Febrile neutropenia is defined in the Therapeutic Guidelines: Antibiotic as a temperature of 38°C or higher, and a neutrophil count of less than 0.5 x 109 cells/L (or less than 1.0 x 109 cells/L and predicted to fall to lower than 0.5 x 109 cells/L).

Febrile neutropenia is a common complication of chemotherapy treatment. It often presents with a fever following chemotherapy and is associated with significant morbidity and mortality. As a result, patients receiving chemotherapy who present with a fever should be treated early with a broad-spectrum antibiotic. Empiric therapy is utilised when the causative organism is unknown, and therapy is initiated with an antimicrobial targeted at the most likely pathogen(s) to provide a broad spectrum of cover until the causative organism can be determined.

It is important when treating oncology patients that the administration of antimicrobial therapy is not delayed. The intensity of empiric antimicrobial therapy is dependent upon whether the patients are considered low or high risk. Oral therapy may be suitable for low risk patients, however even outpatient management needs to be closely monitored. High risk patients should be admitted to hospital for empiric intravenous antimicrobial therapy and monitoring.

The new generation of cephalosporins play an important role in the early management of febrile neutropenia or suspected neutropenia. The use of broad-spectrum third generation cephalosporins, such as cefepime and ceftazidime as monotherapy, are considered as effective and safe as the combination of a beta-lactam and an aminoglycoside.

Cephalosporins target their bactericidal activity towards the cell wall. They bind to penicillin-binding proteins and interfere with the synthesis of peptidoglycan in the cell wall, resulting in cell lysis and death of the cell. While all cephalosporins contain the beta-lactam ring, they possess different levels of antimicrobial activity.

The new generation of cephalosporins have a broader spectrum of activity than traditional cephalopsporins. Cefepime and ceftazidime have a broader coverage against most gram-negative bacteria especially Pseudomonas aeruginosa and other blood-born organisms, and as a result are indicated for use in the empirical treatment of febrile neutropenia.

Cefepime is indicated for the empiric treatment of sepsis in neutropenic or otherwise immunocompromised patients. The recommended dosage for adults is 2g by intravenous (IV) injection every eight hours. IV injections of cefepime can be administered slowly, as an IV push over 3-5 minutes, or by IV infusion over 30 minutes. Dose adjustments are required in patients with renal impairment, the standard initial dose should be given and then subsequent doses should be adjusted according to creatinine clearance. Cefepime is compatible for administration with 5% glucose, 0.9% sodium chloride and Hartmann’s solution.

Ceftazidime is also indicated for the empiric treatment of sepsis in neutropenic or otherwise immunocompromised patients. The recommended dosage for an adult is 2g IV every eight hours. The IV injection can be administered slowly as an IV push over 3-5 minutes, or by IV infusion over 15-30 minutes. Dose adjustments are also required in patients with renal impairment. Adults with renal impairment should initially be given a 1g dose and then adjustment should be made according to the patient’s creatinine clearance. Ceftazidime is compatible for administration with 5% glucose, 0.9% sodium chloride and Hartmann’s solution.

References:

  1. Rossi S (ed). Australian Medicines Handbook. Adelaide: Australian Medicines Handbook Pty Ltd; 2014.
  2. Antibiotic Expert Group. Therapeutic Guidelines: Antibiotic. Version 14. Melbourne: Therapeutic Guidelines Limited; 2010.
  3. DBL Cefepime (cefepime hydrochloride) Australian approved product information. Melbourne: Hospira Pty Ltd. Approved 7 October 2010, amended 21 June 2012.
  4. Fortum (ceftazidime as pentahydrate) Australian approved product information. Melbourne: Aspen Pharmacare Australia Pty Ltd. Approved 13 December 1993, amended 14 November 2013.
  5. Burridge N, Deidum D (eds). Australian Injectable Drugs Handbook. 5th ed. Collingwood, Vic., Society of Hospital Pharmacists of Australia, 2011.
  6. eviQ Cancer Treatments Online. Eveleigh: Cancer Institute NSW: 2013.
  7. Lyman G. Rolston K. How we treat Febrile Neutropenia in Patients Receiving Cancer Chemotherapy. J Oncol Pract. 2010 May; 6(3): 149-52.
  8. Paul M, Yahav D, Fraser A, Leibovici L. Empirical antibiotic monotherapy for febrile neutropenia systematic review and meta-analysis of randomised controlled trials. J Antimicrob Chemother. 2006 Feb; 57(2): 176-89.
  9. Yamamura D, Gucalp R, Carlisle P, Cimino M, Roberts J, Rotstein C. Open randomized study of cefepime versus piperacillin-gentamicin for treatment of febrile neutropenic cancer patients.  Antimicrob Agents Chemother. 1997 Aug; 41(8): 1704-8.
  10. Solimando D (ed). Drug Information Handbook for Oncology. 7th ed., Hudson, OH, Lexi-Comp Inc., 2008.

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