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Phenotype submission - Febrile Neutropenia or Neutropenic Fever

Neutropenic Fever

Authoritative source

Summary from authoritative source:


Fever in neutropenic patients is defined as a single oral temperature of ≥38.3°C (101°F) or a temperature of ≥38.0°C (100.4°F) sustained over a one-hour period. Neutropenia is defined as ANC < 1,500 cells/microL but can be part of pancytopenia i.e., there is no requirement for it to be isolated to one cell line.
Neutropenic fever is a concern among neutropenic persons, especially treatment associated neutropenia such as chemotherapy. The risk of clinically important infection rises as the neutrophil count falls below 500 cells/microL and is higher in those with a prolonged duration of neutropenia (>7 days). In most cases, the infectious etiology is unable to be determined and gets marked as a fever of unknown origin (FUO). The definition of FUO is neutropenic cases with a fever greater than 38.3 C, without any clinically or microbiologically defined infection
Risk factors: Indwelling IV catheters, especially central venous catheter (CVC), chemotherapy within 6 weeks


• Microbiologically documented infection – Neutropenic fever with a clinical focus of infection and an associated pathogen
• Clinically documented infection – Neutropenic fever with a clinical focus (e.g., cellulitis, pneumonia) but without the isolation of an associated pathogen
• Unexplained fever – Neutropenic fever with neither a clinical focus of infection nor an identified pathogen


Level of neutropenia determines risk status with < 500 ANC generally considered high risk. Severe neutropenia is as an ANC <500 cells/microL or an ANC that is expected to decrease to <500 cells/microL over the next 48 hours, and profound neutropenia as an ANC <100 cells/microL.
Work up would include CBC with WBC differential, blood cultures.
Bacteremia is documented in only 10 to 25 percent of neutropenic fever episodes, and clinically documented infections are found in 20 to 30 percent. Most documented infections during neutropenia are due to bacteria. Fungi and viruses can also be pathogens, particularly in high-risk patients.


It is critical to recognize neutropenic fever early and to initiate empiric systemic antibacterial therapy promptly to avoid progression to a sepsis syndrome and possibly death. In all cancer patients presenting with neutropenic fever, empiric antibacterial therapy should be initiated immediately after blood cultures have been obtained and before any other investigations have been completed.

Phenotype Development

  • We are using the phrases Febrile Neutropenia and Neutropenic fever as synonyms
  • This phenotype is a combination of neutropenia + infection or fever. i.e. if a person with neutropenia also has at the same time severe infection (systemic) or fever, we can consider them to have febrile neutropenia or neutropenic fever.
  • We found other work that used the combination of neutropenia and infection as the definition of febrile neutropenia. The assumption was that severe infections are expected to have a fever.
  • We defined significant infections as any infection of upper urinary tract, respiratory tract, infection of bone, infection due to bacteria (anaerobic, Gram positive, Gram Negative), cellulitis, sepsis or bactermia.
  • Because this is considered by most experts as a ‘medical emergency’ and treated as an inpatient or emergency room - we limited this definition to only those events were a person had a visit that was either inpatient or ER.
  • We decided to anchor the index date on either fever or significant infection and limit the events to those that also had a neutropenia within 1 day (before or after)

Regular expression used in CohortExplorer


Potential problems with this phenotype:

  • Miss rate/False negative/Sensitivity - because we are limiting to visits that are inpatient or ER, this cohort definition is not appropriate for data sources that do not have complete capture of such visits. Incomplete or bad classification of visit categories to inpatient or ER is a threat to this cohort definition. We expect the majority of persons with Neutropenic fever to be monitored in an inpatient setting, but it is possible that some individuals would be managed outpatient (especially during Chemotherapy).
  • Index date misclassifiation - We do not expect significant index date misclassification.
  • Specificity - We expect this cohort definition to be specific.

Cohort Submission:

C208: Neutropenic Fever (3Pe, 30Era)

Phenotype evaluation:

Insights from Cohort Diagnostics:

  • Incidence rate: while the rate was found to be monotonically stable, we found that the rates were different by data source. e.g. The US data sources representing the persons with Medicare and Medicaid benefits appear to have a rate that was 5x more than those with employer sponsored health insurance. This was consistent with our expectation as they are different underlying population.
  • Characterization:
    On index date: Antinfective utilization appeared high > 70%, > 20% had acute renal failure, > 10% dehydration, > 30% had blood microbiologically examination, > 10% were managed as critical care, > 20% had a chest x ray, > 10% ambulance service

Overall this phenotype appears to have good population level characteristics consistent with the target provided in clinical description.

Performance characteristics
PheValuator pending

see https://data.ohdsi.org/PhenotypeLibrary/ cohort id
C208: [P] Neutropenic Fever (3Pe, 30Era)