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

Author: 

Samihah Moazam, Christopher Philip Eades, Eavan Gabrielle Muldoon, Caroline B Moore, Malcolm D Richardson, Riina Rautemaa-Richardson
Mycoses 2020 Jan 25[Online ahead of print]

Abstract: 

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.