Head-to-head comparison of culture-based and direct-from-specimen molecular testing for carbapenemase-producing Gram-negative bacilli: a year-long comparative study in a moderate-prevalence setting

<h2>Abstract</h2><h3>Objectives</h3> An efficient testing and isolation strategy is essential to contain the spread of carbapenemase-producing gram-negative bacilli (CPGNB). We compared the performance of a culture-based strategy utilising chromID CARBA SMART agar followed by confirmation with conventional PCR, against direct molecular testing with the Cepheid Xpert Carba-R assay, for the detection of CPGNB in rectal swab samples obtained from patients admitted to our hospital from 9 April 2019 to 15 March 2020. <h3>Methods</h3> Detection of CPGNB by either method constituted the reference standard. In addition to routine screening for <i>Enterobacterales</i>, non-fermenting Gram-negative bacilli (NFGNB) isolated on culture were also identified and subjected to whole genome sequencing for the detection of carbapenemase genes. We also calculated the number of patient contacts averted or generated by each strategy, and the difference in laboratory personnel hands-on time between strategies. <h3>Results</h3> Of the 29,446 samples tested (from 17,097 unique patients), 693 (2.35%) were positive for CPGNB (for on-panel targets) by either testing strategy. Xpert Carba-R detected carbapenemase in 625/693 samples (sensitivity: 90.2%), compared with 301/693 samples (sensitivity: 46.3%) for the culture-based strategy if NFGNB were disregarded, and 449/693 samples (sensitivity: 64.8%) for the culture-based strategy if NFGNB were included, while requiring less hands-on time (average of 1.3 minutes versus 89.97 minutes). Xpert Carba-R averted 6,983 potential contacts (for test-concordant specimens) and 21,780 potential contacts (for test-discordant specimens) in total. <h3>Conclusions</h3> Direct molecular testing with Xpert Carba-R outperformed the culture-based strategy for detection of CPGNB, demonstrating superior sensitivity and reduced hands-on time. It also routinely detected carbapenemases in NFGNB; these should be included in hospital surveillance.