Rapid detection of invasive Mycobacterium chimaera disease via a novel plasma-based next-generation sequencing test

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Abstract
There is an ongoing outbreak of Mycobacterium chimaera infections among patients exposed to contaminated heater-cooler devices used during cardiac surgery. Recognition of M. chimaera infection is hampered by its long latency and non-specific symptoms. Standard diagnostic methods using acid-fast bacilli (AFB) culture often require invasive sampling, have low sensitivity, and can take weeks to result. We describe the performance of a plasma-based next-generation sequencing test (plasma NGS) for the diagnosis of M. chimaera infection. We conducted a retrospective study of 10 patients with a history of cardiac surgery who developed invasive M. chimaera infection and underwent testing by plasma NGS between February 2017 and April 2018. Plasma NGS detected M. chimaera in 9 of 10 patients (90%) with invasive disease in a median of 4 days from specimen collection, including all 8 patients with disseminated infection. In 7 of these 9 cases (78%), plasma NGS was the first test to provide microbiologic confirmation of M. chimaera infection. In contrast, AFB cultures required a median of 20 days to turn positive, and the median time for confirmation of M. chimaera was 41 days. Of 24 AFB blood cultures obtained in this cohort, only 4 (17%) were positive. Invasive procedures were performed in 90% of cases, and in 5 patients (50%), mycobacterial growth was achieved only by culture of these deep sites. Plasma NGS can accurately detect M. chimaera noninvasively and significantly faster than AFB culture, making it a promising new diagnostic tool.

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