Meningococcal sepsis

N.meningitides featured in  Question 10 from the second paper of 2002: "Outline the diagnostic features, complications and treatment of patients  with meningococcal sepsis." It also appeared in the ABG interpretation scenario for Question 3.1 from the second paper of 2015, where the trainees were expected to identify the meningococcaemia on the basis of "fever, headache and a widespread rash". The patient also had a horrific blood gas with features of hypoadrenalism, consistent with Waterhouse-Friedrichsen syndrome.

A good NEJM review article is available which covers this territory well. It is the source for most of the information offered in the summary below. If one wished to cultivate an intimate acquaintance with N.meningitides, one may consider reading Rouphael and Stephens' massive opus from 2012.

The microorganism

  • Gram-negative aerobic diplococcus 
  • An encapsulated organism, resistant to opsonization- its capsule protects it against complement-mediated bacteriolysis and phagocytosis by neutrophils, Kupffer cells, and spleen macrophages.
  • A fastidious bacterium: it dies within hours on extracorporeal surfaces.
  • A well-adapted human pathogen: its transferrin-binding proteins steal iron from the human host.
  • It readily invades the meninges, and many patients with menigococcal sepsis will also have meningitis.
  • It is virtually defenceless against antibiotics.  Antibiotic resistance to anything except for sulfonamides is very rarely seen. Usually, straightforward benzylpenicillin is enough.

Defence against N.meningitides:

  • Antibody-mediated immunity is the most potent defence
  • The peak incidence of the disease occurs in the first year of life
    (following the loss of maternal antibody)
  • Progressively less common throughout childhood
  • Extremely rare in immunocompetent adults
  • Becomes more common in the post-splenectomy state

Diagnostic features of meningococcal sepsis

  • Abrupt onset of high fever
  • Myalgias, arthralgias, headache, decreased level of consciousness
  • Petechial or purpuric rash
  • Hypotension and shock
  • Characteristic severe myocardial depression
  • Blood or CSF cultures positive for N.meningitidis
  • PCR of peripheral blood (apparently, it is useful for diagnosis of meningococcal disease)

Complications of meningococcal sepsis

Management of meningococcal sepsis

Antibiotics:

  • Most strains are susceptible to penicillin.
  • The Sanford Guide recomends ceftriaxone 2g bd or benzylpenicillin 2.4g q4h
  • Chloramophenicol is an alternative, but apparently there has gradualyl been a worldwide development of resistance (and, worldwide there has been a gradual resistance developing to the use of chloramphenicol, as it is a dangerous drug perhaps better suited as a chemotherapy agent for haematological malignancy).
  • Supportive management consists of vasopressor support and fluid resuscitiation, with correction of DIC-associated coagulopathy
  • Corticosteroids may be useful if meningitis is present, but in the absence of meningitis they are not indicated except as management of relative adrenal insufficiency.
  • Plasma exchange may improve survival if commenced early, but the evidence for it is not robust.

References

Rosenstein, Nancy E., et al. "Meningococcal disease." New England Journal of Medicine 344.18 (2001): 1378-1388.

Mautner, L. S., and W. Prokopec. "Waterhouse-Friderichsen Syndrome."Canadian Medical Association journal 69.2 (1953): 156.

Kumar, Ajay, et al. "Plasma exchange and haemodiafiltration in fulminant meningococcal sepsis." Nephrology Dialysis Transplantation 13.2 (1998): 484-487.

Pathan, N., S. N. Faust, and M. Levin."Pathophysiology of meningococcal meningitis and septicaemia."  Archives of disease in childhood 88.7 (2003): 601-607.

Rouphael, Nadine G., and David S. Stephens. "Neisseria meningitidis: biology, microbiology, and epidemiology." Neisseria meningitidis. Humana Press, 2012. 1-20.

Pollard, A. J., et al. "Emergency management of meningococcal disease."Archives of disease in childhood 80.3 (1999): 290-296.

Van Deuren, Marcel, Petter Brandtzaeg, and Jos WM van der Meer. "Update on meningococcal disease with emphasis on pathogenesis and clinical management." Clinical microbiology reviews 13.1 (2000): 144-166.

Nassif, Xavier. "Interaction mechanisms of encapsulated meningococci with eucaryotic cells: what does this tell us about the crossing of the blood–brain barrier by Neisseria meningitidis?." Current opinion in microbiology 2.1 (1999): 71-77.

Yunis, A. A. "Chloramphenicol toxicity: 25 years of research." The American journal of medicine 87.3N (1989): 44N-48N.