Factory contamination of medical device likely source of M. chimaera infection in patients in multiple countries

Identifying the likely moment of contamination during the production of heater-cooler units could help stop the outbreak. But at least one patient in the study might have been infected from a locally contaminated heater-cooler unit in the operating room. The authors caution against prematurely closing the outbreak investigation since hospital water systems and another brand of heater-cooler units, Maquet, was also found to be contaminated during production and use. Therefore, the infectious risk might persist despite controlling contamination at the LivaNova production line.

Infection with M. chimaera bacteria during open-heart surgery can cause prosthetic valve endocarditis (infection of the inner lining of the heart) and spread to the rest of the body. It is rare during open-heart surgery (UK estimates suggest 1 in 5000 patients), but potentially fatal. Since 2013, over 100 cases of M. chimaera infection have been reported in the EU, the US, and Australia, and many countries have issued guidance to reduce the risk of infection.

Previous studies have suggested a link to contaminated heater-cooler units used during open-heart surgery, but until now, there has been no firm evidence linking the global outbreak to a source, whether at a production site or local hospitals.

The new study analysed the DNA from a total of 250 M. chimaera samples. This included samples from 21 open-heart surgery patients in Switzerland, Germany, the Netherlands, and the UK, as well as samples collected from LivaNova and Maquet heater-cooler units, other water-containing medical devices, tap water, and drinking water dispensers in hospitals. LivaNova and Maquet contributed samples from their production sites.

In addition, the researchers included samples from patients with M. chimaera from Switzerland, Germany, the Netherlands and the UK who had not undergone open-heart surgery.

The similarity of samples from almost all patients with M. chimaera infection following open-heart surgery strongly points to a common source of infection. Based on high degrees of similarity between isolates of M. chimaera in these patients' samples, samples from LivaNova heater-cooler units and from the LivaNova production site, the authors say that it is probable that LivaNova heater-cooler units represent the common source of infection and that contamination occurred during production.

The researchers also compared their findings to publically available datasets containing samples from open-heart surgery patients from the US and Australia, matching 12 additional patients to the LivaNova production site.

Professor Stefan Niemann, National Centre for Mycobacteria, Forschungszentrum Borstel, Germany, and co-author of the study says: "Molecular epidemiological investigation by applying whole genome sequencing is the most powerful tool for tracing pathogen transmission. Our study closes the missing gap and provides evidence that the international health-care related M. chimaera outbreak can most likely be attributed to a point source."

Professor Dr Hugo Sax, University Hospital Zurich, Switzerland, and co-author of the study, adds: "Local contamination of heater-cooler units with M chimaera also occurred and at least one patient could have been infected through this route. Operating rooms and other hospital settings with patients at increased risk of infection should be devoid of such uncontrolled water sources."

The authors note that they were not able to link individual patients to individual heater-cooler units. Whereas in total there was a large number of samples, there were relatively few samples taken from tap water, heater-cooler water, and air samples to reliably pinpoint exact transmission events.