A 50 year old man presented with acute onset confusion and a severe headache. He was taking Mycophenolate mofetil and prednisolone as anti-rejection drugs for the kidney transplant he had had in the past. He had not travelled recently, had no pets and had not been in contact with anyone else unwell. The doctors diagnosed a possible meningitis or encephalitis and started IV Cefotaxime and IV Aciclovir. The patient was then transferred to the Critical Care Unit who called me in the middle of the night for further advice. Bleary eyed I was wondering why I was being called at 3am as there are hospital guidelines to cover meningitis? And who was going to tell my cat it wasn’t time to be fed yet!?
The team had covered for the usual causes but they had forgotten the unusual suspects related to immunosuppression, such as Listeria monocytogenes and tuberculosis. The bit of their story that made me prick up my ears was the history of rash with penicillins the previous year. Unless you think of listeriosis you won’t realise that the penicillin allergy is a problem. It was easy to rule out tuberculosis as the patient had a BCG scar showing he had been vaccinated, and had had a T spot blood test before his kidney transplant which indicated he had not had tuberculosis in the past. This left listeriosis.
The team had covered for the usual causes but they had forgotten the unusual suspects related to immunosuppression, such as Listeria monocytogenes and tuberculosis. The bit of their story that made me prick up my ears was the history of rash with penicillins the previous year. Unless you think of listeriosis you won’t realise that the penicillin allergy is a problem. It was easy to rule out tuberculosis as the patient had a BCG scar showing he had been vaccinated, and had had a T spot blood test before his kidney transplant which indicated he had not had tuberculosis in the past. This left listeriosis.
I recommended changing his Cefotaxime to IV Meropenem rather than adding in Amoxicillin (as it’s a penicillin) and continuing the IV Aciclovir, just in case this was in fact viral.
The following morning the patient had a lumbar puncture which showed a raised lymphocyte count with a high protein and low glucose. This paradoxical association of raised lymphocytes (more common in viral meningitis) with a high protein and low glucose (seen in bacterial meningitis) is highly suggestive of either L. monocytogenes or tuberculosis! And sure enough by the following day the microbiology laboratory had grown L. monocytogenes and the diagnosis was confirmed.
Interpretation of CSF
The following morning the patient had a lumbar puncture which showed a raised lymphocyte count with a high protein and low glucose. This paradoxical association of raised lymphocytes (more common in viral meningitis) with a high protein and low glucose (seen in bacterial meningitis) is highly suggestive of either L. monocytogenes or tuberculosis! And sure enough by the following day the microbiology laboratory had grown L. monocytogenes and the diagnosis was confirmed.
Interpretation of CSF
Click for larger image
What is listeriosis, who gets it and why is it forgotten about?
L. monocytogenes is the bacterium which causes the condition listeriosis, where the bacterium invades a person’s blood stream but L. monocytogenes can also be a relatively rare cause of meningitis and encephalitis in the UK. This Gram-positive bacillus has the ability to invade the central nervous system and survive in brain cells causing both encephalitis and meningitis. There are about 180 cases per year of listeriosis in the UK, but only about 15% of these are meningitis or encephalitis. It is therefore unlikely in patients with a normal immune system however it is important to consider L. monocytogenes in the differential of ANY patient with an underlying immunosuppression.
Listeria meningitis is unusual outside of certain patient groups:
Although rare in the general population don’t miss it in the above patient groups!
How do patients acquire Listeria monocytogenes?
L. monocytogenes is not normally part of the normal human bacterial flora; it is an example of an exogenous infection. Whilst a small proportion of humans can be carriers of the bacterium, the main hosts are herbivores such as sheep and cattle. Listeriosis occurs after the bacterium is acquired by eating contaminated food.
The food industry has a particular problem with L. monocytogenes because unlike many bacteria it is able to survive and continue to replicate at temperatures as low as 5oC. This means that any precooked food kept chilled before being served can be a source of infection if it has been contaminated. These include items such as pre-packed sandwiches, unpasteurised cheeses, cooked sliced meats, pate, smoked salmon, etc. The food standards agency produces guidance on how to minimise the risk of listeriosis
Listeriosis is a notifiable disease in the UK in the context of food poisoning; this allows Public Health England (PHE) to investigate cases to see whether there is an ongoing risk to public safety. If there has been a breach of guidelines relating to food safety then it is possible that those responsible could face criminal charges, including potentially manslaughter if someone dies. In practice this is very difficult to prove because the incubation period from exposure to infection can be from 3-70 days, and during this time an individual can be exposed to multiple potential sources of infection and the specific source may be long gone by the time PHE know about the case. It is then almost impossible to prove the source, or the person responsible, beyond reasonable doubt.
How is listeria meningitis treated?
The key to successful treatment of listeria meningitis is to consider it in the first place! The conventional treatment for meningitis in the UK is Cefotaxime or Ceftriaxone 1st line, with Chloramphenicol for those with a severe beta-lactam allergy. But Cefotaxime, Ceftriaxone and Chloramphenicol do not treat listeria meningitis! Therefore, if you don’t consider listeriosis the patient is unlikely to be treated until it’s too late; untreated listeria meningitis leads to inevitable brain damage and death.
The first line treatment of listeria meningitis is: Amoxicillin 2g 4-hourly (6x/day) for 3 weeks in combination with Gentamicin 1mg/kg BD or TDS (depending on renal function) for the first 7 days. As with my 3am patient, problems arise when the patient is allergic to beta-lactams as the Amoxicillin then cannot be used. Some suggested options are given below:
My patient was started on treatment for listeriosis very soon after admission. He received 3 weeks of treatment and made a full recovery. Despite an extensive investigation and testing of various foods from retail establishments in the community it remained unclear where he acquired his infection from. Fortunately there were no other cases of infection.
So what do you need to remember?
L. monocytogenes is the bacterium which causes the condition listeriosis, where the bacterium invades a person’s blood stream but L. monocytogenes can also be a relatively rare cause of meningitis and encephalitis in the UK. This Gram-positive bacillus has the ability to invade the central nervous system and survive in brain cells causing both encephalitis and meningitis. There are about 180 cases per year of listeriosis in the UK, but only about 15% of these are meningitis or encephalitis. It is therefore unlikely in patients with a normal immune system however it is important to consider L. monocytogenes in the differential of ANY patient with an underlying immunosuppression.
Listeria meningitis is unusual outside of certain patient groups:
- Extremes of age – both neonates and the elderly have immune systems that don’t work very well, particularly impaired cell mediated immunity
- Pregnancy – a degree of immune tolerance develops in pregnancy to allow the foetus, which has half of its genetics from its father, to be carried to term but unfortunately this tolerance can also extend to microorganisms; 10-15% of cases of listeriosis are associated with pregnancy
- Drug-induced immunosuppressed patients – chemotherapy, steroids and transplant related medications all impair the immune system
Although rare in the general population don’t miss it in the above patient groups!
How do patients acquire Listeria monocytogenes?
L. monocytogenes is not normally part of the normal human bacterial flora; it is an example of an exogenous infection. Whilst a small proportion of humans can be carriers of the bacterium, the main hosts are herbivores such as sheep and cattle. Listeriosis occurs after the bacterium is acquired by eating contaminated food.
The food industry has a particular problem with L. monocytogenes because unlike many bacteria it is able to survive and continue to replicate at temperatures as low as 5oC. This means that any precooked food kept chilled before being served can be a source of infection if it has been contaminated. These include items such as pre-packed sandwiches, unpasteurised cheeses, cooked sliced meats, pate, smoked salmon, etc. The food standards agency produces guidance on how to minimise the risk of listeriosis
Listeriosis is a notifiable disease in the UK in the context of food poisoning; this allows Public Health England (PHE) to investigate cases to see whether there is an ongoing risk to public safety. If there has been a breach of guidelines relating to food safety then it is possible that those responsible could face criminal charges, including potentially manslaughter if someone dies. In practice this is very difficult to prove because the incubation period from exposure to infection can be from 3-70 days, and during this time an individual can be exposed to multiple potential sources of infection and the specific source may be long gone by the time PHE know about the case. It is then almost impossible to prove the source, or the person responsible, beyond reasonable doubt.
How is listeria meningitis treated?
The key to successful treatment of listeria meningitis is to consider it in the first place! The conventional treatment for meningitis in the UK is Cefotaxime or Ceftriaxone 1st line, with Chloramphenicol for those with a severe beta-lactam allergy. But Cefotaxime, Ceftriaxone and Chloramphenicol do not treat listeria meningitis! Therefore, if you don’t consider listeriosis the patient is unlikely to be treated until it’s too late; untreated listeria meningitis leads to inevitable brain damage and death.
The first line treatment of listeria meningitis is: Amoxicillin 2g 4-hourly (6x/day) for 3 weeks in combination with Gentamicin 1mg/kg BD or TDS (depending on renal function) for the first 7 days. As with my 3am patient, problems arise when the patient is allergic to beta-lactams as the Amoxicillin then cannot be used. Some suggested options are given below:
- If mild beta-lactam allergy - IV Meropenem
- If severe beta-lactam allergy - IV Co-trimoxazole (Septrin)
My patient was started on treatment for listeriosis very soon after admission. He received 3 weeks of treatment and made a full recovery. Despite an extensive investigation and testing of various foods from retail establishments in the community it remained unclear where he acquired his infection from. Fortunately there were no other cases of infection.
So what do you need to remember?
- L. monocytogenes is a rare cause of meningitis and encephalitis in the UK, but it should be considered in any immunosuppressed patient
- Conventional treatments of meningitis and encephalitis do not cover L. monocytogenes, so if it is suspected the patient’s management should be modified to include additional cover for this bacterium
- Beta-lactam allergy makes treating listeriosis particularly difficult, so if in doubt discuss with a Microbiologist or Infectious Diseases Physician
- Listeriosis is a food borne pathogen and therefore ALL cases are notifiable to Public Health England
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