Treatment outcome in patients with chronic pulmonary aspergillosis by azole-resistantaspergillus fumigatus

Introduction: One of the emerging problems is that the percentage of azole-resistant A. fumigatus is increasing worldwide. There are few reports clearly indicating azoles are clinically ineffective to azole-resistant A. fumigatus with chronic pulmonary aspergillosis (CPA) patients. Aims: To test the hypothesis that treatment outcome is poorer in CPA patients with azole-resistant A.fumigatus than in those with azole-sensitive. Materials and Methods: We retrospectively reviewed medical records of 64 CPA patients with isolation of A. fumigatus. From 2012 to 2015, 75 isolates from these patients were identified as A. fumigatus with genetic analysis of internal transcribed spacer, Domein 1/Domein 2 and β-tubulin. Susceptibility test for antifungal drugs was performed by Clinical and Laboratory Standards Insitute•M38-2. Results: There were 4 itraconazole (ITCZ) resistant isolates (5.3%) and 2 voriconazole (VRCZ) resistant isolates (2.7%). The 2 VRCZ resistant strains were also resistant to ITCZ. Three of 4 azole resistant A.fumigatus strains have CYP51A mutations(G448S, M220I, F219C). Azole-resistant A.fumigatus was isolated after long term ITCZ treatment. One of VRCZ resistant strain had not been treated with VRCZ, suggesting cross resistance. The effectiveness of ITCZ and VRCZ to CPA patients with azole sensitive A.fumigatus were 41% (11/27) and 75% (6/8) respectively. Azole antifungal drugs were ineffective for all 4 patients infected with azole-resistant A.fumigatus . Conclusion: This study suggests CPA by azole resistance A.fumigatus have poor treatment outcome with azole antifungal treatment.