Positive Aspergillus PCR as a marker of azole resistance or sub-therapeutic antifungal therapy in patients with chronic pulmonary aspergillosis

Mycoses. 2020 Apr;63(4):376-381. doi: 10.1111/myc.13052. Epub 2020 Feb 5.

Abstract

Background: Chronic pulmonary aspergillosis (CPA) is a progressive respiratory disease, caused most commonly by A fumigatus, with significant morbidity and mortality. Azole resistance in A fumigatus is a growing concern worldwide, with resistance to itraconazole reported in up to 50% of patients.

Aim: The aim of this study was to determine whether a positive Aspergillus PCR (polymerase chain reaction) is a marker of resistance in CPA patients on azole therapy.

Methods: Patients were selected via a consecutive database search for the first 50 CPA patients with a positive Aspergillus PCR from January to September 2016. Data were collected regarding concurrent and subsequent culture results, current therapy and serum antifungal levels. PCR-positive patients not on therapy were included as the control group.

Results: Twenty-three patients were on therapy (15 itraconazole, 4 voriconazole and 4 posaconazole). Cycle threshold (Ct) values ranged from 20.8 to 37.9; no significant difference was found between each treatment and the control group (P = .47). In treated patients, concurrent azole-resistant A fumigatus was found in 75% of A fumigatus-positive cultures (6/8). All of the resistant isolates in the itraconazole group showed therapy resistance. Twenty per cent of all itraconazole levels were sub-therapeutic. No significant difference was found in serum itraconazole levels for patients on itraconazole with a positive PCR versus negative PCR (P = .44).

Conclusion: Positive sputum, Aspergillus-specific PCR can be associated with azole resistance in CPA patients on therapy.

Keywords: Aspergillus fumigatus; antifungal resistance; azoles; polymerase chain reaction.

MeSH terms

  • Antifungal Agents / therapeutic use
  • Aspergillus / drug effects
  • Aspergillus / genetics
  • Aspergillus / isolation & purification
  • Aspergillus fumigatus / drug effects
  • Aspergillus fumigatus / isolation & purification*
  • Azoles / therapeutic use*
  • Drug Resistance, Fungal*
  • Female
  • Fungal Proteins / genetics
  • Humans
  • Male
  • Polymerase Chain Reaction
  • Pulmonary Aspergillosis / drug therapy*
  • Retrospective Studies

Substances

  • Antifungal Agents
  • Azoles
  • Fungal Proteins