Critical Alerts

• Time-critical: Antibiotics within 60 minutes: Mortality doubles with each hour of delay
• Fever may be only sign: Immunocompromise masks typical sepsis findings
• Assume serious infection until proven otherwise: Empiric broad-spectrum coverage
• Mucositis = portal of entry: GI tract is common source
• No pus = no abscess: May not form with low neutrophil counts
• G-CSF may be indicated: Consult oncology

Key Diagnostics

Emergency Treatments

Overview

Neutropenic sepsis (febrile neutropenia) is a medical emergency defined by fever in a patient with severe neutropenia, typically resulting from cancer chemotherapy. Due to impaired immune response, patients may deteriorate rapidly and require immediate empiric antibiotic therapy without waiting for culture results.

Diagnostic Criteria

Febrile Neutropenia Definition:

• Fever: Temperature ≥38.3°C (101°F) once OR ≥38.0°C (100.4°F) sustained for >1 hour
• Neutropenia: ANC <500/μL OR ANC <1000/μL with predicted decline to <500/μL

ANC Calculation:

ANC = WBC × (% Neutrophils + % Bands) / 100

Classification by Severity

Risk Stratification (MASCC Score)

Multinational Association for Supportive Care in Cancer (MASCC):

Epidemiology

• Incidence: 10-50% of patients receiving chemotherapy
• Mortality: 5-10% overall; higher with documented infection
• Most common pathogens: Gram-positive organisms (60-70% of documented infections)
• Gram-negative bacteremia mortality: 18-40% if not treated promptly

Etiology

Common Pathogens:

Common Infection Sites:

• Bloodstream (primary or line-related)
• Respiratory tract
• GI tract (mucositis, enterocolitis, typhlitis)
• Skin and soft tissue
• Urinary tract
• Perianal region

Life-Threatening Presentations

High-Risk Clinical Features

• Profound neutropenia (<100/μL)
• Expected duration of neutropenia >7 days
• Hematologic malignancy
• Inpatient at fever onset
• Significant comorbidities
• Hemodynamic instability
• Clinical deterioration on antibiotics

Non-Infectious Fever in Neutropenic Patients

However: ALWAYS treat as infection until proven otherwise

Clinical Assessment

Immediate:

• Vital signs
• Source assessment (skin, mucous membranes, lungs, abdomen, lines)
• Calculate ANC

Laboratory Studies

Imaging

Note: Infiltrates may be minimal or absent due to lack of neutrophils

Additional Studies (If Indicated)

• Viral PCR (respiratory, HSV, CMV)
• Fungal markers (Galactomannan, β-D-glucan) if prolonged neutropenia
• Lumbar puncture if meningeal signs (ensure platelet count adequate)

Admission Criteria

• All high-risk febrile neutropenia (MASCC <21)
• Hemodynamic instability
• Significant comorbidities
• Uncertain compliance or follow-up
• Inadequate home support

ICU Criteria

• Septic shock
• Respiratory failure
• Altered mental status
• Multi-organ dysfunction
• Need for vasopressors

Outpatient Management (Low-Risk Only)

Eligibility (MASCC ≥21, CISNE low risk):

• Expected neutropenia <7 days
• No significant comorbidities
• Hemodynamically stable
• Expected adherence
• 24/7 access to medical care
• Caregiver available

Outpatient Regimen:

Daily Follow-Up required initially

Follow-Up

Condition Explanation

• "Your immune system is weakened from chemotherapy, making you very susceptible to infection."
• "Fever in this situation is an emergency because infections can progress very rapidly."
• "We need to start antibiotics right away, even before we know exactly what the infection is."

Prevention Strategies

• Handwashing (patients and contacts)
• Avoid sick contacts
• Food safety (avoid raw foods)
• Avoid crowds during nadir
• Daily temperature monitoring at home

Warning Signs (For Home Monitoring)

• Temperature ≥38.0°C (100.4°F)
• Chills or rigors
• New cough or shortness of breath
• Diarrhea
• Pain at catheter site
• Any new symptoms

Hematologic Malignancy (AML, ALL, MDS)

• Prolonged and profound neutropenia
• Higher risk for invasive fungal infections
• May need antifungal prophylaxis
• Longer antibiotic courses

Solid Tumor with Neutropenia

• Shorter nadir period
• Lower infection risk
• May be candidate for outpatient therapy

HSCT Recipients

• Multiple immune defects beyond neutropenia
• Risk of opportunistic infections
• Extended prophylaxis protocols
• GVHD complicates picture

Asplenic Patients

• Encapsulated organism risk
• Ensure Neisseria, H. influenzae, pneumococcal coverage

Performance Indicators

Documentation Requirements

• ANC and date of last chemotherapy
• Source assessment findings
• Blood culture timing (before antibiotics)
• Antibiotic choice and timing
• Risk stratification score
• Oncology consultation
• Disposition plan

Diagnostic Pearls

• Fever may be the ONLY sign: Low threshold for empiric treatment
• Physical exam may be unremarkable: Can't form abscesses without neutrophils
• Normal CXR doesn't exclude pneumonia: CT more sensitive
• ANC <500 is the cutoff: <100 is very high risk
• Avoid rectal exam: Risk of bacteremia
• Calculate MASCC score: Guides disposition

Treatment Pearls

• Antibiotics within 60 minutes: Every hour delay increases mortality
• Monotherapy usually sufficient: Cefepime, pip-tazo, or meropenem
• Add vancomycin only if indicated: Not routinely required
• Consider fungal coverage after 4-7 days fever: If not improving
• G-CSF is not first-line: Discuss with oncology
• Line removal may be needed: For persistent infection

Disposition Pearls

• Most require admission: Outpatient only for low-risk
• ICU for shock or respiratory failure: Early escalation
• Daily monitoring if outpatient: Cannot miss deterioration
• Expect defervescence in 3-5 days: If not improving, reassess