Reevaluation of Positivity Cutoff Values for the Pneumococcal Urinary Antigen Detection Assay.

Abstract

T o improve the clinical diagnosis of pneumococcal infection in bacteremic and nonbacteremic community-acquired pneumonia (CAP), a Luminex technology-based multiplex urinary antigen detection (UAD) diagnostic assay was developed and validated. The UAD assay is a limit assay based on defined positivity cutoff limits and can simultaneously detect 13 different serotypes of Streptococcus pneumoniae by capturing serotype-specific S. pneumoniae polysaccharides (PnPSs) excreted in human urine. UAD assay validation and clinical validation of the corresponding positivity cutoff values were described in a previous publication in this journal (1). This assay was originally developed for use in the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) study (2) (adults (cid:2) 65 years of age). After the completion of sample testing in support of CAPiTA and study 6115A1-4007 (Distribu-tion of PCV 13 Serotype Streptococcus pneumoniae in Adults 50 Years and Older Presenting to Select U.S. Hospitals with Radiographically Confirmed Community-Acquired Pneumonia) (3), a critical component used in the UAD assay was received by an outside supplier and, as part of our laboratory’s standard practice, was qualified for use in the UAD assay, passing all prospectively set acceptance criteria. This new reagent was used in the UAD assay for a number of epidemiological studies to study the burden of the 13 serotypes covered by Prevnar 13 in subjects with community-acquired pneumonia. Upon review of the interim UAD results generated in support of the U.S. study 1147, it was noted that the percent positivity for serotype 5 was higher than expected for the U.S. population and higher