[Clin Infect Dis 2011;52:e56-93]
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:
- Nasopharyngeal swab for viral respiratory panel PCR
- Sputum for C&S and Mycoplasma/Chlamydophila/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 & 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
- 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.