Febrile neutropenia

Last reviewed: 24 Feb 2023
Last updated: 13 Dec 2022



History and exam

Key diagnostic factors

  • recent chemotherapy
  • fever
More key diagnostic factors

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
Other diagnostic factors

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
More risk factors

Diagnostic investigations

1st investigations to order

  • CBC and differential
  • urinalysis and renal function tests (BUN and creatinine)
  • liver function tests (LFTs)
  • blood cultures
  • chest x-ray
More 1st investigations to order

Investigations 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
More investigations to consider

Treatment algorithm


high risk of complication or death: initial presentation

low risk of complication or death: initial presentation


persistent fever beyond 3-5 days of treatment



Lynne Strasfeld, MD

Associate Professor of Medicine

Department of Medicine, Division of Infectious Diseases

Oregon Health and Science University




LS declares that she has no competing interests.


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.


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




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


Bone Marrow Transplant Program

Division of Hematology/Oncology

University of Florida College of Medicine




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

Matthew Falagas, MD, MSc, DSc


Alfa Institute of Biomedical Sciences





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




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.

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