Neutropenic Fever and Empiric Therapy

Synonym: Febrile Neutropenia

Definition of Neutropenic Fever

Fever:

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

Neutropenia:

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

Profound neutropenia: ANC <100/cu.mm

Prolonged neutropenia: Neutropenia for >7 days

Risk Assessment in Neutropenic Fever

Multinational Association for Supportive Care in Cancer (MASCC) scoring system 1http://www.mascc.org/mascc-fn-risk-index-score :

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 2Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR; Infectious Diseases Society of America. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011 Feb 15;52(4):e56-93. doi: 10.1093/cid/cir073. PubMed PMID:  21258094.