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

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 if 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 -September 2016. Data was 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 20.8-37.9; no significant difference was found between each treatment and the control group (P =0.47). 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 =0.44).
Conclusion: Positive sputum, Aspergillus-specific PCR can be associated with azole resistance in CPA patients on therapy.