SPECT/CT [EBM]

Description

SPECT uses different radiopharmaceuticals, including technetium Tc99m methylene diphosphonate, gallium citrate Ga 67, and indium In 111Supplementary anatomic information is provided by CT

Comments

Can facilitate correct diagnosis of osteomyelitis


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Evidence

The value of adding SPECT/CT to conventional three-phase nuclear bone scan was investigated in 31 patients in whom bone infection was suspected on the basis of clinical findings and abnormal scintigraphy findings. Osteomyelitis was confirmed or excluded by biopsy, surgery, or prolonged clinical follow-up. SPECT/CT findingswere consistent with the ultimate diagnosis in 7 patient with documented osteomyelitis and in 19 patients without bone infection. There were two false-positive results andtwo false-negative results, and one scan was indeterminate (sensitivity, 78%; specificity, 86%). The investigators concluded that SPECT/CT is more frequently accuratethan three-phase bone scan for the diagnosis of osteomyelitis.[11] Level of evidence: 2


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Differential diagnosis

Septic arthritis

Septic arthritis is a rheumatologic emergency usually occurring as a result of occult bacteremiaPatients present with fever, rigors, and joint painThe knee is most commonly affectedSignificant joint effusion is usually present, and aspiration will reveal purulent fluidMay be complicated by osteomyelitis if not promptly diagnosed or when due to highly virulent organismsMRI can distinguish septic arthritis from osteomyelitis or may detect secondary infection of the contiguous bones

Soft tissue infection

Includes cellulitis, myositis, and abscessesMost commonly caused by S. aureusOften begins as superficial cellulitisUncomplicated cases remain localized to subcutaneous tissuesInfection may progress to include deeper tissues or may lead to the formation of a localized inflammatory abscessTechnetium Tc 99m bone scan is used to differentiate cellulitis from osteomyelitis. Findings in patients with cellulitis are positive only in the first two phases of the triple-phase bone scan, but normal uptake is seen in the third phase

Gaucher disease

Autosomal recessive deficiency of -glucocerebrosidaseThe hallmark of type 1 in adults is skeletal disease due to substrate buildup in the bones, which is manifested by bone pain and anemiaHepatomegaly and splenomegaly are seen, as well as bleeding and bruisingDiagnosed on the basis of a low level of glucocerebrosidase in blood

Charcot arthropathy

Charcot arthropathy (also known as Charcot joint or neuropathic osteoarthropathy) presents with swelling, warmth, and edema of the affected areaSkin ulceration is uncommon, whereas osteomyelitis is usually preceded by a skin ulcerInvolves the midfoot, whereas osteomyelitis usually affects the forefootMRI findings are useful in differentiating between the two disease entities

Bone tumors (primary and metastatic)

May be difficult to distinguish from osteomyelitis because clinical findings are often noncontributory, and radiologic features can be similarThe penumbra sign (a higher signal intensity feature of the thin layer of granulation tissue that lines the abscess cavity on T1-weighted MRI) and a high CRP level supportthe diagnosis of osteomyelitis and may aid in the exclusion of a tumorBiopsy is the definitive diagnostic test

TreatmentBack to Top

Summary approach

The goals of treatment are as follows:Eradication of infectionRelief of painPreservation of articular function and normal bone growthRestoration or preservation of the neurologic statusPreservation of the integrity of the affected l imbPrevention of recurrenceRestoration of anatomic contours ( eg , cosmetic reconstruction for craniofacial osteomyelitis)

Osteomyelitis, particularly chronic osteomyelitis, is characterized by a high rate of relapse, even when treated aggressivelyThe best treatment approach is a combination of antimicrobial and surgical therapy. Treatment of osteomyelitis, in general, involves the following components:

Debridement of necrotic tissueTreatment with antibioticsManagement of dead spaceCoverage with soft tissuesSurveillance and monitoring ( ie , patient follow-up, imaging studies)

In patients with chronic osteomyelitis, antibiotic therapy alone is inadequate. Radical debridement is required to eliminate necrotic bone and create a viable, vascularizedenvironment. Inadequate debridement leads to high recurrence rates in patients with chronic osteomyelitis. Thus, surgery involves removal of sequestrum and resection of scarred and infected bone and tissue
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Drug therapy:

Antimicrobial agents must be able to penetrate the areas of ongoing infectionThe selection of the appropriate antibiotic depends on the causative organism, the results of antibiotic susceptibility testing, and intrinsic host factors. Identification of theoffending organism through blood or tissue culture is beneficial in guiding treatmentIn very ill patients or those in whom biopsy results are pending, empiric antibiotic therapy should be designed to treat the most likely etiologic organism based on theclinical circumstances, and the antibiotic regimen should then be tailored to the causative pathogen once the biopsy results are availableIn patients who are not severely ill (septic), empiric antibiotic therapy should not be initiated until a biopsy has been obtained for histology and culture. Initiation of antibiotic therapy before biopsy may suppress growth of the organism even several days or a week after treatment is stoppedAfter the specimen is collected via debridement or bone biopsy, parenteral antimicrobial therapy is initi ated based on the likely et iologic organisms and local antibioticresistance patterns. Initial empiric antibiotic therapy should consist of parenteral penicillins ( eg , aqueous penicillin G, nafcillin, ampicillin, and piperacillin-tazobactam),imipenem-cilastatin, vancomycin, or cephalosporins ( eg , cefazolin, ceftriaxone, and cefepime) or an oral fluoroquinolone ( eg , ciprofloxacin, levofloxacin); parenteralantibiotics were the standard of care in adults with osteomyelitis until the development of the fluoroquinolones made oral treatment feasible in some cases due to their highbioavailability and broad spectrum of activity. If multiple organisms are suspected, patients may require broad-spectrum antibiotics or combination therapySome other oral antibiotics, such as l inezolid, sulfamethoxazole-trimethoprim, and clindamycin, may be suitable for treating osteomyelitis due to sensitive organisms, butthey are usually used only to complete therapy after a favorable response to intravenous therapy. In addition to the results of antibiotic susceptibility testing, otherconsiderations in selecting an oral agent involve pharmacokinetic parameters, such as bioavailability and bone penetrationRifampin, which is well absorbed orally, is sometimes administered in conjunction with antistaphylococcal agents in the treatment of osteomyelitis due to S. aureusOnce the diagnosis of osteomyelitis is confirmed and the etiologic organism identified, treatment with the appropriate antibiotic (see Table 2) should be initiatedimmediately to improve the long-term prognosis. Delaying treatment can lead to complications, such as prolonged fever, limited range of motion persistent pain, fractures,and amputationsLocal antibiotic delivery with the use of surgically placed antibiotic-impregnated implants has been used as an adjunctive therapy, but evidence on efficacy is limitedOutpatient intravenous therapy with the use of a peripherally inserted central catheter, a Hickman catheter, or a Groshong catheter is another option. The use of long-termintravenous catheters in adults may decrease the length of hospitalization, allow for outpatient parenteral therapy, and reduce costThe optimal duration of antibiotic therapy has not been fully determined, as there is considerable variation in clinical presentation, but the general recommendation is 4 to 6weeks. Some experts have achieved good results with treatment for 2 weeks after appropriate debridement in patients with uncomplicated infection (Cierny-Mader stage 2)who are otherwise healthy; other patients require extensive surgery, sometimes in stages, and prolonged antibiotic therapy until all of the necrotic material is removed, thebone is stabilized, and soft tissue coverage is achieved

Treatment of osteomyelitis due to unusual organisms, such as mycobacteria and fungi, may require more prolonged therapy ( eg , 6-9 months for tuberculosis of thebone, 12 months for coccidioidomycosis); guidelines specific to such pathogens should be consultedSome patients, particularly those with a prosthetic joint or other foreign material that cannot be removed, require long-term suppressive therapy to preventsymptomatic relapse

Table 2. Antibiotic Therapy for Osteomyelitis-causing Microorganisms

Microorganism Antibiotic of Choice Other OptionsMethicillin-sensitive S. aureus Nafcillin, 1.0 or 1.5 g

intravenously every 4 to 6 hours,orCefazolin, 2 g intravenously every8 hours

Clindamycin, 600 mgintravenously every 6 hours, orVancomycin, 1 g intravenouslyevery 12 hours, orCiprofloxacin, 750 mg orally every12 hours, orLevofloxacin, 500 mg/d orally,

plus rifampin, 600 mg/d orally

MRSA Vancomycin, 1 g intravenously every 12hours

Linezolid, 600 mg intravenously ororally every 12 hours, orLevofloxacin, 500 mg/d orally,plus rifampin, 600 mg/d orally

Penicillin-sensitive streptococci(group A or B -hemolyticstreptococci, S. pneumoniae )

Penicillin G, 12 to 20 million U/dintravenously as a continuous infusion orin 6 divided doses

Ceftriaxone, 1 to 2 g intravenouslyor intramuscularly every 24 hours,orCefazolin, 1 to 2 g intravenouslyevery 8 hours, orClindamycin, 600 mgintravenously every 6 hours, orErythromycin, 500 mgintravenously every 6 hours, orVancomycin, 1 g intravenouslyevery 12 hours

Enterococci and other relativelypenicillin-resistant streptococci(minimum inhibitory concentration>0.5 g/mL)

Penicillin G, 20 million U/dintravenously as a continuous infusion orin 6 divided doses, with or withoutgentamicin, 1 mg/kg intravenously every8 hours, for the first 1 to 2 weeks of treatment

Vancomycin, 1 g intravenously every 12hours, with or without gentamicin, 1mg/kg intravenously every 8 hours, forthe first 1 to 2 weeks of treatment

Gram-negative enteric bacilli Ciprofloxacin, 400 mg intravenously or750 mg orally every 12 hours for 2

weeks

Ceftriaxone, 1 to 2 g intravenously every24 hours

P. aeruginosa Cefepime, 2 g intravenously every 12hours

Ciprofloxacin, 750 mg orally every12 hours, or
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Note: Some experts recommend thataminoglycosides be used in conjunctionwith -lactams for at least some portionof the treatment course

Ceftazidime, 2 g intravenouslyevery 8 hours, orImipenem-cilastatin, 500 mgintravenously every 6 hours, orPiperacillin, 2 to 4 g intravenouslyevery 4 hours, orPiperacillin-tazobactam, 3.375 gintravenously every 6 hours

Anaerobes Clindamycin, 600 mg intravenously or300 to 450 mg orally every 6 hours Ampicillin-sulbactam, 1.5 to 3 gintravenously every 6 hours orMetronidazole (for gram-negativeanaerobes), 500 mg intravenouslyevery 8 hours

Mixed infections (aerobic andanaerobic organisms)

Ampicillin-sulbactam, 1.5 to 3 gintravenously every 6 hours

Imipenem, 500 mg intravenously every 6hours

MRSA = methicillin-resistant S. aureus

Non-drug therapy:

The principles of surgical intervention include bone debridement, reconstruction, and dead space management; bone stabilization; coverage with soft tissue; and restorationof vascularitySurgery depends on the extent, location, and duration of the infection and i s indicated when antimicrobial therapy is not sufficient to resolve the infection, as is usually thecase in patients with chronic infection, infected nonunion of fractures, or foreign bodies (including prostheses and fixation devices). Surgical treatment is always required inpatients with abscesses, devascularized tissue, or sequestraSurgical debridement is not indicated if hematogenous osteomyelitis is diagnosed early. However, if antibiotic therapy alone is ineffective, debridement may be necessary,along with an additional 4- to 6-week course of antibiotic therapyIn patients with osteomyelitis associated with an infected prosthesis (contiguous focus of infection), it is usually necessary to remove the prosthetic device. A combinedantimicrobial and surgical approach is appropriate in patients with open fractures or in those with prosthetic joint infectionsIn patients with osteomyelitis associated with vascular insufficiency, the goal of surgery is to revascularize the limb and preserve the maximum amount of foot function(foot salvage). Debridement coupled with antimicrobial therapy for at least 6 weeks is recommended in patients with good oxygen tension at the involved siteSurgical placement of antibiotic-impregnated implants ( eg , polymethyl methacrylate, calcium sulfate) helps to obliterate the dead space after debridement, as well asdelivering high tissue levels of antibiotics, but evidence on efficacy is limitedHyperbaric oxygen therapy has been suggested as a complementary therapy, but data regarding its usefulness as an adjunctive treatment remain inconclusive

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Medications

Penicillins

Indication

Treatment of bacterial osteomyelitis

Dose information

Aqueous penicillin G:

12 to 20 million U/d intravenously by continuous infusion or in six divided doses

Nafcillin:

1 to 2 g intravenously every 4 hours

Ampicillin-sulbactam:

1.5 to 3 g intravenously every 6 hours

Piperacillin-tazobactam:

3.375 g intravenously every 6 hours

Major contraindications

Hypersensitivity to cephalosporins (piperacillin-tazobactam)Hypersensitivity to corn (penicillin G and nafcillin)Hypersensitivity to penicillins

Comments

Extensive experience in use for treatment of osteomyelitisUsually well tolerated

Imipenem-cilastatin

Indication
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Imipenem-cilastatin is used to treat bacterial osteomyelitis

Dose information

500 mg intravenously every 6 hours


Atrioventricular blockHypersensitivity to amide local anesthetic or carbapenemsShock

Comments

Extensive experience in use for treatment of osteomyelitisUsually well tolerated

Clindamycin

Indication

Clindamycin is used to treat bacterial osteomyelitis

Dose information

150 to 450 mg orally or 600 mg intravenously or intramuscularly every 6 hours (up to 2,700 mg/d)


Hypersensitivity to clindamycin or lincomycinPseudomembranous coliti sUlcerative colitis

Comments

Has exceptional bioavailability and bone penetrationHas antibiotic effects against most gram-positive bacteriaMay be given orally after initial parenteral therapy for 2 weeks

Linezolid [EBM]

Indication

Linezolid is used to treat bacterial osteomyelitis

Dose information

600 mg intravenously or orally every 12 hours


Monoamine oxidase inhibitor therapy

Comments

Effective against MRSA, methicillin-resistant coagulase-negative staphylococci, and vancomycin-resistant Enterococcus faeciumCan be administered orally, with 100% bioavailability and good penetration into bones, joints, and soft tissueResistance has developed in vancomycin-resistant E. faecium and MRSA strains in patients receiving prolonged therapy, as is sometimes required when an infected devicecannot be removed

Evidence

The use of linezolid to t reat gram-positive orthopedic infections was evaluated in 51 consecutive patients who were not candidates for treatment with vancomycin.Infections included chronic osteomyelitis or prosthetic joint infection in most cases, which were most often caused by S. aureus (n = 27) or coagulase-negativestaphylococci ( n = 19); 38 were determined to be methicillin resistant. Remission was achieved in 32 patients, obviating the need for long-term suppression. The duration of treatment ranged from 2 to 19 weeks; follow-up was from 3 to 50 months. Seventeen patients required long-term suppression, mostly because of prostheses or otherhardware that could not be removed. One patient experienced clinical and microbiologic failure. Adverse events included thrombocytopenia ( n = 5), anemia ( n = 5), andreversible optic and irreversible peripheral neuropathy after 24 months.[12] Level of evidence: 2


Fluoroquinolones [EBM]

Indication


Dose information

Ciprofloxacin:

500 to 750 mg orally or 400 mg intravenously every 12 hrs
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Levofloxacin:

500 to 750 mg orally every 24 hours


Hypersensitivity to quinolones

Comments

Used in the treatment of osteomyelitis because of low toxicity and good bone penetrationOral fluoroquinolones have excellent bioavailability and are used as an alternative to extended parenteral therapy

Generally limited activity against Streptococcus species, Enterococcus species, and many anaerobesLevofloxacin is effective against gram-positive, gram-negative, and some anaerobic organisms but is less effective against P. aeruginosa than ciprofloxacin. Because of itshigh serum and bone concentrations and its long serum half-life, levofloxacin is considered ideal for the treatment of osteomyelitisFourth-generation quinolones ( eg , moxifloxacin, gemifloxacin) have better activity against several gram-positive organisms, gram-negative organisms, and some anaerobesUse in the treatment of osteomyelitis caused by S. aureus and Staphylococcus epidermidis has produced varied results. Resistance to second- and third-generationquinolones is increasingNot recommended in patients with skeletal immaturity due to the risk of possible cartilage damageUse should be limited because of the risk of resistance

Evidence

A meta-analysis of seven randomized, controlled trials (RCTs) comparing fluoroquinolones versus -lactams for the treatment of osteomyelitis showed thatfluoroquinolones are as effective as -lactams. There was no statistical difference between the two antibiotic classes in terms of treatment success (OR, 0.99), bacteriologicsuccess (OR, 0.88), superinfections (OR, 1.75), relapses (OR, 1.23), or adverse events (OR, 0.47).[13] Level of evidence: 2


Vancomycin

Indication

Vancomycin is used to treat bacterial osteomyelitis

Dose information

1,000 mg or 15 mg/kg intravenously every 12 hours


Hypersensitivity to corn or vancomycin

Comments

Provides excellent coverage against S. aureus , making it useful against osteomyelitis due to MRSAInitial doses should be based on actual body weight, with subsequent doses adjusted for patient response, serum concentrations, and clinical judgment. Initial dosingintervals are typically every 12 hours to t arget serum concentrations four to five times greater than the bacterial minimum inhibitory concentration. Depending on theindividual patient, dosing regimens may range from 15 mg/kg to 20 mg/kg actual body weight every 8 to 12 hours. Continuous infusion regimens are unlikely tosubstantially improve outcomes compared to intermittent dosingGuidelines produced by the American Society of Health System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious DiseasesPharmacists recommend monitoring trough serum concentrations to ensure optimal efficacy; in patients with osteomyelitis, serum trough concentrations should bemaintained at 15 to 20 mg/L. Trough concentrations should be measured at a steady state before the next dose (usually after the fourth dose and before the fifth dose).Monitoring may be repeated until target concentrations are achieved, at which time the frequency may decrease. Patients receiving long-term therapy for osteomyelitis orother infections may require weekly measurement of trough concentrations

Cephalosporins

Indication


Dose information

Cefazolin:

1 to 2 g intravenously every 8 hours

Ceftriaxone:

1 to 2 g intravenously or intramuscularly every 24 hours

Cefepime:

2 g intravenously every 12 hours


Hypersensitivity to cephalosporins

Jaundice (ceftriaxone)Comments
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Extensive experience in use for treatment of osteomyelitisUsually well toleratedCeftriaxone can be administered once daily, making outpatient intravenous therapy a convenient option

Rifampin

Indication

Rifampin is used as an adjunctive treatment to facilitate elimination of intraleukocytic bacteria

Dose information

600 mg orally once a day


Hypersensitivity to rifamycinLiver disease

Comments

To prevent antibiotic resistance, rifampin should not be used alone

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Non-drug treatments

Surgical debridement

Description

Removal of all infected and necrotic bone and soft tissue, along with adherent and surrounding scar tissueAtraumatic soft tissue handling and maintenance of blood supply are important requirements

Comments

Antibiotics do not adequately penetrate necrotic tissue, and, thus, if such material is not completely removed, it remains a nidus of infection and a cause of recurrenceTissues with scarring also must be removed, as they slow wound healing, produce tension, and act as a reservoir of infectionSerial debridement is sometimes necessary to eliminate necrosis and, if necessary, establish a wound bed that will foster a graft or other therapeutic implantThe significant dead space of bone and soft tissue resulting from debridement is poorly vascularized and, therefore, susceptible to progression of bone infection. This spacemust be addressed ( eg , with antibiotic beads and bone grafting) in order to impede the progression of disease and preserve the integrity of the skeletal portionSeveral techniques can be used for reconstruction of bone defects, including healing by secondary intention, closed irrigation and suction systems, use of antibiotic-impregnated implants, autologous bone grafting, and vascularized free fibula and iliac bone grafting

Surgical placement of antibiotic-impregnated implants

Serves a dual purpose of filling and stabilizing dead space and delivering antibiotic directly to the infected sitePolymethyl methacrylate beads are used most commonly and have been shown to produce good clinical results, with a 92% success rate for staged wound management,when impregnated with clindamycin, vancomycin, or tobramycinDisadvantages of antibiotic-impregnated polymethyl methacrylate beads are their lack of absorbability, necessitating removal and replacement with a graft or otherstabilizing mechanism, and the belief that local delivery of antibiotics is not sufficient (systemic therapy is usually given in addition)Other materials, such as calcium sulfate, which is bioabsorbable and does not require removal, have also been used for antibiotic delivery and wound stabilization, but dataare limited

Hyperbaric oxygen therapy [EBM]

Wounds typically have a decreased oxygen supply that prevents optimal leukocyte function and wound healing. Exposure to high concentrations of oxygen under increasedatmospheric pressure is believed to promote wound healing, despite the necessarily intermittent nature of the treatmentsSerious adverse events include seizures and pressure-related traumas, such as pneumothorax. Other adverse effects include earaches and barotraumatic otitisThe quality of studies evaluating this modality is limited; additional studies are needed to determine its value

Evidence

A systematic literature review was conducted to determine whether hyperbaric oxygen therapy is an effective adjunctive treatment for hypoxic wounds. The category of chronic osteomyelitis was addressed as a specific subset. Five studies of moderate quality, none of which were RCTs and all of which differed significantly in their design,were identified for further analysis. In all studies, hyperbaric oxygen therapy was used in addition to standard therapy with antibiotics and surgical debridement. Fourstudies found remission rates of 85% associated with hyperbaric oxygen therapy and standard care, and the remaining study found that standard care alone resulted in ahigher rate of remission than standard care combined with hyperbaric oxygen therapy. The reviewers concluded that RCTs must be conducted to determine whetherhyperbaric oxygen therapy adds significantly to the efficacy of standard care.[14] Level of evidence: 2


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Special circumstances

Comorbidities

Coexisting disease:

Diabetes mellitus (type 1 or type 2) or peripheral vascular disease tends to give rise to contiguously spread osteomyelitis of the foot. Different organisms are responsible for
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the infection in these circumstances (compared to hematogenously spread infection), so the treatment approach is differentAny infection may worsen glycemic control, so blood glucose levels should be monitored carefully in patients with diabetes and osteomyelitis. It may be necessary toincrease the insulin dose

Coexisting medication:

Certain antibiotics interact with various medications, particularly warfarinPatients taking warfarin should have their clotting profile monitored closely during treatment for osteomyelitis

Special patient groups:

Allergies to specific antibiotics should be carefully documented and should guide antibiotic therapy

Patient satisfaction/lifestyle priorities

Relief of pain and systemic toxemia are likely to be the patient's immediate prioritiesMaintenance of bony integrity and stability are long-term goals of treatment

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Consultation

Prompt diagnostic evaluation should take place as soon as osteomyelitis is suspected, and if the suspicion is strong, a hospital referral should be made while awaiting theresults of laboratory investigationsPatients with a history of musculoskeletal symptoms and systemic symptoms ( eg , fever, malaise, anorexia) should be referred immediately for diagnostic evaluationAny CRP, ESR, or leukocyte count abnormalities or abnormal radiographic findings should prompt referral, although the results of these investigations may be normal,especially soon after the onset of symptomsPatients requiring bone biopsy or surgical debridement should be referred to an orthopedic surgeon and possibly an infectious disease special ist

Patients with bony pain and loss of bone stability and patients with continuing pain and/or systemic symptoms ( eg , fever, malaise, anorexia) following open fracture ororthopedic surgery should be referred to the hospital immediatelyConsultation with a rheumatologist should be obtained in patients with an underlying connective tissue disease requiring immunosuppressive therapy

Follow-upMonitoring

The follow-up of a patient with osteomyelitis depends largely on the type of diseaseAll patients should be evaluated clinical ly with respect to ongoing symptoms ( eg , pain) and clinical signs of persistent infection (fever, erythema, drainage)Serum CRP levels and ESR should be measured on a weekly basis during the course of treatment. CRP levels decrease faster than ESR in patients in whom treatment issuccessful. An ESR that returns to normal during the course of therapy is also a favorable prognostic sign. Persistent elevation of the CRP level, but not the ESR, at 4 to 6weeks indicates persistent osteomyelitisPatients who undergo surgical intervention for vertebral osteomyelitis should be assessed for improvement of axial skeletal pain. ESR and CRP levels should be monitoredto determine the response to treatment, and imaging studies can be done to determine if there is cessation of cortical destruction with subsequent osseous fusionPatients should be monitored for adverse reactions to antimicrobial agents with complete blood count and liver and kidney function tests; however, monitoring should betailored to the particular antibiotic

Prognosis

Early initiation of antibiotic therapy, before extensive destruction of the bone occurs, produces the best resultsEven with appropriate medical and surgical treatment, 20% to 30% of patients with osteomyelitis experience recurrence within 2 years. Recurrent osteomyelitis isassociated with high resistance to therapy and may result in bone deformities. Recurrence indicates that initial therapy may have only arrested the progression of the diseaseOsteomyelitis associated with vascular insufficiency:

Remission rates of 25% to 88% have been reported in patients with diabetes who receive antibiotic therapy, either alone or in combination with surgicaldebridementRecurrent infections have been reported to occur in up to 36% of patients. Remission of infection is more likely to occur than eradication. Abscesses and necroticregions that warrant drainage also occur in 20% of cases of recurrent infectionPatients with diabetes develop foot ulcers at an annual incidence close to 2%. Of these patients, 15% will develop osteomyelitis, approximately 36% of whom willrequire lower-extremity amputation

Before the advent of antibiotics, osteomyelitis was associated with a high mortality rate. Death from osteomyelitis is now rare, with a mortality rate of less than 5% forvertebral osteomyelitis

Complications

Treatment failure:

The most common complicationIf treatment proves unsuccessful ( eg , persistent radiographic abnormalities, persistently elevated serum markers), several possibilities should be considered, including thepresence of an unrecognized pathogen and the need for (further) debridement.Consideration should be given to obtaining additional material for culture (at least severaldays after antibiotic therapy is stopped) and revising antibiotic therapy if indicated. If an effort was made to treat the infection despite the presence of a foreign body ( eg ,prosthesis or fixation device), removal should be reconsideredAntibiotic therapy is continued for an additional 4 to 6 weeks after further surgical treatment. In some cases ( eg , multiple relapses, presence of a foreign body that cannot beremoved), suppressive antibiotic therapy is given for a prolonged (often indefinite) period

Abscess formation:

May occur with acute or chronic infectionChronic osteomyelitis is characterized by the development of sinus tracts that allow drainage from infected bone through the overlying soft tissue to the skin. In some cases,partial healing occurs, resulting in blockage of the tract, deep abscess formation, and a symptomatic flare-up of pain, fever, and localized erythema and swellingSpontaneous drainage may occur, but surgical intervention may be required

Squamous cell carcinoma of the sinus tract:

Chronic discharge of purulent material leads to metaplasia of the epithelial lining of the sinus tract, with subsequent development of carcinoma
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Rareseen in 0.23% to 1.6% of patients

Sepsis:

In patients with osteomyelitis due to a vascular deficiency, antibiotics may not be enough to treat the infection; severe infections may be life or limb threateningShould be suspected in the presence of systemic signs and symptoms, such as fever, tachycardia, and hypotension

Central nervous system disease:

In patients with vertebral osteomyelitis, epidural and subdural abscesses may result from posterior extension of the infection; meningitis also may result. Paravertebral,retropharyngeal, mediastinal, subphrenic, or retroperitoneal abscesses may result from anterior or lateral extensionApproximately 15% of patients may present with motor and sensory deficits

Bone deformity:

May occur as a result of recurrent osteomyelitis, which is associated with high resistance to therapy

Soft tissue deformity:

Surgical debridement often leaves a large bony defect t ermed 'dead space,' which must be managed appropriately to halt disease progression and maintain the integrity of the skeletal part. Dead bone and scar tissue must be replaced with durable vascularized tissueA free vascularized bone graft, usually obtained from the fibula or ilium, has been used to fil l the dead space. Local tissue flaps or free flaps may also be used. As analternative, cancellous bone grafts may be placed beneath local or transferred tissues where structural augmentation is needed

Other complications include the following:

Limited range of motionPersistent painFractures

AmputationsAvascular necrosis and growth disturbance due to physeal damage

Patient EducationPatients should be informed of the following:

The variety of adverse reactions that may occur as a result of drug therapy, which vary according to the medication usedThe signs and symptoms of recurrence (bone pain, redness, warmth, swelling, fever, chills, and malaise), as approximately 20% to 30% of patients withosteomyelitis experience a recurrence within 2 years, even with medical and surgical treatmentThe possibility of complications that may result from osteomyelitis, including sepsis (signified by the presence of systemic signs and symptoms, such as fever,tachycardia, and hypotension), abscess formation, squamous cell carcinoma (rare), limited range of motion, persistent pain, fractures, and amputation

Patients with diabetes should be advised to have an annual foot examination and should be given instructions on proper foot care to prevent the occurrence of ulcers, whichmay lead to osteomyelitis

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Online information for patients

American Academy of Orthopaedic Surgeons: InfectionsCleveland Clinic: OsteomyelitisMayo Clinic: Osteomyelitis

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Summary of evidence

Evidence

Prevention

An observational study of 2,847 patients receiving antibiotic prophylaxis for elective surgical procedures showed that surgical wound infections occurred in 0.6% of those

who received antibiotics preoperatively, 1.4% of those who received antibiotics perioperatively (RR, 2.4 compared to the preoperative group), 3.3% of those who receivedantibiotics postoperatively (RR, 5.8), and 3.8% of those who received early antibiotic treatment (RR, 6.7). Administration of antibiotics during the preoperative period wasassociated with the lowest risk of surgical wound infection.[1] Level of evidence: 1

Diagnosis

CRP:

An observational study was conducted to determine the value of CRP in predicting healing versus infection or other complications in 52 patients undergoing soft tissuereconstructions following open fractures of the lower limbs, chronic infection, osteomyelitis, and nonunion. Of 41 patients whose CRP level peaked 4 or fewer days aftersurgery, 15% developed infection or required further surgery. Of 11 patients whose CRP level peaked more than 4 days postoperatively, 82% developed infection orrequired further surgery. Of 25 patients who achieved complete healing of a fracture, al l had CRP levels 8 mg/L. The investigators concluded that persistent elevation of CRP after the fourth postoperative day predicts complications in this sett ing.[2] Level of evidence: 2

Bone biopsy:

A prospective study evaluated the sensitivity and specificity of fine-needle bone biopsy in 30 patients in whom osteomyelitis was suspected. The diagnosis of osteomyelitiswas confirmed by conventional means in 15 patients. The sensitivity of fine-needle bone biopsy for diagnosing osteomyelitis was 87%, and the specificity was93%.[3] Level of evidence: 2

MRI:
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A meta-analysis conducted to determine the diagnostic test performance of MRI for osteomyelitis of the foot identified 16 studies that met the inclusion criteria. Thecombined diagnostic OR for MRI was 42.1, and the specificity at

osteomyelitis in adults: medical topics: first consult

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