Background: Febrile neutropenia (FN) is a serious complication of myelosuppressive chemotherapy, defined by fever occurring in the context of neutropenia. Prompt recognition and treatment are essential to reduce morbidity and mortality. This algorithm focuses on "high-risk" FN as defined in the ‘Early versus Late Stopping of Antibiotics in high-risk FN’ (ELSA-FN) randomised control trial as expected absolute neutrophil count (ANC) <500 cells/mm3 for ≥7 days. This trial will study if early stopping of antibiotics (after 48 hours of being afebrile) is non inferior to continuing antibiotics in terms of safety and a number of secondary outcomes such as antimicrobial resistance.
Cases: Patients must be less than 18 years of age and are defined by clinical diagnosis and/or documentation of FN with treatment.
Case Inclusion Criteria:
Individual's medical record includes documentation of fever defined as:
A temperature of >38.0°C during the encounter or admitted with a reason for admission of fever
+
Individual’s medical record includes a documented neutropenia as defined as:
Absolute neutrophil count (ANC) of <500 cells/μL or absolute white cell count (WCC) of <1000 cells/μL in the absence of reported (ANC) within 24 hours of fever or within 48 hours of admission if the reason for admission is fever.
+
High-Risk FN Criteria (ELSA-FN definition): The patient meets either of the following criteria:
The patient has a diagnosis of leukaemia or lymphoma and is undergoing dose-intensive treatment phases.
The patient has any malignant or non-malignant diagnosis and is undergoing hematopoietic cell transplantation (HCT) and is within day 0-100 of the transplant date.
+
Antibiotic Criteria (ELSA-FN definition): encounter includes intravenous administration of antibiotics within 24 hours of fever and neutropenia.
Exclusion Criteria:
Individual’s electronic medical record indicates that the neutropenia is due to a condition other than chemotherapy or bone marrow transplantation (e.g., congenital neutropenia, autoimmune neutropenia). Patients must not have a clinically or microbiologically defined infection when ceasing antibiotics for febrile neutropenia.
Control Exclusion Criteria:
Covariates: Relevant covariates are: 1) age, 2) cancer diagnosis, 3) HSCT or chemotherapy regimen, and 4) date of FN diagnosis.
Tables:
Table 1: ICD-9 and ICD-10 Codes for Febrile Neutropenia
| System | Code | Description |
| ICD-9 | 99.29 | Neutropenia Due to Drugs |
| ICD-9 | 288.0 | Neutropenia |
| ICD-10 | D70 | Neutropenia |
| ICD-10 | R50.81 | Fever Present |
| ICD-10 | B99.9 | Unspecified infectious disease (Fever) |
Rationale and Considerations:
• Emphasis on Clinical Criteria: The algorithm focuses on the combined presence of fever and neutropenia, as these are the defining features of FN.
• Treatment: The algorithm uses the prescription of antibiotics as a treatment indicator, which is a standard approach to managing FN.
• Exclusion Criteria: Exclusion criteria is included to remove cases of neutropenia with other causes.
• Covariates: Covariates are important for controlling for potential confounding factors and for stratifying analyses.