What is the definition of neutropenic fever?

Definition of Neutropenic Fever

Neutropenic fever is defined as an oral temperature >38.3°C (101°F) as a single measurement or ≥38.0°C (100.4°F) sustained over a 1-hour period, in a patient with an absolute neutrophil count (ANC) <500 cells/mm³ or <1000 cells/mm³ with a predicted decrease to <500 cells/mm³. 1

Temperature Criteria

• Single oral temperature measurement of >38.3°C (101°F) 1
• OR temperature ≥38.0°C (100.4°F) sustained for at least 1 hour 1
• Axillary temperatures are discouraged as they may not accurately reflect core body temperature 1
• Rectal temperature measurements should be avoided during neutropenia to prevent tissue trauma and potential bacteremia 1

Neutrophil Count Criteria

• Absolute neutrophil count <500 cells/mm³ 1
• OR neutrophil count <1000 cells/mm³ with a predicted decline to <500 cells/mm³ 1
• Some guidelines further categorize neutropenia as:
  • Severe neutropenia: ANC <500 cells/mm³ 1
  • Profound neutropenia: ANC <100 cells/mm³ 1

Clinical Significance

• Neutropenic fever represents a medical emergency requiring urgent evaluation and treatment 1, 2
• Empirical antibiotic therapy should be initiated within 2 hours of presentation due to the risk of rapid progression of infection 1
• Mortality rates vary significantly:
  • 5% overall in patients with solid tumors (1% in low-risk patients) 1
  • Up to 11% in some hematological malignancies 1
  • 18% in Gram-negative bacteremia and 5% in Gram-positive bacteremia 1
  • Mortality correlates with MASCC score: 3% if score >21, up to 36% if score <15 1

Important Considerations

• The duration of neutropenia is a critical risk factor for infection severity, with protracted neutropenia (≥7 days) associated with higher risk 1, 3
• Risk stratification is often based on duration of neutropenia: low risk (≤5 days), intermediate risk (6-9 days), high risk (≥10 days) 3, 4
• Symptoms and signs of inflammation may be minimal or absent in severely neutropenic patients, making fever often the only sign of infection 1
• At least half of neutropenic patients who become febrile have an established or occult infection 1
• At least one-fifth of patients with neutrophil counts <100 cells/mm³ have bacteremia 1

Clinical Application

• These definitions are general criteria to identify patients requiring empirical antibiotic therapy, but clinical judgment remains essential 1
• Some patients may require antibiotics during neutropenia even if they don't strictly meet these criteria 1
• Prompt initiation of empirical broad-spectrum antibiotics is crucial, as infection can progress rapidly in neutropenic patients 1, 2
• The choice of empirical therapy should be guided by local antimicrobial resistance patterns and individual patient risk factors 1