Sepsis in the neutropenic host

This chapter deals with the nightmare which ensues when a patient without an immune system encounters the angry soup of multi-resistant organisms in a large teaching hospital. It has not been updated for some number of years, and is viewed by its author as derelict. The newer summary of sepsis in the bone marrow transplant recipient covers virtually the same territory, but better.

The petri dish

An immunocompetent host typically suffers sepsis at the hands of known, commonly found enemies:

  • E. coli
  • Pseudomonas aeruginosa
  • Klebsiella
  • Streptococci
  • Staphylococci

An immunocompromised neutropenic host has much more to offer to a bacterium with ambition. There is a list of organisms which one needs to consider in addition to the above.

  • Pneumocystis jirovecii
  • Herpes simplex virus (HSV)
  • Varicella zoster virus (VZV)
  • Serratia marcescens
  • Enterobacter cloacae
  • Enterococcus sp.
  • Streptococcus pneumoniae
  • Candida sp.
  • Aspergillus sp.
  • Cytomegalovirus
  • Nocardia sp.
  • Legionella sp.
  • Listeria monocytogenes
  • Cryptococcus
  • Toxoplasma gondii
  • Strongyloides stercorales
  • Clostridium difficile

The cultures and serologies


  • Blood cultures (x 2 or 3)
  • Aspergillus galactomannan
  • Atypical mycobacteria serology


  • Urine culture
  • Streptococcal urinary antigen
  • Legionella urinary antigen


  • Sputum culture (or BAL specimen)
  • Acid-fast bacilli


  • Cryptococcal antigen
  • Acid-fast bacilli


  • C. difficile toxin
  • Ova, cysts, parasites... sometimes becomes relavant, eg. in a recent traveller

So; the list of differentials is pretty broad. A broad cover is therefore deployed.

The neutropenic broadside: empiric therapy for fever of unknown origin

  • Vancomycin -to cover beta-lactam resistant gram-positives
  • Meropenem - to cover gram-negatives like Pseudomonas and the anaerobes, as well as to work synergistically with vancomycin
  • Caspofungin - to cover candida species which might be resistant to fluconazole, such as Candida glabrata
    • Voriconazole might be substituted if pulmonary infection is suspected (where caspofungin doesnt penetrate very well)
    • Amphotericin might be substitited if one wishes to cover even more broadly, eg. for Zygomycetes or Cryptococcus
  • Ganciclovir - to cover cytomegalovirus
  • Trimethoprim/sulfamethoxazole - to cover P.jirovecii

If CNS involvement is suspected:

  • Vancomycin -to cover beta-lactam resistant gram-positives
  • Ampicillin - to cover Listeria
  • Ceftriaxone - to cover Strep pneumoniae
  • Amphotericin - to cover Cryptococcus
  • Trimethoprim/sulfamethoxazole - to cover P.jirovecii

If diarrhoea is present

  • Metronidazole-to cover C.difficile


An excellent resource for this topic are the chapters in Oh's Manual dealing with severe sepsis (ch 61, by A Raffaele de Gaudio) and with the immunocomrpomised host (ch 59, by Steve Wesselingh and Martyn A H French).

An older, yet similarly respectable source is Shoemaker (2005); Chapter 155 (Infections in the immunocompromised patient) by Andrew Githaiga, Magdaline Ndirangu and David L. Paterson covers this topic with great detail.

The Surviving Sepsis Campaign has these published guidelines to peruse.

There is a particularly useful UpToDate article on this topic, available only to their customers and their friends.