Question of the Week

For December 27, 2016

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RifampinAmpicillin plus gentamicinAcyclovirChloramphenicolTrimethoprim–sulfamethoxazole

Key Learning Point View Case Presentation

The antimicrobial treatment of choice for bacterial meningitis that is due to Listeria monocytogenes is ampicillin plus gentamicin.

Detailed Feedback

Listeria monocytogenes, a gram-positive rod, is a foodborne pathogen with a tropism for the central nervous system. L. monocytogenes outbreaks have been associated with unpasteurized milk, soft cheeses, and deli-style meats. Illness, though rare in the general population, is an important cause of disease in newborns, pregnant women, older adults, and people with impaired, cell-mediated immunity, such as transplant recipients and patients with AIDS. In 1995, the Centers for Disease Control and Prevention reported that L. monocytogenes accounted for 20% of bacterial meningitis cases among people >60 years of age. Presentation may be more subacute (>24 hours) than it is with other forms of bacterial meningitis. Cerebrospinal fluid Gram stain may be positive in only 30% to 40% of cases.

Pregnant women are also at increased risk for listeria infection. In this population, it causes chorioamnionitis in the woman (not meningitis), which at the time of delivery can lead to neonatal meningitis. Because of this risk, pregnant women are advised to avoid foods that may be sources of listeria infection, such as soft cheeses and deli meats.

In adults with suspected bacterial meningitis, empiric ceftriaxone and vancomycin should be administered immediately to cover the most common etiologic agents; dexamethasone is also administered in most patients with suspected meningitis, given evidence showing a reduction in neurologic sequelae among patients with pneumococcal meningitis who received dexamethasone. Empiric addition of ampicillin is recommended for treatment of bacterial meningitis in people >50 years of age. Ampicillin or penicillin is the preferred agent for treating L. monocytogenes infections. Synergy with aminoglycosides, such as gentamicin, has been demonstrated in vitro, and these agents are often used in conjunction with penicillins in treating Listeria meningitis.

Trimethoprim–sulfamethoxazole is the treatment of choice for a patient with a penicillin allergy.

Cephalosporins have limited activity against L.monocytogenes, and high reported rates of failure have been associated with chloramphenicol and rifampin.

Acyclovir is an antiviral agent with no activity against bacteria.

Last reviewed May 2021.

Citations

van de Beek D et al. Community-acquired bacterial meningitis in adults. N Engl J Med 2006 Jan 6; 354:44. > View Abstract

Clauss HE and Lorber B. Central nervous system infection with Listeria monocytogenes. Curr Infect Dis Rep 2008 Sep 4; 10:300.   > View Abstract

Tunkel AR et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004 Nov 1; 39:1267.   > View Abstract

35 Comments

  1. Surapee P. December 27, 2016 at 2:09 am - Reply

    My answer on day 27 Dec. is incorrect.An 82-year-old man with meningitis received ceftriaxone and vancomycin and the answer of antibiotic should add to this patient is ampicillin plus gentamicin I think why use this old and common medication to this case and a gram-positive rod pathogen of this case is Listeria monocytogenes.What is the Gram-Positive rod Bacteria.

    • Barbara Beeler December 27, 2016 at 7:04 pm - Reply

      Gram positive rods were seen in the CSF. Gram positive rods include Listeria, Clostridia, Bacillus and Corynebacteria. Therefore, the treatment for Listeria is strongly supported. (I was taught in medical school, decades ago that Tubercule bacillus can stain purple w/ gram stain if the technique is less than perfect, but I haven’t read anything about that lately. This could be urban legend.) As the article explains, Listeria is being seen in persons over the age of 60 presenting with meningitis. The drug of choice for Listeria meningitis is ampicillin with gentamicin for the reasons they explain. I agree this is a great case for learning. Notice they also mention that the gram stain doesn’t always help and CDC recommends that treatment for Listeria be included in the treatment of meningitis of unknown etiology for adults over 60 if the etiology is unknown in addition to the other medications mentioned.

    • Hossain Jabbari December 28, 2016 at 6:44 am - Reply

      Thank you for presenting this interesting case.
      I see some short- comings in management of meningitis this patient:
      Empirical therapy of meningitis should include “Ampicillin” from the beginning as followws to cover listeria monocytogen:
      Vancomycin 15 mg/kg q8h plus ampicillin 2 g q4h plus a third-generation cephalosporin (ceftriaxone 2 g q12h or cefotaxime 2 g q4-6h)
      In this patient regimen, we don’t see it. Although some guidelines talk about adding ampicillin when L. Monocytogen is suspected, but most agree adding it from beginning.
      When small gram positive rods was ssen, then, to avoid Vancomycin nephrotoxic side effects in an 82 years old patient who is receiving Gentamicin too, even it is possible to continue just with “Ampicillin+ Gentamicin”, as specific therapy because no other agents rather than Listeria could explain such a possibility.

  2. 261103 December 27, 2016 at 3:10 am - Reply

    I have turned on the light.

  3. Conor T McCartney December 27, 2016 at 11:17 am - Reply

    another week, another great question

  4. Jonathan C Weissler December 27, 2016 at 11:19 am - Reply

    Could also be Nocardia, which is a gram positive rod. Bactrim would cover both Nocardia and Listeria.

  5. Mohammed w .omar December 27, 2016 at 11:39 am - Reply

    A great teaching and learning case, I enjoy raeding it as usual.

  6. Frank Baudino December 27, 2016 at 11:46 am - Reply

    After empiric antibiotics but before LP maybe CT brain?

    • Sina NI December 27, 2016 at 1:39 pm - Reply

      Hi
      Tnx for thia great case
      In answer to dear frank: Because this man only has a Lowered LOC and a Low LOC is not an indication for CT before LP
      The were like 5-6 indications for that (like focal neurological defecits,…) but lowered LOC wasn’t one of them
      Hope this helps

  7. steve K December 27, 2016 at 11:49 am - Reply

    My thought exactly… Bactrim

  8. John ngigi December 27, 2016 at 12:00 pm - Reply

    I like the case vignette.

  9. Peter H Berczeller MD December 27, 2016 at 12:21 pm - Reply

    It should be noted that on microscopic examination of the CSF, Listeria organisms may be mistaken for slide artefacts. Delay in appropriate treatment can thus be caused by having to wait for a positive culture in order to make the correct diagnosis.

  10. Dr Jay December 27, 2016 at 12:29 pm - Reply

    That was an excellent question!!

  11. Mostafa December 27, 2016 at 2:50 pm - Reply

    When we sure about listeria, do we need continue previous Antibiotics which we were empirically started instead treatment just by Ampicillin+ Gentamicin?

  12. Dufaye December 27, 2016 at 2:52 pm - Reply

    I am sory but in Europe Listeria Monocytogenes do cause meningitis, even meningoencephalitis in pregnant women!

  13. Wm. Mattey MD December 27, 2016 at 3:35 pm - Reply

    Thanks for the interesting case. Very informative.

  14. Gerald Burke MD December 27, 2016 at 4:22 pm - Reply

    an excellent means to learn and/or relearn internal medicine.

    in the process, you require the responder to get involved in clinical decision-making relatively painlessly.

    well done!

  15. Vick Atamyan December 27, 2016 at 4:38 pm - Reply

    Very good case for CME.

  16. Rahul M December 27, 2016 at 10:46 pm - Reply

    Why no empiric acyclovir on presentation even prior to LP? Fever, confusion, depressed alertness, meningismus should buy him some urgent acyclovir, no? Probably even before you prep the LP? Not sure one should even cancel empiric acyclovir had he gotten it only based on just a prelim CSF result with only gram stain and no speciation or HSV PCR. Viral infections can have CSF PMN predominance early. Agree of course also with Amp/gent given gram stain.

  17. Vincenzo December 28, 2016 at 12:57 am - Reply

    Why starting empiric treatment BEFORE lumbar puncture: in this way sensitivity of gram stain can be affected?

  18. Tulin isik December 28, 2016 at 4:20 am - Reply

    Great case and nice presentation
    Thank you

  19. Dr Poligar Shankar December 28, 2016 at 4:40 am - Reply

    We were taught that aminoglycosides are not useful in meningitis unless given intrathecally. Wonder when did this principle became invalid?

    Classic ‘old’ reference: “Parenteral therapy with gentamicin or tobramycin produced low concentrations of aminoglycoside (less than 1.0 mug/ml) in the lumbar, ventricular, and cisternal CSF. ”
    (Kaiser AB, McGee ZA. Aminoglycoside therapy of gram-negative bacillary meningitis. N Engl J Med. 1975 Dec 11;293(24):1215-20. – PMID: 1102982; DOI: 10.1056/NEJM197512112932401 )

    • Anbarasan December 31, 2016 at 3:28 am - Reply

      Gentamycin doesnot penetrate biological membranes because of its polar nature. But it is true only when the membranes are intact. In inflammed meninges the tight junctions are disrupted and in such conditions aminoglycosides do penetrate meninges. Same id the reason why aminoglycosides are used in intensive phase of tubercular meningitis

      • D. BOUROS December 31, 2016 at 12:41 pm - Reply

        CORRECT!!!

  20. drjosh December 28, 2016 at 8:58 am - Reply

    Thanks! Best wishes for the New Year…Doctor Josh

  21. christian obasohan December 28, 2016 at 1:46 pm - Reply

    Thanks a lot great question,however in my opinion a CT before LP is much essential for this kind of patient given his age,repeated vomiting,LOC ,neck stiffness.All this are pointer of increase ICP much more when mention was not mase of the B.P and Pulse even the elevated temperature are all features you could find which may be due to loss of cerebral thermo-regulation in the brain that occurs with a haemorrhagic CVA.If the facility is available, there is nothing to loss but much to gain by doing so.

  22. alireza adelkhah December 29, 2016 at 4:41 am - Reply

    Thanks. But genta not.penetrate from BBB

  23. Dr.Subhi Bajis, M,B,B,CH DCH MSc/MFM MD December 29, 2016 at 10:39 am - Reply

    Thank you for this intrested question .
    Treatment of choice for listeria meningitis is by ampicillin 2 gm IV q4 – 6 h plus gentamicin 1.7 mg IV 8h for 3 weeks. Or trimethoprim ( TMP)/ Sulfamethoxazole (SMX) 3 – 5 mg ( trimethoprim ) q6h IV for 3 weeks as an alternative in case of penicillin allergy.

  24. elias azar December 30, 2016 at 7:08 am - Reply

    I love these questions
    Thanks a million

  25. Mohammed Hussein December 31, 2016 at 6:53 am - Reply

    Thank you, NEJM for these nice mcq’s.

  26. elias azar January 1, 2017 at 8:40 am - Reply

    Super I learned a lot

  27. Justine January 1, 2017 at 3:21 pm - Reply

    I suffered listeriosis septicaemia when I was 21 weeks pregnant. Symptoms – flu-like: temperature 40.5 deg C, terrible headache/back pain. Baby died within 24 hrs of feeling unwell; went in to spontaneous labour after she died. I presented to hospital in labour.

    I was given amoxil IV after the birth for a few days.I had a temperature for days and the headache and back pain persisted for days (> week). Placental swabs confirmed the diagnosis.

    My question – I always thought my headache/back pain was a manifestation of meningitis but the comments above say pregnant women don’t get meningitis. What were my symptoms due to then? I wondered if I hadn’t got amoxil whether I too would have died?

  28. Soumaila Boubacar January 2, 2017 at 8:38 pm - Reply

    This is a good traning method

  29. Faisal khan January 3, 2017 at 11:31 am - Reply

    Interesting case

  30. saleh awdaly January 6, 2017 at 3:43 pm - Reply

    Thank you for your kind, and updated practical case , moreover we are going to be perfect if we continue reading and studying while practicing the medicine .

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