- Clinical science
Neutropenic fever is an oncologic emergency common in patients receiving chemotherapy. A decrease in a patient's absolute neutrophil count (ANC) can lead to potentially life-threatening infections, and the risk of serious infection is directly associated with the extent and duration of neutropenia. Because the immune response is impaired in neutropenia, symptoms can be mild and even a low-grade temperature (38°C) should be considered a fever. Initial workup should consist of peripheral and, if applicable, central line blood cultures; further investigation is guided by localization of clinical signs. Empiric antibiotic therapy should be started within the first hour of onset to minimize mortality risk. Treatment should be adjusted as soon as further findings are available.
See also fever.
The diagnostic workup should be guided by the pre-test probability of the diagnoses under consideration. The following list includes commonly used methods for diagnosing or ruling out possible etiologies in patients with neutropenic fever. See also .
- CBC with differential
- Blood cultures x 2 sets (at least)
- Culture from any suspected site of infection
- Urinalysis with reflex urine culture
- Serum lactate
- Blood glucose
- Type and screen
- Coagulation studies (e.g., INR, PTT)
- CXR for patients with respiratory symptoms
- Further imaging (e.g., CT) should be guided by history and clinical findings.
- See also “Focused diagnostics” and “Differential diagnoses by affected system” in fever.
- There are several methods of assessing risk of mortality in patients with neutropenic fever, including evaluating clinical risk factors and using a validated risk assessment tool.
- Risk assessment should be used to determine appropriate clinical therapy (e.g., high-risk patients should be treated as inpatients with IV antibiotics, while select low-risk patients may be considered for outpatient therapy).
The presence of even one high-risk feature is enough to consider inpatient therapy.
- Inpatient status at the time of fever onset
- Anticipated prolonged (> 7 days) neutropenia
- Profound (ANC < 100 cells/mm3) neutropenia
- Clinical instability (e.g., hypotension, altered mental status)
- Acute abdominal pain, nausea/vomiting, and/or diarrhea
- New pulmonary infiltrate and/or hypoxemia
- Intravascular catheter infection
- Hepatic insufficiency
- Renal insufficiency
- Uncontrolled cancer
- Induction chemotherapy for acute myelogenous leukemia or in preparation for allogeneic HCT
- Presence of oral and/or gastrointestinal mucositis
- Underlying chronic obstructive pulmonary disease
- Poor functional status
- Advanced age
- Alemtuzumab use 
- Anticipated brief (≤ 7 days) neutropenia
- Clinical stability
- No hepatic or renal insufficiency
- No or few comorbidities
MASCC score 
- Standardized and validated tool for evaluating risk in patients with neutropenic fever
|Clinical burden of symptoms|| |
|Absence of hypotension|| |
|Absence of COPD|| |
|Solid tumor or hematologic malignancy with no previous fungal infection|| |
|Absence of severe dehydration|| |
|Patient status when fever occurred|| |
|Age < 60 years|| |
In general, any patient who does not strictly fulfill the criteria for being at low risk should be treated as a high-risk patient.
|Common bacterial pathogens in neutropenic fever |
- Empiric antibiotic therapy should be initiated immediately after two sets of blood cultures have been obtained
- Low-risk patients who can tolerate oral intake and have a caregiver, telephone, and access to transportation may be treated with oral antibiotics on an outpatient basis.
- High-risk patients require admission and broad-spectrum IV antibiotics to avoid sepsis and life-threatening complications
- Once the patient is clinically stable and/or a source has been determined, consider narrowing antibiotics
- If fever persists, reassess for fungal or viral infection and adapt treatment accordingly.
Low-risk patients (MASCC ≥ 21) 
|Recommended empiric regimen|
|No penicillin allergy and not taking fluoroquinolone prophylaxis|
|Taking fluoroquinolone prophylaxis|| |
High-risk patients (MASCC score < 21) 
|Recommended empiric regimen|
|No penicillin allergy|
|Penicillin allergy and not taking fluoroquinolone prophylaxis|
|Penicillin allergy and taking fluoroquinolone prophylaxis|
Suspected necrotizing or intraabdominal infection
Risk factors for MRSA
and/or a complication associated with a high risk of MRSA infection
|Risk factors for VRE|
|Risk factors for ESBL|
|Risk factors for CPE|
|Risk factors for a suspected infection include previous infection and colonization or treatment in a hospital with high rates of endemicity.|
Any recurrent fever should be considered a new episode of infection.
Fluoroquinolones should only be considered for treatment in patients not previously taking a fluoroquinolone for prophylaxis. If the patient develops a neutropenic fever while on a fluoroquinolone, they should be treated as high-risk and started on an antipseudomonal beta-lactam.
- For low-risk patients, empiric antifungal therapy is not routinely recommended.
- For high-risk patients, consider empiric antifungal therapy in the following situations:
- Persistent or recurrent fever after 4 days of intravenous antibiotic therapy and expected duration of neutropenia > 7 days
- Reassessment does not yield a cause.
- Clinically unstable and suspected fungal infection (e.g., positive galactomannan, 1,3-β-d-Glucan assay, and/or imaging concerning for invasive fungal infection)
- Choose one of the following for empiric antifungal therapy regimens:
- Patients who received antifungal prophylaxis should be switched to a different agent effective against molds (e.g., from voriconazole to amphotericin B).
- Empiric antiviral treatment: only recommended for patients with clinical or laboratory evidence of active viral disease and in patients with possible influenza exposure.
- G-CSF or GM-CSF: Use is not routinely recommended. 
- Indications for indwelling catheter removal in patients with suspected CLABSI: 
- Identify and treat sepsis.
- Peripheral and central blood cultures x 2 sets
- Assess risk and start appropriate empiric antibiotic therapy (within one hour).
- Consider additional diagnostic workup based on likely source
- Identify and control the source of infection
- Parenteral fluid resuscitation and electrolyte replacement
- Antipyretic therapy
- Pain management
- Pulse oximetry monitoring
- Supplemental oxygen (if hypoxic)
- Urinary catheter removal and replacement (if applicable)
- Consider the removal of indwelling intravascular catheters.
- Isolation precautions (e.g., no plants in the room, visitors wear face masks, good hand hygiene)
- Hematology/oncology and infectious disease consultation
- ICU transfer if hemodynamically unstable