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.


  • The patient must be examined to determine the potential sites of infection and the causative organisms
  • Frequently, fever is the only indication of infection in the neutropenic patient
  • Complete history should be taken including underlying comorbidities, prior prophylactic antibiotic, concomitant steroid use, recent surgical procedure, exposure to pets, travel, tuberculosis (TB) exposure, etc
  • Thorough physical exam should be done especially at the most commonly infected sites (eg oropharynx, sinuses, skin, lungs, gastrointestinal tract, perineum)

Laboratory Tests

  • Complete blood count (CBC) with differential leukocyte count and platelet count, creatinine, urea nitrogen, electrolytes, hepatic transaminases, total bilirubin
    • Check levels in order to plan supportive care and baseline to monitor for possible occurrence of drug toxicity
  • At least 2 blood cultures (BC) from a peripheral vein site and any indwelling venous catheter, if present
  • Site-specific cultures may be considered
    • Stool: Consider enteric pathogen screen, Clostridium difficile assessment in patients with diarrhea
    • Urine: Perform if patient has urinary catheter, urinary tract infection (UTI) or abnormal urinalysis, or routinely among febrile neutropenic girls
    • Skin: Aspirate or biopsy of skin lesions or wounds
    • Vascular access cutaneous site if inflammation is present (routine, fungal, mycobacterial)
    • Consider viral cultures of mucosal or cutaneous vesicular or ulcerated lesions and of throat or nasopharynx for respiratory symptoms especially during outbreaks
  • Chest x-ray for patients with respiratory symptoms or if outpatient management is planned
  • Consider urinalysis, pulse oximetry
    • In urinalysis, absence of pus cells does not rule out a urinary tract infection in neutropenic patients

Risk Assessment

  • Risk assessment for complications of severe infection is done at the first sign of fever, guiding the type of empirical antibiotic treatment [oral vs intravenous (IV)], place of therapy (outpatient or inpatient), number of antibiotic regimen (monotherapy or two-drug therapy), and the duration of antibiotic treatment

High Risk for Severe Infections

  • Absolute neutrophil count ≤100 neutrophils/mm3 (profound neutropenia)
  • Anticipated prolonged neutropenia (lasting >7 days)
  • Presence of significant comorbid medical conditions which may include the following:
    • New-onset mental-status or neurologic changes
    • Hemodynamic instability (eg hypotension)
    • Gastrointestinal symptoms including nausea and vomiting, new-onset abdominal pain, diarrhea
    • Chronic lung disease or new pulmonary infiltrates
    • Intravascular catheter infection
  • Hepatic (aminotransferase levels >5x the normal value) and renal (creatinine clearance of <30 mL/minute) insufficiencies
  • Age ≥60 years old

Low Risk for Severe Infections

  • No appearance of illness
  • Neutropenia <7 days
  • No abdominal pain
  • No neurological or mental changes
  • Malignancy that is in remission
  • No comorbid complications (eg hypoxia, shock, etc)
  • Absolute neutrophil count ≥100 neutrophils/mm3
  • Absolute monocyte count ≥100 cell/mm3
  • Normal x-ray
  • Near-to-normal renal & hepatic function tests
  • Expected neutropenia resolution <10 days
  • No IV catheter-site infection
  • Early evidence of bone marrow recovery
  • Peak temp <39°C


  • Oral antibiotics are an option for adults at low risk for complications
    • Should only be considered in patients in whom there is no obvious focus of bacterial infection or any symptom or sign suggesting systemic infection (eg hypotension, rigors) other than fever
  • Change from intravenous (IV) to oral therapy may be done if oral medications are tolerated and patient is clinically stable
  • Patients with neutrophil counts that are recovering are better candidates for outpatient therapy than patients with decreasing counts and no indication of bone marrow recovery
  • Inpatients who meet criteria for being at low risk may be transitioned to outpatient treatment provided emergency medical care is accessible (preferably within 1 hour) and presence of family support or homecare giver and frequency of clinical follow-up are ascertained
  • Initial administration of antibiotics should be given 1 hour after admission of patients with febrile neutropenia
    • Delay in antibiotic administration is associated with significantly longer hospital stay and increased mortality
  • Monotherapy (eg antipseudomonal beta-lactam, carbapenem, or extended-spectrum cephalosporin) may be a sufficient treatment for uncomplicated cases
  • Two-drug therapy (eg a beta-lactam with an aminoglycoside or a fluoroquinolone) is given in complicated infections
  • Re-admission is recommended should fever persist or recur or new signs of infection appear within 48 hours
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