Neutropenic fever

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  • ANC = (total WBC) x (%segs + %bands)
  • Nadir usually occurs 5-10d after chemo
  • Duration of neutropenia depends on type of cancer treatment
    • Solid tumor treatments: <5d
    • Hematologic malignancies: 14d or longer
  • (Leukemia or lymphoma) + chemo most commonly associated with neutropenia

Neutropenic fever definition

  • ANC <500 OR <1000 with predicted nadir of <500 in 48h AND
  • Fever ≥ 38.3˚C (100.9˚F) once OR sustained temperature ≥38 (100.4) for >1hr
    • Oral temperature (do not obtain rectal temp; risk of inducing bacteremia[1])

Common Causes

Definitive cause only found in 30%

High-Risk/Special Infections

Clinical Features

  • Fever
  • Classic manifestations of infection are frequently NOT seen
  • Check skin, oral cavity, perianal area, entry sites of indwelling cath sites

Differential Diagnosis

Oncologic Emergencies

Related to Local Tumor Effects

Related to Biochemical Derangement

Related to Hematologic Derangement

Related to Therapy


AVOID rectal temp or digital rectal exam

  • CBC
  • Chemistry
  • LFTs
  • Urinalysis/Urine culture
    • May not show WBCs or leuk esterase given neutropenia
  • Sputum studies
  • Blood culture x 2
    • 20-30cc blood (adult); 3-9cc (child)
    • May take both samples from CVC (if present)
  • Culture any indwelling catheters
  • LP
    • If neuro findings or suspicious
  • Site-specific specimens
  • Stool (if indicated)
  • CXR
  • CT (if necessary)
    • Sinuses
    • Chest
    • A/P
  • Patient should be placed and maintained on neutropenic isolation precautions during there stay in the ED and while in the hospital


Therapy is aimed at treating multiple flora that include Gram Negatives, Gram Positive Bacteria, Pseudomonas and if there is an indwelling catheter or high risk, then MRSA.




  • Low risk patients
    • Brief (<7d duration) of neutropenia with few comorbidities[4]
    • Consider discharge it patient scores ≥21 using the MASCC risk index scoring system
    • Score ≥21 associated with <5% risk for severe complications and mortality <1%

MASCC Risk Index

  • The MASCC study was an international collaboration to derive and validate a scoring system to identify low-risk patients for complications of febrile neutropenia.[5]
Characteristic Points

No or Mild Symptoms

Moderate Symptoms

Severe Symptoms




No Hypotension(SBP<90) 5
Solid tumor OR no previous fungal infection 4
No dehydration requiring IV fluids 3
Outpatient status at fever onset 3
Age <60yr 2


  • Clinical Index of Stable febrile Neutropenia
  • 230 febrile neutropenia, chemo-therapy induced, retrospective analysis of MASCC vs. CISNE[6]
    • MASCC was ~55% specific and CISNE was ~98% specific with PPV ~98%

See Also


  1. Fleischman RJ. Emergency Complications of Malignancy. In: Cydulka RK, Fitch MT, Joing SA, Wang VJ, Cline DM, Ma O. eds. Tintinalli's Emergency Medicine Manual, 8e. McGraw-Hill; Accessed December 09, 2020.
  2. 2.0 2.1 Friefeld AG et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the IDSA. Clin Infect Dis. 2011; 52(4):e56-93 fulltext
  3. Hughes WT, Armstrong D, Bodey GP, et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clinical Infectious Disease 2002; 34:730-751
  4. Freifeld AG et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the IDSA. Clin Infect Dis. 2011; 52(4):e56-93.
  5. Klatersky et al. The Multinational Association for Supportive Care in Cancer Risk Index: A Multinational Scoring System for Identifying Low-Risk Febrile Neutropenic Cancer Patients. J Clin Onc 18:3038-3051.
  6. Coyne et al. Application of the MASCC and CISNE Risk-stratification Scores to Identify Low-Risk Febrile Neutropenic Patients in the Emergency Department. Ann Emerg Med. 2016 Dec 29. pii: S0196-0644(16)31352-X. doi: 10.1016/j.annemergmed.2016.11.007.