The presentation can be early, delayed, or late as outlined previously. Virulent pathogens typically cause early infections, most of which are acquired around the time of surgery and usually present acutely with swelling, erythema, induration at the incision site, and wound drainage. Delayed infections may also be acquired around the time of surgery, but low virulent organisms typically cause them. Late infections, however, are mostly hematogenous and often without fever, draining wounds, or local signs of infection. Overall, symptoms are very non-specific, and most patients present with joint swelling or persistent pain that worsens progressively. Other common clinical presentations include wound dehiscence, purulence around the prosthesis, sinus tract communicating with the joint cavity, joint instability, and ambulation difficulties.

The accurate diagnosis of prosthetic joint infection often involves the combination of multiple factors including symptoms, signs, synovial fluid cell count, serum inflammatory markers, and culture.[6][15][16]

The threshold for diagnosing a prosthetic joint infection using some of these parameters is much lower compared to the septic arthritis of a native joint. For example, unlike septic arthritis, when synovial fluid cell counts are typically tens of thousands, a synovial fluid white blood cell count (WBC) of more than 4200 cells/microliter supports hip prosthetic joint infection, while a WBC count of more than 1700 cells/microliter supports knee prosthetic joint infection. Neutrophil predominance is typically a common feature.

Culture is an important tool for the diagnosis of prosthetic joint infection. Aspirated joint fluid culture should be sent in multiple sets of culture media. Also, obtaining multiple intraoperative culture samples is encouraged. This is especially important for the recovery and accurate diagnosis of prosthetic joint infection caused by low virulence organisms because having just one positive culture is not enough to make a diagnosis. The sensitivity of synovial fluid culture is only 85%, so a negative culture does not rule out infection. However, the specificity of synovial fluid culture is approximately 95%, and positive cultures often imply the presence of prosthetic joint infection.

Imaging may have some role in diagnosis, but it is mostly complimentary.

Plain Radiographs are the most important study. Even though overall sensitivity and specificity are low, plain imaging may provide useful clues about joint effusion, joint alignment, bone-cement or metal bone interface lucencies, periosteal reactions, and patchy osteolysis.[17] In addition, it might show bone resorption surrounding the implant or transcortical sinus tracts [18][19].[18]

Physicians seldom order CT and MRI scans, but when requested, the scans may show bony erosion, abscess, sinus tract, or loosening of the prosthesis.

Technetium bone scans there are variable modalities that are indicated when an infection is suspected clinically but can not be confirmed by arthrocentesis or lab analysis. Although it has low specificity of 30-40 %, it is highly sensitive to up to 99%. The modalities available are Tc-99m (technetium) which can reveal inflammation and In-111 (indium) that reveal leukocyte. In addition, a triple scan can differentiate infection from fracture or bone remodeling.

Positron Emission Tomography (PET): FDG-PET scan (using fluorinated glucose to detect areas of high metabolic activity). This is a highly sensitive and specific modality [20].

The updated version of the Musculoskeletal Infection Society (MSIS) 2018 criteria for prosthetic joint infections are evidence-based and validated criteria [21]: 

Diagnosis can be made if one major criterion is present. Either a sinus tract or two positive cultures with phenotypically identical organisms. 

With regards to minor criteria, a combined score of 6 or more is diagnostic of infection. Whilst a score between 2 and 5 requires additional intraoperative findings to confirm the diagnosis. The following is a list of the minor criteria and intraoperative findings along with their allocated points for the scoring system.

Minor criteria (preoperative diagnosis):

 Serum

• Elevated CRP (>10mg/L) or D-dimer (>860ng/mL) ... 2 points
• Elevated ESR (>30mm/h) ... 1 point

 Synovial

• Elevated synovial WBC (>3,000 cells/µl) or LE ... 3 points
• Positive alpha-defensin ... 3 points
• Elevated synovial PMN (>80%) ... 2 points
• Elevated synovial CRP (>6.9mg/L) ... 1 point

Intraoperative findings suggestive of infection:

• Positive histology ... 3 points
• Purulence in affected joint ... 3 points
• Single positive culture ... 2 points

Cobmined with the preoperative score a combined score of 6 or more was considered infected, whilst a score between 4 and 5 was inconclusive, and a score of 3 or less was not infected [21].

Management of prosthetic joint infection necessitates a multidisciplinary team approach [22]. Treatment often includes a combination of medical (longterm antibiotics) and multiple surgeries.

Treatment principles include:

• Cure (eradication of infection, return of joint function, and alleviation of symptoms)
• Palliative approach (may include suppressive antibiotics, joint fusion, and symptom control).

Antibiotic therapy is often necessary but should be delayed until after culture materials (at least joint aspiration culture) are obtained. The exception is in the rare situation of sepsis or overwhelming infection. Empirical antibiotic therapy should be tailored according to the timing of infection. As a general guide, the antibiotic choice should at least provide adequate coverage against Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus (MRSA)), coagulase-negative staphylococcus, and aerobic gram-negative bacilli. Antibiotics with excellent activity against biofilms such as Rifampin and fluoroquinolones are often included in treatment. Other possible oral antibiotic choices for prosthetic joint infection include minocycline, linezolid, and trimethoprim-sulfamethoxazole.[23][24][25]

Surgical options can be further categorized into five options as follow:

Debridement and retention: As the name implies, the implant is left in place, but the joint cavity is debrided with or without removal of the synovial polyethylene lining. This is typically the surgical approach for early prosthetic joint infection provided the implant is stable, symptom duration is less than 3 weeks, there are no sinus tracts, and the isolated pathogen is susceptible to active biofilm antibiotics. The other indication would be an acute hematogenous infection with symptoms duration of fewer than 72 hours. Prolonged antibiotics for 3 to 6 months are often necessary (three months for retained hip and 6 months for retained knee joint).

One-stage exchange: This is the surgical approach commonly employed in Europe but not the standard of care in the United States. It involves the removal of the infected prosthesis and simultaneously replaced with a new one. This is indicated when the patient is not immunocompromised with minimal medical comorbidities and soft tissues are healthy. there should be no prolonged use of antibiotics and no bone grafts implanted. The organism has to be of low virulence with known antibiotic sensitivity preoperatively. It is often accompanied by two weeks of intravenous antibiotics followed by 3 to 6 months of oral antibiotics. This approach has the advantage of being of lower cost, shortened hospital stay, and patient's immobilization. But, this is at the expense of carrying a high risk of residual infection.

Two-stage exchange: This is the standard of care in the United States and offers the best chance of cure especially for delayed and late prosthetic joint infections. In its simplified version, it involves complete removal of the infected prosthesis, placement of a joint spacer (which could be antibiotic-impregnated), antibiotic therapy for two to eight weeks, and subsequent placement of a new prosthesis. Patients have to be fit enough to afford multiple procedures and have adequate bone stock. The decision on reimplantation requires confirmation by clinical examination, normal lab analysis, and negative cultures 2 weeks after the completed antibiotic course.

Resection Arthroplasty (Implant removal without replacement): This is a reasonable approach for elderly, non ambulatory patients with high operative risks or when there is no functional benefit expected by prosthesis exchange. Other indications would be inadequate bone stock and poor soft tissues, recurrent infections,  multiple previous failed revision surgeries. Arthrodesis often accompanies it.

Above Knee Amputation: Indicated when prosthetic knee joint infection is resistant to all conservative and surgical options and patients continue to experience severe persistent pain. Also, indicated in severe bone and soft tissue loss and vascular compromise.

Chronic Suppressive antibiotic therapy: This is often employed when surgery is not an option, for example, bedridden debilitated patients or those with multiple severe co-morbidities.

• Aseptic loosening of the prosthesis

• Aseptic lymphocyte-dominant vasculitis-associated lesion

• Bone and joint infections due to tuberculosis

• Crystal deposition disease

• Osteoarthritis

A missed prosthetic joint infection or one that is not treated appropriately can result in persistence of infection with deletarious consequences including disability and impaired quality of life.

Two novel methods recently added to the diagnostic armamentarium of prosthetic joint infection include:

• Sonification: This employs the use of sound energy to agitate particles in a tissue sample with the goal of increasing the yield of culture from the explanted prosthetic material.
• Synovial fluid Alpha Defensin and leukocyte esterase: These are two markers that can be easily assessed from synovial fluid, and both correlate with the presence of prosthetic joint infection.

The management of a prosthetic joint infection is best done with an interprofessional team consisting of an orthopedic surgeon, infectious disease expert, rehabilitation specialist, nurse and pharmacist. These patients are often left bedridden for long periods, and hence a physical therapy consult is recommended for joint movement and muscle training. A dietary consult may help prevent muscle wasting, and the nurse should ensure that the patient has prophylaxis against deep vein thrombosis and pressure ulcers. The pharmacist should check up on cultures and make sure that the patient is on the right antibiotics. After discharge, most patients need active physical therapy for months to regain joint motion and muscle strength.[26][27][28] (Level V)

Outcomes

There are no large randomized clinical trials on prosthetic joint infections and outcomes are based on small retrospective case series and case reports. The success of the different procedures varies from 0-100%, depending on the severity of the infection, time of treatment, patient co-morbidity and duration of infection. The difficulty in dealing with prosthetic joint infections is whether to remove all the hardware but this also leaves the patient with a disability. Use of spacers has been useful, but it is not the answer to all type of prosthetic joint infections. Overall, good results have been obtained with delayed exchange arthroplasty with success rates ranging from 40-80%. Unfortunately, the majority of patients do have some degree of pain, joint instability and limited use of the joint after an infection.[29][24][30] (Level 5)