Febrile neutropenia is having a fever of ≥38.3 ºC or ≥38 ºC over an hour and neutropenia that is having an absolute neutrophil count (ANC) of <500 neutrophils/mm3 or an ANC <1000 neutrophils/mm3 expected to decline to ≤500 neutrophils/mm3 over the next 48 hours.
The risk of febrile neutropenia is directly proportional to the duration and severity of neutropenia.
Fever is frequently the only indication of infection in the neutropenic patient.


  • Patient must be monitored closely for nonresponse, secondary infections, adverse effects and drug-resistant organisms
  • It may be necessary to change or add antibiotics as the clinical course progresses


Granulocyte Colony-Stimulating Factor (G-CSF)
  • Eg Filgrastim (biosimilars Filgrastim-sndz, Filgrastim-aafi), Lenograstim, Pegfilgrastim (biosimilars Pegfilgrastim-cbqv, Pegfilgrastim-jmdb), Tbo-filgrastim
  • Recommended as prophylaxis in patients with fever and neutropenia at high-risk (≥20%) for infection-associated complications or with prognostic factors for poor clinical outcome
  • May be considered in patients with intermediate-risk (10-20%) if patients has any of the following: History of chemotherapy or radiotherapy, persistent neutropenia, bone marrow involvement, recent surgery, open wounds, liver impairment (bilirubin >2), renal dysfunction (creatinine clearance <50), advanced age (>65 years of age) currently undergoing high-intensity chemotherapy
  • Should not be used in patients with prior treatment of G-CSF
  • It was shown to reduce the risk of febrile neutropenia by at least 50% in patients with solid tumors without significant effect on tumor response or overall survival
  • Can also be used in patients with decreased bone marrow reserve due to extensive radiotherapy or in patients who are neutropenic due to HIV
  • Primary prophylaxis with Filgrastim or Pegfilgrastim have shown success in recent meta-analysis of randomized controlled trials
  • Secondary prophylaxis is indicated if dose reduction is below threshold or delay of chemotherapy is undesirable

  • Fluoroquinolone prophylaxis is recommended for high-risk patients with febrile neutropenia or profound neutropenia
    • Use of fluoroquinolones is discouraged in low-risk patients
    • Should be considered in patients with >7 days expected duration of neutropenia
  • Trimethoprim/sulfamethoxazole or an oral 3rd-generation cephalosporin are alternative treatment for patients with intolerance to fluoroquinolones
  • Use of Ciprofloxacin or Levofloxacin in cancer patients undergoing intensive chemotherapy have been recommended based on recent update of the Cochrane meta-analysis
  • Recommended for patients at high-risk for febrile neutropenia or profound/protracted neutropenia
  • Includes azoles (Fluconazole, Ketoconazole, Itraconazole), amphotericin B, and echinocandins (Caspofungin, Micafungin, Anidulafungin)
  • The use of an inactivated influenza and pneumococcal vaccines for all cancer patients with active disease or undergoing chemotherapy should be considered

Follow Up

  • Patient should be re-evaluated for hospital admission after 2-3 days of empiric broad-spectrum antibiotic therapy if with presence of any of the following:
    • Persistent fever despite 2-3 days intake of empiric broad-spectrum antibiotics
    • Fever re-occurs after period of defervescence
    • New signs and symptoms of infection occurs
    • Oral therapy is no longer tolerated
    • Additional antimicrobials or a change in the treatment regimen is needed
    • Test results showed new causative agent not covered by present antimicrobial regimen
  • Re-admission is recommended should fever persist or recur or new signs of infection appear within 48 hours
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