Aerosolized Lipid Amphotericin B for Complementary Therapy and/or Secondary Prophylaxis in Patients with Invasive Pulmonary Aspergillosis: A Single-Center Experience.

BACKGROUND: Experience with aerosolized lipid amphotericin B (aeLAB) as therapy or secondary prophylaxis in patients with invasive pulmonary aspergillosis (IPA) is anecdotal. METHODS: We performed a single-center retrospective cohort study to evaluate the efficacy of systemic antifungal therapy with and without aeLAB in patients with proven or probable IPA. Complete or partial response at 3 months was the primary end-point. Clinical response and mortality at 12 months, occurrence of adverse drug reactions and respiratory fungal colonization were secondary end-point. RESULTS: Eleven patients (39%) received aeLAB in addition to systemic antifungal therapy (group A), and 22 (61%) received systemic antifungal therapy only (group B). The use of aeLAB was not standardized. Amphotericin B lipid complex was used in all patients but one, who received liposomal amphotericin B. Five patients received aeLAB as antifungal complementary therapy and 6 received it as secondary prophylaxis. Except for the requirement of inhaled corticosteroids and home oxygen therapy, more frequent in group A, both groups were similar in baseline conditions. A better (nonsignificant) clinical outcome was observed at 3 months in patients receiving aeLAB. Only uncontrolled baseline condition was associated with one-year mortality in univariate analysis (p = 0.002). A multivariate Cox regression analysis suggests that aeLAB, corrected for uncontrolled underlying disease, reduces mortality at 12 months (HR 0.258; 95% CI 0.072-0.922; p = 0.037). CONCLUSION: Although no significant difference was observed in the main variable (3-month clinical response) and in spite of methodological limitations of the study, the possible survival benefit of aeLAB, adjusted for the control of the underlying disease, could justify the performance of well-controlled studies with a greater number of patients.

Aerosolized amphotericin B as prophylaxis for invasive pulmonary aspergillosis: a meta-analysis.

OBJECTIVES: Invasive pulmonary aspergillosis (IPA) is associated with high mortality in high-risk (immunosuppressed) patients. Many studies have investigated whether prophylactic inhalation of amphotericin B (AMB) reduces the incidence of IPA, but no definitive conclusions have been reached. The present meta-analysis was performed to evaluate the efficacy of prophylactic inhalation of AMB for the prevention of IPA. METHODS: MEDLINE and other databases were searched for relevant articles published until December 2013. Randomized controlled trials that compared aerosolized AMB with placebo were included. Two reviewers independently assessed and extracted the data of all trials. RESULTS: Six animal studies and two clinical trials involving 768 high-risk patients were eligible. The animal studies showed lower overall mortality rate among animals that underwent aerosolized AMB prophylaxis (odds ratio (OR) 0.13, 95% confidence interval (CI) 0.08-0.21). Similarly, the clinical trials showed a lower incidence of IPA among patients who underwent aerosolized AMB prophylaxis (OR 0.42, 95% CI 0.22-0.79). CONCLUSIONS: This analysis provides evidence supporting the notion that the prophylactic use of aerosolized AMB effectively reduces the incidence of IPA among high-risk patients.

Aerosolized amphotericin B lipid complex as adjunctive treatment for fungal lung infection in patients with cancer-related immunosuppression and recipients of hematopoietic stem cell transplantation.

STUDY OBJECTIVE: Aerosolized amphotericin B lipid complex (aeABLC) has been successfully used to prevent fungal disease. Experience with aeABLC as treatment of fungal lung disease is limited. DESIGN: We evaluated the safety and efficacy of aeABLC adjunct therapy for fungal lung disease in a retrospective study of 32 immunosuppressed adults. All values are given as ± standard deviation. SETTING: National Cancer Institute-designated Comprehensive Cancer Center. PATIENTS: Acute leukemia (69%) and severe neutropenia (63%) were common. Fifty-six percent of patients had undergone allogeneic hematopoietic stem cell transplantation 185 ± 424 days prior to aeABLC was commenced. MEASUREMENT AND MAIN RESULTS: High-dose corticosteroids were administered during aeABLC in 28% of patients. Fungal lung disease was proven or probable in 41% of patients. Most patients (78%) received concurrent systemic antifungal therapy for a median of 14 ± 18 days before aeABLC. The median cumulative aeABLC dose was 1050 ± 2368 mg, and the median duration of aeABLC therapy was 28 ± 130 days. Most patients (78%) received 50 mg aeABLC twice daily. Partial or complete resolution of fungal lung disease was noted in 50% of patients. In three patients (9%) modest cough, mild bronchospasm, and transient chest pain with accompanying nausea and vomiting resolved completely after discontinuation of aeABLC. No patient required hospitalization for drug toxicity or had a serious (grade III or IV) drug-related adverse event. CONCLUSION: Treatment with aeABLC was tolerated without serious toxicity and may be considered in the setting of severe immunosuppression, cancer, and/or hematopoietic stem cell transplantation in patients with difficult-to-treat fungal lung disease.