How Reliable Is the Alpha-defensin Immunoassay Test for Diagnosing Periprosthetic Joint Infection? A Prospective Study

Abstract

BackgroundA key issue in the treatment of periprosthetic joint infection (PJI) is the correct diagnosis. The main problem is lack of diagnostic tools able to diagnose a PJI with high accuracy. Alpha-defensin has been proposed as a possible solution, but in the current literature, there is a lack of independent validation.Questions/purposesWe performed a prospective study to determine (1) what is the sensitivity, specificity, and positive and the negative predictive values of the alpha-defensin immunoassay test in diagnosing PJI; and (2) which clinical features may be responsible for false-positive and false-negative results?MethodsPreoperative aspiration was performed in all patients presenting with a painful hip/knee arthroplasty, including both primary and revision implants. Metallosis, other inflammatory comorbidities, and previous/concomitant antibiotic therapy were not considered as exclusion criteria. An inadequate amount of synovial fluid for culture was an exclusion criterion. A total of 156 patients (65 knees, 91 hips) were included in this prospective study. At the time of revision, synovial fluid samples were taken to perform the alpha-defensin assay. During surgical débridement of tissue, samples for cultures and histologic evaluation were taken, and samples were cultured until positive or until negative at 14 days. A diagnosis of PJI was confirmed in 29 patients according to the International Consensus Group on PJI.ResultsThe sensitivity of the alpha-defensin immunoassay was 97% (95% confidence interval [CI], 92%–99%), the specificity was 97% (95% CI, 92%–99%), the positive predictive value was 88% (95% CI, 81%–92%), and the negative predictive value was 99% (95% CI, 96%–99%). Among four false-positive patients, two had metallosis and one had polyethylene wear. The false-negative case presented with a draining sinus, and intraoperative cultures were also negative.ConclusionsAlpha-defensin assay appears to be a reliable test, but followup evaluation is needed to estimate longer term performance of the test. The authors believe that alpha-defensin has demonstrated itself to be sufficiently robust that PJI diagnostic criteria now should include this test. Future studies are needed to compare the differences among the diagnostic capability of the available tests, in particular when metallosis is present, because metallosis may predispose the test to a false-positive result.Level of EvidenceLevel I, diagnostic study.

Periprosthetic Distal Femur Fractures: Review of Current Treatment Options

“…If signs of loosening and osteolysis are noted, then a thorough infectious workup to include: serological markers (ESR and CRP) and preoperative joint aspiration with with synovial white cell count (WCC), polymorphonuclear (PMN) cell proportion and microbiological analysis. In a recent prospective study, the Alpha-defensin immunoassay test was found to have a sensitivity of 97% and specificity of 97% for diagnosing periprosthetic joint infection and is now recommended to be included in the workup [21]. Antecedent knee or thigh pain may indicate pre-existing component loosening and should be included in the history.…”

Update on the diagnosis and management of the periprosthetic knee joint infection

“…The authors thereby concluded that the test is at least equivalent to intraoperative frozen section and is a useful tool to confirm the absence of PJI. 20 Bonanzinga et al 21 have since performed another prospective study using alpha-defensin levels. Using a cohort of 156 patients (65 knees, 91 hips), alpha-defensin immunoassays from the joint fluid were compared to tissue samples sent for culture and histological assessment taken during surgical debridement.…”

Cultura dos tecidos profundos na artroplastia total primária do quadril: valor prognóstico para infecção periprotética

“…Em casos mais graves, com extensa multiplicação bacteriana, o diagnóstico costuma ser óbvio devido à formação de fístula, febre, soltura dos implantes e dor intensa 39 . No entanto, casos de infecção de baixo grau apresentam um desafio maior porque frequentemente não estão associados a uma sintomatologia exuberante 40 . Os métodos diagnósticos menos invasivos carecem de sensibilidade e especificidade satisfatórios.…”

“…Os métodos diagnósticos menos invasivos carecem de sensibilidade e especificidade satisfatórios. E os métodos com maior sensibilidade e especificidade geralmente são invasivos, pela análise laboratorial de material obtido por artrocentese 40,41 . Exemplos recentes incluem a medida da concentração intra-articular de proteína C reativa, alfa-defensina e leucócito esterase [40][41][42] .…”

“…Acreditamos que seja prudente realizar um seguimento clínico diferenciado para pacientes com cultura positiva. Esse grupo de pacientes pode se beneficiar de uma vigilância mais rigorosa, com realização precoce de testes laboratoriais de alta sensibilidade em caso de suspeita de infecção, como a dosagem intraarticular de alfa defensina, proteína c reativa e esterase leucocitária [40][41][42] . É importante ponderar o risco/benefício dessa prática: por um lado, devemos considerar o alto custo relacionado ao tratamento da IPP e suas devastadoras consequências na qualidade de vida do paciente 11,35 .…”