Caspofungin or Micafungin as Empiric Antifungal Therapy for Persistent Fever and Neutropenia

Evaluation of Caspofungin or Micafungin as Empiric Antifungal Therapy in Adult Patients With Persistent Febrile Neutropenia: A Retrospective, Observational, Sequential Cohort Analysis

Invasive fungal infections are an important cause of morbidity and mortality in patients with neutropenia who are receiving chemotherapy for cancer. Early diagnosis of these infections is difficult and fever may be the only sign. A delay in treatment while a diagnosis is pursued may lead to increased morbidity and mortality. There are now several echinocandins available with similar in vitro spectrum of activity. Caspofungin is the only echinocandin Food and Drug Administration (FDA) approved for empiric antifungal therapy in febrile neutropenia. Although all echinocandin antifungal agents have similar spectrum of activity, there are limited data on the use of micafungin in patients with persistent fever and neutropenia (FN). In November 2006 the Pharmacy and Therapeutics Committee at Brigham & Women's Hospital / Dana Farber Cancer Institute (BWH/DFCI) switched from caspofungin to micafungin as our formulary echinocandin. Given the limited clinical data on the use of micafungin as empiric antifungal therapy in patients with FN, we sought to evaluate the safety and effectiveness of micafungin, compared with caspofungin, for this indication using a sequential cohort analysis of patients treated before and after the formulary change at Brigham and Women's Hospital.

Objectives

This retrospective cohort analysis of converting from caspofungin to micafungin as empiric antifungal therapy for cancer patients who are persistently febrile and neutropenic after receiving broad spectrum antibiotics at Brigham & Women's Hospital / Dana Farber Cancer Institute (BWH/DFCI) is designed to evaluate the following objectives:

• Safety of micafungin in this patient population
• Effective dose of 100 mg daily of micafungin compared to 70mg x1, then 50 mg daily of caspofungin
• Economic impact of converting or formulary echinocandin from micafungin to caspofungin

Study Design

• Retrospective cohort analysis - limited to medical records

• Data to be collected include the following:

  • Demographic information: including: gender, age, race
  • Past medical history and admitting diagnoses
  • Laboratory results: Liver function tests (LFTs), Including alanine aminotransferase (ALT), aspartate aminotransferase (AST), Total bilirubin, as well as serum fungal assays: Serum Galactomannan assay, 1.3-BD Glucan assay
  • Concomitant medications and duration of therapy for all systemic: antibiotics and antifungals
  • All invasive breakthrough fungal infection details, including speciation and outcomes during echinocandin therapy
  • Dosing, duration, and adverse events associated with echinocandin therapy

Inclusion Criteria:

• All patients admitted to BWH/DFCI who received at least 2 doses of caspofungin with an Absolute Neutrophil Count (ANC) < 500, for persistent febrile neutropenia from 11/1/2005 - 10/31/2006, as there first antifungal agent.
• All patients admitted to BWH/DFCI who received at least 2 doses of micafungin with an Absolute Neutrophil Count (ANC) < 500 for persistent febrile neutropenia from 11/1/2006 - 10/31/2007 as there first antifungal agent

Exclusion Criteria:

• Patients receiving an echinocandin antifungal agent (micafungin or caspofungin) for an indication other then empiric therapy in febrile neutropenia
• Patients receiving therapy for an active or on-going invasive fungal infection
• Patients who received both caspofungin and micafungin during the same admission
• Patients with an ANC > 500 at when either micafungin or caspofungin was started
• Patients who received another antifungal agent for persistent febrile neutropenia, e.g., voriconazole, amphotericin B liposome, posaconazole, etc... Before they received an echinocandin (caspofungin or micafungin) will be excluded