Septic arthritis

Septic (infectious) arthritis is an infection of the joint space, which can occur in a native joint or a prosthetic joint. Patients with underlying joint diseases (e.g., rheumatoid arthritis) are at an increased risk of septic arthritis. Routes of infection include hematogenous spread (most common), direct inoculation (e.g., iatrogenic, penetrating trauma), and contiguous spread. Patients with native joint infections usually present with an acutely swollen, painful joint, limited range of motion, and fever, whereas patients with prosthetic joint infections (PJIs) usually have a milder, chronic course, which often makes diagnosis more challenging. All patients with suspected septic arthritis should undergo prompt arthrocentesis for synovial fluid analysis. Early administration of empiric antibiotic therapy and therapeutic arthrocentesis is indicated for native joint infections to prevent cartilage destruction. PJIs typically necessitate surgical debridement, including removal of the prosthesis in some cases; empiric antibiotics are not recommended unless the patient is critically ill. Targeted antibiotics should be initiated in all patients once culture and sensitivity results are available.

Routes of spread

• Hematogenous spread (most common)
  • From a distant site (e.g., abscesses, wound infection, septicemia)
  • Disseminated infection (e.g., gonorrhea)
• Direct contamination
  • Iatrogenic (e.g., joint injection, arthrocentesis , arthroscopy ) ^[1]
  • Trauma (e.g., open wounds around the joint , penetrating trauma)
• Contiguous spread (e.g., septic bursitis, osteomyelitis)

Risk factors for septic arthritis

• Prosthetic implant
• Interventions (e.g., intra-articular injections)
• Underlying joint disease, especially rheumatoid arthritis
• Immunosuppressed state
• Diabetes mellitus
• Age > 80 years
• Chronic skin infections
• IV drug use
• Endocarditis (polyarticular septic arthritis)

Causative organisms

• Staphylococcus aureus
  • Most common in adults and children > 2 years
  • Frequently found in patients with arthritis following invasive joint procedures ^[2]
• K. kingae: most common in infants and children ≤ 2 years ^[3]
• Streptococci
• N. gonorrheae
• Gram-negative rods esp. E. coli and P. aeruginosa
• S. epidermidis
• H. influenzae
• M. tuberculosis and atypical mycobacteria
• B. burgdorferi (Lyme disease)

• Acute onset
• Classical triad of fever, joint pain, and restricted range of motion
• Arthritis
  • Usually monoarticular
  • Most commonly affected joints: knees (followed by hip, wrists, shoulders, and ankles)
  • Joints are swollen, red, warm, and painful.

Prosthetic joint infection (PJI) ^[4][5]

• Etiology
  • Early onset (< 3 months of placement): most commonly S. aureus
  • Delayed onset (3–12 months of placement); : coagulase-negative staphylococci, particularly S. epidermidis
  • Late onset (> 12 months of placement): most commonly S. aureus
• Clinical features
  • Usually prolonged, low-grade course
  • Minimal swelling, with or without a sinus that drains pus
  • Can present acutely (see “Clinical features” above)
• Management: See “Diagnostics” and “Treatment” sections.

In order to avoid infection, strict aseptic precautions should be ensured in any procedure that involves penetration of the joint space.

Bacterial coxitis ^[6]

• Description: septic arthritis of the hip (rare)
• Etiology: S. aureus and group A streptococcus account for the majority of cases
• Clinical findings
  • Joint pain (may be referred to the groin or knee)
  • Patient's hip is often flexed and externally rotated (this decreases intraarticular pressure and alleviates pain)
  • See “Clinical features” above
• Management: See “Diagnostics” and “Treatment” sections.

Bacterial coxitis is an orthopedic emergency that requires urgent management to avoid joint destruction.

Gonococcal arthritis

• Gonococcal arthritis is the most common form of arthritis in sexually active young adults.
• See “Purulent gonococcal arthritis” and “Arthritis-dermatitis syndrome.”
• See “Targeted antimicrobial therapy for septic arthritis.”

In a young, sexually active adult presenting with classic symptoms of septic arthritis, gonococcal infection must be ruled out.

Lyme arthritis

• See “Lyme arthritis.”

Approach

Any red, painful joint with a reduced range of motion should be considered infectious until proven otherwise. The absence of fever does not rule out a diagnosis of septic arthritis. ^[7]

• All patients ^[7][8][9]
  • Arthrocentesis with synovial fluid analysis and culture (gold standard)
  • Blood cultures in patients with fever or acute onset of symptoms
  • X-rays of the affected joint
• Suspected PJI ^[8]
  • Diagnostic criteria for PJIs can be used alongside clinical features to establish a diagnosis. ^[10]
  • Prompt specialist consultation is recommended (e.g., orthopedic surgery, infectious diseases).
  • Advanced imaging (e.g., MRI, nuclear medicine studies) may be necessary.
  • Intraoperative samples (e.g., of infected periprosthetic tissue) for culture are usually required.
• Suspected gonococcal arthritis ^[11]
  • Additional cultures and PCR testing of swabs from mucosal sites are recommended.
  • See also “Disseminated gonococcal infection.”

Maintain a high index of suspicion for septic arthritis in patients with underlying joint diseases (e.g., osteoarthritis, rheumatoid arthritis) who present with joint pain, as the signs and symptoms of an acute flare and an infection often overlap. ^[7]

Arthrocentesis ^[12]

• Definition: a diagnostic and/or therapeutic procedure in which synovial fluid is aspirated from a joint using a sterile needle
• Indication: : all patients with suspected septic arthritis ^[8]
• Additional clinical applications
  • Synovial fluid analysis: to determine the etiology of joint effusion, e.g., septic arthritis or crystal arthropathy
  • Suspected hemarthrosis: by confirming the presence of blood within the joint
  • Therapeutic arthrocentesis: to decompress an effusion or hemarthrosis
• Important considerations
  • Skin or subcutaneous infection (e.g., cellulitis) surrounding the affected joint is an absolute contraindication. ^[12]
  • Consider specialist input prior to arthrocentesis in patients receiving anticoagulants.
  • Consider inoculating synovial fluid into blood culture bottles to improve the sensitivity of cultures. ^[7]

Infection of the skin overlying the affected joint is an absolute contraindication to arthrocentesis due to the risk of introducing pathogens into the joint. ^[7]

Do not delay joint aspiration in suspected septic arthritis as early detection and treatment are imperative to prevent cartilage destruction. ^[13]

Synovial fluid analysis (SFA) in septic arthritis

• Appearance: : often yellow-green and turbid (nonspecific) ^[7]
• Cell count
  • ↑ WBC count (e.g., > 50,000/mm³) ^[7][11]
  • Neutrophil (PMN) dominance of > 90%
• Glucose levels: lower than blood glucose levels
• Gram stain ^[7][11][14]
  • To guide empiric antibiotic therapy for native joint infection
  • A negative Gram stain does not rule out septic arthritis.
• Culture and sensitivity testing: to guide targeted antibiotic therapy ^[7]

Synovial fluid WBC count may be much lower in PJI than septic arthritis in a native joint. WBC count > 1100/mm³ (≥ 64%) should raise suspicion for PJI. ^[11]

Neutrophil predominant leukocytosis on SFA may also be present in crystal arthropathy (e.g., acute gout flare). Interpret SFA in close conjunction with clinical features and risk factors.

Laboratory studies ^[7][9][11]

Routine studies

• Blood cultures (for aerobic and anaerobic organisms)
  • Patients with fever or acute onset of symptoms ^[8]
  • Positive in 25–50% of cases of septic arthritis and 25–70% of cases of gonococcal arthritis ^[11]
• CBC, CRP, ESR: Leukocytosis and elevated inflammatory markers may be seen (nonspecific).
• BMP and liver chemistries: to guide antibiotic selection ^[9]

Additional studies

• Serum procalcitonin ^[7]
  • Consider if diagnostic arthrocentesis is not feasible or in patients with comorbid inflammatory arthritis.
  • Levels > 0.2–0.3 ng/mL provide supportive evidence of a bacterial infection of bones or joints.
• Coagulation panel: Perform prior to arthrocentesis in patients on anticoagulation.
• Culture and PCR testing for N. gonorrhoeae : For suspected gonococcal arthritis ^[11]

Uric acid levels have no diagnostic value in the evaluation of swollen joints. ^[9]

Inflammatory markers may be normal in septic arthritis. ^[11]

Imaging of the affected joint ^[7][11][15]

• Imaging findings of septic arthritis are nonspecific and should be interpreted in conjunction with the clinical picture.
• May be useful to evaluate for other causes of acute joint pain (e.g., fractures, osteomyelitis, chondrocalcinosis).
• Ultrasound and fluoroscopy is also useful to guide arthrocentesis in difficult joints, e.g., hip, sacroiliac joint. ^[15]

X-ray

• Indication: preferred initial imaging modality (prosthetic and native joints) ^[7][15]
• Supportive findings
  • May be unremarkable in early septic arthritis
  • Soft tissue swelling, gas within periarticular soft tissue, and synovial effusion may be seen ^[12]
  • Radiodense foreign bodies can be detected
  • Osteolysis may be seen in concurrent osteomyelitis (2–3 weeks after onset). ^[15][16]
  • Loosening of the prosthesis and periosteal reactions may be seen in PJIs.

Ultrasound

• Indication: Consider in patients with suspected foreign body (e.g., history of penetrating trauma) and negative x-rays. ^[15]
• Supportive findings ^[15][16][17]
  • Joint effusion with or without synovial thickening
  • Inflammatory changes in periarticular soft tissue
  • Effusions and small collections
  • Can detect radiolucent foreign bodies, if present.

CT or MRI

• Indications: Consider CT or MRI in the following situations ^[7][15]
  • Chronic infection and/or suspected osteomyelitis
  • History of penetrating trauma or suspected foreign body (as an alternative to ultrasound)
• Supportive findings ^[11][15]
  • Similar to ultrasound findings
  • Bone marrow edema
  • Can detect intra- or periarticular foreign bodies

Nuclear medicine studies (e.g., scintigraphy, PET-CT) ^[8][18]

• Indication: Consider in the workup of PJIs (not routinely recommended).
• Findings: focal increase in radiotracer uptake in the affected joint

Nuclear medicine studies can not distinguish between septic arthritis and inflammatory arthritis and are hence not recommended in the diagnostic workup of septic arthritis in a native joint. ^[15]

Diagnostic criteria for prosthetic joint infections

There are several diagnostic criteria for PJI that can be used alongside clinical features to establish a diagnosis. Clinical judgment plays an important role in determining the likelihood of PJI even in patients who do not fulfill the diagnostic criteria. ^[8][10]

Infectious Diseases Society of America (IDSA) diagnostic criteria for PJI (for all joints) ^[8]

Musculoskeletal Infection Society (MSIS) for hip and/or knee PJI ^[10]

A diagnosis of PJI can be made even if the IDSA and/or MSIS criteria are not fulfilled. Clinical judgment based on clinical features and diagnostic findings plays an important role in determining the diagnosis. ^[8]

Based on clinical features and imaging

See also “Differential diagnoses of inflammatory arthritis.”

Viral arthritis

• Etiology: parvovirus B19, hepatitis B virus, hepatitis C virus, rubella virus, HIV
• Pathophysiology
  • Direct invasion of the virus (e.g., rubella, enteroviruses)
  • Immune complex formation (e.g., hepatitis B, hepatitis C, parvovirus)
• Clinical features
  • Symmetric involvement of multiple small joints
  • Sudden onset
  • Possibly accompanied by rash and fever
  • Usually no destruction of the joint
• Diagnostics
  • History and clinical findings are the mainstays of establishing a diagnosis
  • Serology: antibodies against the suspected virus
  • Synovial joint analysis
    • Very variable (can be normal or inflammatory)
    • Not routinely used since viral isolation is usually not successful
  • For other diagnostic tests, see “Diagnostics” above.
• Therapy
  • Supportive treatment only (usually self-limited)
  • See “Hepatitis B”, “Hepatitis C“, “Rubella“, “Parvovirus B19-associated arthritis”, and “HIV-associated arthritis.”

Fungal arthritis ^[19]

• Etiology: Histoplasma species, Sporothrix schenckii, Blastomyces species, Coccidioides species
• Clinical features
  • Very variable with acute and chronic courses
  • Often with symptoms of disseminated infection (e.g., pulmonary symptoms)
• Diagnostics
  • Synovial fluid analysis may show normal, inflammatory, or septic findings
  • Synovial fluid culture
  • Possibly serologic studies: positive antibodies against the pathogen (e.g., in coccidioidal arthritis)
• See also: “Overview of fungal infections” in the “General mycology”

Miscellaneous

• Avascular osteonecrosis, including Legg-Calvé-Perthes disease in children
• Bursitis

Based on synovial fluid analysis ^[11]

Synovial fluid analysis comprises a group of tests that examine synovial fluid to help differentiate between subtypes of arthritis.

The differential diagnoses listed here are not exhaustive.

Approach

• Native joint infection
  • Serial therapeutic arthrocentesis
  • Empiric antibiotic therapy guided by Gram stain and clinical features
  • Targeted antibiotic therapy once antibiogram is available
• Prosthetic joint infection (PJI)
  • Orthopedic consultation for surgical intervention (debridement with/without exchange arthroplasty)
  • Infectious disease consultation for targeted antibiotic therapy once antibiogram is available
  • All patients require a prolonged course of pathogen-specific systemic antibiotics. ^[8]

Evacuation of purulent material from the joint and systemic antibiotic therapy are the mainstays of treatment in septic arthritis.

Joint drainage

Native joints ^[9]

• Therapeutic arthrocentesis (drained to dryness) is indicated in all patients.
• Repeat arthrocentesis as often as needed; SFA should be performed at each aspiration.
• Signs of improvement include a reduction in synovial fluid volume, cell count, and percentage of PMNs with each aspiration. ^[9][17]
• Consider surgical drainage if symptoms persist despite serial arthrocentesis ; ; examples of surgery include: ^[9][11]
  • Serial lavage via arthroscopy or tidal irrigation systems ^[17]
  • Arthrotomy and open debridement ^[9][17]

If effusion persists beyond 7 days of arthrocentesis, arthroscopic or open drainage is indicated. ^[17]

Prosthetic joints ^[8]

Surgery to remove pus and infected tissue from the affected joint is typically required; examples include:

• Debridement of infected periarticular tissue with retention of prosthesis
• Exchange arthroplasty (e.g., one-stage exchange arthroplasty, two-stage exchange arthroplasty)
• Arthrodesis

Consult orthopedic surgery early in patients with suspected prosthetic joint infection.

Empiric antibiotic therapy

• Indication: septic arthritis of a native joint (after diagnostic arthrocentesis has been performed) ^[11]
• Antibiotic coverage
  • Should be guided by Gram stain results on SFA
  • In patients with negative Gram stain but a high likelihood of septic arthritis, select empiric antibiotics based on clinical features and patient history.
• Special patient groups: Consult infectious diseases for appropriate antibiotic selection in the following groups of patients. ^[9]
  • Patients with risk factors for atypical infection
  • Patients with risk factors for methicillin-resistant Staphylococcus aureus (MRSA)
  • Patients at high risk for Gram-negative infections

Empiric antibiotic therapy is not routinely recommended for PJIs.

Adult patients

Intraarticular injection of antibiotics is not recommended. ^[3]

Pediatric patients ^[3]

Targeted antibiotic therapy

Switch from empiric antibiotic therapy to culture-specific antibiotics once the antibiogram is available in patients with native joint infections. Initiation of targeted antibiotic therapy directly (i.e., without preceding empiric therapy) is sufficient for PJI. Specialist consultation is advised especially in patients with PJIs.

Agents

Duration of therapy ^[9]

The total duration of antibiotic therapy is variable and should be adjusted according to signs of clinical and laboratory evidence of improvement.

• Native joint infections ^[3]
  • Nongonococcal arthritis: 4–6 weeks
  • Gonococcal arthritis: typically 7 days
• PJI: weeks to months

Supportive therapy

• Acute phase
  • Analgesics and immobilization for pain relief
  • VTE prophylaxis as needed
  • Perioperative management if surgery is indicated
  • Optimal joint positioning to prevent deformation and contractures ^[17]
• Following the acute phase
  • Early mobilization ^[17][27]
  • Physiotherapy

Native joint infections

• Initiate empiric antibiotic therapy for septic arthritis.
• Serial therapeutic arthrocentesis
• Repeat synovial fluid analysis at each arthrocentesis to monitor response to therapy.
• Tailor antibiotics as needed once the antibiogram is available.

Prosthetic joint infections

• Consult orthopedics for surgical intervention (e.g., debridement, exchange arthroplasty, or arthrodesis).
• Initiate pathogen-specific antibiotics once the antibiogram is available (preferably in consultation with infectious diseases specialists)

Empiric antibiotic therapy for septic arthritis is not routinely recommended for PJIs unless the patient is critically ill.

• Joint destruction ^[28]
• Osteomyelitis
• Sepsis
• Children: growth arrest

We list the most important complications. The selection is not exhaustive.