Oncology Patient Presenting with New Fever Clinical Pathway, Emergency Department and Outpatient Specialty Care – Prolonged Febrile Neutropenia (FN)

Oncology Patient Presenting with New Fever Clinical Pathway, Emergency Department and Outpatient Specialty Care – Prolonged Febrile Neutropenia (FN)

Inpatient Management of Oncology Patients with Prolonged Febrile Neutropenia (FN)

This table provides considerations and additional framework for prolonged febrile neutropenia (FN).

In patients with ongoing neutropenia and persistent fevers after 5 days of broad-spectrum empiric antibiotics, consideration should be given to other etiologies for fever. As timely diagnosis and treatment of invasive fungal infection (IFI) is essential for limiting morbidity and improving survival, it is important to evaluate for and empirically treat IFI through count recovery.

Definition of Prolonged Febrile Neutropenia (FN) 5 days of ANC < 200 and documented daily fever
Differential Diagnoses
  • Invasive Fungal Infection (IFI)
    • Increased risk for IFI: AML, relapsed ALL, recipient of high-dose steroids, allogeneic hematopoietic stem cell transplant (alloHSCT), multiple immunosuppressive medications, or prolonged neutropenia before onset of fever (regardless of
      cancer type)
  • Other processes to consider
    • Occult site bacterial infection, anaerobic bacterial infection, viral infection,
      drug-induced fever, malignancy, immune dysregulation/hemophagocytic lymphohistiocytosis (HLH), cytokine release syndrome (CRS)
Updated History and Physical Exam
  • Perform detailed oral exam and skin exam including hands, feet, perineum
  • Signs of invasive infection
    • Erythema, induration, or pain at catheter sites
    • Exam findings may be subtle in the setting of neutropenia and decreased inflammatory capacity
Antimicrobial Choice
  • Initiate anti-mold therapy
    • Start caspofungin if receiving fluconazole or no fungal prophylaxis
  • Acute clinical worsening/deterioration (e.g., new hypotension, respiratory failure),
    use Sepsis Pathway
    • Consider broadening anti-mold medications in discussion with ICID
    • Consider de-escalation after 24-72 hrs if no additional bacterial etiology identified
  • Focal abdominal/anal/rectal symptoms
    • Ensure adequate anaerobic coverage
      (add metronidazole or transition to piperacillin-tazobactam)
  • Empiric changes to antibiotics are generally NOT recommended for patients who are clinically stable with no focal signs/symptoms
Laboratory Studies
  • Respiratory symptoms
    • Consider COVID-19, influenza, RSV testing based on time of year
    • Additional respiratory viral testing is only recommended if it will facilitate stopping antibiotics and/or limit additional work-up
  • Patients who have undergone alloHSCT
    • Consider blood-based viral PCR testing (e.g., adenovirus, CMV)
  • Concern for immune dysregulation
    • Consider ferritin and proinflammatory cytokine panel/CXCL9
  • Sending beta D glucan and galactomannan routinely as part of the work-up for FN is
    not recommended
Imaging
  • CT chest and abdomen w/IV contrast for fungus once ANC > 200
    • Post-count recovery imaging is optimal
    • Reserve pre-count recovery imaging for severe clinical concern, as it is associated with lower sensitivity
    • Pre-recovery imaging does not eliminate the need for post-recovery imaging
  • CT Sinus with IV contrast for fungus once ANC > 200 in patients with localizing
    sinus symptoms
    • Reserve pre-count recovery imaging for severe clinical concern, as it is associated with lower sensitivity
Consults
  • New skin lesions
  • High concern for fungal infection, clinical worsening/decompensation, management of identified infectious etiology or for input on additional work-up
    • Consider ICID consult
  • Concern for immune dysregulation
    • Consider DIRT consult