Evaluation of the Xpert Flu Rapid PCR Assay in High-Risk Emergency Department Patients

Abstract

We prospectively evaluated the performance of Cepheid's GeneXpert Xpert Flu assay in a target population of 281 adults presenting to the emergency department with an acute respiratory illness who met Centers for Disease Control and Prevention (CDC) criteria for recommended antiviral treatment. Compared with the Prodesse ProFlu؉ assay, Xpert Flu had an overall sensitivity of 95.3% and specificity of 99.2%. The majority of patients seeking care for influenza and other respiratory viruses present to episodic outpatient care settings, such as emergency departments (EDs) or other urgent or primary care settings, where rapid diagnosis and treatment are critical (1). Due to nonspecific symptoms, a provider's clinical diagnosis of influenza has low sensitivity, leading providers to rely on diagnostic testing for an accurate influenza diagnosis (2). Most commercially available real-time PCR (rt-PCR) tests are typically run in batches and require separate nucleic acid extraction, which significantly delays the results. The current antigen detection tests are rapid but have poor-to-moderate sensitivities, ranging from 10% to 70% (3). Rapid random-access PCR-based influenza tests, such as the GeneXpert Xpert Flu assay (Cepheid, Sunnyvale, CA, USA), may have clinical utility in filling this diagnostic gap, since it has a reported time to result of approximately 80 min and has a significantly higher sensitivity than rapid antigen detection tests (4).Prior to integration into routine clinical use, the clinical performance of Xpert Flu in the target population requires evaluation. Although clinicians in the outpatient episodic care setting may test an array of patients, accurate and rapid influenza testing with Xpert Flu would be most important in patients for whom the test result would impact clinical management, namely, those who meet the Centers for Disease Control and Prevention (CDC) criteria for antiviral therapy and are at risk for potential influenza-related complications. Several of these conditions, such as advanced age and pneumonia, have been associated with the decreased sensitivity of rapid antigen-based testing, highlighting the importance of evaluating Xpert Flu in this population (5). In order to fully translate rapid PCR-based testing into clinical practice, we prospectively evaluated the sensitivity and specificity of Xpert Flu in adult ED patients with an acute undifferentiated respiratory illness who met CDC criteria for recommended antiviral treatment.Adult ED patients with an undifferentiated acute respiratory illness who met CDC criteria for recommended influenza antiviral treatment at an urban university-affiliated tertiary-care ED were prospectively enrolled between December 2012 and March 2013. After written consent was obtained, as approved by the Johns Hopkins University institutional review board (IRB), a nasopharyngeal swab was collected from each patient and placed in 3 ml of viral transport medium (MicroTest M4RT; Remel, Lenexa, KS, USA). All the samples were aliquoted, stored at Ϫ70°C until com...

Necessity to critically review the automatic results of the Xpert Flu assay

“…A finding that supports this hypothesis is that the median Ct value of false-negative specimens was significantly higher than that of concordantly positive specimens ( Supplementary Table 1). However, sensitivity of the Xpert Flu assay has previously been reported to be higher than 93% compared to another molecular assay (Dugas et al, 2014;Novak-Weekley et al, 2012). Most of the discordant results in our study were obtained in comparison with the Allplex Respiratory Panel 1 (Table 1).…”

Rapid diagnostic test for respiratory infections

“…With minimal sample handling and after dispensing the sample into individual devices, the extraction, application and detection of RVs is performed on one single piece of equipment. [38][39][40] As is true of viral antigen detection tests, they have been developed commercially from tests aimed at detecting one specific virus (RSV and/or influenza) evolving into "multiplexes" capable of simultaneously detecting the majority of possible viruses involved in these processes. All this with a result obtention time of between 15 and 90 min, with a minimal work load (around 2 min), Fig.…”

Métodos de diagnóstico rápido de las infecciones respiratorias

“…No obstante, en los últimos años se vienen desarrollando TAAN en diferentes formatos de fácil y rápida ejecución, sin pérdida de eficiencia respecto a los procedimientos moleculares clásicos. Con una mínima manipulación de la muestra y tras dispensarla en dispositivos individuales, realizan en un mismo equipo la extracción, amplificación y detección de los VR [38][39][40] .…”