Pulsed echinocandin therapy in azole intolerant or multiresistant chronic pulmonary aspergillosis: A retrospective review at a UK tertiary centre

Clin Respir J. 2020 Jun;14(6):571-577. doi: 10.1111/crj.13171. Epub 2020 Mar 5.

Abstract

Introduction: Chronic pulmonary aspergillosis (CPA) is a fungal disease with high mortality and morbidity. Guidelines suggest treatment with azoles as first-line therapy. However, patients often develop treatment intolerance or increasingly azole resistance.

Objectives: This retrospective review assesses outcomes in azole resistant or intolerant patients with CPA treated with cyclical echinocandin therapy.

Methods: We retrospectively examined records of 25 patients with CPA treated with cyclical caspofungin, 6 of whom were either azole-resistant or azole intolerant. Baseline characteristics, high-resolution computed tomography severity scores, forced expiratory volume after 1 minute (FEV1), forced vital capacity (FVC), body mass index and serology (Aspergillus fumigatus-specific IgG, Aspergillus fumigatus-specific IgE, total IgE and CRP) were assessed before and after caspofungin.

Results: Of the six patients, four (66%) started caspofungin due to intolerance and two (33%) due to pan-azole resistance. On treatment, there was stability in FEV1 with an overall mortality of 33% during the follow-up period with a median survival of 875.5 days (IQR 529-1024). No significant change in serology (A. fumigatus-specific IgG and CRP was seen.

Conclusions: With pulsed echinocandin therapy, azole-intolerant or pan-resistant CPA patients have similar mortality rates to azole-naïve CPA patients. Pulsed echinocandin therapy may present a strategy to stabilize CPA in patients with pan resistance or intolerance to, azole therapy.

Keywords: CPA; azoles; caspofungin; drug resistance; echinocandins; fungal; pulmonary aspergillosis.

MeSH terms

  • Administration, Intravenous
  • Adult
  • Aged
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / therapeutic use*
  • Aspergillus fumigatus / immunology
  • Azoles / standards*
  • Azoles / therapeutic use
  • Biomarkers / blood
  • Caspofungin / administration & dosage
  • Caspofungin / therapeutic use
  • Chronic Disease
  • Drug Resistance, Fungal / physiology
  • Echinocandins / administration & dosage
  • Echinocandins / therapeutic use*
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Pulmonary Aspergillosis / diagnostic imaging
  • Pulmonary Aspergillosis / drug therapy*
  • Pulmonary Aspergillosis / mortality
  • Pulmonary Aspergillosis / physiopathology
  • Respiratory Function Tests / methods
  • Retrospective Studies
  • Tomography, X-Ray Computed / methods
  • United Kingdom / epidemiology

Substances

  • Antifungal Agents
  • Azoles
  • Biomarkers
  • Echinocandins
  • Enzyme Inhibitors
  • Caspofungin