Approach to Septic Arthritis

Am Fam Physician. 2011 Sep 15;84(6):653-660.

Prompt diagnosis and treatment of infectious arthritis can help prevent significant morbidity and mortality. The acute onset of monoarticular joint pain, erythema, heat, and immobility should raise suspicion of sepsis. Constitutional symptoms such as fever, chills, and rigors are poorly sensitive for septic arthritis. In the absence of peripheral leukopenia or prosthetic joint replacement, synovial fluid white blood cell count in patients with septic arthritis is usually greater than 50,000 per mm3. Isolation of the causative agent through synovial fluid culture is not only definitive but also essential before selecting antibiotic therapy. Synovial fluid analysis is also useful to help distinguish crystal arthropathy from infectious arthritis, although the two occasionally coexist. Almost any microorganism can be pathogenic in septic arthritis; however, septic arthritis is caused by nongonococcal pathogens (most commonly Staphylococcus species) in more than 80 percent of patients. Gram stain results should guide initial antibiotic choice. Vancomycin can be used for gram-positive cocci, ceftriaxone for gram-negative cocci, and ceftazidime for gram-negative rods. If the Gram stain is negative, but there is strong clinical suspicion for bacterial arthritis, treatment with vancomycin plus ceftazidime or an aminoglycoside is appropriate. Evacuation of purulent material with arthrocentesis or surgical methods is necessary. Special consideration should be given to patients with prosthetic joint infection. In this population, the intraarticular cutoff values for infection may be as low as 1,100 white blood cells per mm3 with a neutrophil differential of greater than 64 percent.

Septic arthritis is a key consideration in adults presenting with acute monoarticular arthritis. Failure to initiate appropriate antibiotic therapy within the first 24 to 48 hours of onset can cause subchondral bone loss and permanent joint dysfunction.1,2 The incidence of septic arthritis ranges widely, between four and 29 cases per 100,000 person-years, and depends on population variables and preexisting structural joint abnormalities.1

Because of the lack of a limiting basement plate in synovial tissues, the most common route of entry into the joint is hematogenous spread during bacteremia.37 Pathogens may also enter through direct inoculation (e.g., arthrocentesis, arthroscopy, trauma) or contiguous spread from local infections (e.g., osteomyelitis, septic bursitis, abscess).35 Once in the joint, microorganisms are deposited in the synovial membrane, causing an acute inflammatory response.2,7 Inflammatory mediators and pressure from large effusions lead to the destruction of joint cartilage and bone loss.2,7 A history, physical examination, and joint fluid analysis are warranted to ensure timely joint-preserving interventions.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendation Evidence rating References

Suspicion of septic arthritis should be pursued with arthrocentesis, and synovial fluid should be sent for white blood cell count, crystal analysis, Gram stain, and culture.

C

2123

In addition to antibiotic therapy, evacuation of purulent material is necessary in patients with septic arthritis; arthrocentesis and surgical methods are appropriate.

C

48

Intraarticular white blood cell cutoff values for infection as low as 1,100 per mm3 (1.10 × 109 per L) with a neutrophil differential of greater than 64 percent can help diagnose prosthetic joint infection.

C

66


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.xml.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

View Table

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendation Evidence rating References

Suspicion of septic arthritis should be pursued with arthrocentesis, and synovial fluid should be sent for white blood cell count, crystal analysis, Gram stain, and culture.

C

2123

In addition to antibiotic therapy, evacuation of purulent material is necessary in patients with septic arthritis; arthrocentesis and surgical methods are appropriate.

C

48

Intraarticular white blood cell cutoff values for infection as low as 1,100 per mm3 (1.10 × 109 per L) with a neutrophil differential of greater than 64 percent can help diagnose prosthetic joint infection.

C

66


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.xml.

Diagnosis

HISTORY

Patients presenting with acute joint swelling, pain, erythema, warmth, and joint immobility should be screened for risk factors associated with septic arthritis (Table 1812). A prospective study in the Netherlands of patients diagnosed with septic arthritis found that 84 percent of adults had an underlying medical condition and 59 percent had a previous joint disorder.13 In a review of musculoskeletal infections in patients with human immunodeficiency virus infection, about 0.5 percent of hospitalized patients had septic arthritis, regardless of CD4 lymphocyte count or disease stage.14 Particular vigilance is needed during a monoarticular flare-up of rheumatoid arthritis, because patients on immunosuppressive medications, but not biologic therapy, have a fourfold increased risk of septic arthritis.8 Many patients with rheumatoid arthritis are treated with anti–tumor-necrosis-factor-α, which further increases the risk of infection twofold.15

Table 1.

Risk Factors for Septic Arthritis

Contiguous spread

Skin infection, cutaneous ulcers8,9

Direct inoculation

Previous intraarticular injection8,10

Prosthetic joint: early and delayed8 (Table 6)

Recent joint surgery8,10

Hematogenous spread

Diabetes mellitus8,10

Human immunodeficiency virus infection11

Hematogenous spread

Immunosuppressive medication9,11

Intravenous drug abuse11

Osteoarthritis9

Other cause of sepsis9

Prosthetic joint: late8 (Table 6)

Rheumatoid arthritis8,9

Sexual activity (specifically for gonococcal arthritis)12

Other factors

Age older than 80 years8


Information from references 8 through 12.

Table 1.   Risk Factors for Septic Arthritis

View Table

Table 1.

Risk Factors for Septic Arthritis

Contiguous spread

Skin infection, cutaneous ulcers8,9

Direct inoculation

Previous intraarticular injection8,10

Prosthetic joint: early and delayed8 (Table 6)

Recent joint surgery8,10

Hematogenous spread

Diabetes mellitus8,10

Human immunodeficiency virus infection11

Hematogenous spread

Immunosuppressive medication9,11

Intravenous drug abuse11

Osteoarthritis9

Other cause of sepsis9

Prosthetic joint: late8 (Table 6)

Rheumatoid arthritis8,9

Sexual activity (specifically for gonococcal arthritis)12

Other factors

Age older than 80 years8


Information from references 8 through 12.

Constitutional symptoms such as fever, chills, or rigors may be present in patients with septic arthritis, although their sensitivities are 57, 27, and 19 percent, respectively.6  A detailed review of systems should be performed to exclude other forms of inflammatory arthritis (Table 26,16).

Table 2.

Differential Diagnosis of Acute Arthritis

Diagnosis Etiology

Crystal-induced arthritis

Calcium oxalate, gout, cholesterol, pseudogout, hydroxyapatite crystals

Infectious arthritis

Bacteria, fungi, mycobacteria, spirochetes, viruses

Inflammatory arthritis

Behçet syndrome,* rheumatoid arthritis,* sarcoid, systemic lupus erythematosus,* Still disease,* seronegative spondyloarthropathy (e.g., ankylosing spondylitis, psoriatic arthritis, reactive arthritis, inflammatory bowel disease–related arthritis), systemic vasculitis*

Osteoarthritis

Erosive/inflammatory variants*

Other

Amyloidosis, avascular necrosis, clotting disorders/anticoagulant therapy, familial Mediterranean fever,* foreign body, fracture, hemarthrosis, hyperlipoproteinemia,* meniscal tear

Systemic infection

Bacterial endocarditis, human immunodeficiency virus infection

Tumor

Metastasis, pigmented villonodular synovitis


*—Not usually monoarticular.

Information from references 6 and 16.

Table 2.   Differential Diagnosis of Acute Arthritis

View Table

Table 2.

Differential Diagnosis of Acute Arthritis

Diagnosis Etiology

Crystal-induced arthritis

Calcium oxalate, gout, cholesterol, pseudogout, hydroxyapatite crystals

Infectious arthritis

Bacteria, fungi, mycobacteria, spirochetes, viruses

Inflammatory arthritis

Behçet syndrome,* rheumatoid arthritis,* sarcoid, systemic lupus erythematosus,* Still disease,* seronegative spondyloarthropathy (e.g., ankylosing spondylitis, psoriatic arthritis, reactive arthritis, inflammatory bowel disease–related arthritis), systemic vasculitis*

Osteoarthritis

Erosive/inflammatory variants*

Other

Amyloidosis, avascular necrosis, clotting disorders/anticoagulant therapy, familial Mediterranean fever,* foreign body, fracture, hemarthrosis, hyperlipoproteinemia,* meniscal tear

Systemic infection

Bacterial endocarditis, human immunodeficiency virus infection

Tumor

Metastasis, pigmented villonodular synovitis


*—Not usually monoarticular.

Information from references 6 and 16.

PHYSICAL EXAMINATION

The physical examination should determine if the site of inflammation is intraarticular or periarticular, such as a bursa or skin. Generally, intraarticular pathology results in severe limitation of active and passive range of motion, and the joint is often held in the position of maximal intraarticular space. For example, a septic knee will be extended fully. Conversely, pain from periarticular pathology occurs only during active range of motion, and swelling will be more localized.

Although septic arthritis is usually monoarticular, up to 20 percent of cases are oligoarticular.1 In native joints, the knee is the most commonly affected, followed by the hip, shoulder, ankle, elbow, and wrist.3,4,17,18 Infections of axial joints, such as the sternoclavicular or sacroiliac joint, may occur; however, they are more common in patients with a history of intravenous drug abuse.11,19

LABORATORY EVALUATION

Serum markers, such as white blood cell (WBC) count, erythrocyte sedimentation rate,10,17 and C-reactive protein levels,9 are often used to determine the presence of infection or inflammatory response. Patients with confirmed septic arthritis have been found to have normal erythrocyte sedimentation rates and C-reactive protein levels.9 When elevated, these markers may be used to monitor therapeutic response. Because pathogenesis may be hematogenous, blood cultures are positive in 25 to 50 percent of patients with septic arthritis.1,9,20

SYNOVIAL FLUID ANALYSIS

Because the clinical presentation of septic arthritis may overlap with other causes of acute arthritis (Table 26,16), arthrocentesis is needed to identify the causative infectious agent. Synovial fluid should be evaluated at the bedside and then sent for WBC count with differential, crystal analysis, Gram stain, and culture2123  (Table 31921,2426). In synovial fluid, a WBC count of more than 50,000 per mm3 (50 × 109 per L) and a polymorphonuclear cell count greater than 90 percent have been directly correlated with infectious arthritis, although this overlaps with crystalline disease.1,6 Lower synovial fluid WBC counts may occur in persons with disseminated gonococcal disease, peripheral leukopenia, or joint replacement.6,19,22 Septic arthritis can coexist with crystal arthropathy; therefore, the presence of crystals does not preclude a diagnosis of septic arthritis.27

Table 3.

Synovial Fluid Analysis

Arthritis diagnosis Color Transparency Viscosity WBC count (per mm3) PMN cell count (%) Gram stain Culture PCR test Crystals

Normal

Clear

Transparent

High/thick

< 200

< 25

Negative

Negative

Negative

Negative

Noninflammatory

Straw

Translucent

High/thick

200 to 2,000

< 25

Negative

Negative

Negative

Negative

Inflammatory: crystalline disease

Yellow

Cloudy

Low/thin

2,000 to 100,000

> 50

Negative

Negative

Negative

Positive

Inflammatory: noncrystalline disease

Yellow

Cloudy

Low/thin

2,000 to 100,000

> 50

Negative

Negative

Negative

Negative

Infectious: Lyme disease

Yellow

Cloudy

Low

3,000 to 100,000 (mean: 25,000)

> 50

Negative

Negative

Positive (85 percent)

Negative

Infectious: gonococcal

Yellow

Cloudy-opaque

Low

34,000 to 68,000

> 75

Variable (< 50 percent)

Positive (25 to 70 percent)

Positive (> 75 percent)

Negative

Infectious: nongonococcal

Yellow-green

Opaque

Very low

> 50,000 (> 100,000 is more specific)

> 75

Positive (60 to 80 percent)

Positive (> 90 percent)

Negative*


note: These are general guidelines in the interpretation of synovial fluid. Many parameters vary widely and must be interpreted in the clinical context. Three bedside observations (color, transparency, and viscosity) are quick and easy to assess. With normal transparent fluid, words can be read clearly through the fluid. The words become less crisp and gradually obscured with increasing turbidity. Viscosity is assessed by observing the fluid dropping from the syringe. Normal viscosity has a long, stringy tail.

PCR = polymerase chain reaction; PMN = polymorphonuclear; WBC = white blood cell.

*—Crystalline disease can coexist with septic arthritis. A positive result does not exclude infection.

Information from references 19 through 21, and 24 through 26.

Table 3.   Synovial Fluid Analysis

View Table

Table 3.

Synovial Fluid Analysis

Arthritis diagnosis Color Transparency Viscosity WBC count (per mm3) PMN cell count (%) Gram stain Culture PCR test Crystals

Normal

Clear

Transparent

High/thick

< 200

< 25

Negative

Negative

Negative

Negative

Noninflammatory

Straw

Translucent

High/thick

200 to 2,000

< 25

Negative

Negative

Negative

Negative

Inflammatory: crystalline disease

Yellow

Cloudy

Low/thin

2,000 to 100,000

> 50

Negative

Negative

Negative

Positive

Inflammatory: noncrystalline disease

Yellow

Cloudy

Low/thin

2,000 to 100,000

> 50

Negative

Negative

Negative

Negative

Infectious: Lyme disease

Yellow

Cloudy

Low

3,000 to 100,000 (mean: 25,000)

> 50

Negative

Negative

Positive (85 percent)

Negative

Infectious: gonococcal

Yellow

Cloudy-opaque

Low

34,000 to 68,000

> 75

Variable (< 50 percent)

Positive (25 to 70 percent)

Positive (> 75 percent)

Negative

Infectious: nongonococcal

Yellow-green

Opaque

Very low

> 50,000 (> 100,000 is more specific)

> 75

Positive (60 to 80 percent)

Positive (> 90 percent)

Negative*


note: These are general guidelines in the interpretation of synovial fluid. Many parameters vary widely and must be interpreted in the clinical context. Three bedside observations (color, transparency, and viscosity) are quick and easy to assess. With normal transparent fluid, words can be read clearly through the fluid. The words become less crisp and gradually obscured with increasing turbidity. Viscosity is assessed by observing the fluid dropping from the syringe. Normal viscosity has a long, stringy tail.

PCR = polymerase chain reaction; PMN = polymorphonuclear; WBC = white blood cell.

*—Crystalline disease can coexist with septic arthritis. A positive result does not exclude infection.

Information from references 19 through 21, and 24 through 26.

Measuring synovial fluid glucose or protein is not useful because results are neither sensitive nor specific for septic arthritis.6 Polymerase chain reaction (PCR) testing may help isolate less common organisms, such as Borrelia species,24,25 and should be ordered if there is a high level of clinical suspicion. The sensitivities of synovial fluid, Gram stain, and culture vary by pathogenic organism.

IMAGING

There are no data on imaging studies that are pathognomonic for acute septic arthritis. Plain films establish a baseline and may detect fractures, chondrocalcinosis, or inflammatory arthritis. Ultrasonography is more sensitive for detecting effusions, particularly in difficult-to-examine joints, such as the hip.28 Magnetic resonance imaging findings that suggest an acute intraarticular infection include the combination of bone erosions with marrow edema.29 Imaging may allow guided arthrocentesis, particularly in difficult-to-examine joints (e.g., hip, sacroiliac, costochondral).

Organisms

Almost any microorganism may be pathogenic in septic arthritis. Bacterial causes of septic arthritis include staphylococci (40 percent), streptococci (28 percent), gram-negative bacilli (19 percent), mycobacteria (8 percent), gram-negative cocci (3 percent), gram-positive bacilli (1 percent), and anaerobes (1 percent).30  There are various characteristic presentations depending on the pathogen, underlying medical conditions, or exposures (Table 47,18,20,3134). Clinical presentations can be broadly grouped into three categories: nongonococcal, gonococcal, and other (e.g., Lyme disease, mycobacterial, fungal).

Table 4.

Clinical Presentations of Septic Arthritis

Clinical history or exposure Joint involvement Pathogen

Cleaning fish tank7,31

Small joints (fingers, wrists)

Mycobacterium marinum

Dog or cat bite7,32

Small joints (fingers, toes)

Capnocytophaga species, Pasteurella multocida

Ingestion of unpasteurized dairy products7,32

Monoarticular: sacroiliac joint

Brucella species

Intravenous drug use7,18,32

Axial joints, such as sternoclavicular or sacroiliac

Pseudomonas aeruginosa, Staphylococcus aureus

Nail through shoe20

Foot

P. aeruginosa

Sexual activity32

Tenosynovial component in hands, wrists, or ankles

Neisseria gonorrhoeae

Soil exposure/gardening

Monoarticular: knee, hand, or wrist

Nocardia species, Pantoea agglomerans, Sporothrix schenckii

Soil or dust exposure containing decomposed wood (north-central and southern United States)

Monoarticular: knee, ankle, or elbow

Blastomyces dermatitidis

Southwestern United States, Central and South America (primary respiratory illness)33

Knee

Coccidioides immitis

Systemic lupus erythematosus (particularly if functional hyposplenism)34

N. gonorrhoeae, Proteus species, Salmonella species

Terminal complement deficiency7

Tenosynovial component in hands, wrists, or ankles

N. gonorrhoeae


note: Clinical presentations of septic arthritis vary widely from the typical acute, monoarticular large joint arthritis. Distinctive presentations may occur with certain organisms or historical background.

Information from references 7, 18, 20, and 31 through 34.

Table 4.   Clinical Presentations of Septic Arthritis

View Table

Table 4.

Clinical Presentations of Septic Arthritis

Clinical history or exposure Joint involvement Pathogen

Cleaning fish tank7,31

Small joints (fingers, wrists)

Mycobacterium marinum

Dog or cat bite7,32

Small joints (fingers, toes)

Capnocytophaga species, Pasteurella multocida

Ingestion of unpasteurized dairy products7,32

Monoarticular: sacroiliac joint

Brucella species

Intravenous drug use7,18,32

Axial joints, such as sternoclavicular or sacroiliac

Pseudomonas aeruginosa, Staphylococcus aureus

Nail through shoe20

Foot

P. aeruginosa

Sexual activity32

Tenosynovial component in hands, wrists, or ankles

Neisseria gonorrhoeae

Soil exposure/gardening

Monoarticular: knee, hand, or wrist

Nocardia species, Pantoea agglomerans, Sporothrix schenckii

Soil or dust exposure containing decomposed wood (north-central and southern United States)

Monoarticular: knee, ankle, or elbow

Blastomyces dermatitidis

Southwestern United States, Central and South America (primary respiratory illness)33

Knee

Coccidioides immitis

Systemic lupus erythematosus (particularly if functional hyposplenism)34

N. gonorrhoeae, Proteus species, Salmonella species

Terminal complement deficiency7

Tenosynovial component in hands, wrists, or ankles

N. gonorrhoeae


note: Clinical presentations of septic arthritis vary widely from the typical acute, monoarticular large joint arthritis. Distinctive presentations may occur with certain organisms or historical background.

Information from references 7, 18, 20, and 31 through 34.

NONGONOCOCCAL ARTHRITIS

Septic arthritis is caused by nongonococcal pathogens in more than 80 percent of patients.2 Nongonococcal arthritis often affects older persons, is acute in nature, and is monoarticular in more than 80 percent of patients.12 Synovial fluid cultures are positive in more than 90 percent of patients with nongonococcal arthritis, as opposed to blood cultures, which are positive in only 50 percent of patients.12,30

Gram-positive staphylococci and streptococci are the causative agents in the majority of bacterial arthritis cases in which an organism is identified,3 and are associated with drug abuse, cellulitis, abscesses, endocarditis, and chronic osteomyelitis.18 Staphylococcus aureus is the organism most commonly found in patients with septic arthritis in the United States and other developed countries,30,35 and Streptococcus species is the next most common.30,36 The presence of methicillin-resistant S. aureus (MRSA) is an emerging clinical problem. Although data are mostly limited to case reports, the incidence of MRSA ranges between 5 and 25 percent of bacterial arthritis cases, and tends to affect older persons, involve the shoulder, and the health care–associated MRSA strain.37,38

Gram-negative bacilli represent approximately 14 to 19 percent of septic arthritis cases12,18 and are associated with invasive urinary tract infections, intravenous drug use, older age, compromised immune system, and skin infections.18 The two most common gram-negative organisms detected in adults are Pseudomonas aeruginosa and Escherichia coli.10,12,17,18 Historically, Haemophilus influenzae infection has occurred more often in children,2,39 although this may be tempered by widespread H. influenzae type b vaccination.40

GONOCOCCAL ARTHRITIS

Patients with disseminated Neisseria gonorrhoeae infection are usually young, healthy, and sexually active.30 Disseminated gonococcal infection may have various clinical musculoskeletal presentations, with or without associated dermatitis. Patients typically display a migratory pattern of arthralgias, tenosynovial inflammation, or nonerosive arthritis.6,23,30 Blood cultures are seldom positive, and synovial fluid cultures are variable, with a positive result in only 25 to 70 percent of patients with gonococcal arthritis.19,23 When a disseminated gonococcal infection is suspected, cultures should be taken from potentially infected mucosal sites (e.g., urethra, rectum, pharynx, cervix).30,41 PCR testing has a sensitivity of 76 percent and a specificity of 96 percent for N. gonorrhoeae, and may be useful in patients with culture-negative disease if the clinical scenario is unclear or similar to a reactive arthritis.26

OTHER INFECTIONS

Fungal arthritis usually has an insidious onset and indolent course.42,43  Pathogen-specific clinical scenarios are presented in Table 4.7,18,20,3134 Synovial fluid cultures or biopsy can confirm the diagnosis.

Mycobacterial infectious arthritis is also indolent, which can cause a considerable delay in diagnosis, although joint damage does not occur as rapidly as it does in bacterial infections.31 Articular Mycobacterium tuberculosis infection typically affects the hip or knee; is usually caused by reactivation from past dissemination; and may occur without other manifestations of active tuberculosis.31,42 Synovial fluid culture is positive in 80 percent of patients with M. tuberculosis infection.34 Acid-fast smears are not helpful and are often negative.31 Histology is not specific because it may mimic other granulomatous diseases, although synovial biopsy will be positive for M. tuberculosis in about 95 percent of cases.34

Borrelia burgdorferi infection initially causes viral-like migratory arthralgias of Lyme disease. Late disease is characterized by an intermittent oligoarthritis that usually involves the knee or other large joints.44 The diagnosis of Lyme arthritis can be made with a two-step serologic testing process involving enzyme-linked immunosorbent assay, followed by confirmation with a Western blot or immunoblot test.45 B. burgdorferi cannot be cultured from synovial fluid46; however, PCR testing is positive in 85 percent of patients with Lyme arthritis, making it a confirmatory test.47 It should be noted that PCR testing cannot distinguish live from dead organisms.46

Management

Empiric intravenous antibiotic treatment of septic arthritis should be based on the organism found in the Gram stain of the synovial fluid, or on the suspicion of a pathogen from the patient's clinical presentation (Table 47,18,20,3134). Treatment options include vancomycin for gram-positive cocci, ceftriaxone (Rocephin) for gram-negative cocci, and ceftazidime (Fortaz) for gram-negative rods (Table 532). If the Gram stain is negative but there is suspicion of bacterial arthritis, vancomycin plus either ceftazidime or an aminoglycoside is appropriate.32 Adjustments to the administration route and the duration of treatment should be based on the clinical response and microbiology results. The Sanford Guide (http://www.sanfordguide.com; subscription required) is a resource for the management of infectious syndromes. It includes dosing options for patients with renal insufficiency and drug allergies, and lists common drug interactions.

Table 5.

Empiric Antibiotic Therapy for Suspected Bacterial Arthritis

Gram stain result Antibiotic

Gram-positive cocci

Vancomycin

Gram-negative cocci

Ceftriaxone (Rocephin)

Gram-negative rods

Ceftazidime (Fortaz), cefepime (Maxipime), piperacillin/tazobactam (Zosyn), or carbapenems

If patient is allergic to penicillin or cephalosporins: aztreonam (Azactam) or fluoroquinolones

Negative Gram stain

Vancomycin plus either ceftazidime or an aminoglycoside


note: A general guide for antibiotic selection should be used to help determine dosages for individual patients.

Information from reference 32.

Table 5.   Empiric Antibiotic Therapy for Suspected Bacterial Arthritis

View Table

Table 5.

Empiric Antibiotic Therapy for Suspected Bacterial Arthritis

Gram stain result Antibiotic

Gram-positive cocci

Vancomycin

Gram-negative cocci

Ceftriaxone (Rocephin)

Gram-negative rods

Ceftazidime (Fortaz), cefepime (Maxipime), piperacillin/tazobactam (Zosyn), or carbapenems

If patient is allergic to penicillin or cephalosporins: aztreonam (Azactam) or fluoroquinolones

Negative Gram stain

Vancomycin plus either ceftazidime or an aminoglycoside


note: A general guide for antibiotic selection should be used to help determine dosages for individual patients.

Information from reference 32.

The duration of therapy in patients with nongonococcal septic arthritis is typically three to four weeks. Therapy for disseminated gonococcal infection involves a third-generation cephalosporin, such as ceftriaxone, for 24 to 48 hours after improvement begins, followed by oral therapy.41 The clinical response should be rapid, with symptoms improving within 24 to 48 hours. Treatment then may be switched to oral cefixime (Suprax), or ciprofloxacin (Cipro) if quinolone resistance is not a concern, for at least one week.41 Treatment of chlamydia also should be considered in the absence of appropriate testing.41 Treatment of fungal arthritis is species-dependent, but usually includes an oral azole or parenteral amphotericin B.42,43 Lyme arthritis responds well to parenteral ceftriaxone or oral doxycycline.47

In addition to antibiotic therapy, evacuation of purulent material is necessary. Guidelines from 2006 do not distinguish between arthrocentesis and surgical methods.48 Repeated daily joint aspirations are successful during the first five days of treatment.49 With each aspirate, synovial fluid WBC count, polymorphonuclear cell count, Gram stain, and culture should be evaluated to ensure clinical response. Open or arthroscopic techniques can be used to surgically drain the infected joint. Arthroscopic drainage is associated with rapid recovery and low morbidity.50 Direct visualization of the joint tissue facilitates the lysis of adhesions, drainage of purulent pockets, and debridement of necrotic material.

Prognosis

Before antibiotics were available, two-thirds of patients died from septic arthritis.51 Current mortality rates of bacterial arthritis range from 10 to 20 percent, depending on the presence of comorbid conditions, such as older age, coexisting renal or cardiac disease, and concurrent immunosuppression.3,9,52 Factors associated with death include age 65 years or older, and infection in the shoulder, elbow, or at multiple sites.52

After completing antimicrobial therapy, patients with S. aureus septic arthritis regain 46 to 50 percent of their baseline joint function.9 In contrast, adults with pneumococcal septic arthritis who survive infection (the mortality rate is approximately 20 percent) will return to 95 percent of their baseline joint function after completing antimicrobial therapy.3 Morbidity (e.g., amputation, arthrodesis, prosthetic surgery, severe functional deterioration) occurs in one-third of patients with bacterial arthritis, usually affecting older patients, those with preexisting joint disease, and those with synthetic intraarticular material.52

Special Considerations

Prosthetic joint infections occur in 0.86 to 1.1 percent of knee arthroplasties53,54 and in 0.3 to 1.7 percent of hip arthroplasties.53,55 These infections may result in failure of the joint replacement. In prosthetic joint infections, bacterial adherence to prosthetic surfaces forms biofilms, which can lead to increased resistance to the host's immune system and to antimicrobials.5658

Prosthetic joint infections are usually caused by gram-positive cocci, including coagulase-negative staphylococci and S. aureus.53,54 Other organisms, such as gram-negative bacilli53,59 and mycobacteria,60 have also been implicated. Polymicrobial infections after hip and knee arthroplasties have been reported in up to 20 percent of patients.61 Risk factors for the development of prosthetic joint infections include previous fracture, seropositive rheumatoid arthritis, high body mass index, revision arthroplasty, and surgical site infections.59,61,62  Table 619,6365 lists the three categories of prosthetic joint infections with typical pathogenesis, timing, clinical presentation, and mode of infection.

Table 6.

Phases of Prosthetic Joint Infections

Infection Timing after joint replacement Clinical presentation Mode of infection Common pathogens

Early

Less than three months

Erythema, warmth, fever, chills, joint pain, effusion, excessive perioperative drainage

During implantation

Staphylococcus aureus, gram-negative bacilli

Delayed

Three to 24 months

Persistent pain and/or aseptic loosening

During implantation

Coagulase-negative staphylococci, Propionibacterium acnes

Late

More than 24 months

Sudden-onset joint pain; fever and leukocytosis less likely

Hematogenous

Same as native joints


Information from references 19, and 63 through 65.

Table 6.   Phases of Prosthetic Joint Infections

View Table

Table 6.

Phases of Prosthetic Joint Infections

Infection Timing after joint replacement Clinical presentation Mode of infection Common pathogens

Early

Less than three months

Erythema, warmth, fever, chills, joint pain, effusion, excessive perioperative drainage

During implantation

Staphylococcus aureus, gram-negative bacilli

Delayed

Three to 24 months

Persistent pain and/or aseptic loosening

During implantation

Coagulase-negative staphylococci, Propionibacterium acnes

Late

More than 24 months

Sudden-onset joint pain; fever and leukocytosis less likely

Hematogenous

Same as native joints


Information from references 19, and 63 through 65.

A key distinction in the diagnostic workup of patients with a prosthetic joint infection is that the intraarticular WBC cutoff values for infection may be as low as 1,100 per mm3 (1.10 × 109 per L), with a neutrophil differential of greater than 64 percent.66 This low WBC count, combined with occasionally more indolent clinical presentations, can make diagnosis problematic. Diagnostic imaging modalities include fluorodeoxyglucose positron emission tomography and combined leukocyte-marrow imaging.67,68 Antimicrobial treatment must be effective against surface-adhering, biofilm-producing bacteria.58,63 Debridement, exchange, or permanent removal of the prosthesis may be necessary, depending on the clinical scenario.65 In some persons, long-term suppressive antimicrobial therapy may be warranted.63 Research is being performed on the development of antibiofilm technology to reduce the incidence of prosthetic joint infections.56,57

The use of prophylactic antibiotics for invasive dental, genitourinary, gastrointestinal, and other invasive procedures within the first two years after prosthetic joint implantation is controversial. The American Academy of Orthopaedic Surgeons recommends that physicians strongly consider antibiotic prophylaxis in patients with one or more risk factors (i.e., comorbidities, immunosuppression, and previous infection).69 However, a more recent prospective case-control study does not support this recommendation, showing no change in the incidence of prosthetic joint infections with antibiotic prophylaxis.70 The decision to use prophylactic antibiotics should be made on a case-by-case basis with input from the orthopedic surgeon and with consideration of underlying comorbidities.

The Authors

DIANE LEWIS HOROWITZ, MD, is an attending physician in the Division of Rheumatology at North Shore–Long Island Jewish Health System, Manhasset, NY.

ELENA KATZAP, DO, is a fellow in the Department of Rheumatology, North Shore–Long Island Jewish Health System.

SCOTT HOROWITZ, MD, is an infectious disease hospitalist at the North Shore–Long Island Jewish Health System at Franklin Hospital, Valley Stream, NY.

MARIA-LOUISE BARILLA-LaBARCA, MD, is an attending physician and fellowship program director of the Division of Rheumatology at North Shore–Long Island Jewish Health System.

Address correspondence to Maria-Louise Barilla-LaBarca, MD, North Shore–LIJ Health System, 2800 Marcus Ave., Ste. 200, Lake Success, NY 11042 (e-mail: mbarilla@lij.edu). Reprints are not available from the authors.

Author disclosure: Dr. Scott Horowitz and his wife, Dr. Diane Horowitz, disclose that he is on the speakers' bureaus of Merck/Schering-Plough (Avelox) and Pfizer (Vfend and Zyvox). However, none of the drugs that are the basis of his affiliations are mentioned in this article, and the topic is not directly related to his affiliations. The other authors have no relevant financial affiliations to disclose.

REFERENCES

1. Mathews CJ, Weston VC, Jones A, Field M, Coakley G. Bacterial septic arthritis in adults. Lancet. 2010;375(9717):846–855.

2. Goldenberg DL. Septic arthritis. Lancet. 1998;351(9097):197–202.

3. Ross JJ, Saltzman CL, Carling P, Shapiro DS. Pneumococcal septic arthritis: review of 190 cases. Clin Infect Dis. 2003;36(3):319–327.

4. Cooper C, Cawley MI. Bacterial arthritis in an English health district: a 10 year review. Ann Rheum Dis. 1986;45(6):458–463.

5. McCarthy DJ. Joint sepsis: a chance for cure. JAMA. 1982;247(6):835.

6. Margaretten ME, Kohlwes J, Moore D, Bent S. Does this adult patient have septic arthritis? JAMA. 2007;297(13):1478–1488.

7. Smith JW, Piercy EA. Infectious arthritis. Clin Infect Dis. 1995;20(2):225–230.

8. Kaandorp CJ, Van Schaardenburg D, Krijnen P, Habbema JD, van de Laar MA. Risk factors for septic arthritis in patients with joint disease. A prospective study. Arthritis Rheum. 1995;38(12):1819–1825.

9. Weston VC, Jones AC, Bradbury N, Fawthrop F, Doherty M. Clinical features and outcome of septic arthritis in a single UK Health District 1982–1991. Ann Rheum Dis. 1999;58(4):214–219.

10. Le Dantec L, Maury F, Flipo RM, et al. Peripheral pyogenic arthritis. A study of one hundred seventy-nine cases. Rev Rhum Engl Ed. 1996;63(2):103–110.

11. Ross JJ, Shamsuddin H. Sternoclavicular septic arthritis: review of 180 cases. Medicine (Baltimore). 2004;83(3):139–148.

12. Shirtliff ME, Mader JT. Acute septic arthritis. Clin Microbiol Rev. 2002;15(4):527–544.

13. Kaandorp CJ, Dinant HJ, van de Laar MA, Moens HJ, Prins AP, Dijkmans BA. Incidence and sources of native and prosthetic joint infection: a community based prospective survey. Ann Rheum Dis. 1997;56(8):470–475.

14. Vassilopoulos D, Chalasani P, Jurado RL, Workowski K, Agudelo CA. Musculoskeletal infections in patients with human immunodeficiency virus infection. Medicine (Baltimore). 1997;76(4):284–294.

15. Galloway JB, Hyrich KL, Mercer LK, et al. Risk of septic arthritis in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the BSR Biologics Register (BSRBR). Paper presented at: American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting; October 2009; Philadelphia, Pa.

16. Schumacher HR, Chen LX. Musculoskeletal signs and symptoms: monoarticular joint disease. In: Klippel JH, ed. Primer on the Rheumatic Diseases. 13th ed. New York, NY: Springer; 2008:42–46.

17. Morgan DS, Fisher D, Merianos A, Currie BJ. An 18 year clinical review of septic arthritis from tropical Australia. Epidemiol Infect. 1996;117(3):423–428.

18. Deesomchok U, Tumrasvin T. Clinical study of culture-proven cases of non-gonococcal arthritis. J Med Assoc Thai. 1990;73(11):615–623.

19. Goldenberg DL. Bacterial arthritis. In: Ruddy S, Harris ED, Sledge CB, Kelley WN, eds. Kelley's Textbook of Rheumatology. 6th ed. Philadelphia, Pa.: Saunders; 2001:1469–1483.

20. Bockenstedt LK. Infectious disorders: Lyme disease. In: Klippel JH, Stone JH, Crofford LJ, White PH, eds. Primer on the Rheumatic Diseases. 13th ed. New York, NY: Springer; 2008:282–289.

21. Schumacher HR Jr. Synovial fluid analysis and synovial biopsy. In: Ruddy S, Harris ED, Sledge CB, Kelley WN, eds. Kelley's Textbook of Rheumatology. 6th ed. Philadelphia, Pa.: Saunders; 2001:605–619.

22. Shmerling RH, Delbanco TL, Tosteson AN, Trentham DE. Synovial fluid tests. What should be ordered? JAMA. 1990;264(8):1009–1014.

23. O'Brien JP, Goldenberg DL, Rice PA. Disseminated gonococcal infection: a prospective analysis of 49 patients and a review of pathophysiology and immune mechanisms. Medicine (Baltimore). 1983;62(6):395–406.

24. Mathews CJ, Kingsley G, Field M, et al. Management of septic arthritis: a systematic review. Ann Rheum Dis. 2007;66(4):440–445.

25. Jalava J, Skurnik M, Toivanen A, Toivanen P, Eerola E. Bacterial PCR in the diagnosis of joint infection. Ann Rheum Dis. 2001;60(3):287–289.

26. Liebling MR, Arkfeld DG, Michelini GA, et al. Identification of Neisseria gonorrhoeae in synovial fluid using the polymerase chain reaction. Arthritis Rheum. 1994;37(5):702–709.

27. Yu KH, Luo SF, Liou LB, et al. Concomitant septic and gouty arthritis—an analysis of 30 cases. Rheumatology (Oxford). 2003;42(9):1062–1066.

28. Zieger MM, Dörr U, Schulz RD. Ultrasonography of hip joint effusions. Skeletal Radiol. 1987;16(8):607–611.

29. Graif M, Schweitzer ME, Deely D, Matteucci T. The septic versus non-septic inflamed joint: MRI characteristics. Skeletal Radiol. 1999;28(11):616–620.

30. Ryan MJ, Kavanagh R, Wall PG, Hazleman BL. Bacterial joint infections in England and Wales: analysis of bacterial isolates over a four year period. Br J Rheumatol. 1997;36(3):370–373.

31. Gardam M, Lim S. Mycobacterial osteomyelitis and arthritis. Infect Dis Clin North Am. 2005;19(4):819–830.

32. Ohl CA. Infectious arthritis of native joints. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pa.: Churchill Livingstone; 2010:1443–1456.

33. Chapman SW. Blastomyces dermatitidis. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 4th ed. New York, NY: Churchill Livingstone; 1995:2353–2364.

34. Harrington JT. Mycobacterial and fungal infections. In: Ruddy S, Harris ED, Sledge CB, Kelley WN, eds. Kelley's Textbook of Rheumatology. 6th ed. Philadelphia, Pa.: Saunders; 2001:1493–1505.

35. Cunningham R, Cockayne A, Humphreys H. Clinical and molecular aspects of the pathogenesis of Staphylococcus aureus bone and joint infections. J Med Microbiol. 1996;44(3):157–164.

36. Schattner A, Vosti KL. Bacterial arthritis due to beta-hemolytic streptococci of serogroups A, B, C, F, and G. Analysis of 23 cases and a review of the literature. Medicine (Baltimore). 1998;77(2):122–139.

37. Ross JJ, Davidson L. Methicillin-resistant Staphylococcus aureus septic arthritis: an emerging clinical syndrome. Rheumatology (Oxford). 2005;44(9):1197–1198.

38. Gupta MN, Sturrock RD, Field M. Prospective comparative study of patients with culture proven and high suspicion of adult onset septic arthritis. Ann Rheum Dis. 2003;62(4):327–331.

39. Goldenberg DL, Cohen AS. Acute infectious arthritis. A review of patients with nongonococcal joint infections (with emphasis on therapy and prognosis). Am J Med. 1976;60(3):369–377.

40. Howard AW, Viskontas D, Sabbagh C. Reduction in osteomyelitis and septic arthritis related to Haemophilus influenzae type B vaccination. J Pediatr Orthop. 1999;19(6):705–709.

41. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2006. http://www.cdc.gov/std/treatment/2006/urethritis-and-cervicitis.htm. Accessed November 16, 2010.

42. Ytterberg SR. Infectious disorders: mycobacterial, fungal, and parasitic arthritis. In: Klippel JH, Stone JH, Crofford LJ, White PH, eds. Primer on the Rheumatic Diseases. 13th ed. New York, NY: Springer; 2008: 290–295.

43. Kohli R, Hadley S. Fungal arthritis and osteomyelitis. Infect Dis Clin North Am. 2005;19(4):831–851.

44. Bacon RM, Kugeler K, Mead PS; Centers for Disease Control and Prevention (CDC). Surveillance for Lyme disease—United States, 1992–2006. MMWR Surveill Summ. 2008;57(10):1–9.

45. Centers for Disease Control and Prevention (CDC). Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. MMWR Morb Mortal Wkly Rep. 1995;44(31):590–591.

46. Hu L. Lyme arthritis. Infect Dis Clin North Am. 2005;19(4):947–961.

47. Steere A. Borrelia burgdorferi (Lyme disease, Lyme borreliosis). In: Mandell GL, Douglas RG, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pa.: Churchill, Livingstone/Elsevier; 2010:3071–3081.

48. Coakley G, Mathews C, Field M, et al.; British Society for Rheumatology Standards, Guidelines and Audit Working Group. BSR & BHPR, BOA, RCGP and BSAC guidelines for management of the hot swollen joint in adults. Rheumatology (Oxford). 2006;45(8):1039–1041.

49. Rosenthal J, Bole GG, Robinson WD. Acute nongonococcal infectious arthritis. Evaluation of risk factors, therapy, and outcome. Arthritis Rheum. 1980;23(8):889–897.

50. Parisien JS, Shaffer B. Arthroscopic management of pyarthrosis. Clin Orthop Relat Res. 1992;(275):243–247.

51. Dickie AS. Current concepts in the management of infections in bones and joints. Drugs. 1986;32(5):458–475.

52. Kaandorp CJ, Krijnen P, Moens HJ, Habbema JD, van Schaardenburg D. The outcome of bacterial arthritis: a prospective community-based study. Arthritis Rheum. 1997;40(5):884–892.

53. Phillips JE, Crane TP, Noy M, Elliott TS, Grimer RJ. The incidence of deep prosthetic infections in a specialist orthopaedic hospital: a 15-year prospective survey. J Bone Joint Surg Br. 2006;88(7):943–948.

54. Peersman G, Laskin R, Davis J, Peterson M. Infection in total knee replacement: a retrospective review of 6489 total knee replacements. Clin Orthop Relat Res. 2001;(392):15–23.

55. Choong PF, Dowsey MM, Carr D, Daffy J, Stanley P. Risk factors associated with acute hip prosthetic joint infections and outcome of treatment with a rifampin-based regimen. Acta Orthop. 2007;78(6):755–765.

56. Trampuz A, Osmon DR, Hanssen AD, Steckelberg JM, Patel R. Molecular and antibiofilm approaches to prosthetic joint infection. Clin Orthop Relat Res. . 2003;(414):69–88.

57. Stewart PS, Costerton JW. Antibiotic resistance of bacteria in biofilms. Lancet. 2001;358(9276):135–138.

58. Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science. 1999;284(5418):1318–1322.

59. Berbari EF, Hanssen AD, Duffy MC, et al. Risk factors for prosthetic joint infection: case-control study. Clin Infect Dis. 1998;27(5):1247–1254.

60. Eid AJ, Berbari EF, Sia IG, Wengenack NL, Osmon DR, Razonable RR. Prosthetic joint infection due to rapidly growing mycobacteria: report of 8 cases and review of the literature. Clin Infect Dis. 2007;45(6):687–694.

61. Marculescu CE, Cantey JR. Polymicrobial prosthetic joint infections: risk factors and outcome. Clin Orthop Relat Res. 2008;466(6):1397–1404.

62. Jämsen E, Huhtala H, Puolakka T, Moilanen T. Risk factors for infection after knee arthroplasty. A register-based analysis of 43,149 cases. J Bone Joint Surg Am. 2009;91(1):38–47.

63. Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint infections. N Engl J Med. 2004;351(16):1645–1654.

64. Schafroth M, Zimmerli W, Brunazzi M, Ochsner PE. Infections. In: Ochsner PE, ed. Total Hip Replacement: Implantation Technique and Local Complicaitons. Berlin: Springer; 2003:65–90.

65. Zimmerli W. Infection and musculoskeletal conditions: prosthetic-joint-associated infections. Best Pract Res Clin Rheumatol. 2006;20(6):1045–1063.

66. Ghanem E, Parvizi J, Burnett RS, et al. Cell count and differential of aspirated fluid in the diagnosis of infection at the site of total knee arthroplasty. J Bone Joint Surg Am. 2008;90(8):1637–1643.

67. Kwee TC, Kwee RM, Alavi A. FDG-PET for diagnosing prosthetic joint infection: systematic review and metaanalysis. Eur J Nucl Med Mol Imaging. 2008;35(11):2122–2132.

68. Love C, Marwin SE, Palestro CJ. Nuclear medicine and the infected joint replacement. Semin Nucl Med. 2009;39(1):66–78.

69. American Academy of Orthopaedic Surgeons. Information statement: antibiotic prophylaxis for bacteremia in patients with joint replacements. http://www.aaos.org/about/papers/advistmt/1033.asp. Accessed December 5, 2010.

70. Berbari EF, Osmon DR, Carr A, et al. Dental procedures as risk factors for prosthetic hip or knee infection: a hospital-based prospective case-control study [published correction appears in Clin Infect Dis. 2010;50(6):944]. Clin Infect Dis. 2010;50(1):8–16.


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