The Alpha-Defensin Immunoassay and Leukocyte Esterase Colorimetric Strip Test for the Diagnosis of Periprosthetic Infection: A Systematic Review and Meta-Analysis.
BACKGROUND
Synovial biomarkers have recently been adopted as diagnostic tools for periprosthetic joint infection (PJI), but their utility is uncertain. The purpose of this systematic review and meta-analysis was to synthesize the evidence on the accuracy of the alpha-defensin immunoassay and leukocyte esterase colorimetric strip test for the diagnosis of PJI compared with the Musculoskeletal Infection Society diagnostic criteria.


METHODS
We performed a systematic review to identify diagnostic technique studies evaluating the accuracy of alpha-defensin or leukocyte esterase in the diagnosis of PJI. MEDLINE and Embase on Ovid, ACM, ADS, arXiv, CERN DS (Conseil Européen pour la Recherche Nucléaire Document Server), CrossRef DOI (Digital Object Identifier), DBLP (Digital Bibliography & Library Project), Espacenet, Google Scholar, Gutenberg, HighWire, IEEE Xplore (Institute of Electrical and Electronics Engineers digital library), INSPIRE, JSTOR (Journal Storage), OAlster (Open Archives Initiative Protocol for Metadata Harvesting), Open Content, Pubget, PubMed, and Web of Science were searched for appropriate studies indexed from inception until May 30, 2015, along with unpublished or gray literature. The classification of studies and data extraction were performed independently by 2 reviewers. Data extraction permitted meta-analysis of sensitivity and specificity with construction of receiver operating characteristic curves for each test.


RESULTS
We included 11 eligible studies. The pooled diagnostic sensitivity and specificity of alpha-defensin (6 studies) for PJI were 1.00 (95% confidence interval [CI], 0.82 to 1.00) and 0.96 (95% CI, 0.89 to 0.99), respectively. The area under the curve (AUC) for alpha-defensin and PJI was 0.99 (95% CI, 0.98 to 1.00). The pooled diagnostic sensitivity and specificity of leukocyte esterase (5 studies) for PJI were 0.81 (95% CI, 0.49 to 0.95) and 0.97 (95% CI, 0.82 to 0.99), respectively. The AUC for leukocyte esterase and PJI was 0.97 (95% CI, 0.95 to 0.98). There was substantial heterogeneity among studies for both diagnostic tests.


CONCLUSIONS
The diagnostic accuracy for PJI was high for both tests. Given the limited number of studies and the large cost difference between the tests, more independent research on these tests is warranted.


METHODS
Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Princess Elizabeth Orthopaedic Centre, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom michaelcharleswyatt@icloud.com.
M C
MC
Wyatt
University of Bristol, Bristol, United Kingdom.
A D
AD
Beswick
University of Bristol, Bristol, United Kingdom.
S K
SK
Kunutsor
Princess Elizabeth Orthopaedic Centre, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom.
M J
MJ
Wilson
University of Bristol, Bristol, United Kingdom.
M R
MR
Whitehouse
University of Bristol, Bristol, United Kingdom.
A W
AW
Blom
D015415:Biomarkers / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D003124:Colorimetry; D006801:Humans; D011237:Predictive Value of Tests; D016459:Prosthesis-Related Infections / Q000175:diagnosis* / Q000378:metabolism; D012680:Sensitivity and Specificity; D023084:alpha-Defensins / Q000378:metabolism*
D015415:Biomarkers; D023084:alpha-Defensins; C021443:leukocyte esterase; D002265:Carboxylic Ester Hydrolases