Febrile Neutropenia

(Aspergillus fumigatus pictured left)

Today we discussed issues related to Febrile Neutropenia. In adults with underlying malignancies, we define febrile neutropenia as:

• Fever: single measurement >38.3 Celsius, or sustained temperature >38 Celsius for more than 1 hour.
• Neutropenia: absolute neutrophil count less than 500 cells/microL. Remember that this is often a dynamic process and your patients ANC may be above 500, but the expected nadir is below.

Think about the immune deficits of your patient: Think about their underlying malignancy, chemotherapy, and other past medical history. With low levels of functioning neutrophils, there is already an impairment in Phagocyte function - these patients will be at risk for Gram + and Gram - bacterial infections, and also Fungal infections like Candida and Aspergillus. Is there an associated deficit in Humoral Immunity (eg CLL, Multiple Myeloma), or Cellular Immunity (eg HIV, immunosuppressive agents)?

Look for potential localizing sources of Infection: A careful history and physical exam to assess for an underlying etiology. In particular, pay close attention to lines and indwelling venous catheters - making your patient more prone to G+ infections. Also look for evidence of Mucositis. Remember that in the absence of neutrophils, the signs of inflammation may be severely blunted. Your investigations will reflect potential sources of infection - blood cultures from peripheral veins and lines, urine cultures, chest x-ray, possibly a CT scan of the chest or abdomen if clinically indicated.

Treatment: This is a potential emergency. Patients will need broad coverage for Gram + and G- (including Pseudomonas) upfront. Antifungal agents should be added if the neutropenia is persisting for more than 5(ish) days. Many hospitals have their own protocols that reflect coverage for particular organisms unique or more prevalent in their environment. Some patients have febrile neutropenia but do not appear to be unwell. Based on certain clinical criteria, they may be considered "Low Risk" and have treatment as an outpatient on oral therapy (eg Cipro + Amoxicillin/Clavulanate). These patients must be very carefully selected, and the hospital must be able to closely follow up with them should their condition deteriorate.

1. Here is a trial from NEJM describing an outpatient management plan for Febrile Neutropenia in "low risk" patients.
   
2. Here are the Infectious Diseases Society of America's 2002 Guidelines for Febrile Neutropenia. There are 2009 guidelines that should be out shortly, so stay posted.

(Ecthyma Gangrenosum pictured left - this is a cutaneous manifestataion of Pseudomonas common in patients with febrile neutropenia)