Febrile Neutropenia

[Clin Infect Dis 2011;52:e56-93]


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Febrile = oral temperature ≥ 38.3°C once or ≥ 38°C for ≥ 1 hour

Neutropenia = absolute neutrophil count [ANC] < 0.5 x 109/L



  • Blood and urine cultures
  • CBC with differential, electrolytes, creatinine, AST, bilirubin
  • If respiratory symptoms:
    • CXR
    • Nasopharyngeal swab for viral respiratory panel PCR
    • Sputum/tracheal aspirate for C&S and Mycoplasma/Chlamydia/Legionella PCR
  • Careful physical examination required including skin, oral mucosa, perianal area, respiratory system and abdomen.


- Piperacillin-tazobactam monotherapy is recommended first-line in patients who are hemodynamically stable and no evidence of catheter-related infection, skin and soft tissue infection (SSTI), or pneumonia.

- Ceftazidime monotherapy is not recommended as it:

  • has no reliable Gram positive (Enterococci, Streptococci, Staphylococci) activity compared to piperacillin-tazobactam
  • may promote antimicrobial resistance (extended-spectrum ß-lactamases (ESBL) and AmpC cephalosporinases)
  • is not optimal in patients with profound (< 0.1 x 109/L)/prolonged neutropenia.

- Cefepime monotherapy is an alternative to piperacillin-tazobactam:

  • good streptococcal activity
  • activity against methicilin-susceptible S. aureus
  • activity against Amp C cephalosporinase-producing Gram negative organisms (but not against ESBL)
  • lacks enterococcal coverage.

- Carbapenem monotherapy is an alternative to piperacillin-tazobactam. In order to prevent the selection of carbapenem resistance, carbapenems should not be used first-line unless:

  • known/suspected infection with ESBL/Amp C cephalosporinase-producing organisms.
  • penicillin allergy.

Combination therapy (β-lactam plus an aminoglycoside and vancomycin)

  • provides increased coverage of potential pathogens, including resistant strains.
  • is recommended until C&S results available in patients who are hemodynamically unstable or with septic shock.

Recommendations for the Use of Vancomycin in Febrile Neutropenia

- Empiric vancomycin should not be used routinely in febrile neutropenic patients.

- Empiric vancomycin therapy should be considered in:

  • clinically obvious central venous catheter-related infections (tunnel infection)
  • skin or soft tissue infections
  • pneumonia
  • hemodynamic instability
  • patients with positive blood culture for Gram-positive organisms not yet identified (NB: Leuconostoc spp, Pediococcus spp are resistant to vancomycin.)
  • known colonization with MRSA.

- Vancomycin therapy should be discontinued on day 2-3 if cultures negative for ß-lactam resistant Gram positive organisms.