The Alpha-defensin Test for Periprosthetic Joint Infection Responds to a Wide Spectrum of Organisms

Carl Deirmengian, Keith Kardos, Patrick Kilmartin, Simmi Gulati, Patrick Citrano, Robert E Booth Jr, Carl Deirmengian, Keith Kardos, Patrick Kilmartin, Simmi Gulati, Patrick Citrano, Robert E Booth Jr

Abstract

Background: The alpha-defensin test has been previously demonstrated to be highly accurate in the diagnosis of prosthetic joint infection (PJI), nearly matching the Musculoskeletal Infection Society definition for PJI. However, the relationship between alpha-defensin levels and differing infecting organism has not yet been investigated.

Questions/purposes: The purpose of this study is to describe the breadth of organisms that can trigger a positive synovial fluid alpha-defensin test result in the setting of PJI and also to assess the magnitude of the alpha-defensin result in terms of various pathogen characteristics.

Methods: Between December 2012 and March 2014, one laboratory processed 2319 synovial fluid samples for alpha-defensin testing. The present study reviewed the results of the 1937 samples that simultaneously had a synovial fluid culture performed; these came from 418 surgeons in 42 states. The overall culture-positive rate was 49% (244 of 498) among alpha-defensin-positive synovial fluids and 1% (19 of 1439) among alpha-defensin-negative synovial fluids. The organisms recovered from 244 alpha-defensin-positive, culture-positive fluids were recorded and grouped based on various characteristics, including Gram type, species, virulence, oral pathogenicity, and source joint. Alpha-defensin-negative samples served as uninfected controls. Median alpha-defensin levels were calculated for each group, and Dunn's multiple comparison test for nonparametric data was used to identify any statistically significant (p < 0.05) organism-specific differences in the alpha-defensin level.

Results: The alpha-defensin test for PJI was positive in the setting of a wide spectrum of organisms typically causing PJI. The median alpha-defensin level for all 244 alpha-defensin-positive, culture-positive samples (4.7 [interquartile range {IQR}, 3.7-5.3]) was higher than negative controls (0.26 [IQR, 0.22-0.33]) with a median difference of 4.4 (p < 0.001). There were no differences in the median alpha-defensin levels when performing a multiple comparison test among Gram-positive organisms (4.7 [IQR, 3.6-5.3]), Gram-negative organisms (4.8 [IQR, 4.2-5.3]), yeast (4.1 [IQR, 2.2-5.1]), virulent organisms (4.7 [IQR, 3.8-5.2]), less virulent organisms (4.8 [IQR, 3.6-5.4]), oral pathogens (4.5 [IQR, 3.2-5.2]), knees (4.7 [IQR, 3.7-5.3]), hips (4.9 [IQR, 4.1-5.8]), or shoulders (5.3 [IQR, 4.0-10.7]) with all comparisons having a p > 0.999.

Conclusions: The alpha-defensin test provides consistent results regardless of the organism type, Gram type, species, or virulence of the organism and should be seriously considered to be a standard diagnostic tool in the evaluation for PJI. Future research should focus on the performance of this test in specific clinical scenarios such as the immediate postoperative period in the setting of severe immunocompromise and in the setting of a native joint.

Level of evidence: Level III, diagnostic study.

Figures

Fig. 1
Fig. 1
Synovial fluid samples, from patients undergoing arthroplasty, having both an alpha-defensin test and synovial fluid culture, were included in this study. The figure depicts the overall breakdown of results.
Fig. 2
Fig. 2
Synovial fluid samples with both a positive alpha-defensin result and a positive culture were grouped by organism type. Median values and the interquartile ranges are plotted on a log scale. *** = Different with statistical significance.
Fig. 3
Fig. 3
Synovial fluid samples with both a positive alpha-defensin result and a positive culture were grouped by organism species. Median values and the IQRs are plotted on a log scale. *** = Different with statistical significance.
Fig. 4
Fig. 4
Synovial fluid samples with both a positive alpha-defensin result and a positive culture were grouped by organism virulence. Median values and the IQRs are plotted on a log scale. *** = Different with statistical significance.
Fig. 5
Fig. 5
Synovial fluid samples with both a positive alpha-defensin result and a positive culture were grouped by oral pathogenicity. Median values and the IQRs are plotted on a log scale. *** = Different with statistical significance.
Fig. 6
Fig. 6
Synovial fluid samples with both a positive alpha-defensin result and a positive culture were grouped by the anatomic source. Median values and the IQRs are plotted on a log scale. *** = Different with statistical significance.

References

    1. Bémer P, Plouzeau C, Tande D, Léger J, Giraudeau B, Valentin AS, Jolivet-Gougeon A, Vincent P, Corvec S, Gibaud S, Juvin ME, Héry-Arnaud G, Lemarié C, Kempf M, Bret L, Quentin R, Coffre C, de Pinieux G, Bernard L, Burucoathe C; Centre de Référence des Infections Ostéo-articulaires du Grant Ouest (CRIOGO) Study Team. Evaluation of 16S rDNA PCR sensitivity and specificity for diagnosis of prosthetic-joint infection: a prospective multicenter cross-sectional study. J Clin Microbiol. 2014;52:3583–3589.
    1. Bingham J, Clarke H, Spangehl M, Schwartz A, Beauchamp C, Goldberg B. The alpha defensin-1 biomarker assay can be used to evaluate the potentially infected total joint arthroplasty. Clin Orthop Relat Res. 2014;472:4006–4009. doi: 10.1007/s11999-014-3900-7.
    1. Bjerke-Kroll BT, Christ AB, McLawhorn AS, Sculco PK, Jules-Elysee KM, Sculco TP. Periprosthetic joint infections treated with two-stage revision over 14 years: an evolving microbiology profile. J Arthroplasty. 2014;29:877–882. doi: 10.1016/j.arth.2013.09.053.
    1. Chen A, Fei J, Deirmegian C. Diagnosis of periprosthetic infection: novel developments. J Knee Surg. 2014;27:259–265. doi: 10.1055/s-0034-1371768.
    1. Deirmengian C, Kardos K, Kilmartin P, Cameron A, Schiller K, Booth RE, Jr, Parvizi J. The alpha-defensin test for periprosthetic joint infection outperforms the leukocyte esterase test strip. Clin Orthop Relat Res. 2015;473:198–203. doi: 10.1007/s11999-014-3722-7.
    1. Deirmengian C, Kardos K, Kilmartin P, Cameron A, Schiller K, Parvizi J. Combined measurement of synovial fluid alpha-defensin and c-reactive protein levels: highly accurate for diagnosing periprosthetic joint infection. J Bone Joint Surg Am. 2014;96:1439–1445. doi: 10.2106/JBJS.M.01316.
    1. Deirmengian C, Kardos K, Kilmartin P, Cameron A, Schiller K, Parvizi J. Diagnosing periprosthetic joint infection: has the era of the biomarker arrived? Clin Orthop Relat Res. 2014;472:3254–3262. doi: 10.1007/s11999-014-3543-8.
    1. Gallo J, Kolar M, Dendis M, Loveckova Y, Sauer P, Zapletalova J, Koukalova D. Culture and PCR analysis of joint fluid in the diagnosis of prosthetic joint infection. New Microbiol. 2008;31:97–104.
    1. Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, Lehrer RI. Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest. 1985;76:1427–1435. doi: 10.1172/JCI112120.
    1. Gomez E, Cazanave C, Cunningham SA, Greenwood-Quaintance KE, Steckelberg JM, Uhl JR, Hanssen AD, Karau MJ, Schmidt SM, Osmon DR, Berbari EF, Mandrekar J, Patel R. Prosthetic joint infection diagnosis using broad-range PCR of biofilms dislodged from knee and hip arthroplasty surfaces using sonication. J Clin Microbiol. 2012;50:3501–3508. doi: 10.1128/JCM.00834-12.
    1. Jacovides CL, Kreft R, Adeli B, Hozack B, Ehrlich GD, Parvizi J. Successful identification of pathogens by polymerase chain reaction (PCR)-based electron spray ionization time-of-flight mass spectrometry (ESI-TOF-MS) in culture-negative periprosthetic joint infection. J Bone Joint Surg Am. 2012;94:2247–2254. doi: 10.2106/JBJS.L.00210.
    1. Parvizi J, Gehrke T, International Consensus Group on Periprosthetic Joint I Definition of periprosthetic joint infection. J Arthroplasty. 2014;29:1331. doi: 10.1016/j.arth.2014.03.009.
    1. Ryu SY, Greenwood-Quaintance KE, Hanssen AD, Mandrekar JN, Patel R. Low sensitivity of periprosthetic tissue PCR for prosthetic knee infection diagnosis. Diagn Microbiol Infect Dis. 2014;79:448–453. doi: 10.1016/j.diagmicrobio.2014.03.021.
    1. Shanmugasundaram S, Ricciardi BF, Briggs TW, Sussmann PS, Bostrom MP. Evaluation and management of periprosthetic joint infection—an international, multicenter study. HSS J. 2014;10:36–44. doi: 10.1007/s11420-013-9366-4.
    1. Sheehan E. CORR Insights: The alpha-defensin test for periprosthetic joint infection outperforms the leukocyte esterase test strip. Clin Orthop Relat Res. 2015;473:204–205. doi: 10.1007/s11999-014-3794-4.
    1. Spangehl MJ, Masri BA, O’Connell JX, Duncan CP. Prospective analysis of preoperative and intraoperative investigations for the diagnosis of infection at the sites of two hundred and two revision total hip arthroplasties. J Bone Joint Surg Am. 1999;81:672–683.
    1. Zeller V, Lhotellier L, Marmor S, Leclerc P, Krain A, Graff W, Ducroquet F, Biau D, Leonard P, Desplaces N, Mamoudy P. One-stage exchange arthroplasty for chronic periprosthetic hip infection: results of a large prospective cohort study. J Bone Joint Surg Am. 2014;96:e1. doi: 10.2106/JBJS.L.01451.

Source: PubMed

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