Int. J. Oral Maxillofac. Surg. 2014; 43: 1236–1242 http://dx.doi.org/10.1016/j.ijom.2014.05.014, available online at http://www.sciencedirect.com
Review Paper TMJ Disorders
Temporomandibular joint replacement periprosthetic joint infections: a review of early diagnostic testing options
L. G. Mercuri* Institute of Biomaterials, Tribocorrosion and Nanomedicine, Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, USA
L.G. Mercuri: Temporomandibular joint replacement periprosthetic joint infections: a review of early diagnostic testing options. Int. J. Oral Maxillofac. Surg. 2014; 43: 1236–1242. # 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Abstract. 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.1,2 Further studies have suggested that both the incidence and prevalence of periprosthetic joint infection (PJI) are increasing 0901-5027/01001236 + 07
with time, with the overall infection burden expected to rise to >6% in coming years.3 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
Key words: temporomandibular joint replacement; periprosthetic joint infections. Accepted for publication 19 May 2014 Available online 19 July 2014
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).4
# 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
TMJ PJI: review of early diagnostic testing While there has been discussion of this topic in the TMJ TJR literature and preliminary management algorithms have been presented,4–6 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).7
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.8 Classification of PJI
The classification system most widely used today in orthopaedics is the one proposed by Fitzgerald Jr. et al.9 This classification defines the time at which contamination occurs, establishes the likely etiological agent involved, and the best management strategy (Table 2). 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.10
Table 1. Musculoskeletal Infection Society (MSIS) workgroup definition for periprosthetic joint infection. 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
Table 2. Classification of orthopaedic periprosthetic joint infections. 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
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Risk factors
Patient, surgical, and postoperative related risk factors in orthopaedic PJI have been spelled out and must be considered11–19 (Table 3). Diagnostic testing
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). Serology
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.7 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.20 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.21 When used in conjunction with ESR, the CRP level has a specificity of 1.00 for diagnosing PJI.7,21 Repeated measurements Table 3. Patient, surgical, and postoperative related risk factors in orthopaedic periprosthetic joint infections. 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 3. Obesity 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
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Table 4. Laboratory and imaging studies available to assist in determining the diagnosis of a periprosthetic joint infection. Test
Positive value
Sensitivity
Specificity
Comments
ESR
30 mm/h
0.86
0.82
CRP Synovial CRP Synovial fluid WBC
>10 mg/l >10 mg/l 1.1–4.0 109 cells/l, 64–69% PMNs Purple colour 1–10 neutrophils/HPF
0.76 0.70–0.84 0.84–1.0
1.0 with " ESR 0.97–1.0 0.88–0.98
Does not always increase in chronic deep infections Repeat during treatment to follow trends Viscosity of fluid limits usefulness Discontinue antibiotics 2 weeks before aspiration
0.93–1.0 0.67–0.80
0.84–1.0
Real-time results, simple, inexpensive Antibiotics may skew results
Synovial fluid culture
0.56–0.75
0.95–1.00
Gram stain
Low
Sonicate culture Molecular (16S PCR) Wound cultures Plain imaging Ultrasound CT MRI Technetium-99 m Gallium-67 Indium-111 Technetium, gallium, or indium FDG-PET LeukoScan
0.785 High High Low Low Low Low Low Moderate Moderate High
High (organism) 0.98 High High Low Low Low Low Low Moderate Moderate High
Aspiration must be done under sterile conditions. Superior to tissue culture Not sensitive in diagnosing PJI
Moderate 0.83
Moderate 0.80
LERS Histology
No different than synovial fluid culture Does not supply antibiotic sensitivity results Aspiration better than swab No differentiation of infection and loosening Confirms effusion and facilitates aspiration Non-specific Non-specific, defines soft tissue Non-specific positive for 1 year after TJR Alone Alone Considered the imaging test of choice when imaging is required Results of individual studies heterogeneous Anti-granulocyte scintigraphy
ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; WBC, white blood cell count; PMNs, polymorphonuclear leucocytes; LERS, leucocyte esterase reagent strip; HPF, high-power field; 16S PCR, 16S ribosomal RNA (rRNA) gene polymerase chain reaction (PCR); CT, computed tomography; MRI, magnetic resonance imaging; TJR, total joint replacement; FDG-PET, 18F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET).
of the CRP level showing a rising or falling trend are more useful for deciding on management and planning follow-up.
Imaging
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.22,23 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.23 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.24 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 pain25,26 (Table 5). 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.27 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 Table 5. Intrinsic causes of TMJ TJR increasing pain and swelling, and decreasing mandibular function. Intrinsic causes of TMJ TJR problems Infection Heterotopic bone formation Aseptic component or screw loosening Dislocation Neuroma formation Material sensitivity Synovial entrapment syndrome Component or screw fracture Osteolysis TMJ TJR, temporomandibular joint total joint replacement.
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.28 Nuclear medicine
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%.12 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.29,30 Anti-granulocyte scintigraphy (LeukoScan) with monoclonal antibodies or antibody fragments may provide another attractive approach to detect a PJI. A
TMJ PJI: review of early diagnostic testing 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.31 Synovial fluid
Synovial metaplasia, the theorized result of traction or motion providing the biological signal that stimulates differentiation and organization of individual cells into synovial tissue,32 has been reported around breast implants,33 orthopaedic,34 and TMJ TJR devices.35,36 Westermark also describes the formation of a pseudo-capsule around the TMJ TJR articulation.35 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.28 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.28 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.37–39 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.39 Sonication
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.40 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.40 Histopathology
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%).41 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.42,43 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
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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.44 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.45 Molecular diagnostics
The use of molecular methods to diagnose PJI has been the subject of several studies.46–50 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.46 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%.47 Real-time PCR has shown good correlation with the severity of infection.48 However, more studies must be carried out and molecular techniques should not substitute conventional diagnostic methods.49 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.50 TMJ TJR PJI diagnosis and management algorithm
Based on a review of the orthopaedic PJI literature and the American Academy of Orthopedic Surgeons’ (AAOS) clinical practice guideline for the diagnosis of PJIs51 (Table 6), practical diagnostic and management algorithms were developed for early and delayed TMJ TJR PJIs (Table 7). Early TMJ TJR PJI
As with any diagnosis, the clinical history and physical examination are important. A
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Table 6. AAOS clinical practice guideline for the diagnosis of periprosthetic joint infection. 1. Recommends against initiating antibiotic treatment in patients with suspected PJI until after cultures from the joint have been obtained (Grade of Recommendation: Strong) 2. Recommends risk stratification of the patients (Grade of Recommendation: Consensus) 3. Recommends that for patients in whom diagnosis of PJI cannot be reached, performing other tests, such as nuclear imaging (labelled-leucocyte imaging combined with bone or bone marrow imaging, 18F-fluorodeoxyglucose positron emission tomography (PET) imaging, gallium imaging, or labelled-leucocyte imaging) is an option. Bone scan alone without labelling of the white cells has no role in the diagnosis of PJI (Grade of Recommendation: Weak) 4. Recommends ordering serology (ESR and CRP level) for workup of patients with suspected PJI. There is no evidence supporting the role of white blood cell count and/or white blood cell differential in the diagnosis of PJI (Grade of Recommendation: Strong) 5. Recommends that for patients with abnormal serology (defined as ESR >30 mm/h and CRP level >1 mg/dl) aspiration of the joint be performed (Grade of Recommendation: Strong) 6. Recommends that joint aspirate fluid be sent for microbiological culture, synovial fluid white blood cell count, and differential (Grade of Recommendation: Strong) 7. Recommends against the use of intraoperative Gram stain to rule out periprosthetic joint infection (Grade of Recommendation: Strong) 8. Recommends that patients be off antibiotics for 2 weeks before obtaining intra-articular culture (Grade of Recommendation: Consensus) AAOS, American Academy of Orthopedic Surgeons; PJI, periprosthetic joint infection; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein.
Table 7. Early and late periprosthetic joint infection diagnostic testing and management algorithm. History Clinical Serology Synovial fluid WBC Synovial fluid culture Imaging (plain, CT) Nuclear medicine Management
Early PJI
Late PJI
Days to 3 weeks to years
+
+
Stable components
Unstable component(s)
+
+
Incision and drainage, debridement, antibiotics*
Two-stage removal/replacementy
Pain, swelling, fistula ESR and CRP +
PJI, periprosthetic joint infection; ESR, erythrocyte sedimentation rate (>30 mm/h); CRP, Creactive protein (>10 mg/l); WBC, white blood cell count; CT, computed tomography. * Wolford et al.5 y Mercuri.6
suspected PJI occurring within days or 3 weeks or longer after TMJ TJR with complaints of increasing pain and diffuse swelling with no evidence of localized erythema, no fever, and no drainage, present a difficult
diagnostic dilemma unless there is clinical evidence of a draining skin or auditory canal fistula directly communicating with the device. This sign is pathognomonic of a TMJ TJR PJI and requires delayed TMJ TJR PJI management (Table 7).6 Intrinsic causes for these signs and symptoms should be ruled out (Table 5) by imaging (plain film or CT). Since ESR and CRP can be equivocal in late PJI, their value as diagnostic tests is diminished in a suspected delayed TMJ TJR PJI. Sterile aspiration of the TMJ TJR articulation to obtain fluid for WBC analysis (>1.1–4.0 109 cells/l; 64–68% PMNs) and culture is indicated. Labelled-leucocyte imaging (e.g., leucocytes labelled with indium-111) combined with bone marrow imaging with the use of technetium-99m-labelled sulfur colloid is more accurate than technetium-99 alone, combined bone and gallium-67 imaging, or labelled-leucocyte and bone imaging, when compared head to head, and it is considered the imaging test of choice when imaging is utilized.52 Because there is no single PJI diagnostic test that offers perfect sensitivity and specificity, this field continues to evolve. New assays will become available in the future that will be incorporated into any diagnostic algorithm as they are developed and subjected to clinical testing. 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. Funding
None. Competing interests
None declared. Ethical approval
Not required. Patient consent
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sonication improves diagnosis of implant related infection. Acta Orthop 2012;83: 299–304. 47. Marı´n M, Garcia-Lechuz JM, Alonso P, Villanueva M, Alcala´ L, Gimeno M, et al. Role of universal 16S rRNA gene PCR and sequencing in diagnosis of prosthetic joint infection. J Clin Microbiol 2012;50:583–9. 48. Miyamae Y, Inaba W, Kobayashi N, Choe H, Yukizawa Y, Ike H, et al. Different diagnostic properties of C-reactive protein, real-time PCR, and histopathology of frozen and permanent sections in diagnosis of periprosthetic joint infection. Acta Orthop 2013;84:524–9.
49. Ribeiro M, Monteiro FJ, Ferraz MP. Infection of orthopedic implants with emphasis on bacterial adhesion process and techniques used in studying bacterial–material interactions. Biomatter 2012;2:176–94. 50. Reumann MK, Weiser MC, Mayer-Kuckuk P. Musculoskeletal molecular imaging: a comprehensive overview. Trends Biotechnol 2010;28:93–101. 51. Parvizi J, Della Valle CJ. AAOS clinical practice guideline: diagnosis and treatment of periprosthetic joint infections of the hip and knee. J Am Acad Orthop Surg 2010;18: 771–4.
52. Love C, Marwin SE, Palestro CJ. Nuclear medicine and the infected joint replacement. Semin Nucl Med 2009;39:66–70.
Address: Louis G. Mercuri 604 Bonnie Brae Place River Forest IL 60305 USA Tel.: +1 708 771 2770 E-mail: [email protected]
Review Paper TMJ Disorders
Temporomandibular joint replacement periprosthetic joint infections: a review of early diagnostic testing options
L. G. Mercuri* Institute of Biomaterials, Tribocorrosion and Nanomedicine, Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, USA
L.G. Mercuri: Temporomandibular joint replacement periprosthetic joint infections: a review of early diagnostic testing options. Int. J. Oral Maxillofac. Surg. 2014; 43: 1236–1242. # 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Abstract. 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.1,2 Further studies have suggested that both the incidence and prevalence of periprosthetic joint infection (PJI) are increasing 0901-5027/01001236 + 07
with time, with the overall infection burden expected to rise to >6% in coming years.3 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
Key words: temporomandibular joint replacement; periprosthetic joint infections. Accepted for publication 19 May 2014 Available online 19 July 2014
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).4
# 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
TMJ PJI: review of early diagnostic testing While there has been discussion of this topic in the TMJ TJR literature and preliminary management algorithms have been presented,4–6 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).7
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.8 Classification of PJI
The classification system most widely used today in orthopaedics is the one proposed by Fitzgerald Jr. et al.9 This classification defines the time at which contamination occurs, establishes the likely etiological agent involved, and the best management strategy (Table 2). 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.10
Table 1. Musculoskeletal Infection Society (MSIS) workgroup definition for periprosthetic joint infection. 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
Table 2. Classification of orthopaedic periprosthetic joint infections. 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
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Risk factors
Patient, surgical, and postoperative related risk factors in orthopaedic PJI have been spelled out and must be considered11–19 (Table 3). Diagnostic testing
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). Serology
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.7 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.20 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.21 When used in conjunction with ESR, the CRP level has a specificity of 1.00 for diagnosing PJI.7,21 Repeated measurements Table 3. Patient, surgical, and postoperative related risk factors in orthopaedic periprosthetic joint infections. 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 3. Obesity 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
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Table 4. Laboratory and imaging studies available to assist in determining the diagnosis of a periprosthetic joint infection. Test
Positive value
Sensitivity
Specificity
Comments
ESR
30 mm/h
0.86
0.82
CRP Synovial CRP Synovial fluid WBC
>10 mg/l >10 mg/l 1.1–4.0 109 cells/l, 64–69% PMNs Purple colour 1–10 neutrophils/HPF
0.76 0.70–0.84 0.84–1.0
1.0 with " ESR 0.97–1.0 0.88–0.98
Does not always increase in chronic deep infections Repeat during treatment to follow trends Viscosity of fluid limits usefulness Discontinue antibiotics 2 weeks before aspiration
0.93–1.0 0.67–0.80
0.84–1.0
Real-time results, simple, inexpensive Antibiotics may skew results
Synovial fluid culture
0.56–0.75
0.95–1.00
Gram stain
Low
Sonicate culture Molecular (16S PCR) Wound cultures Plain imaging Ultrasound CT MRI Technetium-99 m Gallium-67 Indium-111 Technetium, gallium, or indium FDG-PET LeukoScan
0.785 High High Low Low Low Low Low Moderate Moderate High
High (organism) 0.98 High High Low Low Low Low Low Moderate Moderate High
Aspiration must be done under sterile conditions. Superior to tissue culture Not sensitive in diagnosing PJI
Moderate 0.83
Moderate 0.80
LERS Histology
No different than synovial fluid culture Does not supply antibiotic sensitivity results Aspiration better than swab No differentiation of infection and loosening Confirms effusion and facilitates aspiration Non-specific Non-specific, defines soft tissue Non-specific positive for 1 year after TJR Alone Alone Considered the imaging test of choice when imaging is required Results of individual studies heterogeneous Anti-granulocyte scintigraphy
ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; WBC, white blood cell count; PMNs, polymorphonuclear leucocytes; LERS, leucocyte esterase reagent strip; HPF, high-power field; 16S PCR, 16S ribosomal RNA (rRNA) gene polymerase chain reaction (PCR); CT, computed tomography; MRI, magnetic resonance imaging; TJR, total joint replacement; FDG-PET, 18F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET).
of the CRP level showing a rising or falling trend are more useful for deciding on management and planning follow-up.
Imaging
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.22,23 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.23 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.24 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 pain25,26 (Table 5). 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.27 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 Table 5. Intrinsic causes of TMJ TJR increasing pain and swelling, and decreasing mandibular function. Intrinsic causes of TMJ TJR problems Infection Heterotopic bone formation Aseptic component or screw loosening Dislocation Neuroma formation Material sensitivity Synovial entrapment syndrome Component or screw fracture Osteolysis TMJ TJR, temporomandibular joint total joint replacement.
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.28 Nuclear medicine
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%.12 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.29,30 Anti-granulocyte scintigraphy (LeukoScan) with monoclonal antibodies or antibody fragments may provide another attractive approach to detect a PJI. A
TMJ PJI: review of early diagnostic testing 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.31 Synovial fluid
Synovial metaplasia, the theorized result of traction or motion providing the biological signal that stimulates differentiation and organization of individual cells into synovial tissue,32 has been reported around breast implants,33 orthopaedic,34 and TMJ TJR devices.35,36 Westermark also describes the formation of a pseudo-capsule around the TMJ TJR articulation.35 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.28 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.28 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.37–39 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.39 Sonication
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.40 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.40 Histopathology
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%).41 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.42,43 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
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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.44 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.45 Molecular diagnostics
The use of molecular methods to diagnose PJI has been the subject of several studies.46–50 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.46 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%.47 Real-time PCR has shown good correlation with the severity of infection.48 However, more studies must be carried out and molecular techniques should not substitute conventional diagnostic methods.49 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.50 TMJ TJR PJI diagnosis and management algorithm
Based on a review of the orthopaedic PJI literature and the American Academy of Orthopedic Surgeons’ (AAOS) clinical practice guideline for the diagnosis of PJIs51 (Table 6), practical diagnostic and management algorithms were developed for early and delayed TMJ TJR PJIs (Table 7). Early TMJ TJR PJI
As with any diagnosis, the clinical history and physical examination are important. A
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Table 6. AAOS clinical practice guideline for the diagnosis of periprosthetic joint infection. 1. Recommends against initiating antibiotic treatment in patients with suspected PJI until after cultures from the joint have been obtained (Grade of Recommendation: Strong) 2. Recommends risk stratification of the patients (Grade of Recommendation: Consensus) 3. Recommends that for patients in whom diagnosis of PJI cannot be reached, performing other tests, such as nuclear imaging (labelled-leucocyte imaging combined with bone or bone marrow imaging, 18F-fluorodeoxyglucose positron emission tomography (PET) imaging, gallium imaging, or labelled-leucocyte imaging) is an option. Bone scan alone without labelling of the white cells has no role in the diagnosis of PJI (Grade of Recommendation: Weak) 4. Recommends ordering serology (ESR and CRP level) for workup of patients with suspected PJI. There is no evidence supporting the role of white blood cell count and/or white blood cell differential in the diagnosis of PJI (Grade of Recommendation: Strong) 5. Recommends that for patients with abnormal serology (defined as ESR >30 mm/h and CRP level >1 mg/dl) aspiration of the joint be performed (Grade of Recommendation: Strong) 6. Recommends that joint aspirate fluid be sent for microbiological culture, synovial fluid white blood cell count, and differential (Grade of Recommendation: Strong) 7. Recommends against the use of intraoperative Gram stain to rule out periprosthetic joint infection (Grade of Recommendation: Strong) 8. Recommends that patients be off antibiotics for 2 weeks before obtaining intra-articular culture (Grade of Recommendation: Consensus) AAOS, American Academy of Orthopedic Surgeons; PJI, periprosthetic joint infection; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein.
Table 7. Early and late periprosthetic joint infection diagnostic testing and management algorithm. History Clinical Serology Synovial fluid WBC Synovial fluid culture Imaging (plain, CT) Nuclear medicine Management
Early PJI
Late PJI
Days to 3 weeks to years
+
+
Stable components
Unstable component(s)
+
+
Incision and drainage, debridement, antibiotics*
Two-stage removal/replacementy
Pain, swelling, fistula ESR and CRP +
PJI, periprosthetic joint infection; ESR, erythrocyte sedimentation rate (>30 mm/h); CRP, Creactive protein (>10 mg/l); WBC, white blood cell count; CT, computed tomography. * Wolford et al.5 y Mercuri.6
suspected PJI occurring within days or 3 weeks or longer after TMJ TJR with complaints of increasing pain and diffuse swelling with no evidence of localized erythema, no fever, and no drainage, present a difficult
diagnostic dilemma unless there is clinical evidence of a draining skin or auditory canal fistula directly communicating with the device. This sign is pathognomonic of a TMJ TJR PJI and requires delayed TMJ TJR PJI management (Table 7).6 Intrinsic causes for these signs and symptoms should be ruled out (Table 5) by imaging (plain film or CT). Since ESR and CRP can be equivocal in late PJI, their value as diagnostic tests is diminished in a suspected delayed TMJ TJR PJI. Sterile aspiration of the TMJ TJR articulation to obtain fluid for WBC analysis (>1.1–4.0 109 cells/l; 64–68% PMNs) and culture is indicated. Labelled-leucocyte imaging (e.g., leucocytes labelled with indium-111) combined with bone marrow imaging with the use of technetium-99m-labelled sulfur colloid is more accurate than technetium-99 alone, combined bone and gallium-67 imaging, or labelled-leucocyte and bone imaging, when compared head to head, and it is considered the imaging test of choice when imaging is utilized.52 Because there is no single PJI diagnostic test that offers perfect sensitivity and specificity, this field continues to evolve. New assays will become available in the future that will be incorporated into any diagnostic algorithm as they are developed and subjected to clinical testing. 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. Funding
None. Competing interests
None declared. Ethical approval
Not required. Patient consent
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17. Bongartz T, Halligan CS, Osmon DR, Reinalda MS, Bamlet WR, Crowson CS, et al. Incidence and risk factors of prosthetic joint infection after total hip or knee replacement in patients with rheumatoid arthritis. Arthritis Rheum 2008;59:1713–20. 18. Dowsey MM, Choong PF. Obesity is a major risk factor for prosthetic infection after primary hip arthroplasty. Clin Orthop Relat Res 2008;466:153–8. 19. Del Pozo JL, Patel R. Clinical practice. Infection associated with prosthetic joints. N Engl J Med 2009;361:787–94. 20. Malhotra R.. Arthroplasty-associated infections. New York: MedScape; 2013, July 26. Available from: http://emedicine.medscape.com/article/1247719-overview#showall [accessed March 2014]. 21. Vergidis P, Patel R. Novel approaches to the diagnosis, prevention and treatment of medical device-associated infections. Infect Dis Clin North Am 2012;26:173–86. 22. Miller TT. Imaging of hip arthroplasty. Semin Musculoskelet Radiol 2006;10:30–5. 23. Sofka CM, Potter HG, Adler RS, Pavlov H. Musculoskeletal imaging update: current applications of advanced imaging techniques to evaluate the early and long-term complications of patients with orthopedic implants. HSS J 2006;2:73–7. 24. Tigges S, Stiles RG, Roberson JR. Appearance of septic hip prostheses on plain radiographs. Am J Roentgenol 1994;163:377–9. 25. Osmon DR, Berbari EF, Berendt AR, Lew D, Zimmerli W, Steckelberg JM, et al. Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2013;56:e1. 26. Gemmel F, Van den Wyngaert H, Love C, Welling MM, Gemmel P, Palestro CJ. Prosthetic joint infections: radionuclide state-ofthe-art imaging. Eur J Nucl Med Mol Imaging 2012;39:892–6. 27. Sofka CM. Current applications of advanced cross-sectional imaging techniques in evaluating the painful arthroplasty. Skeletal Radiol 2007;36:183–6. 28. Parvizi J, Azzam K, Ghanem E, Austin MS, Rothman RH. Periprosthetic infection due to resistant staphylococci: serious problems on the horizon. Clin Orthop Relat Res 2009;467:1732–9. 29. Zhuang H, Chacko TK, Hickeson M, Stevenson K, Feng Q, Ponzo F, et al. Persistent non-specific FDG uptake on PET imaging following hip arthroplasty. Eur J Nucl Med Mol Imaging 2002;29:1328–33. 30. Kwee TC, Kwee RM, Alavi A. FDG-PET for diagnosing prosthetic joint infection: systematic review and meta-analysis. Eur J Nucl Med Mol Imaging 2008;35:2122–32. 31. Xing D, Ma XL, Ma JX, Wang J, Chen Y, Yang Y. Use of anti-granulocyte scintigraphy with 99mTc-labeled monoclonal antibodies for the diagnosis of periprosthetic infection in patients after total joint arthroplasty: a
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