A. fumigatus in HCT Patients: Trends in Antifungal Resistance and Predictors of Response

A. Chan, J. Kriengkauykiat, B. Tegtmeier, J. Ito, S. Dadwal

Author address: 

City of Hope Natl. Med. Ctr., Duarte, CA


Background: Invasive aspergillosis (IA) causes significant morbidity and mortality in HCT patients. Azole class of antifungal (AF) agents are first line therapy for IA. Resistance of Aspergillus to multiple azoles leading to treatment failure has been reported. In the US, susceptibility breakpoints have not been established. The aim of this study is to investigate whether susceptibility to AFs has changed during the past decade among A. fumigatus strains isolated from HCT patients and correlate susceptibility to outcomes. Methods: All A. fumigatus strains isolated from HCT recipients that were banked between 2002 to 2014 were tested for AF susceptibility (MIC and MEC). A retrospective review was performed linking HCT recipients from whom strains were isolated. Data was collected on demographics, clinical factors that could affect response to AF treatment (HCT type, conditioning regimen, GvHD, immunosuppressant use), AF use, and response to treatment at 14- and 90-days. Results: 83 HCT isolates were evaluated. MICs for azoles were trending up through the years with increasing resistance noted. 59 patients were treated for proven/probable IA. Treatment response (N=12) and failure (N=47) arms did not differ significantly in age, type of donor, hematologic diagnosis, neutropenic status, nor in use of steroids. Significant factors for AF 14-day treatment response vs. failure included: chronic GVHD (8 vs 49%, p 0.02) and bacterial co-infection (33 vs 85%, p<0.01). The correlation between 14-day and 90-day response was R2=0.43, p<0.01. Patients with isolates of MIC>1 compared to MIC≤1 for either amphotericin B (0 vs 22%) or voriconazole (0 vs 24%) had no response to treatment at 14 days. This trend was not observed at 90 days. Conclusions: Azole MICs for A. Fumigatus strains over the last decade has increased. Early response to therapy is associated with AF susceptibility.

abstract No: 

    • ICAAC 55th (2015)