Mycobacterium chimaera Genomics With Regard to Epidemiological and Clinical Investigations Conducted for an Open Chest Postsurgical Mycobacterium chimaera Infection Outbreak

Abstract

Background Post-surgical infections due to Mycobacterium chimaera appeared as a novel nosocomial threat in 2015, with a worldwide outbreak due to contaminated heater-cooler units used in open chest surgery. We report the results of investigations conducted in France including whole genome sequencing comparison of patient and HCU isolates. Methods We sought M. chimaera infection cases from 2010 onwards through national epidemiological investigations in healthcare facilities performing cardiopulmonary bypass together with a survey on good practices and systematic heater-cooler unit microbial analyses. Clinical and HCU isolates were subjected to whole genome sequencing analyzed with regards to the reference outbreak strain Zuerich-1. Results Only two clinical cases were shown to be related to the outbreak, although 23% (41/175) heater-cooler units were declared positive for M. avium complex. Specific measures to prevent infection were applied in 89% (50/56) healthcare facilities although only 14% (8/56) of them followed the manufacturer maintenance recommendations. Whole genome sequencing comparison showed that the clinical isolates and 72% (26/36) of heater-cooler unit isolates belonged to the epidemic cluster. Within clinical isolates, 5 to 9 non-synonymous single nucleotide polymorphisms were observed, among which an in vivo mutation in a putative efflux pump gene observed in a clinical isolate obtained for one patient under antimicrobial treatment. Conclusions Cases of post-surgical M. chimaera infections were declared to be rare in France, although heater-cooler units were contaminated as in other countries. Genomic analyses confirmed the connection to the outbreak and identified specific single nucleotide polymorphisms, including one suggesting fitness evolution in vivo.

Mitigation of nontuberculous mycobacteria in hospital water: challenges for infection prevention

“…More recently, MALDI-TOF and whole-genome sequencing (WGS) with evaluation of single nucleotide polymorphisms (SNP) of patient and environmental isolates have been utilized adjunctively in outbreak investigations with good reproducibility [28 ▪ ,43 ▪▪ ,46 ▪ ,47,48,49 ▪ ]. In fact, retrospective analysis of prior outbreaks using WGS and SNP has been performed, most notably to confirm the source of a widespread M. chimaera outbreak in heater-cooler units used in open chest surgery [43 ▪▪ ].…”

“…Genotypic methods have emerged as an important method of accurate identification of NTM species, as well as to confirm outbreak and pseudo-outbreak sources [1,8,42]. Emergence of these newer methods of identification has been revolutionary in early identification of mycobacteria present in environmental and clinical samples [28 ▪ ,43 ▪▪ ].…”

“…Pulsed-field gel electrophoresis (PFGE), a genotypic method that defines genetic relatedness based on similarity of electrophoretic banding, subsequently became the standard of practice in the early 1990s, and has since been supplanted by more sophisticated methods of identification including commercial DNA probes, PCR amplification followed by PCR restriction-enzyme analysis (PRA), and 16s rRNA rpoB, hsp65 , and other gene sequencing [1,2,8,42,44,45]. More recently, MALDI-TOF and whole-genome sequencing (WGS) with evaluation of single nucleotide polymorphisms (SNP) of patient and environmental isolates have been utilized adjunctively in outbreak investigations with good reproducibility [28 ▪ ,43 ▪▪ ,46 ▪ ,47,48,49 ▪ ]. In fact, retrospective analysis of prior outbreaks using WGS and SNP has been performed, most notably to confirm the source of a widespread M. chimaera outbreak in heater-cooler units used in open chest surgery [43 ▪▪ ].…”

“…In fact, retrospective analysis of prior outbreaks using WGS and SNP has been performed, most notably to confirm the source of a widespread M. chimaera outbreak in heater-cooler units used in open chest surgery[43 …”

Whole Genome Sequencing in the Management of Non-Tuberculous Mycobacterial Infections

“…The first outbreak investigation began in 2013 at the University Hospital Zurich in patients with confirmed presence of M. chimaera after cardiac surgery [103]. WGS epidemiological analysis in other studies demonstrated that aerosols from the water tanks in the heatercooler units contaminated with M. chimaera can be airborne disseminated to patients and the surrounding environment [87,[104][105][106][107][108]. In this context, Götting et al found the genetically related M. chimaera contaminated the air of the heater-cooler units as well as medical instruments in the operating room [109].…”