Genomic Analysis of Cardiac Surgery–Associated Mycobacterium chimaera Infections, United States

A surgical heater-cooler unit has been implicated as the source for Mycobacterium chimaera infections among cardiac surgery patients in several countries.We isolated M. chimaera from heater-cooler units and patient infections in the United States.Whole-genome sequencing corroborated a risk for these units acting as a reservoir for this pathogen.M ycobacterium chimaera is a species in the Mycobac- terium avium complex (MAC) (1).MAC is the most frequently reported cause of nontuberculous mycobacterium (NTM) infection in the United States, although disseminated M. chimaera infections are relatively rare (2).In 2012, investigators in Switzerland found that some patients with disseminated M. chimaera infections had undergone open-chest cardiac surgeries, during which they were exposed to heater-cooler units (HCUs) (3).These devices, Stöckert 3T Heater-Cooler Units (LivaNova PLC, https:// www.livanova.com;formerly Sorin Group Deutschland GmbH), manufactured in Germany, were unknowingly contaminated with M. chimaera (4,5).In the same year, a Pennsylvania hospital identified a cluster of invasive M. chimaera infections among open-chest cardiac surgery patients exposed to LivaNova 3T HCUs contaminated with M. chimaera (6), which prompted notification of ≈1,300 patients with exposure to these units (7).Additional cases of disseminated M. chimaera infection among cardiac surgery patients have emerged worldwide, with evidence implicating bioaerosols produced by contaminated Liva-Nova 3T HCUs as the source of post-cardiac surgery M. chimaera infections (8,9).We report the relationships among HCU-associated isolates from patients and LivaNova 3T HCUs in the United States and their context among the global outbreak.The Study During 2015-2016, we collected NTM isolates from 3T HCU water (n = 38 isolates) and suspected patient cases (n = 24 isolates) from 8 US locations.We identified isolates and conducted high-throughput whole-genome sequencing using the Illumina Miseq system (https://www.illumina.com).We selected Pennsylvania isolate 2015-2271 (USA_PA_PAT_9) for Pacific Biosciences (https:// www.pacb.com)single-molecule real-time sequencing (10).We downloaded publicly available M. chimaera genomes from isolates collected in Australia, Denmark, Italy, New Zealand, the United Kingdom, and Switzerland from the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA).We included Zürich CHE_HCU_1 isolate as a representative of the genotype isolated from HCUs, patients, and manufacturing sites in Europe (9).For each isolate, we mapped the sequence reads to the M. chimaera strain CDC 2015-22-71 reference genome (GenBank accession no.NZ_CP019221.1) to detect single-nucleotide polymorphisms (SNPs) (Appendix, http:// wwwnc.cdc.gov/EID/article/25/3/18-1282-App1.pdf).We reconstructed phylogenetic relationships among M. chimaera isolates collected from post-cardiac surgery patients and HCUs in 8 locations across the United States, as well as HCU-associated strains from Australia, New Zealand, and Europe (Table ; Appendix Figure 1).We compared all HCU-associated isolates with 7 M. chimaera respiratory isolates obtained from US patients with no history of cardiac surgery.We identified 18,190 SNPs in the 3.82-Mb core genome (62.8% of the reference genome) among 126 M. chimaera isolates.The NeighborNet splitstree (Appendix) of M. chimaera showed 3 groups (HCU1, HCU2, and non-HCU; Figure 1).Clade HCU1 (n = 112 isolates; Figure 2) is a discrete cluster composed entirely of HCU-associated isolates from case-patients and HCUs (mean pairwise distance 4 SNPs, range 0-23 SNPs; Appendix Figure 2) from Australia, Genomic Analysis of Cardiac Surgery-Associated Mycobacterium chimaeraInfections, United States