Does the Alpha-defensin Immunoassay or the Lateral Flow Test Have Better Diagnostic Value for Periprosthetic Joint Infection? A Meta-analysis.

BACKGROUND: Measuring alpha-defensin concentrations in synovial fluid may help to diagnose periprosthetic joint infection (PJI). There are two commercially available methods for measuring alpha-defensin in synovial fluid: the enzyme-linked immunosorbent assay-based Synovasure® alpha-defensin immunoassay, which gives a numeric readout within 24 hours, and the Synovasure lateral flow test, which gives a binary readout within 20 minutes. There is no compilation of the existing literature to support the use of one of these two tests over the other. QUESTIONS/PURPOSES: Does the immunoassay or the lateral flow test have better diagnostic value (sensitivity and specificity) in diagnosing PJI? METHODS: We followed PRISMA guidelines and identified all studies on alpha-defensin concentration in synovial fluid as a PJI diagnostic marker, indexed to April 14, 2017, in PubMed, JSTOR, Google Scholar, and OVID databases. The search retrieved 1578 records. All prospective and retrospective studies on alpha-defensin as a PJI marker (PJI classified according to the criteria of the Musculoskeletal Infection Society) after THA or TKA were included in the analysis. All studies used only one of the two commercially available test methods, but none of them was comparative. After excluding studies with overlapping patient populations, four studies investigating the alpha-defensin immunoassay and three investigating the lateral flow test remained. Alpha-defensin immunoassay studies included 482 joints and lateral flow test studies included 119. The quality of the trials was assessed according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The heterogeneity among studies was evaluated by the I index, indicating that the heterogeneity of the included studies was low. Pooled sensitivity, specificity, positive and negative likelihood ratios, and receiver operating curves were calculated for each method and compared with each other. RESULTS: The alpha-defensin immunoassay had superior overall diagnostic value compared with the lateral flow test (area under the curve, 0.98 versus 0.75) with higher sensitivity (96% [90%-98%] versus 71% [55%-83%], p < 0.001), but no difference in specificity with the numbers available (96% [93%-97%] versus 90% [81%-95%], p = 0.060). CONCLUSIONS: Measurement of alpha-defensin in synovial fluid is a valuable complement to existing diagnostic criteria, and the immunoassay test detects PJI more accurately than the lateral flow test. The lateral flow test has lower sensitivity, making it difficult to rule out infection, but its relatively high specificity combined with the advantage of a quick response time can make it useful to rule in infection perioperatively. LEVEL OF EVIDENCE: Level III, diagnostic study.

Low accuracy in preoperative tissue biopsies for diagnosing chronic periprosthetic joint infection: an observational retrospective single-centre study.

OBJECTIVE: Diagnosing periprosthetic joint infection (PJI) can be challenging. The ability to distinguish between septic and aseptic failure of a joint prosthesis is crucial for treatment strategy optimisation and prognosis prediction. Preoperative tissue cultures are included in many diagnostic algorithms; however, studies report different degrees of concordance (63%-85%) with intraoperative cultures. This study aimed to investigate the diagnostic performance of tissue biopsies in the preoperative diagnostic process with the 2018 International Consensus Meeting criteria as a reference and to describe the concordance between microbiological findings in pre- and intraoperative biopsies. METHODS: This observational retrospective study included 44 patients requiring revision surgery of a total hip or knee arthroplasty, where the diagnostic workup included biopsies of periprosthetic tissue. The accuracy of preoperative biopsies was calculated, and concordance between microbiological findings in pre- and intraoperative biopsies was described. RESULTS: The accuracy was 59%, with a sensitivity of 50% and specificity of 79%. Full concordance between microbiological findings in pre- and intraoperative biopsies was found in 64% of the cases. CONCLUSION: An open biopsy of periprosthetic tissue cannot reliably confirm or exclude PJI, and, therefore, should not be performed.

Early Staphylococcal Periprosthetic Joint Infection (PJI) Treated with Debridement, Antibiotics, and Implant Retention (DAIR): Inferior Outcomes in Patients with Staphylococci Resistant to Rifampicin.

It is unknown how rifampicin resistance in staphylococci causing a periprosthetic joint infection (PJI) affects outcomes after debridement, antibiotics, and implant retention (DAIR). We thus aimed to compare the risk of relapse in DAIR-treated early PJI caused by staphylococci with or without rifampicin resistance. In total, 81 patients affected by early PJI were included, and all patients were treated surgically with DAIR. This was repeated if needed. The endpoint of relapse-free survival was estimated using the Kaplan-Meier method, and Cox regression models were fitted to assess the risk of infection relapse for patients infected with rifampicin-resistant bacteria, adjusted for age, sex, type of joint, and type of index surgery. In patients with rifampicin-resistant staphylococci, relapse was seen in 80% after one DAIR procedure and in 70% after two DAIR procedures. In patients with rifampicin-sensitive bacteria, 51% had an infection relapse after one DAIR procedure and 33% had an infection relapse after two DAIR procedures. Patients with rifampicin-resistant staphylococcal PJI thus had an increased adjusted risk of infection relapse of 1.9 (95% CI: 1.1-3.6, p = 0.04) after one DAIR procedure compared to patients with rifampicin-sensitive bacteria and a 4.1-fold (95% CI: 1.2-14.1, p = 0.03) increase in risk of infection relapse after two DAIR procedures. Staphylococcal resistance to rifampicin is associated with inferior outcomes after DAIR. These findings suggest that DAIR may not be a useful strategy in early PJI caused by rifampicin-resistant staphylococci.

Patient-related factors associated with superficial surgical site infection and progression to a periprosthetic joint infection after elective primary total joint arthroplasty: a single-centre, retrospective study in Sweden.

OBJECTIVES: Superficial surgical site infection (SSSI) may increase the risk of serious complications such as periprosthetic joint infection (PJI). This study aims to identify patient-related risk factors associated with SSSI and investigate their correlation with the progression of PJI. DESIGN: In this retrospective study, 1191 elective hip and knee prostheses were included. Patients were interviewed 3-5 months after surgery to answer questions about the postoperative period. Patient records were reviewed to determine whether there had been any documentation of wound-healing difficulties or whether antibiotics were prescribed to treat an infection related to arthroplasty surgery. SETTING: Uppsala University Hospital, patients treated between November 2008 and December 2012. PARTICIPANTS: The study population comprised 433 knees and 758 hips. OUTCOME MEASURES: We studied patient-related risk factors (joint, age, sex, the American Society of Anesthesiologists (ASA) classification, body mass index (BMI), smoking, diabetes and rheumatic disease) to determine whether they were associated with (1) SSSI and (2) the progress from SSSI to PJI. RESULTS: 84 (7%) patients of the total cohort developed SSSI. This infection progressed to a PJI in 24 (29%) of the patients. Factors with increased adjusted risk ratios (aRRs) for SSSIs were knee surgery (1.7; 95% CI: 1.1 to 2.7), age≥65 years (1.7; 95% CI: 1.1 to 2.8), BMI≥30 (1.9; 95% CI: 1.0 to 3.4) and ASA classification≥3 (1.7; 95% CI: 1.0 to 2.9). ASA classification≥3 was the only factor showing a significant progression from SSSI to PJI (aRR=3.3; 95% CI: 1.0 to 10.3). CONCLUSIONS: The risk of progressing from an SSSI to a PJI is high. Older patients, patients with obesity, and those with a high ASA classification considered for elective total knee arthroplasty seem to have an increased risk of developing SSSI. Patients with a high ASA classification seem to have an increased risk of progressing from SSSI to PJI.

Linezolid in the treatment of periprosthetic joint infection caused by coagulase-negative staphylococci.

Background: Periprosthetic joint infection (PJI) caused by coagulase-negative staphylococci (CoNS) is increasingly common and is sometimes treated with off-label use of linezolid. Methods: We conducted a retrospective study of patients with PJI caused by CoNS treated with surgical intervention and orally administrated linezolid during the period 1995-2014 (n = 28). Clinical outcomes and adverse events related to linezolid administration were evaluated. Mean time to follow-up was 4.3 years (range: 0.2-12). Results: Twenty-two of 28 patients were infection-free at follow-up. No CoNS strain was resistant to vancomycin, but 16 of 28 were resistant to rifampicin, 23 of 28 to clindamycin and 20 of 27 to quinolones. The mean duration of linezolid treatment was 4.2 weeks (range: 1-12). Eleven of 28 patients had an adverse event related to the antimicrobial treatment, and four had to discontinue linezolid, but all adverse events were reversible within 2 months after discontinuation. Conclusions: Oral linezolid administration combined with adequate surgical treatment may be useful for the treatment of PJIs caused by CoNS.