In 2012, a mysterious microbe began surfacing in a small percentage of patients who had recently undergone open-heart surgery. Within 3 years, Mycobacterium chimaera—a distant cousin of the pathogen that causes tuberculosis—had infected at least 49 people around the world, and killed more than half of them. Scientists eventually traced the outbreak to contaminated medical equipment used during heart surgery, but it remained unclear how M. chimaera could have contaminated the equipment in the first place. Now, a new study concludes that the infections likely originated from the device’s production site in Germany.
“This seems like a cut and dry case,” says Jack Gilbert, a microbial ecologist at the University of Chicago in Illinois who wasn’t involved with the study. “It is fascinating work, [and the authors possess] a unique forensic ability to track infections to a point source.”
The medical device’s manufacturer, LivaNova, based in London, however, has denied that its instrument is the source of the infections and is currently defending itself against lawsuits from patients and families of patients who died. In a statement provided to Science, the company argues that the new study draws too strong a link between the reported infections and its equipment. “LivaNova is concerned that the article expresses a level of certainty about a point source tie to the manufacturing process that is not warranted by the data.”
M. chimaera is commonly found in soil and water. Although physicians have reported occasional lung infections related to the bacterium, it wasn’t considered a public health menace until it began popping up in people 5 years ago. Once it gets into the heart, it inflames the organ’s inner lining and spreads to other parts of the body. It is resistant to most antibiotics and frequently fatal. “Most of the patients we identified have already died,” says microbiologist Erik Böttger at the University of Zurich in Switzerland, who is part of new study. “There’s very little you can do.”
Previously, Böttger and colleagues worked with their international counterparts to narrow down the factors the patients had in common. One operating room device kept surfacing: a heating and cooling unit (HCU) made by LivaNova (previously known as Sorin). During heart surgery, a patient’s blood is circulated through the HCU to regulate their body temperature. Other times, the machines are connected to warming and cooling blankets. About 60% of HCUs in European, U.S., and Australian hospitals are made by LivaNova.
The units heat and cool reservoirs of water, and researchers suspected that as the device ventilated heat or pumped water to the blankets, tiny droplets became aerosolized and spread through the operating room, carrying microbes with them. They sampled the water inside the HCUs at the hospitals where people had been infected, and indeed found M. chimaera in abundance.
In a report published in today’s issue of The Lancet, Böttger and his collaborators investigated whether these far-flung bacteria had a common origin, or whether they were introduced locally at each hospital. They sequenced the whole genomes of the bacteria found in several places: inside 21 patients’ hearts, inside and around their hospitals’ HCU machines, within tap water and drinking water dispensers at the hospitals, and at LivaNova’s production site in Munich, Germany.
The researchers report that 20 of the 21 patients’ bacteria were closely related to each other and to the bacteria inside the HCUs, and conclude that this particular strain likely came from LivaNova’s Munich factory. They discovered strains of M. chimaera elsewhere in the hospitals—the origin of those remains a mystery—but they were all much more distantly related to the killer strain, suggesting a single origin for the outbreak in the patients.
In the course of the investigation, the researchers also found that HCUs produced by a different manufacturer—Maquet, based in Rastatt, Germany—were contaminated with M. chimaera, as was that company’s production facility. That strain, however, isn’t known to have infected anybody.
It’s not clear exactly how M. chimaera could infiltrate the clean rooms inside LivaNova’s and Maquet’s production facilities, but LivaNova has issued cleaning procedures for its device that the company says will eliminate the bacteria. Its statement to Science also notes that the samples from its production facility analyzed in the study were taken before the company overhauled its disinfection procedures in 2014 and therefore don’t reflect the safety of its current product. The company adds that it has updated the device’s vacuum and seal systems to prevent aerosolized particles from escaping, and is loaning these updated units at no charge to hospitals that request them.
Böttger says simply cleaning these machines isn’t good enough, and that any HCU design with an open water tank is fundamentally susceptible to infection—if not from contamination at the factory, then from microbes in the hospital. The U.S. Centers for Disease Control and Prevention and European Centre for Disease Prevention and Control have both issued warnings to hospitals that use the units, but so far there isn’t a widely available alternative.
Patients and their families in the United States have brought lawsuits against LivaNova, which are still being litigated. Böttger hopes that both legal pressure and scientific scrutiny will compel hospitals to remove HCUs that use open water reservoirs from their operating rooms. “We hope that having described this problem, we have finally solved it,” he says.