Neutropenic Fever

Definitions ₍₁₎

• Neutropenia = Absolute Neutrophil Count (ANC) < 1,000/µL
  • Typically occurs 5-15 days after the administration of chemotherapy
• Severe Neutropenia = ANC < 500/µL
• Profound Neutropenia = ANC < 100/µL
• Fever (in a neutropenic patient) = single temperature of 38.3°C or a temperature of 38.0°C sustained over a 1-hour period

Risk-Stratification ₍₂₎

• Talcott Classification
• MASCC Score (Multinational Association for Supportive Care in Cancer) <21
• CISNE (Clinical Index for Stable Febrile Neutropenia)
  • Has been shown to have a higher accuracy for risk-stratifying patients with stable febrile neutropenia

Pathogens

• Bacteria are most common etiology ₍₃₎
  • Staphylococcus epidermidis is most commonly identified pathogen ₍₄₎
• Bacteremia present in ~1/4 patients with neutropenic fever
  • Gram-positive cocci responsible for ~60% of bacteremic cases, Gram-negative infections responsible for ~30% of cases, and polymicrobial infections responsible for ~10% of cases of bacteremia in patients with febrile neutropenia ₍₅₎
• Viruses
  • More prevalent in high-risk patients through reactivation of latent viruses
    • May include herpes simplex virus 1 or 2, herpes zoster, etc.
• Fungi
  • More prevalent in high-risk patients
    • May include Candida or Aspergillus

Evaluation

• Diagnostic evaluation will vary depending on the patient’s presenting symptoms, however, will generally include
  • History and physical exam: looking for rashes, abdominal tenderness, abnormal lung sounds, etc.
  • Blood cultures
  • Chest X-Ray
  • Urinalysis and urine culture
  • CBC with differential (to determine severity of neutropenia)
• If the patient is experiencing abdominal pain or diarrhea
  • Clostridium difficile stool Ag/Toxin testing
  • Consider CT of the abdomen to rule out enterocolitis

Management

• Outpatient: Only if clearly a low-risk patient based on clinical scoring tools, clinical picture, co-morbidities, degree of neutropenia, etc.
  • Fluoroquinolone + amoxicillin/clavulanate (or clindamycin) ₍₆₎
• Inpatient ₍₇₎
  • Empiric antimicrobial therapy is warranted as soon as blood cultures have been drawn
  • Anti-pseudomonal β-lactam agent
    • Cefepime
    • Meropenem
    • Piperacillin-tazobactam
  • Vancomycin not routinely recommended unless there is clinical suspicion for a catheter-related infection, skin/soft-tissue infection, pneumonia, or hemodynamic instability

• Consider G-CSF with subsequent rounds of chemotherapy

References

1. Antimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline Update. Randy A. Taplitz, Erin B. Kennedy, Eric J. Bow, Jennie Crews, Charise Gleason, Douglas K. Hawley, Amelia A. Langston, Loretta J. Nastoupil, Michelle Rajotte, Kenneth V. Rolston, Lynne Strasfeld, and Christopher R. Flowers Journal of Clinical Oncology 2018 36:30, 3043-3054
2. Carmona-Bayonas A;Jiménez-Fonseca P;Virizuela Echaburu J;Antonio M;Font C;Biosca M;Ramchandani A;Martínez J;Hernando Cubero J;Espinosa J;Martínez de Castro E;Ghanem I;Beato C;Blasco A;Garrido M;Bonilla Y;Mondéjar R;Arcusa Lanza MÁ;Aragón Manrique I;Manzan. (n.d.). Prediction of serious complications in patients with seemingly stable febrile neutropenia: Validation of the Clinical Index of Stable Febrile Neutropenia in a prospective cohort of patients from the FINITE study. Retrieved December 31, 2020, from https://pubmed.ncbi.nlm.nih.gov/25559804/
3. Pagano L;Caira M;Nosari A;Rossi G;Viale P;Aversa F;Tumbarello M; ;. (n.d.). Etiology of febrile episodes in patients with acute myeloid leukemia: Results from the Hema e-Chart Registry. Retrieved December 31, 2020, from https://pubmed.ncbi.nlm.nih.gov/21911638/
4. Mikulska M;Viscoli C;Orasch C;Livermore DM;Averbuch D;Cordonnier C;Akova M; ;. (n.d.). Aetiology and resistance in bacteraemias among adult and paediatric haematology and cancer patients. Retrieved December 31, 2020, from https://pubmed.ncbi.nlm.nih.gov/24370562/
5. Klastersky J;Ameye L;Maertens J;Georgala A;Muanza F;Aoun M;Ferrant A;Rapoport B;Rolston K;Paesmans M;. (n.d.). Bacteraemia in febrile neutropenic cancer patients. Retrieved December 31, 2020, from https://pubmed.ncbi.nlm.nih.gov/17689933/
6. Randy A. Taplitz, E. (n.d.). Fever and Neutropenia in Adults with Cancer. Retrieved December 31, 2020, from https://www.idsociety.org/practice-guideline/fever-and-neutropenia-in-adults-with-cancer/
7. Freifeld, A. G., Bow, E. J., Sepkowitz, K. A., Boeckh, M. J., Ito, J. A., Mullen, C. A., . . . Wingard, J. R. (n.d.). Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update by the Infectious Diseases Society of America. Retrieved December 31, 2020, from https://academic.oup.com/cid/article/52/4/e56/382256