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Overview of neutropenic fever syndromes

Eric Bow, MD
John R Wingard, MD
Section Editor
Kieren A Marr, MD
Deputy Editor
Anna R Thorner, MD


Cancer patients receiving cytotoxic antineoplastic therapy sufficient to adversely affect myelopoiesis and the developmental integrity of the gastrointestinal mucosa are at risk for invasive infection due to colonizing bacteria and/or fungi that translocate across intestinal mucosal surfaces. Since the magnitude of the neutrophil-mediated component of the inflammatory response may be muted in neutropenic patients [1], a fever may be the earliest and only sign of infection. It is critical to recognize neutropenic fever early and to initiate empiric systemic antibacterial therapy promptly in order to avoid progression to a sepsis syndrome and possibly death.

This topic will provide an overview of the concepts related to neutropenic fever, including definitions of fever and neutropenia and categories of risk. The risk assessment and diagnostic approach to patients presenting with neutropenic fever are discussed in detail separately. The management of neutropenic fever syndromes in cancer patients at high and low risk for complications and the prophylaxis of infections in such patients are also discussed in detail separately. Granulocyte transfusions are also reviewed elsewhere. (See "Risk assessment of adults with chemotherapy-induced neutropenia" and "Diagnostic approach to the adult presenting with neutropenic fever" and "Treatment of neutropenic fever syndromes in adults with hematologic malignancies and hematopoietic cell transplant recipients (high-risk patients)" and "Treatment and prevention of neutropenic fever syndromes in adult cancer patients at low risk for complications" and "Prophylaxis of infection during chemotherapy-induced neutropenia in high-risk adults" and "Prophylaxis of invasive fungal infections in adults with hematologic malignancies" and "Prophylaxis of invasive fungal infections in adult hematopoietic cell transplant recipients" and "Use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation" and "Granulocyte transfusions".)


Guidelines have been developed for the evaluation and management of fever in neutropenic patients with cancer [2,3]. The recommendations below are generally in keeping with the 2010 Infectious Diseases Society of America (IDSA) guidelines [2] and the 2013 American Society of Clinical Oncology (ASCO) guidelines [4]. These and other IDSA guidelines can be accessed through the IDSA's website [5].


Fever — The definition of fever as an indicator of infection in neutropenic patients has varied. In 1868, Carl Wunderlich proposed that the mean normal body temperature was 37°C (98.6°F) with an upper limit of normal of 38°C (100.4°F), above which fever was defined [6-8]. Despite the observation that there is a range of normal body temperatures, in one survey, a majority (75 percent) of 270 medical professionals reported the belief that normal body temperature is 37°C (98.6°F) [8,9]. A survey of members of the British Society for Haematology regarding their institutional definitions of fever identified 10 definitions of fever, ranging from a single temperature >37.5°C to either a single temperature >39°C or two successive temperatures >38.4°C [10]. These beliefs notwithstanding, the empirically observed mean oral temperature of 148 healthy adults between ages 18 and 40 years was reported as 36.8±0.4°C (98.2±0.7°F) with a range of 35.6°C (96.0°F) to 38.2°C (100.8°F), the latter defining the upper limit of normal [7].

The Infectious Diseases Society of America defines fever in neutropenic patients as a single oral temperature of >38.3°C (101°F) or a temperature of >38.0°C (100.4°F) sustained for >1 hour [2]. We agree with using this definition of fever in neutropenic patients. Similar definitions have been provided from South America, Europe, and Asia [11-13].


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Literature review current through: Sep 2016. | This topic last updated: Dec 2, 2015.
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