febrile neutropenia

Introduction

Febrile neutropenia is a medical emergency

Classification

• high risk:
  • neutropenia for >= 7 days
  • absolute neutrophil count < 100/uL &/or
  • comorbidities: hypotension, pneumonia, abdominal pain, neurologic signs
• low risk:
  • anticipated neutropenia < 7 days
  • few or no comorbidities

Etiology

• typhlitis (necrotizing enterocolitis)
• infection with encapsulated organisms in asplenic patients
  • Streptococcus pneumonia
  • Neisseria meningitidis
  • Haemophilus influenza
• Pseudomonas sepsis
• angioinvasive aspergillosis in leukemia patients on long-term antibiotics

Epidemiology

• chemotherapy: 10% of solid tumors; 80% of hematologic malignancies

Clinical manifestations

• a single temperature > 38.3 C (101.0 F) or 38.0 C (100.4 F) for > 1 hour

Laboratory

• complete blood count (CBC) with differential
  • absolute neutrophil count < 500/uL; < 1000/uL
• liver function tests
• renal function tests
• blood cultures
• lumbar puncture with CSF analysis
  • high index of suspicion only
  • low risk of bleeding

Radiology

• chest X-ray
• computed tomography (CT) of thorax
  • only if chest X-ray is abnormal or if cough & tachypnea
• abdominal CT if typhilitis (necrotizing enterocolitis) is suspected in a patient with RLQ abdominal pain

Complications

• ecthyma gangrenosum especially in patients with Pseudomonas sepsis

Management

• risk stratification
  • hospitalization, unless
    • no significant comorbidities (pneumonia, hypotension)
    • neutropenia expected to resolve within 7 days
  • residence < 1 hour (30 miles) from hospital
  • ability to comply in medical instructions
  • family member or caregiver at home 24 hours/day
  • all patients should receive IV antibiotics within 1 hour of triage
  • after observation for 4 hours, low-risk patients may be discharged with oral antibiotics
  • oral antibiotics should cover Pseudomonas
    • ciprofloxacin + Augmentin
• culturing of body fluids
• pathogens
  • gram negative aerobic bacteria
  • penicillin-resistant viridans Streptococci: ARDS
  • fungi in patients with neutropenia > 7-10 days
    • Candida krusei
    • Candida glabrata
    • Candida parapsilosis
    • Aspergillus
• empiric intravenous (IV) antibiotics for hospitalized patients
  • first line agents (should cover Pseudomonas)
    • cefepime
    • ceftazidime
    • piperacillin-tazobactam (Zosyn)
    • imipenem cilastatin
    • addition of aminoglycoside to beta-lactam antibiotic of no benefit & potential harm
    • history penicillin allergy characterized by mild non-puritic rash is not a contraindication to use of cephalosporin or 3rd generation penicillin
    • aztreonam not recommended due to lack of gram-positive coverage
  • vancomycin or linezolid should be added within 48 h
    • if patient fails to respond to initial therapy
    • if gram positive cocci are cultured from blood
    • high risk for gram positive infection (intravascular catheter)
    • discontinue in 3 days if use not supported by positive culture
  • linezolid or daptomycin for suspected vancomycin-resistant enterococci
  • metronidazole or clindamycin should be added for:
    • perirectal abscess
    • odontogenic infection
    • severe, acute abdominal pain suggesting typhlitis
  • empiric therapy for fungal infections in patients who fail antibacterial therapy after 3-7 days
    • amphotericin B is drug of choice
    • itraconazole is alternative
  • antibiotic therapy should be continued 7 days after
    • cultures are negative
    • signs of infection are gone
    • neutrophil count rises above 500/uL
    • 7 days of therapy adequate for gram-negative sepsis & neutropenia due to hematologic malignancy or hematopoietic stem cell transplantation
  • stop antibiotics if
    • cultures never positive
    • no source of infection identified
    • temperature normal for 48 hours, &
    • neutrophil count > 500/uL
  • antiviral only if clinical or laboratory evidence of viral infection 5 supportive therapy
  • may be treated as outpatient if no significant comorbidities & with reliable home care
  • indications for filgrastim (G-CSF) or GM-CSF
    • absolute neurophil count < 100/uL expected to last > 10 days
  • routine use of filgrastim not indicated
  • prophylactic use of G-CSF or GM-CSF if high risk of febrile neutropenia
    • start filgrastim (G-CSF) on day 2 of next cycle of chemotherapy
    • continue full dose of chemotherapy unless overwise indicated

More general terms

• neutropenia