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What a New Year’s Resolution!

17/1/2020

 
“I’ve got a tricky one for you” said the Respiratory Consultant.
 
“Go on then, tell me what you’ve got” replied the Microbiologist, knowing from previous experience that this would indeed be a tricky case, but looking forward to his colleagues challenge.
 
“I’ve got an elderly chap who has bronchiectasis and I have been treating for an exacerbation without much luck. In fact he’s getting worse. Despite 2 weeks of different IV antibiotics his CT shows progressive cavitation. He has lost a lot of weight over the past couple of months and unless we come up with something I think I’m going to lose this battle”
 
As the discussion went on the Microbiologist started to look at the patients past results. The one bacterium that stood out as being a bit unusual was Mycobacterium abscessus which had grown a few times over the past year in various sputum samples.
 
“Mmmm, what do you think about the M. abscessus?” asked the Microbiologist. “It sounds like this may be more significant than we’d normally give it credit for.”
 
“I’m glad you say that, I thought the same, but didn’t want to influence your thoughts” replied the Respiratory Consultant.
 
“Mmmm, I have only rarely seen it cause clinical disease, although it’s improbable, it is possible, so let me check the latest literature and I’ll meet you on the ward and we’ll go from there” said the Microbiologist already opening a large tome of reference text, muttering to himself …this isn’t going to be covered in Microbiology Nuts & Bolts!!
What is Mycobacterium abscessus?
Mycobacterium abscessus is a non-tuberculous mycobacterium that is normally found in the environment throughout the World. In fact there are 3 subspecies of M. abscessus (abscessus, bolletii and massiliense) but most labs tend to just think in terms of M. abscessus. At the end of the day the bacterium’s full name doesn’t really matter too much.
 
I tend to think of M. abscessus as in a group of mycobacteria which I call the “rapid growing mycobacteria”. This is because, compared to other Mycobacteria spp., M. abscessus grows relatively quickly; within a week in liquid culture. Even when I started in microbiology, in the days before liquid culture when mycobacteria were grown in square glass jars on slopes of Lowenstein-Jensen media, M. abscessus was regarded as being a quick grower. It used to take around 2-4 weeks compared to the usual 8-12 weeks of other Mycobacteria spp. I include M. abscessus, M. fortuitum, M. chelonae, M. smegmatis and M. mucogenicum in my categorisation of rapidly growing Mycobacteria spp.  What really matters, regardless of its speed of growth, is whether a culture is significant and needs treatment or not. I have rarely seen any of the rapidly growing Mycobacteria spp. causing clinical disease and therefore if I’m honest I often tend to forget about them! But just maybe our culture might be significant; it has grown a few times in earlier sputum samples, so it might not just be a coloniser.
 
How does infection with M. abscessus present?
M. abscessus does have the potential to cause infections of the respiratory tract, but usually only in people with some form of underlying lung disease such as cystic fibrosis, bronchiectasis or emphysema.
 
Respiratory infection presents with:
  • Cough - often present for months or years
  • Fever
  • Weight loss
  • Haemoptysis (coughing up blood)
  • Shortness of breath
  • Chest x-ray changes – interstitial or alveolar infiltrates or cavitation
 
Other, less common, clinical manifestations of M. abscessus infection include:
  • Lymphadenitis – enlarged painful lymph glands, often in the neck
  • Disseminated infection – multiple subcutaneous nodules or abscesses in immunosuppressed patients
  • Skin and soft tissue infection - single or multiple abscesses or sinuses, similar to disseminated infection but in an immunocompetent patient
  • Musculoskeletal infection – following direct inoculation of mycobacteria into the skin, bone or joint either from trauma or surgery
  • Prosthetic device infection – infections of prosthetic joints, pacemakers and tympanostomy tubes (also known as grommets) have been described
  • Post-operative infection – this has been described after all sorts of procedures including laser eye surgery, cosmetic surgery and even cardiac surgery, and has often been linked to the use of non-sterile water at some stage during the procedure
 
How is M. abscessus infection diagnosed?
The key to making a diagnosis of M. abscessus infection is, as often the case, firstly to consider it and then take the right microbiological specimens.
 
For respiratory infections, sputum or bronchoalveolar lavage specimens should be taken. As it is fairly common to find M. abscessus as a colonising bacterium, multiple samples (at least 3 sputums over several weeks) need to be positive in a patient with a consistent clinical infection and chest x-ray changes before making the diagnosis.
 
For non-respiratory infection biopsies should be taken from the lesions and cultured. A positive culture from this type of specimen is less likely to be due to colonisation, and if from a normally sterile site then a positive culture proves the diagnosis.
 
M. abscessus in the UK is usually grown in liquid culture in a system like the Becton-Dickinson Mycobacterium Growth Indicator Tubes (BD MGIT), but there are other types of system available. BD MGIT is an automated incubator system, similar to a blood culture incubator, which contains a liquid culture media, growth supplements and antibiotics to suppress non-mycobacterial bacteria. As mycobacteria grow in the tube they use up the available oxygen which then allows a fluorescent compound in the bottom of the tube to fluoresce telling the incubator that the culture is positive. The tube can then be taken out, stained with auramine or Ziehl-Neelsen (ZN) stain and identified by PCR and tested for antimicrobial sensitivity (usually at a reference laboratory). Liquid culture is one of my Top 3 most significant advances in microbiology since I started in the speciality back in 2001.
 
How is M. abscessus infection treated?
Treatment of M. abscessus infection is difficult, not least because it is resistant to the conventional anti-tuberculous drugs such as Rifampicin, Isoniazid, Ethambutol and Pyrazinamide. Also treatment involves prolonged courses of potentially toxic antibiotics, so you definitely want to be sure of the diagnosis before you start down this path. Any abscesses should be drained and infected prosthetic material should be removed whenever possible.
 
Treatment of M. abscessus infection should be under a Respiratory Physician or someone who has experience of treating such infections.
 
Traditionally Clarithromycin has formed part of the treatment of M. abscessus however recently an inducible resistance gene for macrolides has been found in M. abscessus subspecies abscessus and subspecies bolletii. This is a nuisance because it means that whilst the bacterium might test sensitive in vitro it will become resistant in vivo during treatment. Sneaky huh?! All strains of M. abscessus should therefore have sensitivity testing before starting on treatment, including looking for the inducible macrolide resistance gene.
 
The current British Thoracic Society (BTS) guideline for the treatment of M. abscessus is:
Sensitive
OR
​inducible resistance to macrolides
Initial phase ≥ 1 month:
  • IV Amikacin 15mg/kg OD PLUS
  • IV Tigecycline 50mg BD PLUS
  • IV Imipenem 1g BD PLUS
  • PO Clarithromycin 500mg BD
Continuation phase ≥ 12 months after culture negative:
  • Nebulised Amikacin PLUS
  • PO Clarithromycin 500mg BD PLUS
1-3 of the following shown to be sensitive:
  • PO Clofazimine 50-100mg OD
  • PO Linezolid 600mg OD or BD with Pyridoxine 50mg OD
  • PO Minocycline 100mg BD
  • PO Moxifloxacin 400mg OD
  • PO Co-trimoxazole 960mg BD
Resistant to macrolides ​
Initial phase ≥ 1 month:
  • IV Amikacin 15mg/kg OD PLUS
  • IV Tigecycline 50mg BD PLUS
  • IV Imipenem 1g BD
Continuation phase ≥ 12 months after culture negative:
  • Nebulised Amikacin PLUS
2-4 of the following shown to be sensitive:
  • PO Clofazimine 50-100mg OD
  • PO Linezolid 600mg OD or BD with Pyridoxine 50mg OD
  • PO Minocycline 100mg BD
  • PO Moxifloxacin 400mg OD
  • PO Co-trimoxazole 960mg BD
​These drugs can be toxic, and because the treatment course is so long, patients should be monitored closely, including regular  assessment of kidney, liver, hearing, balance and bone marrow function (on initiation of treatment and then at least monthly).
 
The mortality from M. abscessus infection in those completing treatment is about 15% which is very high.
 
Armed with the latest BTS guidelines the Respiratory Consultant and Microbiologist had a long chat with the patient. They explained the infection, the treatment and all of the difficulties in its year-long management; this was going to be some New Year’s resolution for the patient to comply with treatment! Eventually between the three of them they agreed a plan of action. The patient was started on the initial phase cocktail of antibiotics and soon began to feel a bit better. After 6 weeks he had gained weight and was well enough to go home. The plan was to continue to treat for a further 11 months and see how things went, but it was a good start…
 
How are your New Year’s resolutions coming along? Our New Year’s resolution was to stop spending money on vets bills but apparently Guacamole (our ginger moggy) didn’t get the memo and has broken the resolution already…!
Mycobacterium abscessus NY resolutions for cats
Click for larger image

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    Blog Author:

    David Garner
    Consultant Microbiologist
    Surrey, UK

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