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Febrile neutropenia

  • Overview
  • Theory
  • Diagnosis
  • Management
  • Follow up
  • Resources
Last reviewed: 11 Jun 2025
Last updated: 28 Nov 2024

Summary

Definition

History and exam

Key diagnostic factors

  • recent chemotherapy
  • fever
Full details

Other diagnostic factors

  • age >65 years
  • immunosuppressive therapy
  • prior chemotherapy-induced neutropenia
  • low performance status (Eastern Cooperative Oncology Group performance status [ECOG PS] >1)
  • hematologic malignancies
  • advanced-stage disease
  • prior antibiotic regimens
  • low albumin (<3.5 g/dL)
  • elevated bilirubin and liver enzymes (aspartate aminotransferase and alkaline phosphatase)
  • pre-existing organ dysfunction and comorbid conditions
  • low first-cycle nadir absolute neutrophil count (<500 cells/microliter)
  • signs of pneumonia (cough, abnormal breath sounds, shortness of breath)
  • abdominal pain
  • nausea or vomiting
  • diarrhea
  • skin erythema, warmth, tenderness
  • mucositis or oral ulcers
  • infection, inflammation, or ulceration of genital and anal area
  • infected indwelling catheters
  • pyuria
  • chemoradiation therapy
  • recent historical features and exposures
  • sinus tenderness
Full details

Risk factors

  • age >65 years
  • hematologic malignancies
  • low albumin (<3.5 g/dL)
  • elevated bilirubin
  • elevated liver enzymes
  • pre-existing organ dysfunction and comorbid conditions
  • recent chemotherapy
  • low first-cycle nadir absolute neutrophil count (<500 cells/microliter)
  • chemoradiation therapy
  • prior chemotherapy-induced neutropenia
  • female sex
  • low performance status (Eastern Cooperative Oncology Group performance status [ECOG PS] >1)
  • advanced-stage disease
  • immunosuppressive therapy
Full details

Diagnostic tests

1st tests to order

  • CBC and differential
  • urinalysis and renal function tests (BUN and creatinine)
  • liver function tests (LFTs)
  • blood cultures
  • chest x-ray
Full details

Tests to consider

  • gastrointestinal pathogen molecular assay
  • urine culture
  • lumbar puncture
  • fungal cultures and serologies (beta-glucan and galactomannan)
  • viral molecular assay
  • echocardiogram
  • CT scans of the chest, abdomen, and pelvis
Full details

Treatment algorithm

ACUTE

high risk of complication or death: initial presentation

low risk of complication or death: initial presentation

ONGOING

persistent fever beyond 3-5 days of treatment

Contributors

Authors

Lynne Strasfeld, MD

Professor of Medicine

Department of Medicine, Division of Infectious Diseases

Oregon Health and Science University

Portland

OR

Disclosures

LS declares that she has no competing interests.

Acknowledgements

Dr Lynne Strasfeld would like to gratefully acknowledge Dr Kenneth V. I. Rolston, Dr Lior Nesher, Dr Caron Jacobson, and Dr Joseph Antin, previous contributors to this topic.

Disclosures

KVIR has research grants from Merck, Shionogi, and JMI Laboratories for the performance of in vitro studies of novel antimicrobial agents. LN has given two educational lectures sponsored by MSD. CJ and JA declare that they have no competing interests.

Peer reviewers

Alison Freifeld, MD

Professor of Medicine, Infectious Diseases Division

University of Nebraska College of Medicine

Omaha

NE

Disclosures

AF has received payment by Merck for work as an adjudication committee member for clinical trials of letermovir. AF has received an investigator-initiated study grant from Merck.

John Wingard, MD

Price Eminent Scholar and Professor of Medicine

Director

Bone Marrow Transplant Program

Division of Hematology/Oncology

University of Florida College of Medicine

Gainesville

FL

Disclosures

JW has been reimbursed by Pfizer, Merck, Astellas, and Enzon for speaking fees, fees for educational programs, and consulting.

Matthew Falagas, MD, MSc, DSc

Director

Alfa Institute of Biomedical Sciences

Marousi

Athens

Greece

Disclosures

MF declares that he has no competing interests.

Ruth Pettengell, MBChB FRACP PhD

Senior Lecturer in Haematology

Honorary Consultant in Medical Oncology

St George's University of London

London

UK

Disclosures

RP has received speaker fees and been reimbursed by Roche, Amgen, Chigai, and Bayer for attending several conferences. RP is a co-author of the EORTC guidelines referenced in this topic.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Freifeld AG, Bow EJ, Sepkowitz KA, et al. 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.Full text  Abstract

Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the use of WBC growth factors: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2015 Oct 1;33(28):3199-212. Abstract

National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: prevention and treatment of cancer-related infections [internet publication].Full text

Taplitz RA, Kennedy EB, Bow EJ, et al. 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. 2018 Feb 20;36(14):1443-53.Full text  Abstract

Klastersky J, de Naurois J, Rolston K, et al. Management of febrile neutropaenia: ESMO Clinical Practice Guidelines. Ann Oncol. 2016 Sep;27(5 suppl):v111-8.Full text  Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

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