The incidence of a periprosthetic joint infection is uncommon after total joint replacement. Since the clinical, psychological, and economic consequences of this complication are substantial, the development of management algorithms based on early diagnostic testing has been the subject of continued exploration in the orthopaedic literature. While there has been discussion of this topic in the total temporomandibular joint replacement literature and preliminary management algorithms have been established, no diagnostic testing protocols have been proposed or studied for the management of early and/or late periprosthetic joint infections. This paper will review the classification of periprosthetic joint infections, the associated risk factors, the clinical sensitivity and specificity of laboratory and imaging diagnostic studies and their utility in the management of early and late onset orthopaedic periprosthetic joint infections. This review may provide an initial framework for the use of early diagnostic testing for the management of total temporomandibular joint replacement periprosthetic joint infections and stimulate further investigation into this topic.
The Medicare 5% national sample administrative database documents a 1.63% and 1.55% risk of infection within the first 2 years following primary total hip (THA) and knee arthroplasty (TKA), with an additional risk between 2 and 10 years of 0.59% and 0.46%, respectively. Further studies have suggested that both the incidence and prevalence of periprosthetic joint infection (PJI) are increasing with time, with the overall infection burden expected to rise to >6% in coming years.
Despite these statistics revealing the incidence of PJI after total joint replacement (TJR) to be uncommon, the clinical, psychological, and economic consequences of this complication can be substantial. Therefore, the development of management algorithms based on early diagnostic testing has been the subject of continued exploration in the orthopaedic literature.
A retrospective survey of 2476 temporomandibular joint total alloplastic joint replacement (TMJ TJR) cases involving 3368 joints, reported 51 (1.51%) PJI cases occurring in that cohort over a mean of 6 months postoperatively (range 2 weeks to 12 years).
While there has been discussion of this topic in the TMJ TJR literature and preliminary management algorithms have been presented, no diagnostic testing protocols have been proposed or studied for the management of early and/or late PJIs.
This paper will review the classification of PJIs, the associated risk factors, the clinical sensitivity and specificity of laboratory and imaging diagnostic studies and their utility in the management of early and late onset orthopaedic PJIs. This review may provide an initial framework for the use and study of early diagnostic testing for the management of TMJ TJR PJI.
Periprosthetic joint infection
Definition of PJI
Both the orthopaedic community and the Centers for Disease Control and Prevention (CDC) have been frustrated by the lack of a standard definition for PJI. Interpretation of the available literature has become increasingly difficult because centres and investigators use different, and at times conflicting, definitions for PJI. Therefore, in 2011, a Musculoskeletal Infection Society (MSIS) workgroup evaluated the available literature and proposed a definition for PJI that could be adopted universally ( Table 1 ).
|1. Presence of a sinus tract communicating with the prosthesis|
|2. A pathogen isolated by culture from two or more separate tissue or fluid samples obtained from the affected prosthetic joint|
|3. Four of the following six criteria:|
|Elevation of serum erythrocyte sedimentation rate and serum C-reactive protein concentration|
|Elevated synovial white blood cell count|
|Elevated synovial polymorphonuclear percentage|
|Presence of purulence in the affected joint|
|Isolation of a microorganism in one culture of periprosthetic tissue or fluid|
|More than five neutrophils per high-power field in five high-power fields observed in a sample for histological analysis of periprosthetic tissue at ×400 magnification|
PJIs present characteristic signs that can be divided into acute manifestations (severe pain, high fever, toxaemia, heat, rubor, and surgical wound discharge) and chronic manifestations (progressive pain, skin fistulae, and drainage of purulent secretions, without fever). The clinical presentation depends on the virulence of the etiological organism, the nature of the infected tissue, the route of acquisition of the infection, and the duration of disease evolution.
Classification of PJI
The classification system most widely used today in orthopaedics is the one proposed by Fitzgerald Jr. et al. This classification defines the time at which contamination occurs, establishes the likely etiological agent involved, and the best management strategy ( Table 2 ).
|1. Acute postoperative infections occurring within 3 months of surgery
The etiological agents are generally of hospital origin, especially Staphylococcus aureus and Staphylococcus epidermidis
|2. Late deep infections that appear between 3 months and 2 years after surgery
The etiological agents are considered to be of nosocomial origin, since the contamination probably occurred during prosthesis implantation, and generally consist of bacteria from the normal skin flora, such as S. epidermidis
|3. Late haematological infections that occur more than 2 years after surgery
The etiological agents are of community origin and are determined by the apparent source of bacteria: anaerobic bacteria, while cellulitis and skin abscesses are associated with S. aureus or streptococci or enterobacteria originating from the gastrointestinal and genitourinary tracts. Dental infections are associated with bacteremia due to viridans streptococci
Early and delayed infections are thought to be due to organisms introduced at the time of surgery, whereas late infections are more likely to have a hematogenous aetiology. Infecting organisms form microcolonies on the prosthesis surface, and these elaborate exopolysaccharides that coalesce, forming a biofilm. Once formed, organisms within the biofilm are protected from host immune responses and may display reduced susceptibility to antibiotics as a result of changes in metabolic processes and poor diffusion.
Patient, surgical, and postoperative related risk factors in orthopaedic PJI have been spelled out and must be considered ( Table 3 ).
|A. Patient-related risk factors for infection include:|
|1. Previous revision arthroplasty or previous infection associated with a prosthetic joint at the same site|
|2. Tobacco abuse|
|4. Rheumatoid arthritis|
|5. Concurrent neoplasm|
|6. Immunosuppression and diabetes mellitus|
|B. Surgical-related risk factors include:|
|1. Simultaneous bilateral arthroplasty|
|2. Operative time longer than 160 min|
|3. Allogeneic blood transfusion|
|C. Postoperative-related risk factors include:|
|1. Wound healing complications (e.g., superficial infection, haematoma, delayed healing, wound necrosis, and dehiscence)|
|2. Atrial fibrillation, myocardial infarction, urinary tract infection|
|3. Prolonged hospital stay|
|4. Staphylococcus aureus bacteremia|
To date there is no diagnostic test with absolute accuracy, and due to this lack of a ‘gold standard’ for the diagnosis of PJI, diverse and sometimes conflicting criteria have been proposed ( Table 4 ).
|ESR||30 mm/h||0.86||0.82||Does not always increase in chronic deep infections|
|CRP||>10 mg/l||0.76||1.0 with ↑ ESR||Repeat during treatment to follow trends|
|Synovial CRP||>10 mg/l||0.70–0.84||0.97–1.0||Viscosity of fluid limits usefulness|
|Synovial fluid WBC||1.1–4.0 × 10 9 cells/l, 64–69% PMNs||0.84–1.0||0.88–0.98||Discontinue antibiotics 2 weeks before aspiration|
|LERS||Purple colour||0.93–1.0||0.84–1.0||Real-time results, simple, inexpensive|
|Histology||1–10 neutrophils/HPF||0.67–0.80||Antibiotics may skew results|
|Synovial fluid culture||0.56–0.75||0.95–1.00||Aspiration must be done under sterile conditions. Superior to tissue culture|
|Gram stain||Low||High (organism)||Not sensitive in diagnosing PJI|
|Sonicate culture||0.785||0.98||No different than synovial fluid culture|
|Molecular (16S PCR)||High||High||Does not supply antibiotic sensitivity results|
|Wound cultures||High||High||Aspiration better than swab|
|Plain imaging||Low||Low||No differentiation of infection and loosening|
|Ultrasound||Low||Low||Confirms effusion and facilitates aspiration|
|MRI||Low||Low||Non-specific, defines soft tissue|
|Technetium-99 m||Low||Low||Non-specific positive for 1 year after TJR|
|Technetium, gallium, or indium||High||High||Considered the imaging test of choice when imaging is required|
|FDG-PET||Moderate||Moderate||Results of individual studies heterogeneous|
The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level provide excellent diagnostic information for establishing the presence or absence of infection before surgical intervention in patients with pain at the site of a TJR.
ESR values higher than 30 mm/h have been associated with deep infection. However, the ESR is not always elevated in a chronic deep infection. When the ESR is used alone, its specificity and sensitivity reach 0.82 and 0.86, respectively.
The CRP level usually peaks on postoperative day 2 after TJR and then falls back to normal levels in 2–3 weeks. CRP is usually normal in cases of aseptic loosening, but is elevated by more than 10 mg/l in cases of infection.
When used in conjunction with ESR, the CRP level has a specificity of 1.00 for diagnosing PJI. Repeated measurements of the CRP level showing a rising or falling trend are more useful for deciding on management and planning follow-up.
The main imaging method used in diagnosing joint prosthesis infections is plain film X-ray. In orthopaedics, the signs that suggest infection are a radiolucency at the cement–bone interface (in the case of cemented prostheses), or at the metal–bone interface (in uncemented prostheses), with associated osteolysis.
Since it is difficult to distinguish between septic and aseptic osteolysis (relating to mechanical loosening/granulomatous disease) based on a single radiograph, previous radiographs are needed for comparison. In cases of aseptic loosening, there are slow, progressive, and evolving signs of osteolysis. In cases of infectious loosening, this loosening occurs rapidly, in a more aggressive manner, and with greater bone destruction. However, plain imaging should be performed in all patients with suspected PJI despite its low sensitivity and specificity, because it can rule out intrinsic conditions that could cause chronic pain ( Table 5 ).
|Intrinsic causes of TMJ TJR problems|
|Heterotopic bone formation|
|Aseptic component or screw loosening|
|Synovial entrapment syndrome|
|Component or screw fracture|
Computed tomography (CT) may assist in distinguishing between septic and aseptic loosening. The presence of a periosteal reaction or an accumulation of fluid and/or soft tissue adjacent to an area of osteolysis is highly suggestive of infection.
Ultrasound has been reported useful to confirm effusion and to facilitate aseptic aspiration. Implants that are not ferromagnetic (i.e., titanium) are associated with minimal CT or magnetic resonance imaging (MRI) artefacts. CT and MRI may be useful in the evaluation of complex cases. MRI scans provide good resolution for detecting soft tissue abnormalities. However, ultrasound, CT, and MRI abnormalities found may be non-specific.
Three-phase bone scintigraphy using technetium has high sensitivity, but low specificity. Areas of high uptake may represent normal bone growth around the prosthesis, or aseptic or septic loosening. Bone scintigraphy has a high negative predictive value; i.e., loosening (septic or aseptic) is practically ruled out if the scintigraphy result is normal. The use of gallium increases the diagnostic accuracy by 70%.
Positron emission tomography using fluorodeoxyglucose (FDG-PET) presents very divergent results in the literature, with accuracies of 43% to 92%, and for this reason, it is not considered to be a reliable method for prosthesis evaluation.
Anti-granulocyte scintigraphy (LeukoScan) with monoclonal antibodies or antibody fragments may provide another attractive approach to detect a PJI. A recent meta-analysis of the diagnostic value of anti-granulocyte scintigraphy included 13 studies with a total sample size of 522 prostheses and reported estimates of sensitivity and specificity of 83% and 80%, respectively. However, this method has low availability in clinical practice.
Synovial metaplasia, the theorized result of traction or motion providing the biological signal that stimulates differentiation and organization of individual cells into synovial tissue, has been reported around breast implants, orthopaedic, and TMJ TJR devices. Westermark also describes the formation of a pseudo-capsule around the TMJ TJR articulation.
Arthrocentesis should be considered in patients with suspected PJI when the diagnosis is not evident, there is clinical stability, and open surgery is not mandatory. Patients with a chronic painful prosthesis and elevated CRP or ESR should undergo diagnostic arthrocentesis. Analysis of the aspirated synovial fluid should include total cell count and differential leucocyte count, as well as culture for aerobic and anaerobic organisms.
When there is a fistula communicating with the prosthesis or when purulence is present within the joint, a definitive diagnosis of PJI is made when the microorganism is isolated through cultures of material obtained from the joint, fluid arthrocentesis, surgical wound secretions, or surgical debridement. During surgical debridement, multiple specimens should be sent for aerobic and anaerobic cultures.
The quality of microbiological results depends on the first step–obtaining a quality sample. Specimens for culture should be obtained prior to initiation of antibiotic therapy. Antimicrobial therapy should be discontinued at least 2 weeks before open surgery. Perioperative antimicrobial coverage should be deferred until culture specimens have been collected.
It is essential to avoid contamination with normal commensal organisms of the skin. Gram stain tests have shown low sensitivity, but high organism specificity. Synovial fluid culture has a sensitivity of 56–75% and a specificity of 95–100%. For optimal sensitivity and specificity, it should be performed by means of inoculation into a blood culture bottle. Prolonged bacterial culture incubation (e.g., 2 weeks) may be useful for the diagnosis of late-onset PJI in some circumstances.
Fistula cultures have limited value. The sample must be taken by needle aspiration and should never be taken from the specimen swab. Removed implants should be sent for culture.
Organisms associated with a PJI are often found attached to the prosthesis where they may form biofilms. This suggests that obtaining a sample from the prosthesis might improve the diagnosis of PJI. Sonication of a removed implant can increase the culture yield by disrupting adherent bacterial biofilm, an effect that is most notable in samples from patients who have recently received antibiotics. Therefore, this procedure is more sensitive than cultures of periprosthetic tissue even when antibiotics are used within 14 days before surgery.
The sensitivity of sonicate fluid culture (78.5%) has been found to be superior to that of tissue culture (60.8%; P < 0.001), but not significantly different from that of synovial fluid culture (56.3%; P = 0.058). The specificities of sonicate fluid culture, tissue culture, and synovial fluid culture are reported to be 98.8%, 99.2%, and 98.1%, respectively.
Intraoperative frozen sections of periprosthetic tissues provide excellent accuracy in predicting a diagnosis of PJI, but only moderate accuracy in ruling out the diagnosis. Different studies vary in their definition of acute inflammation in the periprosthetic tissue, from an average of 1 to 10 neutrophils per high-power field at a magnification of ×400 (sensitivity 67–80%). There is insufficient information to distinguish 5 from 10 neutrophils per high-power field as the best threshold needed for diagnosis. In addition, there is insufficient information to determine the diagnostic efficacy of frozen sections in patients with an underlying inflammatory arthropathy, as the degree of swelling can vary in the same patient from one area to another. Furthermore, previous treatment with antibiotics may modify the nature of the inflammatory response, leading to the presence of more chronic inflammatory cells (i.e., plasma cells) and fewer neutrophils.
Leucocyte esterase reagent strips
The leucocyte esterase reagent strip (LERS) test is a simple colorimetric strip test that detects the presence of leucocyte esterase in synovial fluid and constitutes a valuable instrument for the diagnosis of PJI. Among other benefits, the LERS provides real-time results, is simple, inexpensive, and can be used either to rule out or to confirm a PJI.
In a study carried out by Parvizi et al. on the basis of clinical, serological, and operative criteria, the leucocyte esterase level correlated strongly with the percentage of polymorphonuclear leucocytes (PMNs) ( r = 0.7769) and total white blood cell count (WBC) ( r = 0.5024) in the aspirate, as well as with the ESR ( r = 0.6188) and the CRP level ( r = 0.4719) in the serum. However, the utility of the strips can be limited by blood or debris in the synovial fluid, rendering them unreadable in nearly one-third of cases.
The use of molecular methods to diagnose PJI has been the subject of several studies. The use of polymerase chain reaction (PCR) hybridization has been studied on implants subject to sonication for the diagnosis of PJI, showing an increase in final diagnosis, but false-positive results must be considered. When 16S rRNA is used in intraoperative periprosthetic samples, the presence of the same microorganism in two of five samples results in sensitivity of 94% and specificity of 100%, and the presence of only one positive sample results in specificity of 96.3% and positive predictive value of 91.7%.
Real-time PCR has shown good correlation with the severity of infection. However, more studies must be carried out and molecular techniques should not substitute conventional diagnostic methods. The use of molecular diagnostics has applicability when conventional techniques for microbiological diagnosis remain negative in the presence of fastidious microorganisms, infections due to Mycobacterium sp., and infections acquired during the use of antibiotics.