Related Experiment Videos
A pilot study of prophylactic aerosolized amphotericin B in patients at risk for prolonged neutropenia
S E Myers1, S M Devine, R L Topper
1University of Chicago Medical Center, Department of Medicine, Illinois 60637.
Abstract:
Invasive aspergillosis continues to be a significant cause of morbidity and mortality in patients with prolonged neutropenia. We performed a phase I trial of escalating doses of aerosolized amphotericin B given by a face mask nebulizer system with a disposable bacterial exhale filter. Five, 10, 15, and 20 mg of drug were dissolved in sterile water and inhaled over 10 to 15 minutes twice daily. Tolerance was studied in 26 patients (18 transplant recipients, and 8 leukemia patients). No side effects were observed at any dose level. Prophylactic treatment ended for 14 patients (54%) when intravenous (IV) amphotericin B was begun empirically for antifungal coverage following fevers. Eleven patients (43%) continued inhaled amphotericin B until blood counts recovered. One patient was taken off study when she developed cardiogenic pulmonary edema. No patient developed clinically suspicious or pathologically documented infection with invasive aspergillosis. Prophylactic aerosolized amphotericin B is well tolerated at 5, 10, 15, and 20 mg twice daily dosing. In addition, prophylactic aerosolized amphotericin B does not appear to sensitize patients to the subsequent use of IV amphotericin B. Although this study suggests that prophylactic inhaled amphotericin B is well tolerated and effective, a large scale controlled trial is needed.
Insights
Inhaled amphotericin B is a safe and well-tolerated prophylactic treatment for patients with neutropenia, preventing invasive aspergillosis. This approach does not hinder subsequent intravenous amphotericin B therapy.
Area of Science:
- Mycology
- Clinical Pharmacology
- Infectious Diseases
Background:
- Invasive aspergillosis poses a significant threat to patients experiencing prolonged neutropenia, leading to high morbidity and mortality.
- Effective prophylactic strategies are crucial for managing this opportunistic fungal infection in immunocompromised individuals.
Purpose of the Study:
- To evaluate the safety and tolerability of escalating doses of aerosolized amphotericin B administered via a face mask nebulizer system.
- To assess the efficacy of inhaled amphotericin B as a prophylactic agent against invasive aspergillosis in high-risk patients.
Main Methods:
- A phase I clinical trial involving 26 patients (18 transplant recipients, 8 leukemia patients).
- Administration of escalating doses (5, 10, 15, 20 mg) of aerosolized amphotericin B twice daily via nebulizer.
- Monitoring for side effects and clinical outcomes, including the development of invasive aspergillosis and the need for empirical intravenous therapy.
Main Results:
- Aerosolized amphotericin B was well tolerated at all tested dose levels, with no observed side effects.
- No patients in the study developed clinically suspected or pathologically confirmed invasive aspergillosis.
- Prophylactic inhaled therapy did not appear to compromise the effectiveness of subsequent intravenous amphotericin B treatment.
Conclusions:
- Prophylactic aerosolized amphotericin B is safe and well-tolerated in patients with prolonged neutropenia at doses up to 20 mg twice daily.
- Inhaled amphotericin B shows promise as an effective prophylactic agent against invasive aspergillosis.
- Further large-scale, controlled trials are warranted to confirm the efficacy and optimal use of prophylactic inhaled amphotericin B.