Summary assessment of public health risk associated with Mycobacterium chimaera infections in patients exposed to heater-cooler devices in Canada

Table of contents

• Risk assessment
• Event summary
• Pathogen characteristics
• Heater-cooler devices
• Summary of literature
• Guidance for Canada
• Risk information
• Summary of risk assessment
• Bibliography
• For more information

Risk assessment

The public health risk of infections with Mycobacterium chimaera (M. chimaera), one type of non-tuberculous mycobacterium (NTM), in Canadian patients exposed to heater-cooler devices (HCD) used during cardiopulmonary bypass is currently not defined, but believed to be low to medium. The number of confirmed cases internationally is small compared to the number of patients exposed to heater-cooler devices while undergoing cardiopulmonary bypass surgery. However, given the long latency period, additional cases should be expected and our understanding of the exact risk is expected to improve as new information becomes available.

To date, only the Stöckert 3T heater-cooler devices manufactured by LivaNova PLC (formerly Sorin Group Deutschland GmbH) before September 2014 have been associated with M. chimaera infections.

In determining public health risk, many factors are considered in estimating the impact or severity of the disease, such as morbidity, mortality and complications, the burden of the disease, as well as its infectiousness, mode of transmission, period of communicability, length of incubation and asymptomatic period. Impact also depends on the availability of interventions that may contain, reduce or eliminate the transmission of the infectious agent, including treatment, prophylaxis and other control measures, and the health system's ability to accommodate a surge in demand.

While the magnitude of risk of exposure to M. chimaera is uncertain, the risk of delaying cardiac surgery is generally considered far greater than the risk posed by this infection, even when the infection risk has not been entirely mitigated. Transmission of NTM, such as M. chimaera, between persons is extremely rare and public health case management is not required.

This assessment is based on limited available evidence and is subject to review and change as new information becomes available.

Event summary

Cases of M. chimaera infection associated with HCDs were first reported in 2014 in Europe and have since been reported internationally.^{Footnote 1}

Tests conducted at the LivaNova manufacturing site in Germany (in 2014-2015) confirmed the presence of M. chimaera in samples taken in the pump assembly area and from newly manufactured HCDs. Genetic epidemiology studies have linked the isolates responsible for patient infections with the organisms recovered from Germany, suggesting the devices became contaminated from a point-source. Although NTM contamination of various HCD brands has been reported, only Sorin / LivaNova HCDs manufactured before September 2014 have been associated with M. chimaera-infected patients.

LivaNova PLC implemented a new disinfection and drying process (involving disinfection of new HCDs prior to shipment) at the production facility in mid-August 2014 to supplement the pre-existing cleaning and disinfection process. In addition, the company implemented monitoring for the presence of NTM at the manufacturing site. In October, 2016 LivaNova issued a field safety notice recommending, if feasible, any 3T HCDs suspected to be contaminated with NTM based on results of healthcare facility's testing or other information known by the hospital, be removed from service, and to contact the manufacturer to arrange for a deep-disinfection service prior to further use. There have been practical challenges identified with the implementation of this recommendation in some centres.

Health Canada issued a risk communication notice in October 2016 to notify healthcare facilities, providers and hospital staff responsible for operating and maintaining HCDs of important safety information on HCDs, the risk of NTM, and reiterating recommendations from the manufacturer.

The Montreal Heart Institute issued a Communication Notice on October 24, 2016, indicating that two patients were diagnosed with M. chimaera infection. These are the first confirmed cases linked to contaminated HCDs used during cardiopulmonary bypass surgery in Canada.

In January 2017 the Canadian Public Health Laboratory Network issued updated interim laboratory testing guidance for the detection of NTM infections in post-operative patients exposed to HCDs. The interim guidance was developed in collaboration with the Public Health Agency of Canada and its Infection Prevention and Control Expert Working Group.

Pathogen characteristics

M. chimaera is a slow growing NTM that was identified as a species of the Mycobacterium avium complex in 2004. This mycobacterium is widespread in nature and can be found in soil and water, including drinking water sources. These bacteria can occasionally cause infection in vulnerable patients, including those with compromised immune systems and underlying medical conditions. Transmission of NTM from person to person is extremely rare.

While M. chimaera infection has been associated with lung infections in vulnerable patients and those with underlying medical conditions, contaminated HCDs provide an unusual mechanism of potential infection by generating aerosols that can carry the organism during cardiopulmonary bypass surgery. This can deposit NTMs directly into the surgical site, which can lead to invasive disease that can be difficult to cure. Although the overall risk of infection from contaminated HCDs is considered low for patients that undergo cardiopulmonary bypass surgery, there are a number of challenges associated with diagnosis and treatment. Due to the nature of this slow growing bacterium, it can take months to years for the infection to evolve and for patients to manifest clinical illness. Symptoms of the infection can be non-specific, making its distinction from other, more common causes of infection, challenging. Infections of M. chimaera are difficult to treat and require prolonged, carefully monitored administration of a combination of antimicrobials. These antimicrobials have their own associated toxicities. Repeat surgery may be required and there is a high rate of treatment failure and fatal outcome associated with invasive infections.

Heater-cooler devices

HCDs are non-sterile devices used in operating rooms during procedures, including cardiopulmonary bypass surgery, where the patient's blood temperature needs to be heated or cooled. The HCD sits outside of the sterile field, but usually within the operating room.

The devices consist of water tanks that provide temperature-controlled water through closed water circuits to warming/cooling blankets or external heat exchangers. Patient temperature regulation is achieved by convection through the blankets or heat exchangers. Water from the closed circuit of heater-cooler devices does not come into contact with patients' blood or bodily fluids. However, multiple studies have confirmed the transmission of NTM via aerosolization of contaminated water in HCDs into the operating room, potentially exposing the patient during surgery.

Summary of literature

A number of challenges in management of the current M. chimaera outbreak have been identified in the literature. This includes limited laboratory capacity for identification of M. chimaera, delayed diagnosis of infection (due to the mycobacterium's long latency period and slow growth), prolonged therapy with multiple agents, poor response to antimycobacterial therapy, and uncertain reliability of HCD decontamination protocols.

In an effort to mitigate risk of exposure and infection, as well as to facilitate earlier diagnosis of infection, the following control measures have been described in the existing literature although there is limited data confirming that these measures prevent infection.

• Healthcare provider notification and education.
• Patient notification.
• Enhanced prospective surveillance.
• Identification of contaminated HCDs by microbiological testing.
• Replacement of contaminated HCDs including accessories, tubing, and connectors to prevent recontamination.
• Use of manufacturer's updated cleaning and disinfection protocols.
• Routine microbiological testing of HCDs in use.^{Footnote 2}
• Engineering solutions to enable air separation between HCD exhaust air and operating room air.
• Improved engineering for alternative design to mitigate transmission of infection.

Guidance for Canada

Hospitals performing cardiopulmonary bypass surgery should identify and assess which HCDs are being used in their facility and increase awareness among health care professionals about the risk of infection associated with these devices.

For additional background information, key messages on this issue and action taken by Health Canada, refer to Health Canada's Risk Communication.

Health Canada encourages healthcare professionals to report any cases of patient infection thought to be associated with the use of devices. The Medical Devices Problem Report Form and Guidelines can be found on the Health Canada Web site.

For information describing clinical syndromes compatible with M. chimaera, as well as patient specimen and testing criteria, refer to the Canadian Public Health Laboratory Network's (CPHLN) Interim laboratory testing guidance for the detection of non-tuberculous Mycobacterium (NTM) infections in post-operative patients exposed to heater-cooler units.

For device testing recommendations, refer to the Canadian Public Health Laboratory Network (CPHLN) Device Testing Recommendations regarding Non-Tuberculous Mycobacteria (NTM) Contamination in Heater-Cooler Units.

For a summary of currently recommended risk mitigation measures from peer reviewed literature and additional background information, refer to the May 2017 (volume 43-5) issue of the Canada Communicable Disease Report.

Risk information

Risk information table

Questions	Evidence from Summary of Literature	Quality of Evidence	Comments
Are there patients at increased risk of infection?	Major cardiothoracic surgery involving cardiopulmonary bypass Implantation of prosthetic cardiac devices Heart transplant Exposure to Stöckert 3T HCDs manufactured before September 2014 by LivaNova PLC (formerly Sorin Group Deutschland GmbH)	Medium	Prosthetic material is not always a prerequisite for infection; a recently reported case occurred after coronary-artery bypass surgery with sternal wires as the only foreign material
Is M. chimaera highly infectious for exposed patients?	The Centers for Disease Control and Prevention (CDC) estimates in hospitals where at least one M. chimaera infection associated with exposure to HCD has been identified, the risk of a patient getting an infection was between approximately 1 in 1000 and 1 in 100 (0.1-1%).	High
Are exposed patients more vulnerable to M. chimaera?	No evidence available	N/A	Cardiac surgery creates a breach in normal host defences
Is M. chimaera likely to cause significant morbidity in affected patients?	Majority of infections were endocarditis, graft infection, disseminated, and other severe infection	Medium	Patients who develop M. chimaera infection are more likely to have increased morbidity with surgical re-interventions and potential complications, prolonged hospital stays, and complications related to treatment side effects and/or treatment failure.
Is M. chimaera likely to cause significant mortality in affected patients?	In Europe, as of 20 January, 2017, at least 15 fatal outcomes have been reported among 53 cases of M. chimaera infection associated with HCD exposure, but not all deaths were attributed to the infection In the USA, as of 28 July, 2016, of the 24 cases identified across 4 US health centres, the crude mortality rate was 46%.	Medium	There are limitations with data informing mortality rate as the study sizes are very small and co-morbidities have been reported. Reported mortality rates range from <28% to 50%. Studies reporting mortality rates at the higher end of the range are most often reporting on cases of severe infection. Timely detection of infection and initiation of therapy may decrease mortality rates.
Is there a significant number or proportion of patients affected among those exposed to HCDs?	Number of confirmed cases is relatively small compared to the number of patients undergoing cardiopulmonary bypass surgery True magnitude of risk is uncertain due to very limited data	Medium	Given the long latency period, additional cases should be expected
Are effective treatment measures available?	M. chimaera infection is difficult to treat as therapy is usually prolonged, requires multiple antimycobacterial agents and often fails to respond to appropriate treatment. Disseminated infection have often required surgical re-interventions with high fatality rates	Low	Patient outcomes are yet to be improved, especially for those with disseminated infection
Are effective control measures available?	Several risk mitigation measures have been recommended Further investigation is required to determine the efficacy of risk mitigation measures in reducing the risk of NTM infection associated with HCDs	Low	The feasibility of implementing and optimizing current risk mitigation measures is yet to be determined

Summary of risk assessment

Likelihood of M. chimaera Infection

Given that the infection is not reportable in many countries, the true number of cases globally is likely unknown. However, the number of known cases world-wide is small compared to the very large number of patients undergoing cardiopulmonary bypass surgeries on an annual basis. This suggests that M. chimaera is not highly infectious for exposed patients despite their vulnerability due to the breach in normal host defences as a result of surgery. Although more cases are likely to be identified due to the long latency period, the current likelihood of infection is considered LOW.

Impact of M. chimaera Infection

The morbidity is important in affected patients. The high mortality rate is estimated based on limited known cases and the number of deaths directly attributable to the infection is currently unknown. Although control measures have been recommended, feasibility of implementation remains a challenge and not all measures can eliminate the risk of infection. Treatment options are available and can be pursued depending on individual patient characteristics such as co-morbidities. Early diagnosis and treatment with effective antimycobacterial therapy may help prevent the progression to severe illness. There may be significant adverse effects to treatment and possible treatment failure for disseminated infections. The impact is currently estimated as a range of LOW to MEDIUM.

Overall risk assessment

Taking into account the likelihood and impact of M. chimaera infection, and based on currently available data, the risk is considered LOW to MEDIUM.

Figure 1 - Risk matrix

Likelihood	Impact
	Very Low	Low	Medium	High
High	Medium risk	Medium risk	High risk	High risk
Medium	Low risk	Medium risk	Medium risk	High risk
Low	Low risk	Low risk	Medium risk	Medium risk
Very Low	Very low risk	Low risk	Low risk	Medium risk

Figure 1 - Text equivalent

The risk matrix has four categories of risk for both likelihood of infection and impact including high, medium, low and very low. Likelihood of infection is displayed along the y axis starting with high followed by medium, low and very low. Impact is displayed along the x axis starting with very low on the left followed by low, medium and high moving to the right.

The 16 cells within the matrix identify level of risk based on likelihood and impact of infection combined.

The likelihood of infection for each category (high, medium, low and very low) combined with very low impact produces the following results in the risk matrix:

• High likelihood of infection combined with very low impact would be medium risk.
• Medium likelihood of infection combined with very low impact would be low risk.
• Low likelihood of infection combined with very low impact would be low risk.
• Very low likelihood of infection combined with very low impact would be very low risk.

The likelihood of infection for each category (high, medium, low and very low) combined with low impact produces the following results in the risk matrix:

• High likelihood of infection combined with low impact would be medium risk
• Medium likelihood of infection combined with low impact would be medium risk
• Low likelihood of infection combined with low impact would be low risk
• Very low likelihood of infection combined with low impact would be low risk

The likelihood of infection for each category (high, medium, low and very low) combined with medium impact produces the following results in the risk matrix:

• High likelihood of infection combined with medium impact would be high risk
• Medium likelihood of infection combined with medium impact would be medium risk
• Low likelihood of infection combined with medium impact would be medium risk
• Very low likelihood of infection combined with medium impact would be low risk

The likelihood of infection for each category (high, medium, low and very low) combined with high impact produces the following results in the risk matrix:

• High likelihood of infection combined with high impact would be high risk
• Medium likelihood of infection combined with high impact would be high risk
• Low likelihood of infection combined with high impact would be medium risk
• Very low likelihood of infection combined with high impact would be medium risk

Based on currently available data, the current likelihood of infection is considered low and impact is estimated as a range of low to medium. Within the image, the shaded boxes low risk to medium risk are formatted in bold to indicate an overall risk of low to medium.

Bibliography

Resources informing this document including peer reviewed publications and relevant international guidance are listed below.

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