BacteriologyEvaluation of the RAPIDEC® CARBA NP and β-CARBA® tests for rapid detection of Carbapenemase-producing Enterobacteriaceae
Introduction
The emergence and rapid dissemination of Carbapenemase-Producing Enterobacteriaceae (CPE) during the last decade represents the most worrisome event in the escalating antibiotic resistance crisis (Nordmann et al., 2011) as CPE have been reported in numerous nosocomial outbreaks worldwide. Most importantly, related infections can be treated only by a few remaining therapeutic options (Canton et al., 2012). Hence, rapid detection of CPE is of paramount importance for the timely choice of the appropriate antibiotic therapy and for the implementation of measures to prevent outbreaks.
Carbapenem resistance may arise from either (i) a concomitant reduced permeability of the outer membrane and an overexpression of enzymes with very low carbapenemase activity (e.g. extended-spectrum beta-lactamases and cephalosporinases) or (ii) the expression of enzymes with significant carbapenemase activity, defined as carbapenemases (Nordmann et al., 2012a). A large variety of acquired carbapenemases has been reported worldwide in CPE. The most prevalent carbapenemases belong to the Ambler class A (KPC), class B (VIM, IMP, and NDM) and class D (OXA-48 and OXA-48-like) (Albiger et al., 2015).
Nowadays several methods are available for the rapid detection of carbapenemase producers including: (I) molecular techniques to identify the most common carbapenemase genes (Findlay et al., 2015), (II) the MALDI-TOF technology that allows the detection of carbapenem degradation products (Hrabak et al., 2013), (III) a recently developed electrochemical assay that allows the detection of carbapenemase-producers (Bogaerts et al., 2016), (IV) immunochromatographic assays detecting KPC, IMP-like, OXA-48 and OXA-48-like β-lactamases (Glupczynski et al., 2016, Kitao et al., 2011) and (V) colorimetric assays relying on the color change of a pH indicator to detect carbapenemase activity (CARBA NP test (Nordmann et al., 2012b) and copies or derivatives (Compain et al., 2016, Noel et al., 2016, Pires et al., 2013)). Here, we compared the performances of two commercially-available colorimetric assays, the RAPIDEC® CARBA NP and the recently developed β-CARBA® test, by using a common panel of CPE.
Section snippets
Strain collection
A collection of 149 clinical enterobacterial isolates was used to assess the performances of the RAPIDEC® CARBA NP (bioMérieux, La Balme-les-grottes, France) and the β-CARBA® (Bio-Rad, Marnes-la-Coquette, France) tests. All the strains were characterized for their β-lactamase content by PCR and sequencing of the corresponding genes. The clinical isolates of worldwide origin were recovered from various clinical samples (sputum, blood cultures, urines, gut flora, etc.) and consisted in 38
Performances of the RAPIDEC® CARBA NP and β-CARBA® tests
Of the 149 tested isolates, 111 were CPE. RAPIDEC® CARBA NP yielded positive results for 104 out of the 111 CPE isolates, while the β-CARBA® test yielded positive results for only 72/111 isolates. Sensitivity and specificity of the RAPIDEC® CARBA NP test were 93.7% and 100%, respectively, values that are in good agreement with those indicated in the manufacturer's specifications (specificity 97.8% and sensitivity 97.8%). By contrast, the sensitivity and specificity of the β-CARBA® test were
Interpretation of the results
Several works have investigated the analytical performances of RAPIDEC® CARBA NP and have reported different sensitivities in detecting CPE, ranging from 90.2% to 99% (Bernabeu et al., 2017, Dortet et al., 2015a, Hombach et al., 2015, Kabir et al., 2016, Noel et al., 2016, Poirel and Nordmann, 2015). On the other hand, with the exception of the work carried out by Noël et al., where they report a value of 84% (Noel et al., 2016), the sensitivity of the RAPIDEC® CARBA NP test is always close to
Conclusion
RAPIDEC® CARBA NP test exhibited better performances than those of the β-CARBA® test and confirmed to be a reliable tool for the rapid detection of CPE. The poor performances of the β-CARBA® test were mostly due to the failure to detect the non KPC A-type carbapenemases and most OXA-48-like producers. Failure to detect most of the OXA-48-like producers by using the β-CARBA® test shall limit the value of this test in geographical areas such as in Europe where those carbapenemase producers are
Funding
This work was funded by in part by bioMérieux and in part by the University of Fribourg.
Conflict of interest
An international patent has been obtained for the Carba NP test (WO2012175637 A1). This work was partially sponsored by bioMérieux, the manufacturer of the RAPIDEC® CARBA NP.
Acknowledgments
We thank D. Uldry for her technical support.
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