Assessment of posaconazole salvage therapy in chronic pulmonary aspergillosis using predefined response criteria

Int J Antimicrob Agents. 2018 Aug;52(2):258-264. doi: 10.1016/j.ijantimicag.2018.06.001. Epub 2018 Jun 12.

Abstract

Objectives: Chronic pulmonary aspergillosis (CPA) is a progressive infection that destroys lung tissue in non-immunocompromised patients. First-line therapies for CPA (itraconazole and/or voriconazole) are often curtailed due to toxicity or the development of drug resistance. Posaconazole is a potential alternative for these patients.

Methods: Use of posaconazole was funded by the National Health Service Highly Specialised National Commissioners on an individual basis for patients who failed or did not tolerate first-line therapy; those who met predefined criteria for improvement at 4 and 6 months (weight gain and/or improvement in St George's Respiratory Questionnaire) continued posaconazole long-term. We recorded response, failure, discontinuation rates, and adverse events.

Results: Seventy-eight patients received posaconazole as salvage therapy. Thirty-four (44%) achieved targets for continuation of therapy. Fourteen (18%) failed therapy; five (36%) patients did not achieve clinical targets at 4 or 6 months of assessment and nine (64%) developed clinical and/or radiological failure. Twenty-eight (36%) discontinued their trial early; 8 (29%) died and 20 (71%) had significant side effects. One patient was non-compliant and another was lost to follow up.

Conclusions: Establishing criteria for therapeutic success offered a clear, safe and sustainable method of identifying patients who benefit from additional therapy, and minimised continuation of ineffective therapy in those who did not.

Keywords: Aspergillus fumigatus; Chronic pulmonary aspergillosis; Posaconazole.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antifungal Agents / therapeutic use*
  • Aspergillus fumigatus / drug effects*
  • Aspergillus fumigatus / growth & development
  • Aspergillus fumigatus / pathogenicity
  • Chronic Disease
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Aspergillosis / drug therapy*
  • Pulmonary Aspergillosis / microbiology
  • Pulmonary Aspergillosis / mortality
  • Pulmonary Aspergillosis / pathology
  • Retrospective Studies
  • Salvage Therapy / methods*
  • Surveys and Questionnaires
  • Survival Analysis
  • Treatment Outcome
  • Triazoles / therapeutic use*

Substances

  • Antifungal Agents
  • Triazoles
  • posaconazole