Galactomannan-guided preemptive vs. empirical antifungals in the persistently febrile neutropenic patient: a prospective randomized study

Int J Infect Dis. 2011 May;15(5):e350-6. doi: 10.1016/j.ijid.2011.01.011. Epub 2011 Mar 11.

Abstract

Background: Patients with neutropenic fever after 4-7 days of broad-spectrum antibiotics are given antifungals empirically. This strategy may lead to over-treatment.

Methods: Patients with hematological malignancies undergoing intensive chemotherapy or hematopoietic stem cell transplantation were randomized to two arms. Patients in the 'preemptive' arm had regular galactomannan (GM) assays, and received caspofungin, amphotericin or voriconazole (CAV) for persistent febrile neutropenia if they had two positive GM results, or a positive GM result and a computed tomography (CT) of the thorax suggestive of invasive pulmonary aspergillosis (IPA). Patients in the 'empirical' arm received CAV in accordance with established guidelines.

Results: Of 27 episodes in the preemptive arm, two cases of IPA were picked up by monitoring. In six episodes, CAV was started despite persistently negative GM readings. One additional patient received CAV for a false-positive GM. Of 25 episodes in the empirical arm, CAV was started empirically in 10, one of whom had CT features of IPA. By intent-to-treat and evaluable-episode analyses, respectively, the preemptive approach saved 11% and 14% of patients from empirical antifungals. Twelve-week survival was 85.2% in the preemptive arm and 84% in the empirical arm.

Conclusions: A preemptive approach may reduce empirical antifungal use without compromising survival in persistently febrile neutropenic patients.

Trial registration: ClinicalTrials.gov NCT00361517.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amphotericin B / administration & dosage
  • Amphotericin B / therapeutic use
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / therapeutic use
  • Caspofungin
  • Drug Therapy, Combination
  • Echinocandins / administration & dosage
  • Echinocandins / therapeutic use
  • Female
  • Fever / physiopathology
  • Galactose / analogs & derivatives
  • Humans
  • Immunocompromised Host
  • Invasive Pulmonary Aspergillosis / complications
  • Invasive Pulmonary Aspergillosis / diagnosis
  • Invasive Pulmonary Aspergillosis / drug therapy*
  • Invasive Pulmonary Aspergillosis / prevention & control
  • Lipopeptides
  • Male
  • Mannans / blood*
  • Middle Aged
  • Mycoses / complications
  • Mycoses / diagnosis
  • Mycoses / drug therapy
  • Mycoses / prevention & control
  • Neutropenia / complications*
  • Opportunistic Infections / complications
  • Opportunistic Infections / diagnosis
  • Opportunistic Infections / drug therapy*
  • Opportunistic Infections / prevention & control
  • Prospective Studies
  • Pyrimidines / administration & dosage
  • Pyrimidines / therapeutic use
  • Radiography, Thoracic
  • Risk Factors
  • Singapore
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Triazoles / administration & dosage
  • Triazoles / therapeutic use
  • Voriconazole

Substances

  • Antifungal Agents
  • Echinocandins
  • Lipopeptides
  • Mannans
  • Pyrimidines
  • Triazoles
  • liposomal amphotericin B
  • galactomannan
  • Amphotericin B
  • Caspofungin
  • Voriconazole
  • Galactose

Associated data

  • ClinicalTrials.gov/NCT00361517