Increase in Pan-Triazole Resistance to Aspergillus-Active Triazoles in Patients with Hematologic Malignancies

A. M. Tatara1 , N. D. Albert2 , P. E. Verweij3 , J. F. Meis3 , R. E. Lewis4 , D. P. Kontoyiannis2

Author address: 

1 Rice Univ., Houston, TX, 2 The Univ. of Texas MD Anderson Cancer, Houston, TX, 3 Radboud Univ. Med. Ctr., Nijmegen, Netherlands, 4 The Univ. of Bologna, Bologna, Italy

Abstract: 

Background: Pan-triazole resistance (PTR) is a growing concern with the widespread use of these agents in patients with hematological malignancies. In this study, we screened for PTR in 290 Aspergillus unselected clinical isolates recovered from respiratory sources in patients with hematological malignancies at the University of Texas MD Anderson Cancer Center (MDACC), collected from 1999-2015. Since Aspergillus-active new triazoles (voriconazole (VRC), posaconazole (PCZ)) were introduced at MDACC after 2002, we evaluated in vitro PTR patterns before and after 2002.Methods: Aspergillus clinical isolates (A. fumigatus, A. flavus, A. terreus, and A. niger) from 1999-2002 (n=183) and from 2003-2015 (n=107) recovered from patients with hematological malignancies at MDACC were screened for resistance to itraconazole (ITRA), VRC, and PCZ using the four-well multidish method[1]. Resistance to all three drugs in the screen was confirmed using the CLSI M38-A2 broth microdilution antifungal susceptibility testing method[2]. Resistance was defined as isolate MIC greater than MIC50 values reported by Pflaller[3]. Changes in PTR of Aspergillus after 2002 were compared by species.Results: PTR isolates were discovered in all Aspergillus species in both periods. A statistically significant increase in the percentage of PTR isolates after 2002 was found in A. fumigatus (6/97 vs. 12/53, p=0.0218) and A. niger (4/21 vs. 10/15, p=0.0061). No significant changes in PTR rates were observed for A. terreus nor A. flavus isolates.Conclusions: Since the widespread use of triazoles, rates of PTR Aspergillus isolates have significantly increased in patients with hematological malignancy at our institution as a species-specific phenomenon. As PCZ and VRC are first-line choices for prophylaxis and treatment for invasive aspergillosis respectively, this change in resistance patterns might have therapeutic implications. Further studies are needed to capture the clinical correlates of PTR and its genomic determinants.
2016

abstract No: 

246

Full conference title: 

ASM Microbe 2016
    • ASM microbe 1st (2016)