Febrile Neutropenia Risk Calculator
Calculate MASCC Risk Index to identify low-risk febrile neutropenia patients eligible for outpatient treatment
Overall severity of symptoms related to infection
History of fungal infection increases risk regardless of tumor type
MASCC Risk Index Criteria
| Characteristic | Finding | Points |
|---|---|---|
| Burden of illness | No symptoms | 5 |
| Mild symptoms | 3 | |
| Moderate/severe symptoms | 0 | |
| Hypotension | No hypotension (SBP ≥ 90 mmHg) | 5 |
| COPD | No COPD | 4 |
| Tumor type | Solid tumor or no prior fungal infection | 4 |
| Dehydration | No dehydration | 3 |
| Status at onset | Outpatient | 3 |
| Age | Age ≥ 60 years | 2 |
Maximum possible score: 26 points. Score ≥21 indicates low risk.
Management Recommendations
Low Risk (MASCC Score ≥21)
Outpatient Management:
- Consider oral antibiotics (ciprofloxacin + amoxicillin-clavulanate)
- Alternative: moxifloxacin monotherapy
- Daily follow-up for first 2-3 days (clinic visit or phone)
- Clear return precautions for worsening symptoms
Prerequisites for Outpatient Care:
- Reliable patient with good support system
- Lives within 1 hour of medical facility
- Able to take oral medications and fluids
- Access to telephone
- No significant comorbidities
High Risk (MASCC Score <21)
Inpatient Management:
- Hospital admission required
- IV broad-spectrum antibiotics (e.g., cefepime, piperacillin-tazobactam)
- Consider adding vancomycin if MRSA risk or catheter infection
- Continuous monitoring of vital signs
- Daily clinical and laboratory assessment
Additional Considerations:
- Consider antifungal coverage if fever persists >4-7 days
- Imaging if focal symptoms or persistent fever
- G-CSF (filgrastim) for high-risk patients
- ICU transfer if septic shock or organ failure
General Management for All Patients
- Antibiotics should be started within 1 hour of presentation
- Obtain blood cultures before starting antibiotics (2 sets, including from catheter if present)
- Urinalysis and culture if urinary symptoms
- Chest X-ray if respiratory symptoms
- Other cultures as clinically indicated (wound, stool, etc.)
- Continue antibiotics until ANC >500 and patient afebrile >24-48 hours
Common Antibiotic Regimens
| Setting | First-Line Options | Notes |
|---|---|---|
| Outpatient (Low Risk) | Ciprofloxacin + Amoxicillin-clavulanate OR Moxifloxacin | Requires reliable patient, close follow-up |
| Inpatient (High Risk) | Cefepime OR Piperacillin-tazobactam OR Meropenem | Broad-spectrum monotherapy |
| MRSA Risk | Above + Vancomycin OR Linezolid | Catheter infection, skin/soft tissue, MRSA history |
| Multi-drug Resistant Risk | Meropenem + Vancomycin ± Aminoglycoside | Prior MDR infections, severe sepsis |
| Persistent Fever (4-7 days) | Add Antifungal: Voriconazole or Caspofungin | Consider fungal infection |
Frequently Asked Questions
What is febrile neutropenia?
Febrile neutropenia is defined as a single oral temperature ≥38.3°C (101°F) or ≥38.0°C (100.4°F) sustained for 1 hour, with an absolute neutrophil count (ANC) <500 cells/mm³ or expected to fall below 500 within 48 hours. It is a medical emergency requiring prompt evaluation and treatment.
What does the MASCC score predict?
The MASCC (Multinational Association for Supportive Care in Cancer) Risk Index predicts the risk of serious medical complications in patients with febrile neutropenia. A score ≥21 indicates low risk (<5% complication rate) and may allow for outpatient management with oral antibiotics.
Can all low-risk patients be treated as outpatients?
Not necessarily. While MASCC score ≥21 identifies low-risk patients, outpatient management requires additional criteria: reliable patient with good support, proximity to medical care (<1 hour), ability to take oral medications, telephone access, and no significant comorbidities. Clinical judgment is essential.
How quickly should antibiotics be started?
Antibiotics should be administered within 1 hour of presentation for febrile neutropenia. Delays in antibiotic administration are associated with increased mortality. Obtain blood cultures first if possible, but do not delay antibiotics if there are logistical issues obtaining cultures promptly.
What antibiotics should I use for outpatient treatment?
Common outpatient regimens for low-risk febrile neutropenia include ciprofloxacin plus amoxicillin-clavulanate, or moxifloxacin monotherapy. The choice depends on local resistance patterns, patient allergies, and institutional protocols. Close follow-up is mandatory.
When should antifungal therapy be added?
Consider adding empiric antifungal therapy (voriconazole or an echinocandin) if fever persists after 4-7 days of appropriate antibiotics and the patient remains neutropenic. Earlier initiation may be warranted in high-risk patients or those with prior fungal infections.
How long should antibiotics be continued?
Continue antibiotics until the ANC is >500 cells/mm³ and the patient has been afebrile for at least 24-48 hours. Some protocols require waiting until ANC >1000. If a specific infection is identified, treat for the appropriate duration for that infection.
Should G-CSF (filgrastim) be used routinely?
G-CSF is not routinely recommended for uncomplicated febrile neutropenia. Consider G-CSF for high-risk patients (predicted prolonged neutropenia >7 days, age >65, poor performance status, pneumonia, invasive fungal infection, or septic shock). Follow institutional guidelines.
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Understanding Febrile Neutropenia Risk Assessment
Febrile neutropenia is a common and potentially life-threatening complication of chemotherapy. It occurs when patients receiving myelosuppressive chemotherapy develop both fever and critically low neutrophil counts. Without functioning neutrophils, patients are at high risk for severe bacterial and fungal infections. Historically, all patients with febrile neutropenia were hospitalized for intravenous antibiotics, but risk stratification tools now allow selected low-risk patients to be treated as outpatients.
The MASCC Risk Index
The Multinational Association for Supportive Care in Cancer (MASCC) Risk Index is the most widely validated tool for identifying low-risk febrile neutropenia patients. Developed in the 1990s and validated in thousands of patients, it uses seven clinical parameters to predict the risk of serious medical complications. A score of 21 or higher indicates low risk, with less than 5% chance of serious complications and less than 1% mortality risk.
Components of the Score
The MASCC score incorporates burden of illness (symptom severity), absence of hypotension, absence of COPD, solid tumor status or absence of prior fungal infection, absence of dehydration, outpatient status at fever onset, and age 60 or older. Burden of illness is the most heavily weighted factor, recognizing that patients with minimal symptoms have better outcomes than those with severe symptoms from infection. The presence of hypotension is also heavily weighted as it indicates potential septic shock.
Outpatient Management Criteria
While a MASCC score of 21 or higher identifies low-risk patients, additional criteria must be met for outpatient management. The patient must be reliable with a good support system, live within one hour of a medical facility, be able to take oral medications and maintain hydration, have telephone access, and lack significant comorbidities. Social and logistical factors are just as important as medical factors in determining suitability for outpatient treatment.
Antibiotic Selection
For low-risk outpatients, oral antibiotics with coverage of gram-positive and gram-negative organisms are used. Common regimens include ciprofloxacin plus amoxicillin-clavulanate, or moxifloxacin monotherapy. These regimens provide broad coverage while being convenient for home administration. High-risk inpatients receive intravenous broad-spectrum antibiotics such as cefepime, piperacillin-tazobactam, or meropenem, with vancomycin added if MRSA risk factors are present.
The Importance of Timing
Febrile neutropenia is a medical emergency. Studies consistently show that delays in antibiotic administration increase mortality. Current guidelines recommend starting antibiotics within one hour of presentation. Blood cultures should be obtained before antibiotics if possible, but antibiotic administration should not be delayed if there are logistical issues obtaining cultures promptly. Time to antibiotics is a critical quality metric in oncology care.
Management of Persistent Fever
If fever persists despite 4-7 days of appropriate antibiotics and the patient remains neutropenic, empiric antifungal therapy should be considered. Invasive fungal infections, particularly with Candida and Aspergillus species, are important causes of persistent fever in neutropenic patients. Voriconazole or an echinocandin are commonly used. Additional imaging and diagnostic studies may be warranted to identify occult infections.
Duration of Antibiotic Therapy
Antibiotics should be continued until the absolute neutrophil count recovers to greater than 500 cells/mm³ and the patient has been afebrile for at least 24-48 hours. Some protocols require waiting until the ANC exceeds 1000. If a specific infection is identified and isolated, antibiotics should be tailored to that organism and continued for the appropriate duration for that infection type.
Prevention Strategies
Primary prevention with prophylactic antibiotics (typically fluoroquinolones) may be considered for very high-risk patients expected to have prolonged neutropenia. G-CSF (filgrastim) is used in chemotherapy regimens with greater than 20% risk of febrile neutropenia to reduce neutropenia duration. Patient education about fever precautions, hand hygiene, food safety, and when to seek care is essential for early detection and treatment of febrile neutropenia.