Listeriosis

L

Can we prevent alemtuzumab-associated listeriosis?

The following is a published case report of someone with MS developing listeriosis congruent with their second course of alemtuzumab treatment. It is clear this patient was not taking her diatary advice very seriously. We have a potential solution for this problem.

Holmøy et al. Listeria monocytogenes infection associated with alemtuzumab – a case for better preventive strategies. BMC Neurol. 2017; 17: 65. Published online 2017 Apr 4.

“We report a patient with multiple sclerosis who developed pyrexia, nausea and abdominal discomfort a few hours after the third and last infusion of her second alemtuzumab cycle. An infusion-related reaction was suspected. The patient had however eaten soft cheese and raw sausage 3 days prior to treatment, and L. monocytogenes septicaemia was diagnosed based on positive blood cultures.”

This case is not too dissimilar to a British patient who developed listeria meningitis towards the end of the 5-days of her initial alemtuzumab infusions. Tragically the British patient died because she was initially thought to have an infusion reaction and not an infection. Based on the British death we now think that a small number of people may be colonised with listeria, i.e. they have the bacteria living in their intestines, and going on a diet just before starting alemtuzumab, HSCT, mitoxantrone, or other chemotherapy regime is not going to help. This is one of the reasons the ABN (Association of British Neurologists) is now recommending prophylactic antibiotics to prevent listeriosis and potentially several other infections for pwMS receiving alemtuzumab (see below). As listeriosis can also occur with HSCT and mitoxantrone we recommend that this advice should be carried over to these treatments as well.

Not all pwMS can take these antibiotics, some may be allergic to them, and other people are unhappy with taking broad-spectrum antibiotics due to their impact on their microbiomes. If this is the case you can use a diet to avoid being exposed to the bacterium that causes listeriosis. The problem is if you intestines are already colonised with the bacterium the diet is unlikely to make much difference in the short-term. This is why the microbiologists at Barts Health and other centres suggest starting the Listeria diet 3 months before alemtuzumab treatment is due to be given. We think this may be unrealistic for our patients because alemtuzumab treatment often needs to be started as soon as possible; a 3-month delay may be unacceptable. We also believe that we shouldn’t rely on antibiotics alone to prevent listeria infection and recommend the listeria-prevention diet to all our patients who are to being treated with alemtuzumab.

To our horror when we audited our patients understanding and adherence to the listeria diet we found that most did not understand what listeriosis is and most were non-adherent with the diet. With the help of some listeriosis experts we have designed a behavioural change programme to activate our patients about the risk of listeriosis with the aim of preventing it. We have converted this programme into a kit that you can order from our ClinicSpeak website using an online form. At a minimum, you should download the accompanying listeriosis diet booklet from our site.

We sincerely hope that by sticking to the diet and taking antibiotic prophylaxis we can prevent listeriosis and any more unnecessary deaths from this complication of alemtuzumab and other chemotherapies.

Please note the risk of listeriosis is relatively low with about 1 in 400 patients being infected. We are very confident that this risk will be at least an order of magnitude lower with strict adherence to the dietary guidelines and the use of prophylactic antibiotics.

CoI: We raised money to develop and produce the listeriosis prevention kit from a Barts-Health crowdfunding campaign. Thank you for being so generous. Sanofi-Genzyme has provided additional funds to produce more kits than we require as a single MS centre, which is allowing us to distribute kits to other MS centres in the UK and to make them available online. If you need kits for your centre please do not hesitate to contact us (bartsmsblog@gmail.com)

ABN guidance on the prevention of Listeria infection after alemtuzumab treatment of multiple sclerosis

David Partridge (Consultant Microbiologist) and David Paling (Consultant Neurologist) advise that Listeria after alemtuzumab is likely to be due to Listeria already colonising the bowel at the time of alemtuzumab treatment. The Listeria-free diet would ideally need to be started ninety days before treatment to reduce this colonisation and minimise risk of infection development. This is too prolonged for most people receiving the first cycle of alemtuzumab, who may have active multiple sclerosis that needs treating. Furthermore, a majority of the neurologists contributing to this advice were not confident that all people with multiple sclerosis would comply with the Listeria-free diet.

  1. So, the consensus was that the safest advice is co-trimoxazole 960mg three times a week for one month.
  2. An alternative approach, if the patient will comply rigorously with the Listeria-free diet is one week of amoxicillin 1g tds or co-trimoxazole 960mg bd to eliminate Listeria from the bowel (for instance for 8 days starting the Friday before treatment on the Monday) followed by the Listeria-free diet for one month after alemtuzumab.
  3. Finally, where alemtuzumab treatment can be predicted some months in advance (for instance with cycles 2 and 3), it would be reasonable to offer a third option to patients who will comply rigorously with the Listeria-free diet: going on the Listeriafree diet for ninety days before, and for one month after, alemtuzumab.

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8 comments

  • A question that has been on my mind relating to diet but not listeriosis:
    It seems that fasting before chemo in cancer patients is objectively beneficial – is there anything published on fasting prior to HSCT?

    Tony

  • Interesting post. Are there any biomarkers for Listeria or Listeriosis exposure? Antibodies? PCR amplification of microbiome material?

    • Yes, but I suspect this is still a research tool and not part of routine clinical practice.

      Siah et al. Improved detection of gastrointestinal pathogens using generalised sample processing and amplification panels. Pathology. 2014 Jan;46(1):53-9.

      We aimed to streamline the diagnosis of gastrointestinal disease by producing multiplexed real time polymerase chain reaction (PCR) panels employing universal sample processing for DNA and RNA containing pathogens. A total of 487 stored, previously characterised stool samples comprising bacterial, viral, protozoan and Clostridium difficile positive samples were tested using four multiplexed real time PCR panels. A further 81 pre-selected clinical samples from a teaching hospital were included to provide an independent validation of assay performance. Improved sensitivity was achieved using the protozoan panels and 16 more mixed infections were observed compared to tests with conventional methods. Using the C. difficile panels, 100% sensitivity was achieved when compared to the gold standard of toxigenic culture. In addition, hypervirulent strains including ribotype 027 could be identified directly from primary sample without the need for ribotyping methods. Bacterial and viral panels detecting Salmonella, Shigella, Campylobacter, Yersinia enterocolitica, Listeria monocytogenes, norovirus groups I and II, rotavirus A, astrovirus, sapovirus, rotavirus B, adenovirus and adenovirus 40/41 performed as well as conventional methods, whilst allowing detection in 3 hours from processing to result. Multiplex real time PCR panels with universal sample preparation allow streamlined, rapid diagnosis of gastrointestinal pathogens whilst extending the characterisation of pathogens present in stool samples from affected patients.

  • Why isn’t your post “Secondary progression — what is really new?” here but rather in Medium?
    It is really hard and really unnecessary to follow different platforms for subjects that are so interlinked. MD is promoting (and in a rather pushy way but ok) his personal opinions about MS, so I don’t get why should you self-censor yourself. This is exactly what is needed now that theory seems to be stuck to obsolete ideas.
    Personally, I can’t follow Medium and would stop this blog too if it’all about clinical directions and happiness.
    Thanks for everything you have offered so far.

    • I have been criticised for using the Barts-MS blog as a platform to self-promote my interests at the expense of the wider Barts-MS group and for dominating the bandwidth in terms of discussion, etc. By moving my musings and non-factual posts off this blog it will hopefully address these concerns. We are expecting other members of the team to start posting more regularly to increase the variety.

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