Insidious Risk of Severe Mycobacterium chimaera Infection in Cardiac Surgery Patients

Abstract

Background: An urgent UK investigation was launched to assess risk of invasive Mycobacterium chimaera infection in cardiothoracic surgery and a possible association with cardiopulmonary bypass heater-cooler units following alerts in Switzerland and The Netherlands.

Methods: Parallel investigations were pursued: (1) identification of cardiopulmonary bypass-associated M. chimaera infection through national laboratory and hospital admissions data linkage; (2) cohort study to assess patient risk; (3) microbiological and aerobiological investigations of heater-coolers in situ and under controlled laboratory conditions; and (4) whole-genome sequencing of clinical and environmental isolates.

Results: Eighteen probable cases of cardiopulmonary bypass-associated M. chimaera infection were identified; all except one occurred in adults. Patients had undergone valve replacement in 11 hospitals between 2007 and 2015, a median of 19 months prior to onset (range, 3 months to 5 years). Risk to patients increased after 2010 from <0.2 to 1.65 per 10000 person-years in 2013, a 9-fold rise for infections within 2 years of surgery (rate ratio, 9.08 [95% CI, 1.81-87.76]). Endocarditis was the most common presentation (n = 11). To date, 9 patients have died. Investigations identified aerosol release through breaches in heater-cooler tanks. Mycobacterium chimaera and other pathogens were recovered from water and air samples. Phylogenetic analysis found close clustering of strains from probable cases.

Conclusions: We identified low but escalating risk of severe M. chimaera infection associated with heater-coolers with cases in a quarter of cardiothoracic centers. Our investigations strengthen etiological evidence for the role of heater-coolers in transmission and raise the possibility of an ongoing, international point-source outbreak. Active management of heater-coolers and heightened clinical awareness are imperative given the consequences of infection.

Keywords: aerosol release; cardiac surgical procedures.; disease outbreaks; equipment contamination; nontuberculous mycobacteria.

Figure 1.

Holes (highlighted by the red circles) close to the flow and return pipes of both heater-cooler circuits and gap between tank sealing plates identified by an aerodynamic particle sizer as areas of aerosol release.

Figure 2.

Mean (n = 6) number of particles released from a series of holes close to the flow and return pipes of the patient circuit. The number of particles detected after the holes had been sealed with adhesive putty is also shown. The mean number of particles detected after the holes had been sealed was similar to that detected when the valves were closed (ie, when the heater-cooler unit was not circulating water), hence an overlapping distribution.

Figure 3.

Assessment of risk of Mycobacterium chimaera infection following cardiac valve repair or replacement in England, 2007–2014. Abbreviations: CI, confidence interval; PY, person-years.

Figure 4.

Comparison of risk of invasive Mycobacterium avium complex disease in persons living with HIV, the general population (defined as individuals not known to be HIV infected or to have undergone cardiac valve repair or replacement), and patients undergoing cardiac valve replacement or repair, England, 2007–2014. Risk of M. avium complex infection was compared for different population groups. For patients undergoing cardiac replacement, these isolates were identified specifically as M. chimaera as part of this investigation. Abbreviations: HIV, human immunodeficiency virus; PY, person-years.

Figure 5.

Recombination-corrected maximum likelihood phylogenetic tree of Mycobacterium chimaera isolates (n = 191). Data were subsampled to one isolate per patient by including only the first isolate from serially sampled patients or one at random in the absence of any sample date information. The tree is midpoint rooted and branch lengths are scaled in units of the number of single-nucleotide polymorphisms (SNPs) per genome. Branches are colored according to their corresponding bootstrap support value, estimated from 100 bootstrap replicates (gray, <70; black, ≥70). Three strongly supported clusters of closely related isolates are annotated on the tree with the corresponding bootstrap value displayed below the branch (defined as clusters supported by a bootstrap value ≥70, comprising >10 isolates, in which isolates are within 13 SNPs of their closest isolate). Isolates within cluster 1 were sampled over 6.6 years across all 4 National Health Service regions. The 2 panels to the right of the tree show the source and region of each isolate in the tree.