Prosthetic Joint Infectious Arthritis

Infections are more common in prosthetic joints than in native joints. They are frequently caused by perioperative inoculations of bacteria into the joint or by postoperative bacteremia resulting from skin infection, pneumonia, invasive instrumentation, urinary tract infection, possibly falls, or rarely dental procedures.

Joint infections develop within 1 year of surgery in two-thirds of cases (1). During the first few months after surgery, Staphylococcus aureus is the cause of infection in approximately 50% of cases; less common causes are mixed flora, gram-negative organisms, and anaerobes (2). Cutibacterium acnes is especially common in infected prosthetic shoulder joints and may require prolonged culture (up to 2 weeks) to detect (3). Candida species can infect prosthetic joints, but Candida infection is rare (4).

Patient-related and surgical risk factors may increase the risk of a prosthetic joint infection.

Patient-specific risk factors include (1).

• Immunosuppression (eg, from prednisone, TNF inhibitors, other biologics)

• Rheumatoid arthritis

• Diabetes mellitus

• Malignancy

• Chronic kidney disease

• Obesity

Surgery-specific risk factors include prior arthroplasty, prior surgical site infection, duration of surgery, postoperative complications (eg, hematoma or wound dehiscence), and concomitant S. aureus bacteremia (2).

Symptoms and signs of prosthetic joint infection are dependent on time from surgery and can be further classified as early, delayed onset, and late onset (1, 2).

Early/acute infection occurs within 3 months of surgery. The onset is sudden, and the joint appears swollen, painful, and erythematous. Systemic symptoms such as fevers and chills are usually present. These infections are typically acquired during the surgical procedure.

Delayed onset infection occurs between 3 to 12 months after surgery. There may be persistent wound drainage (eg, sinus tract) and the joint appears warm, swollen, and painful. The infection is likely acquired during arthroplasty or in the early postoperative period.

Late onset infection occurs more than 12 months after the initial surgery. There is an acute onset of joint pain, tenderness, and erythema in a previously well-functioning joint. The infection is likely acquired by hematogenous seeding from another infection site.

• Arthrocentesis with synovial fluid examination

• Blood tests (blood cultures, erythrocyte sedimentation rate, and/or C-reactive protein)

• Molecular testing (eg, polymerase chain reaction, 16S ribosomal RNA sequencing)

• Imaging studies

The diagnosis of infection in a prosthetic joint often requires a combination of clinical, microbiologic, pathologic, and imaging criteria. There is no standardized approach to diagnosing a prosthetic joint infection, and multiple criteria have been proposed (1–4).

Definitive diagnosis of a prosthetic joint infection can be established when 2 or more cultures from the joint are positive for the same organism. A communication between a sinus tract and the prosthesis may also be diagnostic (2).

Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and D-dimer may all be elevated in prosthetic joint infections. Synovial fluid should be analyzed for cell count and differential as well as culture (aerobic and anaerobic). In early infection, the synovial fluid white blood count (WBC) is typically > 10,000 cells/mcL (10 × 10⁹/L) (5). Blood cultures are positive in approximately 25% of cases (6).

Interpretive criteria for synovial fluid cell count and differential in the presence of a prosthetic joint infection differ from those for native joints. In acute infection (within 90 days of arthroplasty), the synovial fluid WBC count is typically >10,000 cells/microL; in delayed-onset of late-onset infection, the threshold is typically> 3000 cells/microL. The percentage of polymorphonuclear neutrophils (PMNs) is typically > 90% in delayed-onset and > 80% in late-onset infections. A positive synovial fluid alpha-defensin test may be a marker of infection as well (7).

If synovial fluid cultures are negative and clinical suspicion for prosthetic joint infection persists, molecular testing such as 16S ribosomal RNA (rRNA) gene PCR/sequencing may be considered on synovial fluid or periprosthetic tissue specimens. 16S rRNA gene PCR has a pooled sensitivity of approximately 80% and specificity of 94% for diagnosis (8).

Radiographs may show periosteal reaction or loosening of the prosthesis or periosteal reaction but are not diagnostic. Technetium-99m bone scanning and indium-labeled white blood cell scanning are more sensitive than radiographs but lack specificity, particularly in the first 1 to 2 years after surgery (9). Periprosthetic tissue collected at the time of surgery may be sent for culture and histologic analysis (4).

• Arthrotomy with debridement

• Prosthesis replacement

• Long-term systemic antibiotic therapy

Treatment of prosthetic joint infection requires both surgical intervention and prolonged antibiotic therapy. Ideally, treatment should be provided in specialized centers with collaborative teams of orthopedic surgeons and infectious disease specialists.

Surgical management is determined by the acuity and chronicity of infection. For acute prosthetic joint infections, debridement, antibiotics, and implant retention (DAIR) may be an option, provided there is no sinus tract, the prosthesis is mechanically stable, and the wound can be closed (1, 2). For chronic prosthetic joint infection, resection arthroplasty with prosthesis exchange is recommended, performed as either a 1-stage or 2-stage procedure (2). The procedure involves arthrotomy for prosthesis removal with meticulous debridement of all cement, abscesses, and devitalized tissues. Debridement is followed by immediate prosthesis replacement, or placement of an antibiotic-impregnated spacer and then delayed (2 to 4 months) implantation of a new prosthesis using antibiotic-impregnated cement (3).

Long-term empiric antibiotic therapy is initiated after intraoperative culture is performed and usually combines coverage for methicillin-resistant gram-positive organisms (eg, vancomycin ) and aerobic gram-negative organisms (eg, piperacillin/tazobactam or ceftazidime) and is revised based on results of culture and sensitivity testing (1).

For S. aureus prosthetic joint infection treated with DAIR, rifampin-based combination therapy is associated with improved outcomes (4).  After initial pathogen-specific intravenous therapy, rifampin 300 mg to 450 mg orally twice a day is added for biofilm penetration, ideally not within the first 5 days after surgical debridement. Rifampin must always be combined with a companion oral antibiotic to prevent resistance (ideally levofloxacin if susceptible). The total duration of antibiotic therapy for DAIR is typically 12 weeks (5, 6). Some experts recommend longer courses (3 months for hip, 6 months for knee infections), though the optimal duration is uncertain (7).

The overall rate of infection-free success at 5 years depends on the surgical approach, but can be close to 80% after combined medical and surgical treatment (8, 9).

Excision arthroplasty with or without fusion usually is reserved for patients with uncontrolled infection and insufficient bone stock.

In the absence of other indications (eg, valvular heart disease), prophylactic antibiotics are not routinely recommended before dental work in patients with prosthetic joints. Clinical practice guidelines from the American Academy of Orthopaedic Surgeons (AAOS) in collaboration with the Infectious Disease Society of America (ISDA) state that routine use of a systemic prophylactic antibiotic prior to a dental procedure in patients with a hip or knee replacement may not reduce the risk of a subsequent periprosthetic joint infection, based on consistent findings across multiple large studies (1). However, prophylactic antibiotics may be recommended for patients undergoing genitourinary procedures if they are within 2 years of arthroplasty, have individual comorbidities placing them at high risk for infection, or are undergoing urologic procedures associated with a high risk of bacteremia (eg, lithotripsy) (2).

At many centers, patients are screened for S. aureus colonization using nasal cultures. Carriers are decolonized with mupirocin ointment before surgery to implant a prosthetic joint (3).

• Suspect prosthetic joint infectious arthritis in patients with a warm, erythematous, tender joint, or persistent unexplained joint pain, with the highest risk being within a year of surgery.

• Perform joint aspiration and send for culture and synovial fluid analysis; radiographs and routine laboratory studies are seldom helpful.

• Treat with both arthrotomy and debridement and targeted long-term systemic antibiotics.

• Add rifampin to antistaphylococcal antibiotics to increase biofilm penetration.