Nongonococcal Acute Bacterial (Septic) Arthritis

Lyme disease is discussed in our chapter on Spirochetal Infections.

Nongonococcal acute bacterial arthritis is most often due to hematogenous seeding of the joint; direct inoculation from penetrating trauma is rare.

The key risk factors are bacteremia (eg, injection drug use, endocarditis, infection at other sites), damaged joints (eg, rheumatoid arthritis), prosthetic joints, compromised immunity (eg, advanced age, diabetes mellitus, advanced CKD, alcohol use disorder, cirrhosis, or immunosuppressive therapy), and loss of skin integrity (eg, cutaneous ulcer or psoriasis).

Staphylococcus aureus is the most common cause of nongonococcal septic arthritis, accounting for about 50% of all cases.

Methicillin-resistant S aureus (MRSA) and group B Streptococcus are frequent and important causes of septic arthritis.

Gram-negative septic arthritis causes about 10% of cases and is especially common in injection drug users and immunocompromised persons; Escherichia coli and Pseudomonas aeruginosa are the most common pathogens.

Pathologic changes include varying degrees of acute inflammation, with synovitis, effusion, abscess formation in synovial or subchondral tissues, and, if treatment is not adequate, articular destruction.

Diagnostic Essentials

  • Acute onset of inflammatory monoarticular arthritis, most often in large weight-bearing joints and wrists.
  • Common risk factors include previous joint damage and injection drug use.
  • Infection with causative organism commonly found elsewhere in body.
  • Joint effusions are usually large; synovial fluid WBC counts > 50,000/mcL (50 × 109/L) are common.

Clinical Findings

Symptoms and Signs

The onset is acute, with pain, swelling, and heat of the affected joint worsening over hours.

The knee is most frequently involved; other commonly affected sites are the hip, wrist, shoulder, and ankle.

Unusual sites, such as the sternoclavicular or sacroiliac joint, can be involved in injection drug users.

Chills and fever are common but are absent in up to 20% of patients.

Infection of the hip usually does not produce apparent swelling but results in groin pain aggravated by walking.

More than one joint is involved in 15% of cases of septic arthritis; risk factors for multiple joint involvement include rheumatoid arthritis, associated endocarditis, and infection with group B streptococci.

Laboratory Findings

Synovial fluid analysis is critical for diagnosis.

The leukocyte count of the synovial fluid is always inflammatory (> 2000/mcL [2 × 109/L]), usually > 50,000/mcL (50 × 109/L), and often is > 100,000/mcL (100 × 109/L), with 90% or more polymorphonuclear cells (Table 1–2ck).

Synovial fluid cell count in septic arthritis may be lower in immunocompromised patients, especially those on biologic therapies such as TNF inhibitors.

Gram stain of the synovial fluid is positive in 75% of staphylococcal infections and in 50% of gram-negative infections.

Synovial fluid cultures are positive in 70–90% of cases; administration of antibiotics prior to arthrocentesis reduces the likelihood of a positive culture result.

Blood cultures are positive in approximately 50% of patients.


Imaging tests generally add little to the diagnosis of septic arthritis.

Other than demonstrating joint effusion, radiographs are usually normal early in the disease; however, evidence of demineralization may develop within days of onset.

MRI and CT are more sensitive in detecting fluid in joints that are not accessible to physical examination (eg, the hip).

Bony erosions and narrowing of the joint space followed by osteomyelitis and periostitis may be seen within 2 weeks.

Prosthetic Joint Infection

The clinical and laboratory manifestations of prosthetic joint infection are influenced by whether the infection is early (< 3 months after surgery), delayed (3–12 months after surgery), or late (> 12 months after surgery).

Early infections present with acute redness and swelling and are usually caused by S aureus and gram-negative organisms.

Delayed infections often present with subtle manifestations: pain is common but only 50% of patients will have fever.

Less virulent organisms, such as coagulase-negative Staphylococcus, Propionibacterium acnes, and enterococci, are common causes of delayed infections.

Late infections present with acute pain, swelling, and fever and are often caused by hematogenous seeding of S aureus, gram-negative bacilli, and hemolytic streptococci.

Differential Diagnosis

Gout and pseudogout can cause acute, very inflammatory monoarticular arthritis and fever; failure to find crystals on synovial fluid analysis excludes these diagnoses.

The most common articular manifestation of chronic Lyme disease is inflammatory monoarthritis of the knee, which yields synovial fluid that is Gram stain and culture negative.

Acute rheumatic fever commonly involves an inflammatory migratory oligoarthritis.

Pyogenic arthritis may be superimposed on other types of joint disease, notably rheumatoid arthritis.

Septic arthritis must be excluded by joint fluid examination in any patient with rheumatoid arthritis who has a joint strikingly more inflamed than the other joints, especially if the patient is receiving biologic DMARD therapy.


The American Academy of Orthopedic Surgeons advocates prescribing antibiotic prophylaxis for any patient with a prosthetic joint replacement who undergoes a procedure that can cause bacteremia. However, the topic remains controversial.


The effective treatment of septic arthritis requires appropriate antibiotic therapy together with drainage of the infected joint.

Hospitalization is always necessary.

If the likely causative organism cannot be determined clinically or from the synovial fluid Gram stain, treatment should be started with broad-spectrum antibiotic coverage effective against staphylococci, streptococci, and gram-negative organisms.

The recommended initial treatment is to vancomycin (1 g IV q12h, adjusted for age, weight, and renal function) plus a third-generation cephalosporin: ceftriaxone, 1–2 g IV daily (or q12h if concomitant meningitis or endocarditis is suspected); or cefotaxime, 1–2 g IV q8h.

Antibiotic therapy should be adjusted when culture results become available; the duration of antibiotic therapy is usually 4–6 weeks.

Early orthopedic consultation is essential.

Effective drainage is usually achieved through early arthroscopic lavage and debridement.

Options for treating prosthetic joint infections depend, in part, on the timing of the infection and include chronic suppression, debridement without removal of the prosthesis, or one- or two-stage exchange of the prosthesis.


The outcome of septic arthritis depends largely on the antecedent health of the patient, the causative organism (eg, S aureus bacterial arthritis is associated with a poor functional outcome in about 40% of cases), and the promptness of treatment.

The mortality rate is 30% for patients with polyarticular sepsis.

Bony ankylosis and articular destruction commonly occur if treatment is delayed or inadequate.

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