Multisite Evaluation of Cepheid Xpert Carba-R Assay for Detection of Carbapenemase-Producing Organisms in Rectal Swabs.

M Tato,R Cantón,A Dodgson,R Humphries,J Hindler,P Ruiz-Garbajosa,H Wang,J Veltman,M Traczewski,A Mcewan,K C Carroll

doi:10.1128/jcm.00341-16

Abstract

Rapid identification of patients who are colonized with carbapenemase-producing organisms (CPO) is included in multiple national guidelines for containment of these organisms. In a multisite study, we evaluated the performance of the Cepheid Xpert Carba-R assay, a qualitative diagnostic test that was designed for the rapid detection and differentiation of the blaKPC, blaNDM, blaVIM, blaOXA-48, and blaIMP-1 genes from rectal swab specimens. A double rectal swab set was collected from 383 patients admitted at four institutions (2 in the United States, 1 in the United Kingdom, 1 in Spain). One swab was used for reference culture (MacConkey broth containing 1 mg/liter of meropenem and subcultured to a MacConkey agar plate with a 10-μg meropenem disk) and for sequencing of DNA obtained from carbapenem-nonsusceptible isolates for carbapenemase identification. The other swab was used for the Xpert Carba-R assay. In addition to the clinical rectal swabs, 250 contrived specimens (108 well-characterized CPO and 142 negative controls spiked onto negative rectal swabs) were tested. Overall, 149/633 (23.5%) samples were positive by the Xpert Carba-R assay. In 6 samples, multiple targets were detected (4 VIM/OXA-48, 1 IMP-1/NDM, and 1 NDM/KPC). The Xpert Carba-R assay detected 155 targets (26 IMP-1, 30 VIM, 27 NDM, 33 KPC, 39 OXA-48) within a time range of 32 to 48 min. The sensitivity, specificity, and positive and negative predictive values of the Xpert Carba-R assay compared to those of the reference culture and sequencing results were 96.6% (95% confidence interval [CI], 92.2% to 98.9%), 98.6% (95% CI, 97.1% to 99.4%), 95.3%, and 99.0%, respectively. The Cepheid Xpert Carba-R assay is an accurate and rapid test to identify rectal colonization with CPO, which can guide infection control programs to limit the spread of these organisms.

Highlights

The global spread of carbapenemase-producing organisms (CPO) has been highlighted by international health authorities as a critical public health concern [1,2,3]
We evaluated the sensitivity and specificity of a PCR-based method in a cartridge format (Xpert MDRO assay) for detecting carbapenemase genes in rectal and perirectal swabs run on the GeneXpert platform (Cepheid, Sunnyvale, CA)
Meropenem was used instead of ertapenem to improve the specificities for Pseudomonas spp. and Acinetobacter spp., which are intrinsically resistant to ertapenem

Summary

Introduction

The global spread of carbapenemase-producing organisms (CPO) has been highlighted by international health authorities as a critical public health concern [1,2,3]. Bacterial load in rectal or perirectal swabs impacts the accuracy of culturebased tests For these reasons, molecular tests have been developed and claim to overcome most of these limitations. Molecular tests have been developed and claim to overcome most of these limitations These molecular assays comprise multiplex-PCR-based assays [10, 11], isothermal amplification (LAMP)-based assays [12], and microarray-based assays [13, 14]. We evaluated the sensitivity and specificity of a PCR-based method in a cartridge format (Xpert MDRO assay) for detecting carbapenemase genes in rectal and perirectal swabs run on the GeneXpert platform (Cepheid, Sunnyvale, CA). Testing was performed in parallel with a reference culture method [15] This molecular assay included targets for blaKPC, blaNDM, and blaVIM genes but not for blaOXA-48 and blaIMP-1. The evaluation was performed in a multisite prospective study for European marketing authorization under the European directive on in vitro diagnostic medical devices [16]

Methods

Results

Conclusion