Febrile neutropenia initial assessment

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: F and N; fever and neutropenia; FN; hot and low; hot leuk; neutropenic fever; neutropenic fever syndrome; neutropenic sepsis

Overview

Infectious Diseases Society of America (IDSA) recommends that either the clinical judgment criteria or the MASCC assessment tool can be used to stratify risk for patients presenting with fever and neutropenia. Initial assessment should then inform decisions about the type of regimen and appropriate venue for delivery of empirical antibiotics, as well as the timing of hospital discharge. High-risk patients should initially receive IV empirical antibiotic therapy in the hospital, whereas low-risk patients may be candidates for oral and/or outpatient empirical antibiotic therapy.

Initial Assessment

Table 3. MASCC Risk Index Score
Characteristic Burden of febrile neutropenia with no or mild symptomsa No hypotension (systolic blood pressure >90 mmHg) No chronic obstructive pulmonary diseaseb Solid tumor or hematologic malignancy w/o prior fungal infectionc No dehydration requiring parenteral fluids Burden of febrile neutropenia with moderate symptomsa Outpatient status Age <60 years	Weight 5 5 4 4 3 3 3 2
The maximum value of the score is 26. a Burden of febrile neutropenia refers to the general clinical status of the patient as influenced by the febrile neutropenic episode. It should be evaluated on the following scale: no or mild symptoms (score of 5); moderate symptoms (score of 3); and severe symptoms or moribund (score of 0). Scores of 3 and 5 are not cumulative. b Chronic obstructive pulmonary disease means active chronic bronchitis, emphysema, decrease in forced expiratory volumes, need for oxygen therapy and/or steroids and/or bronchodilators requiring treatment at the presentation of the febrile neutropenic episode. c Previous fungal infection means demonstrated fungal infection or empirically treated suspected fungal infection.

Clinical Judgment Criteria

Patients with febrile neutropenia can be stratified at presentation into those with high-risk versus low-risk for complications of severe infection by the clinical judgment criteria as follows:

High-Risk Patient by Clinical Judgment Criteria

Patients with any of the following criteria are considered to be at high risk for serious complications during fever and neutropenia:

• Profound neutropenia (ANC ≤100 cells/mm³) anticipated to extend >7 days
• Presence of any co-morbid medical problems including but not limited to:

— Hemodynamic instability

— Oral or gastrointestinal mucositis that interferes with swallowing or causes severe diarrhea

— Gastrointestinal symptoms, including abdominal pain, nausea and vomiting, or diarrhea

— Neurologic or mental-status changes of new onset d Intravascular catheter infection, especially catheter tunnel infection

— New pulmonary infiltrate or hypoxemia, or underlying chronic lung disease

• Evidence of hepatic insufficiency (defined as aminotransferase levels greater than 5 times of normal values) or renal insufficiency (defined as a creatinine clearance of less than 30 mL/min).

High-risk patients should be hospitalized and receive intravenous empirical antibiotic therapy.

Low-Risk Patient by Clinical Judgment Criteria

Patients with all of the following criteria are considered to be at low risk for serious complications during fever and neutropenia:

• Neutropenia expected to resolve within 7 days
• No active medical co-morbidity
• Stable and adequate hepatic function and renal function.

In general, any patient who does not strictly fulfill criteria for being at low risk should be treated according to guidelines for high-risk patients. Low-risk patients may be candidates for oral and/or outpatient empirical antibiotic therapy.

MASCC Risk Index

The Multinational Association for Supportive Care in Cancer (MASCC) scoring system is a summation of weighted factors, including patient age, history, outpatient or inpatient status, acute clinical signs, the presence of medical comorbid conditions, and severity of fever and neutropenia as assessed by burden of illness. The MASCC Risk Index can be used to identify subgroups of febrile neutropenic patients with high-risk (score <21) or low-risk (score ≥21) for serious complications and death (Table 3). It is also a means to determine which patients require prolonged hospitalization and which may be candidates for oral or once-daily IV regimens and/or for early discharge from the hospital to complete the antibiotic course as outpatients. A fundamental difficulty with the MASCC Risk Index is the indistinct nature of its major criteria: the "burden of febrile neutropenia" and associated symptoms. Without a clear standardized definition of this ‘‘burden’’ of disease, uniform application of the MASCC Risk Index may be confusing.

IDSA Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: Recommendations for Initial Assessment

Class A

"1. Laboratory tests should include a CBC count with differential leukocyte count and platelet count; measurement of serum levels of creatinine and blood urea nitrogen; and measurement of electrolytes, hepatic transaminase enzymes, and total bilirubin. (Quality of Evidence: III)"

"2. At least 2 sets of blood cultures are recommended, with a set collected simultaneously from each lumen of an existing CVC, if present, and from a peripheral vein site; 2 blood culture sets from separate venipunctures should be sent if no central catheter is present. (Quality of Evidence: III)"

"3. Culture specimens from other sites of suspected infection should be obtained as clinically indicated. (Quality of Evidence: III)"

"4. A chest radiograph is indicated for patients with respiratory signs or symptoms. (Quality of Evidence: III)"

Class C

"1. Blood culture volumes should be limited to <1% of total blood volume (usually ~70 mL/kg) in patients weighing <40 kg. (Quality of Evidence: III)"

IDSA Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: Recommendations for Risk Assessment

Class A

"1. Assessment of risk for complications of severe infection should be undertaken at presentation of fever. Risk assessment may determine the type of empirical antibiotic therapy (oral vs IV), venue of treatment (inpatient vs outpatient), and duration of antibiotic therapy. (Quality of Evidence: II)"

"2. Most experts consider high-risk patients to be those with anticipated prolonged (>7 days duration) and profound neutropenia (absolute neutrophil count [ANC] ≤100 cells/mm3 following cytotoxic chemotherapy) and/or significant medical co-morbid conditions, including hypotension, pneumonia, new-onset abdominal pain, or neurologic changes. Such patients should be initially admitted to the hospital for empirical therapy. (Quality of Evidence: II)"

"3. Low-risk patients, including those with anticipated brief (≤7 days duration) neutropenic periods or no or few co-morbidities, are candidates for oral empirical therapy. (Quality of Evidence: II)"

Class B

"1. Formal risk classification may be performed using the Multinational Association for Supportive Care in Cancer (MASCC) scoring system. (Quality of Evidence: I) i. High-risk patients have a MASCC score <21. All patients at high risk by MASCC or by clinical criteria should be initially admitted to the hospital for empirical antibiotic therapy if they are not already inpatients. ii. Low-risk patients have a MASCC score ≥21. Carefully selected low-risk patients may be candidates for oral and/or outpatient empirical antibiotic therapy."