Infectious Disease and Microbiology – Septic Arthritis

Septic arthritis is infection of a joint resulting in acute inflammation of the synovium and joint space. Although bacteria are the most important causes of acute septic arthritis, infection may also be caused by mycobacteria, fungi, and occasionally viruses.

Septic arthritis is a medical and orthopedic emergency because rapidly progressive inflammation can cause irreversible destruction of articular cartilage. Prompt arthrocentesis, antimicrobial therapy, and adequate joint drainage are central to management.

The incidence in the general population is relatively low but increases substantially in patients with preexisting joint disease or prosthetic joints.

Important risk factors include advanced age, rheumatoid arthritis or other chronic joint disease, diabetes mellitus, immunosuppression, malignancy, recent joint surgery, prosthetic joints, intra-articular injections, skin infection, trauma, animal bites, and injection drug use.

Most bacterial septic arthritis results from hematogenous spread during bacteremia. Less commonly, organisms enter through direct inoculation following trauma, surgery, injection, or an animal bite, or by contiguous spread from an adjacent infection such as osteomyelitis.

Once organisms enter the joint, bacterial proliferation and the resulting intense inflammatory response can rapidly damage cartilage. Neutrophils, cytokines, bacterial toxins, and proteolytic enzymes all contribute to articular destruction.

Staphylococcus aureus is the most important and generally the most common cause of native-joint bacterial septic arthritis in adults. Both methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) must be considered.

Streptococci are also important causes. Group B Streptococcus is particularly associated with older adults and patients with underlying illnesses.

Gram-negative bacilli should be considered particularly in older adults, immunocompromised patients, people with urinary or gastrointestinal sources of bacteremia, and patients with healthcare-associated infection.

Pseudomonas aeruginosa has an important association with injection drug use, although other organisms can also occur. The sternoclavicular and sacroiliac joints are unusual sites that should raise suspicion for infection in this population.

Neisseria gonorrhoeae remains an important cause of septic arthritis in sexually active adolescents and young adults. Disseminated gonococcal infection can produce a characteristic syndrome of migratory polyarthralgia, tenosynovitis, and pustular skin lesions, with or without subsequent purulent monoarthritis.

Animal bites can directly inoculate joints. The microbiology depends on the animal and exposure; organisms such as Pasteurella multocida should be considered following cat or dog bites.

A chronic or indolent monoarthritis raises a different microbiologic differential. Important causes include Mycobacterium tuberculosis, nontuberculous mycobacteria, and fungi such as Coccidioides and Sporothrix in appropriate epidemiologic settings.

Patients usually present with acute joint pain, swelling, warmth, and marked limitation of movement. Fever is common but may be absent, particularly in older or immunocompromised patients.

The knee is the most frequently affected native joint, followed by other large joints such as the hip, shoulder, ankle, elbow, and wrist. Most cases are monoarticular, although polyarticular septic arthritis can occur, especially in patients with bacteremia, rheumatoid arthritis, or immunosuppression.

Both active and passive range of motion are usually extremely painful because the pathological process lies within the joint. This can help distinguish septic arthritis from some periarticular disorders such as bursitis or tendinitis.

In infants and young children, presentation can be less specific. Findings include irritability, refusal to move the affected limb (pseudoparalysis), limp, or inability to bear weight. Septic arthritis of the hip is particularly important because it may be difficult to recognize clinically.

The most important diagnostic procedure is urgent arthrocentesis with examination of synovial fluid. Whenever feasible, synovial fluid and blood cultures should be obtained before antibiotics are administered, provided this does not cause a clinically important delay in treatment.

Synovial fluid should generally be sent for cell count with differential, Gram stain, and bacterial culture. Crystal analysis should also be performed when gout or calcium pyrophosphate deposition disease is possible.

Typical bacterial septic arthritis produces turbid or purulent synovial fluid with a high leukocyte count and neutrophilic predominance. A synovial WBC count greater than approximately 50,000 cells/µL increases suspicion for infection, especially with a high proportion of neutrophils.

However, a synovial WBC count below 50,000 cells/µL does not exclude septic arthritis. Lower counts can occur early in infection, in immunocompromised patients, and with certain organisms.

Conversely, very high synovial leukocyte counts are not specific for infection because severe crystal-induced arthritis can produce similar findings. Finding monosodium urate or calcium pyrophosphate crystals also does not completely exclude concomitant septic arthritis.

Synovial-fluid Gram stain has limited sensitivity, so a negative Gram stain cannot rule out infection. Synovial-fluid culture has substantially greater diagnostic importance.

At least two sets of blood cultures should generally be obtained when septic arthritis is suspected, particularly when the patient is febrile or bacteremic. Blood cultures can identify the pathogen even when synovial cultures are negative.

Inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are frequently elevated. They are nonspecific and cannot independently confirm or exclude septic arthritis, but serial measurements can assist in assessing response to treatment.

Peripheral leukocytosis may occur but can also be absent. A normal peripheral WBC count therefore does not exclude joint infection.

When gonococcal infection is suspected, testing should include appropriate nucleic acid amplification tests (NAATs) from relevant genital and extragenital sites because synovial-fluid cultures may be negative.

Plain radiographs are useful as an initial study to identify underlying joint abnormalities, fractures, foreign material, or late destructive changes. Early findings may be limited to soft-tissue swelling and joint effusion.

Ultrasonography is particularly useful for identifying effusions in joints such as the hip and can guide aspiration.

MRI is highly useful when there is concern for associated osteomyelitis, deep soft-tissue infection, abscess, or difficult-to-assess joints, but imaging should not unnecessarily delay diagnostic aspiration of an accessible joint.

The major differential diagnosis includes gout, pseudogout, rheumatoid arthritis, reactive arthritis, traumatic hemarthrosis, osteoarthritis, bursitis, cellulitis, Lyme arthritis, and other inflammatory arthropathies.

Once appropriate cultures have been obtained, empiric intravenous antibiotics should be started promptly when clinical suspicion for bacterial septic arthritis is substantial.

Empiric therapy should generally provide coverage for S. aureus, including MRSA when appropriate, while additional gram-negative coverage is added according to the patient’s age, immune status, Gram-stain findings, exposure history, and local epidemiology.

A commonly used empiric approach for a seriously ill adult with a negative Gram stain is vancomycin plus a third- or fourth-generation cephalosporin, with the exact regimen adjusted to individual risk factors and local resistance patterns.

Once the organism and antimicrobial susceptibility results are known, treatment should be narrowed to targeted therapy. MSSA, for example, is generally better treated with an antistaphylococcal β-lactam such as cefazolin or nafcillin/oxacillin rather than continuing vancomycin when there is no relevant β-lactam contraindication.

The duration of treatment depends on the organism, affected joint, adequacy of drainage, presence of bacteremia or osteomyelitis, and clinical response. Many uncomplicated native-joint bacterial infections require several weeks of antimicrobial therapy, but treatment duration should be individualized rather than applying a fixed IV course to every patient.

Antibiotics alone are usually insufficient. Adequate drainage of the infected joint is a fundamental component of treatment.

Drainage may be accomplished through repeated needle aspiration, arthroscopic irrigation and drainage, or open surgical drainage. The optimal approach depends on the joint involved, amount and persistence of purulent material, organism, underlying joint anatomy, and clinical response.

Early orthopedic consultation is particularly important for hip or shoulder infection, difficult-to-drain joints, extensive infection, failure to improve, or infection involving a prosthetic joint.

Prosthetic-joint infection requires a separate management strategy combining antimicrobial treatment with decisions regarding debridement and implant retention, one-stage exchange, two-stage exchange, or removal of the prosthesis, depending on the clinical circumstances.

Septic arthritis should prompt assessment for the source of bacteremia and associated infections. In appropriate patients, clinicians should consider endocarditis, osteomyelitis, skin and soft-tissue infection, urinary infection, and other potential primary sources.

After adequate control of infection, physical therapy and progressive joint mobilization are important to preserve range of motion and function. Prolonged unnecessary immobilization can contribute to stiffness and functional impairment.

Clinical improvement is assessed through decreasing pain, swelling, fever, and inflammatory markers together with improved joint function. Persistent fever, recurrent effusion, continued bacteremia, or failure of CRP to decline should raise concern for inadequate drainage, resistant organisms, osteomyelitis, abscess, or another uncontrolled infectious focus.

Major complications include rapid cartilage destruction, joint-space narrowing, ankylosis, chronic pain, reduced range of motion, permanent joint dysfunction, osteomyelitis, sepsis, and death.

Children can additionally develop damage to the growth plate or epiphysis, potentially producing impaired limb growth or permanent deformity.

A useful clinical rule is:

Acute hot + swollen + very painful joint = septic arthritis until adequately excluded.

Do not rely on absence of fever, a normal blood WBC count, a negative Gram stain, or synovial WBC <50,000/µL to rule it out.

The core sequence is:

Urgent arthrocentesis → synovial Gram stain/culture + blood cultures → prompt empiric antibiotics → adequate joint drainage → culture-directed therapy.