Neutropenic Fever and Empiric Therapy

Synonym: Febrile Neutropenia

Definition of Neutropenic Fever


  1. Single oral temperature ≥ 38.3 °c (101 °F) or
  2. ≥ 38 °c (100.4 °F) sustained over 1 hour


  1. Absolute Neutrophil Count (ANC) <500 cells/ or
  2. ANC expected to fall <500/ in next 48 hours


Profound neutropenia: ANC <100/

Prolonged neutropenia: Neutropenia for >7 days

Risk Assessment in Neutropenic Fever

Multinational Association for Supportive Care in Cancer (MASCC) scoring system 1 :

mascc risk index
Mnemonic for MASCC scoring variables – A: Age; B: Burden of febrile neutropenia, Blood pressure; C: COPD; D: Dehydration requiring IV fluids; E: Evaluation in outpatient; F: Fungal infection previously

High risk patients – Candidates for Inpatient and Parenteral therapy:

  • MASCC score <21
  • Anticipated prolonged and profound neutropenia
  • Significant medical comorbidities – including hypotension, pneumonia, new-onset abdominal pain, or neurologic changes

Low risk patients – Candidates for Oral therapy:

  • MASCC score ≥21
  • Neutropenia not meeting criteria for ‘high risk’
  • Few or no medical comorbidities

Laboratory Assessment in Neutropenic Fever

For all patients:

  1. CBC including DLC and platelets
  2. RFT – Serum creatinine and BUN
  3. Serum electrolytes
  4. LFT – AST/ALT, Total bilirubin
  5. Atleast 2 sets of blood cultures:
    • If central venous catheter present: 1 set from each lumen of CV catheter and another from peripheral venous site
    • If central venous catheter absent: 2 sets from separate venipuncture

If indicated clinically:

  1. Culture specimens from other sites
  2. Chest Xray
  3. Urinalysis

Oral Empiric Regimens for Low risk Neutropenic Fever

  1. Amoxicillin/Clavulanate + Ciprofloxacin
  2. If on fluoroquinolone prophylaxis – exclude oral fluoroquinolone from empiric therapy
  3. Other: Levofloxacin or Ciprofloxacin monotherapy, or Ciprofloxacin + Clindamycin (if penicillin allergic)

Empiric Regimens for High risk Neutropenic Fever

1st line Monotherapy: Antipseudomonal Beta-lactam agents

  1. Piperacillin-Tazobactam
  2. Cefepime
  3. Meropenem
  4. Imipenem-Cilastin

Fluoroquinolones, Aminoglycosides or Vancomycin may be added for management of complications or antimicrobial resistance.

Modification of initial empiric therapy:

  1. MRSA (Methicillin Resistant Staph Aureus) – Early addition of vancomycin, daptomycin or linezolid
  2. VRE (Vancomycin Resistant Enterococcus) – Early addition of daptomycin or linezolid
  3. ESBLs (Extended spectrum Beta Lactamase producing gram negative organisms) – Early use of Carbapenems
  4. KPCs (Klebsiella Pneumonia Carbapenemase) – Early use of polymyxin/colistin or tigecycline 2

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