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This module will cover the diagnosis and management of febrile neutropenia.


Febrile neutropenia is a serious complication of chemotherapy, characterized by a reduction of neutrophils below normal cell counts. Normally, neutrophils are important for fighting bacterial infections. However, due to reduced numbers, patients have an impaired ability to fight infections.

Due to the blunted immune system of cancer patients, and the reduction in neutrophils, the common signs and symptoms of an infection may be minimized or absent [1]. Therefore, in a neutropenic patient, fever is the most important sign of infection [1].


The diagnosis of febrile neutropenia require the following [1]:

  1. Fever: a single oral temperature greater than 38.3°C or a temperature greater than 38.0°C lasting over one hour.
  2. Neutropenia: absolute neutrophil count less than 0.5x10 9 cells/L.


A fever in a neutropenic patient should be considered a medical emergency. Thus, treatment should be started with empiric antibiotics as soon as possible [2].

Some examples of treatment options are listed below, but generally hospitals will have their own antibiotic treatment protocols. However, the principles of treatment largely remain the same. Patients who are considered high-risk should be admitted to hospital, have vitals monitored on a regular basis, and be treated with IV antibiotics [4]. The choice of antibiotic should have gram positive and gram negative coverage [3]. Even when the pathogen is known, it is important to not narrow the antibiotic hastily, as there is always the possibility of multiple pathogens, especially in patients receiving chemotherapy [3].

Examples of treatment regimens are shown below [4]:

  1. Piperacillin-tazobactam 4.5g IV q8h (provides coverage for Pseudomonas spp.)
  2. Cefepime 2g IV q8h (Useful for patients who have a penicillin allergy)
  3. Vancomycin (do not use empirically, add it into the regimen for patients who remain febrile despite initial therapy, are hemodynamically unstable, have an obvious catheter infection, and known colonization with MRSA [3])

Other potential considerations to include in management are:

  1. Consultation with the Infectious Disease service
  2. Granulocyte colony stimulating growth factor (G-CSF) may have some ability to decrease neutropenia and fever. However, the administration of G-CSF is not routine, and need to be considered on a case-by-case basis.
  3. Removal of central venous catheter or any other infected lines.

Virtual Patient Case

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  1. Freifeld A. G., Bow E. J., Sepkowitz K. A., Boeckh M. J., Ito J. I., Mullen C. A., Raad I. I., Rolston K. V., Young J. A. H., Wingard J. R. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clinical Infectious Diseases. 2011;52(4):e56–e93. doi: 10.1093/cid/cir073
  2. Keng M. K., Sekeres M. A. Febrile neutropenia in hematologic malignancies. Current Hematologic Malignancy Reports. 2013;8(4):370–378. doi: 10.1007/s11899-013-0171-4.
  3. Bow E, Wingard, JR. UpToDate: Overview of neutropenic fever syndromes. 2018. Available at: http://www.uptodate.com. Accessed March 24 2019.
  4. Paul M, Yahav D, Fraser A, Leibovici L. Empirical antibiotic monotherapy for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials. J Antimicrob Chemother 2006 Feb;57(2):176-189.

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