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    Febrile Neutropenia in Adults

    Cardinal Presentations / Presenting Problems, Hematological / Oncological, Infections

    Last Reviewed on Feb 08, 2023
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    By James Reid,Andrew Au


    • Neutropenia can result from decreased production (e.g., drug-induced, infection, malignancy, nutrition deficiency), redistribution (e.g., margination to the spleen), or immune destruction (e.g., autoimmune conditions).
    • Due to a muted immune response, fever may be the principal and only sign of invasive infection in neutropenic patients.
    • Prompt recognition of a neutropenic fever is prudent to ensure initiation of empiric antimicrobial therapy and to avoid progression to a sepsis syndrome.


    • Fever: A single oral temperature of ≥ 38.3° C (101° F) OR a temperature ≥ 38° C (100.4° F) which lasts more than 1h.
    • Neutropenia: An abnormally low number of neutrophils in the blood (ANC < 1.0 x 109/L). The lower the neutrophil count, the greater the risk of infection.
    • Absolute Neutrophil Count (ANC) Calculator https://www.mdcalc.com/calc/19/absolute-neutrophil-count-anc

    Diagnostic Process

    1. History

    • A thorough history should be conducted with emphasis on new site-specific symptoms, recent antibiotic treatment, surgical history, underlying comorbid conditions, and past microbiology records (e., history of antibiotic resistant organisms or bacteremia).

    2. Physical Examination

    • Focus on identifying a focus of infection including, but not limited to: presence of indwelling IV catheters, skin lesions and lymph nodes, oropharynx, chest and lungs, abdomen, genital and perianal/rectal area*, central nervous system.
      • * DRE should be avoided in neutropenic or immunocompromised patients.

    3. Investigations

    Routine Investigations

    • CBC with differential
    • Creatinine, electrolytes
    • Liver function tests, coagulation screen
    • CRP
    • Blood cultures: two sets – one peripheral and one from CVC
    • Microbiologic testing from suspected sites of infection: urinalysis and culture, sputum microscopy and culture, stool microscopy and culture, skin lesion (aspirate, biopsy, swab, culture), chest radiograph, lumbar puncture.

    Further Testing

    • High-resolution chest CT (if pyrexial despite 72h of appropriate antibiotics)
    • Bronchoalveolar lavage

    4. Severity Assessment



    Recommended Antibiotics

    • Levofloxacin 750mg daily PO or Ciprofloxacin 750 mg PO Q12H AND Amoxicillin/Clavulanate 875/125 mg PO Q12H, or
    • Levofloxacin 750mg daily PO or Ciprofloxacin 750 mg PO Q12H AND Clindamycin 600 mg PO Q8H if penicillin allergy.
    • Fluoroquinolones are NOT recommended if significant patient exposure in the past 3 months.
    • Antimicrobial therapy duration: continue until the infection has resolved AND the patient is no longer neutropenic.


    • Formally re-evaluate patient in 2 to 3 days.
    • If AFEBRILE for ≥ 48 hours AND neutrophils ≥ 2 consecutive days and increasing, no positive source of infection identified and patient clinically stable, may discontinue antibiotics and monitor patient.
    • If FEBRILE, admit patient for further investigations and initiation of appropriate antimicrobial therapy.


    Recommended Antibiotics

    • Piperacillin-Tazobactam 4.5 g IV QID, or [1,2]
    • Imipenem 500 mg IV Q6H or Meropenem 1g IV Q8H, or [1,2]
    • Cefepime 2g IV Q8H or Ceftazidime 2g IV Q8H (NOT recommended as monotherapy in areas at risk for ESBL producing bacteria). [1,2]
    • If anaphylaxis allergy to beta-lactams, treat with Vancomycin + Aminoglycoside + Ciprofloxacin.
    • NOTE: avoid aminoglycosides or other nephrotoxic agents in patients receiving cisplatin or other nephrotoxic chemotherapy.

    Adjunct Antibiotics

    • If positive blood culture for gram-positive organism, catheter-related infection, skin or soft-tissue infection, known or suspected MRSA, or suspicion for Clostridium difficile, add:
      • Vancomycin 25 mg/kg IV loading dose, followed by 15 mg/kg IV [3]
    • If anaerobic infection (g., intra-abdominal) suspected, add:
      • Metronidazole 500 mg IV Q12H
    • If resistance suspected or there are complications (g., hypotension, persistent fever, pneumonia, etc.), add: [3]
      • Tobramycin or Gentamicin 6-7 mg/kg IV Q24H, or
      • Ciprofloxacin 400 mg IV Q8-12H, or
    • If atypical pneumonia suspected (g., Legionella or Mycoplasma), add:
      • Azithromycin 500 mg IV daily, or
      • Moxifloxacin 400 mg IV daily or Levofloxacin 750 mg IV daily.

    Antifungal therapy

    • Consider in those with persistent fevers, despite receiving 3-5 days of broad-spectrum antibiotic therapy.

    Related Information


    1. Empiric treatment for febrile neutropenia. (2015). BC Cancer Agency. Available at http://www.bccancer.bc.ca/Documents/BCCA%20Febrile%20Neutropenia%20Guidelines.pdf.

    Reference List

    1. Freifeld, A. G., Bow, E. J., Sepkowitz, K. A., Boeckh, M. J., Ito, J. I., Mullen, C. A., … & Wingard, J. R. (2011). Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clinical infectious diseases, 52(4), e56-e93.

    2. Flowers, C. R., Seidenfeld, J., Bow, E. J., Karten, C., Gleason, C., Hawley, D. K., … & Ramsey, S. D. (2013). Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol, 31(6), 794-810.

    3. Klastersky, J., De Naurois, J., Rolston, K., Rapoport, B., Maschmeyer, G., Aapro, M., & Herrstedt, J. (2016). Management of febrile neutropaenia: ESMO clinical practice guidelines. Annals of Oncology, 27, v111-v118.

    4. Taplitz, R. A., Kennedy, E. B., Bow, E. J., Crews, J., Gleason, C., Hawley, D. K., … & Flowers, C. R. (2018). Outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice Guideline Update. J Clin Oncol, 36(14), 1443-1453.



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