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

Mycopathologia. 2019 Apr;184(2):239-250. doi: 10.1007/s11046-019-00331-0. Epub 2019 Mar 22.

Abstract

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.

Keywords: Aerosolized amphotericin B; Antifungal therapy; Invasive aspergillosis.

MeSH terms

  • Adult
  • Aerosols*
  • Aged
  • Amphotericin B / administration & dosage*
  • Amphotericin B / adverse effects
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / adverse effects
  • Chemoprevention / methods*
  • Complementary Therapies / methods*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Humans
  • Invasive Pulmonary Aspergillosis / drug therapy*
  • Invasive Pulmonary Aspergillosis / prevention & control
  • Male
  • Middle Aged
  • Retrospective Studies
  • Secondary Prevention / methods*
  • Survival Analysis
  • Treatment Outcome

Substances

  • Aerosols
  • Antifungal Agents
  • liposomal amphotericin B
  • Amphotericin B