Background: The emergence of azole resistance globally among Aspergillus species has major clinical and agricultural implications. At our center, isavuconazole (ISA), posaconazole (POS) and voriconazole (VOR) have been used as antifungal prophylaxis in solid organ transplant recipients. We determined susceptibility to azoles and other antifungals among Aspergillus isolates from our center.
Methods: 52 patient isolates of Aspergillus species were collected from the UPMC Microbiology Lab between December 2016 and April 2018. Minimum inhibitory concentrations (MICs) of ISA, POS, VOR, amphotericin B (AmB) and caspofungin (CAS) were measured using EUCAST Antimicrobial Susceptibility Testing methods. Candida parapsilosis ATCC 22019 and Candida krusei ATCC 6258 were used as quality control.
Results: 71% (37/52) of isolates were from solid organ transplant recipients (34 lungs, 2 liver and 1 heart). Aspergillus spp were A. fumigatus (Af, 29), A. terreus (At, 6), A. niger (An), A. flavus (Afl) and Aspergillus calidoustus (Ac; 5 of each species), and A. lentulus (Al) and A. thermomutatus (At; 1 of each species). 13 breakthrough (BT) isolates were recovered from patients on azoles: Ac (5), An (4), Afl (2), Af (1) and At (1). Ac, Afl and An were more likely than other species to be recovered from azole BT (75% (12/16) vs 5% (2/36), p=0.06). For all isolates, ISA, VOR and POSA MIC50 were 0.25 µg/mL, 0.04 µg/mL and 0.25 µg/mL, respectively. One Ac and one At were resistant to all antifungals (azoles, AmB and caspofungin MICs were > 16 µg/mL); both were associated with azole BT. ISA, POS and VOR MIC50 vs. azole BT isolates (0.5, 0.125, 0.5 µg/mL, respectively) were higher than those vs. non BT isolates (0.25, 0.03 and 0.25 µg/mL, respectively; p<0.01 for all).
Conclusion: Despite widespread use of azole prophylaxis in transplant recipients at our center, we did not observe high rates of resistance to azoles or other antifungals among Aspergillus isolates, although azole MICs were higher against BT isolates. Azole BT isolates were more likely to be non-Af species. Clinicians should understand that antifungal resistance rates can vary by center and geographical location, and use their local epidemiology to guide decisions about the utility of specific agents in their populations.
K. Squires, None
R. K. Shields, None
M. H. Nguyen, None