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.

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.
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.
Whole-genome sequencing of US HCU-associated M. chimaera isolates and their comparisons with global HCU-associated isolates provides further evidence for point-source contamination and worldwide dissemination of a M. chimaera strain (3)(4)(5). Twenty-two of 24 (92%) US patient isolates associated with HCU exposure during cardiac surgery phylogenetically clustered with international HCU-derived and post-cardiac surgery patient isolates, including those from Australia, Europe, and New Zealand (HCU1). None of the 8 US non-HCU-associated isolates were genetically similar to the HCU1 or HCU2 clusters. Isolates from US post-cardiac surgery patients were genetically more similar to isolates derived from international LivaNova 3T HCUs (mean pairwise distance 4 SNPs) than M. chimaera isolates from US patients without a history of cardiac surgery (mean pairwise distance 511 SNPs). This evidence supports the hypothesis that US post-cardiac surgery M. chimaera infections were acquired from exposure to factory-contaminated HCUs rather than local populations of waterborne M. chimaera in each hospital. Our analyses revealed that all US M. chimaera isolates associated with LivaNova 3T HCU exposure genetically cluster with HCU1 genotype isolates implicated in the global outbreak of post-cardiac surgery M. chimaera infections. The HCU2 cluster was not observed in the United States but included 2 isolates from HCUs in Australia, as well as a representative genotype of M. chimaera found in HCUs in Europe and at the HCU production site. Consistent with previous findings, this finding suggests the international circulation of a second, less plentiful, strain in the manufacturing site water system (8).
These observations support the hypothesis that the LivaNova 3T HCU design provided suitable conditions for both NTM colonization and aerosolization, particularly by M. chimaera. Even though production site contamination with M. chimaera has been confirmed, the medical community needs to remain alert for HCU-associated NTM infections involving other species (4). HCUs are vulnerable to contamination from in-hospital water sources, use of improper water sources, and improper maintenance, each of which may increase the risk of infection by NTM (including M. abscessus, M. chelonae, and M. gordonae, in addition to M. chimaera) (6). Contaminated HCUs may contain NTM-contaminated biofilms. Furthermore, water from the LivaNova 3T HCUs can become aerosolized during normal function, leading to introduction of potentially infectious particles into the sterile field, onto graft materials, or into the open chest cavity during cardiac surgery. The death rate for HCU-associated M. chimaera infections has been reported to be 50%; the latent period to diagnosis can be up to 5 years postsurgery (4,6,7,9,10), further emphasizing necessary diligence on the part of physicians and cardiac surgery patients to monitor for symptoms of disseminated NTM infection.
Our study has some limitations in methodology. We did not obtain samples from every US hospital that reported LivaNova 3T HCU-associated M. chimaera cases; no submitting hospital collected all 3 types of samples (HCUs, non-HCU samples, and suspected case-patients); and HCU samples were not collected by a single person or according to a standardized collection protocol. Despite these limitations, this analysis of US HCU-associated M. chimaera isolates clearly shows the clustering of isolates from epidemiologically linked US cases to international LivaNova 3T HCU M. chimaera isolates and the HCU1 genotype found within the LivaNova manufacturing site.
In conclusion, the application of WGS has advanced our understanding of M. chimaera present in US LivaNova 3T HCUs and patient cases after the initial analysis of suspected cases in Pennsylvania and Iowa. Given the innate drug resistance and the high death rate of HCU-associated M. chimaera infections, it remains imperative for hospitals to follow Food and Drug Administration guidelines (9) and the manufacturer's instructions to minimize the risk of patient infection. In addition, clinicians should monitor patients who have had cardiac surgery using LivaNova 3T HCUs for signs and symptoms of NTM infection to enable early diagnosis and treatment. From the Greek Khimaira, Latin Chimaera; she-goat. In Greek mythology: a composite creature with the body and head of a lion, a goat's head rising from its back, and a serpent's tail. In science: an individual organism whose body contains cell populations derived from different zygotes, of the same or different species. Each population of cells keeps its own character, and the resulting animal is a mixture of tissues. Chimera also refers to a substance created from proteins or genes of 2 species, as by genetic engineering. Chimerism is rare in humans; ≈40 cases have been reported.