The global outbreak of Mycobacterium chimaera infections in cardiac surgery-a systematic review of whole-genome sequencing studies and joint analysis

BACKGROUND With the increasing dimensions of the international cardiac surgery-associated Mycobacterium chimaera outbreak the hypothesis of a point source arose. OBJECTIVES To review the published evidence of clonality among cardiac surgery-associated M. chimaera isolates evaluated by whole-genome sequencing (WGS) and to perform an integrative genomic analysis of available genome data. DATA SOURCES We searched PubMed and EMBASE for studies applying WGS on cardiac surgery-associated M. chimaera isolates. STUDY ELIGIBILITY CRITERIA We included studies that applied WGS on more than a single M. chimaera isolate. METHODS Two authors independently extracted data from included studies. Available genome data from published studies were subjected to a joint analysis. RESULTS Of 121 identified articles, nine studies were included. M. chimaera isolates from LivaNova heater-cooler devices (HCDs) had a high level of genetic similarity, but were genetically distant from isolates from HCDs produced by other manufacturers. With the exception of a single (11.1%) study, the remaining eight (89.9%) studies reported a high level of genetic proximity between the majority of M. chimaera isolates derived from cardiac surgery-associated patients and LivaNova HCDs. In-depth analysis revealed involvement of three distinct M. chimaera subgroups in the outbreak (1.1, 1.8, 2.1), with 1.1 suggested as causative of the outbreak. Samples taken at the LivaNova production site supported contamination with strains of subgroups 1.1 and 1.8. In the combined analysis of 526 publicly available WGS data sets, nearly all isolates from cardiac surgery-associated patients contained strain 1.1 (50/52, 96.2%), and at least one of the outbreak strains was found in almost all LivaNova HCDs (241/257, 93.8%), with strain 1.1 in particular present in 198/257 (77.0%). CONCLUSIONS HCD contamination during production seems plausible as the predominant point source for the global M. chimaera outbreak. Although HCDs can be contaminated with mixed populations, M. chimaera strains of the subgroup 1.1 caused most infections