The patient turned up at his GP practice clutching a letter to his chest and telling the receptionist “I must see my doctor today!” before bursting in to tears.
The receptionist got a message to the doctor who agreed to slot the patient in to this morning clinic as soon as possible. When the patient was finally seen he presented a letter to the doctor. The letter from Public Health England (PHE) said “patients who have undergone heart surgery (valve and coronary artery bypass grafting) since 2007 were at risk of developing a severe infection, Mycobacterium chimaera. Although the risk remains low patients should contact their GP for further assessment”. The patient explained to his GP that he had had heart valve replacement surgery last year and was now very worried he might be unknowingly infected by a mythological creature.
The receptionist got a message to the doctor who agreed to slot the patient in to this morning clinic as soon as possible. When the patient was finally seen he presented a letter to the doctor. The letter from Public Health England (PHE) said “patients who have undergone heart surgery (valve and coronary artery bypass grafting) since 2007 were at risk of developing a severe infection, Mycobacterium chimaera. Although the risk remains low patients should contact their GP for further assessment”. The patient explained to his GP that he had had heart valve replacement surgery last year and was now very worried he might be unknowingly infected by a mythological creature.
Chimaera - a monstrous creature composed of a lion with the head of a goat rising from its back and a tail that ends with a snake's head!
“Great! Never heard of it” thought the GP, “what do I do now? I probably filed that memo in the ‘I’ll read it later when I have a spare minute’ pile!” …”I know I’ll call the Microbiologist, they seemingly read everything!”
So have you heard about Mycobacterium chimaera and it’s relation to cardiac surgery? Would you know what to do if a patient came in to see you clutching their letter?! No? Then read on…
What is M. chimaera?
Mycobacteria chimaera is a non-tuberculous mycobacterium species; part of what is called the Mycobacterium avium complex, a group of bacteria that are genetically similar and cause similar infections. M. chimaera used to be identified as M. intracelluare but recent changes to the genetic identification of bacteria have now allowed M. chimaera to be distinguished from its closely related cousin. M. chimaera is found throughout the environment, especially in water, including tap water.
It is now known that since 2007 patients undergoing cardiopulmonary bypass operations may have been exposed to M. chimaera from aerosols generated from water tanks of heater cooler units used during this type of surgery (presumably when the relevant type of heater cooler started being used?). These aerosols may settle in the operative field contaminating the wound and any prosthetic material put in to the patient e.g. prosthetic heart valves.
Who is at risk of infection?
The risk is highest for patients who underwent heart valve replacement, 1 in 5,000 operations, but it is much lower for other procedures (e.g. coronary artery bypass grafting) <1 in 100,000 operations. To put this into context the NHS carries out about 5,000 heart valve replacements and 20,000 coronary artery bypass graft procedures every year.
As of writing, there have been 25 cases of M. chimaera infections in the UK but other cases have been identified in other countries.
How does M. chimaera present?
This is where things get a little muddy and confused. The problem is that the clinical presentation of M. chimaera is often very slow and non-specific. The incubation period can be as little as 2 months or as long as 58 months (yep, nearly 5 years after the operation!). In fact the upper limit of the incubation period is not yet known. Immunosuppression is not a particular risk factor for infection.
Infections can present as:
The most common symptoms so far described include fever, malaise, weight loss, cough and shortness of breath. This makes distinguishing infections on the basis of symptoms particularly problematic as most patients undergoing cardiopulmonary bypass have cardiovascular disease and are tired, short of breath and have a cough a lot of the time. So symptoms are not really very helpful from a diagnostic point of view.
How is M. chimaera diagnosed?
Adding to the ambiguity, infection with M. chimaera cannot be diagnosed using conventional diagnostic techniques. These types of bacteria do not grow in routine cultures, so specialist techniques are required.
The mainstay of diagnosis is mycobacterial culture. This uses mycobacteria specific automated liquid culture incubators which with this type of bacterium usually take at least 14 days to grow and can take as long as 42 days before a culture is declared negative. This might sound like a long time but it is better than the solid media methods using Lowenstein-Jensen media which we used when I first started in microbiology these could take up to 12 weeks before they grew anything!
Another method which can be used to supplement culture is 16sRNA PCR, this method detects any bacteria in a sample then uses the genetic sequence to identify the species of bacterium. However, this method has a couple of drawbacks which mean it should not be used instead of culture; firstly 16sRNA is not as sensitive for mycobacteria as other types of bacteria and secondly 16sRNA does not generate any sensitivity testing and therefore it does not help inform any treatment regimens.
How are infections with M. chimaera treated?
Infections with M. chimaera should be treated in the same way as other M. avium complex infections. The current first line regimen includes the combination of a macrolide e.g. Clarithromycin 500mg BD PLUS Rifampicin 600mg BD PLUS Ethambutol 15mg/kg OD PLUS Amikacin 15mg/kg OD. Treatment duration is for 12 to 18 months! It is imperative to try and get a positive culture before starting treatment as the regimen should be tailored to the specific bacterium by looking at sensitivity testing information.
What is the prognosis of M. chimaera infection?
Whilst mycobacterial infections, in general, are often difficult to treat and present late with established infections, these M. chimaera patients are also likely to have multiple comorbidities which mean they do especially badly e.g. cardiovascular disease, diabetes mellitus. This alert from PHE raises specific concerns, as of the 25 cases so far identified in the UK 15 patients have died, including 10 who were already on M. chimaera specific treatment at the time.
So what should we do for these patients who may have been exposed to M. chimaera?
PHE have issued guidance to both primary and secondary care for how to manage these patients. However from the current buzz of activity on the British Infection Association forum these documents are not really very helpful.
The problems are: the rarity of the infection, the commonality of the type surgery, the long incubation period, the non-specific symptoms, the diagnostic difficulties and the seriousness and high mortality from infection if it does occur. These ambiguous factors create the perfect storm and are likely to lead to chaos! Maybe a structured and methodical approach might help…
In Primary Care ask the following question:
Has the patient been on cardiopulmonary bypass since 2007?
NO – reassure the patient and do nothing further
YES - but the patient is well, reassure the patient and make a note of them being at risk in their clinical records but do nothing further
YES - and the patient has symptoms or signs below, discuss with Cardiologist, Infectious Disease Physician or a Microbiologist:
In Secondary Care
Investigate the patient’s symptoms and signs for ALL potential causes not just M. chimaera.
If Infective endocarditis is suspected:
Take 3 sets of mycobacterial blood cultures whilst the patient is off antibiotics; ideally on different days (these require specific blood culture bottles that should be available directly from your pathology department). An alternative method is to send blood samples taken in lithium heparin tubes which can then be inoculated into the mycobacterial blood culture bottle in the laboratory. Do not send EDTA samples as EDTA is inhibitory to the growth of mycobacteria. Consider echocardiography to look for heart valve vegetations if blood cultures are positive.
If wound infection is suspected:
Send pus, tissue or bone for mycobacterial culture. Do not send swabs as these cannot be cultured for mycobacteria.
If disseminated disease is suspected:
Take 3 sets of mycobacterial blood cultures (or lithium heparin blood samples) whilst the patient is off antibiotics. NB It is less important to leave a day between taking each of these samples. Consider sending cultures of any suspect infected tissue e.g. bone, bone marrow, bronchoalveolar lavage.
If ANY of the cultures are positive for M. chimaera then refer the patient to a specialist in the treatment of non-tuberculous infections (usually Respiratory or Infectious Diseases Physicians) as well as a Cardiologist to consider the need for removal of an infected valve, monitoring of treatment and ongoing cardiac damage. Don’t forget to treat any other cause if M. chimaera is not found!
So how do you justify to patients that there is no screening test?
Let’s consider the consequences of doing blood cultures on all asymptomatic at risk patients. If 5,000 asymptomatic heart valve patients were screened there would be a very low positive rate (if any) because the patient doesn’t have symptoms suggesting the bacteria is not in their blood at that time, although they could still go on to have an infection later. The test would lead to false reassurance. Also it would cost a fortune!
A mycobacterial blood culture costs approximately £40 per culture x 3 cultures per patient x 5,000 patients = £600,000 per year and that’s just for the heart valve replacement patients! Add on 20,000 coronary artery bypass graft patients…and the figure reaches £3 million to detect 1 case! Screening would cause massive amounts of anxiety and is more likely to pick up false positives from environmental contamination of blood culture bottles which could result in a “case” being treated with 18 months of unnecessary toxic antibiotics. Let’s not screen but just stick to reassuring asymptomatic patients.
So the GP rang the duty Microbiologist who was relieved that the patient was otherwise well and had no symptoms or signs of infection. The patient was reassured that whilst they had a small risk of infection (1 in 5,000 heart valve replacement) there was nothing more that need to be done at this time. The patient was advised to come back to see the GP if they became unwell. The GP made a note in the patient’s clinical record and called for his next patient… who came in clutching a letter…!
So have you heard about Mycobacterium chimaera and it’s relation to cardiac surgery? Would you know what to do if a patient came in to see you clutching their letter?! No? Then read on…
What is M. chimaera?
Mycobacteria chimaera is a non-tuberculous mycobacterium species; part of what is called the Mycobacterium avium complex, a group of bacteria that are genetically similar and cause similar infections. M. chimaera used to be identified as M. intracelluare but recent changes to the genetic identification of bacteria have now allowed M. chimaera to be distinguished from its closely related cousin. M. chimaera is found throughout the environment, especially in water, including tap water.
It is now known that since 2007 patients undergoing cardiopulmonary bypass operations may have been exposed to M. chimaera from aerosols generated from water tanks of heater cooler units used during this type of surgery (presumably when the relevant type of heater cooler started being used?). These aerosols may settle in the operative field contaminating the wound and any prosthetic material put in to the patient e.g. prosthetic heart valves.
Who is at risk of infection?
The risk is highest for patients who underwent heart valve replacement, 1 in 5,000 operations, but it is much lower for other procedures (e.g. coronary artery bypass grafting) <1 in 100,000 operations. To put this into context the NHS carries out about 5,000 heart valve replacements and 20,000 coronary artery bypass graft procedures every year.
As of writing, there have been 25 cases of M. chimaera infections in the UK but other cases have been identified in other countries.
How does M. chimaera present?
This is where things get a little muddy and confused. The problem is that the clinical presentation of M. chimaera is often very slow and non-specific. The incubation period can be as little as 2 months or as long as 58 months (yep, nearly 5 years after the operation!). In fact the upper limit of the incubation period is not yet known. Immunosuppression is not a particular risk factor for infection.
Infections can present as:
- Infective endocarditis
- Severe disseminated infection (including liver, bone and bone marrow, lungs, lymph nodes, skin, brain and eyes)
- Chronic sternal wound infection
The most common symptoms so far described include fever, malaise, weight loss, cough and shortness of breath. This makes distinguishing infections on the basis of symptoms particularly problematic as most patients undergoing cardiopulmonary bypass have cardiovascular disease and are tired, short of breath and have a cough a lot of the time. So symptoms are not really very helpful from a diagnostic point of view.
How is M. chimaera diagnosed?
Adding to the ambiguity, infection with M. chimaera cannot be diagnosed using conventional diagnostic techniques. These types of bacteria do not grow in routine cultures, so specialist techniques are required.
The mainstay of diagnosis is mycobacterial culture. This uses mycobacteria specific automated liquid culture incubators which with this type of bacterium usually take at least 14 days to grow and can take as long as 42 days before a culture is declared negative. This might sound like a long time but it is better than the solid media methods using Lowenstein-Jensen media which we used when I first started in microbiology these could take up to 12 weeks before they grew anything!
Another method which can be used to supplement culture is 16sRNA PCR, this method detects any bacteria in a sample then uses the genetic sequence to identify the species of bacterium. However, this method has a couple of drawbacks which mean it should not be used instead of culture; firstly 16sRNA is not as sensitive for mycobacteria as other types of bacteria and secondly 16sRNA does not generate any sensitivity testing and therefore it does not help inform any treatment regimens.
How are infections with M. chimaera treated?
Infections with M. chimaera should be treated in the same way as other M. avium complex infections. The current first line regimen includes the combination of a macrolide e.g. Clarithromycin 500mg BD PLUS Rifampicin 600mg BD PLUS Ethambutol 15mg/kg OD PLUS Amikacin 15mg/kg OD. Treatment duration is for 12 to 18 months! It is imperative to try and get a positive culture before starting treatment as the regimen should be tailored to the specific bacterium by looking at sensitivity testing information.
What is the prognosis of M. chimaera infection?
Whilst mycobacterial infections, in general, are often difficult to treat and present late with established infections, these M. chimaera patients are also likely to have multiple comorbidities which mean they do especially badly e.g. cardiovascular disease, diabetes mellitus. This alert from PHE raises specific concerns, as of the 25 cases so far identified in the UK 15 patients have died, including 10 who were already on M. chimaera specific treatment at the time.
So what should we do for these patients who may have been exposed to M. chimaera?
PHE have issued guidance to both primary and secondary care for how to manage these patients. However from the current buzz of activity on the British Infection Association forum these documents are not really very helpful.
The problems are: the rarity of the infection, the commonality of the type surgery, the long incubation period, the non-specific symptoms, the diagnostic difficulties and the seriousness and high mortality from infection if it does occur. These ambiguous factors create the perfect storm and are likely to lead to chaos! Maybe a structured and methodical approach might help…
In Primary Care ask the following question:
Has the patient been on cardiopulmonary bypass since 2007?
NO – reassure the patient and do nothing further
YES - but the patient is well, reassure the patient and make a note of them being at risk in their clinical records but do nothing further
YES - and the patient has symptoms or signs below, discuss with Cardiologist, Infectious Disease Physician or a Microbiologist:
- Infective endocarditis
- Chronic sternal wound infection
- Other chronic infection e.g. fever, malaise, weight loss, joint pains, cough, shortness of breath AND NO OTHER EXPLANATION
In Secondary Care
Investigate the patient’s symptoms and signs for ALL potential causes not just M. chimaera.
If Infective endocarditis is suspected:
Take 3 sets of mycobacterial blood cultures whilst the patient is off antibiotics; ideally on different days (these require specific blood culture bottles that should be available directly from your pathology department). An alternative method is to send blood samples taken in lithium heparin tubes which can then be inoculated into the mycobacterial blood culture bottle in the laboratory. Do not send EDTA samples as EDTA is inhibitory to the growth of mycobacteria. Consider echocardiography to look for heart valve vegetations if blood cultures are positive.
If wound infection is suspected:
Send pus, tissue or bone for mycobacterial culture. Do not send swabs as these cannot be cultured for mycobacteria.
If disseminated disease is suspected:
Take 3 sets of mycobacterial blood cultures (or lithium heparin blood samples) whilst the patient is off antibiotics. NB It is less important to leave a day between taking each of these samples. Consider sending cultures of any suspect infected tissue e.g. bone, bone marrow, bronchoalveolar lavage.
If ANY of the cultures are positive for M. chimaera then refer the patient to a specialist in the treatment of non-tuberculous infections (usually Respiratory or Infectious Diseases Physicians) as well as a Cardiologist to consider the need for removal of an infected valve, monitoring of treatment and ongoing cardiac damage. Don’t forget to treat any other cause if M. chimaera is not found!
So how do you justify to patients that there is no screening test?
Let’s consider the consequences of doing blood cultures on all asymptomatic at risk patients. If 5,000 asymptomatic heart valve patients were screened there would be a very low positive rate (if any) because the patient doesn’t have symptoms suggesting the bacteria is not in their blood at that time, although they could still go on to have an infection later. The test would lead to false reassurance. Also it would cost a fortune!
A mycobacterial blood culture costs approximately £40 per culture x 3 cultures per patient x 5,000 patients = £600,000 per year and that’s just for the heart valve replacement patients! Add on 20,000 coronary artery bypass graft patients…and the figure reaches £3 million to detect 1 case! Screening would cause massive amounts of anxiety and is more likely to pick up false positives from environmental contamination of blood culture bottles which could result in a “case” being treated with 18 months of unnecessary toxic antibiotics. Let’s not screen but just stick to reassuring asymptomatic patients.
So the GP rang the duty Microbiologist who was relieved that the patient was otherwise well and had no symptoms or signs of infection. The patient was reassured that whilst they had a small risk of infection (1 in 5,000 heart valve replacement) there was nothing more that need to be done at this time. The patient was advised to come back to see the GP if they became unwell. The GP made a note in the patient’s clinical record and called for his next patient… who came in clutching a letter…!
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