Febrile Neutropenia

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

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Definitions

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

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

Investigations:

• Blood and urine cultures
• CBC with differential, electrolytes, creatinine, AST, bilirubin
• If respiratory symptoms:
  • CXR
  • Nasopharyngeal swab for viral respiratory panel PCR
  • Sputum for C&S and Mycoplasma/Chlamydia/Legionella PCR

Careful physical examination required including skin, oral mucosa, perianal area, respiratory system and abdomen.

Monotherapy:

- Piperacillin-tazobactam monotherapy is recommended first-line in patients who are hemodynamically stable, and no evidence of catheter-related infection, skin & 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 methicillin-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 infection
• 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.

Prophylaxis:

- Quinolone prophylaxis may increase likelihood of Gram positive infections and Gram negative resistance.