Patterns of susceptibility of Aspergillus isolates recovered from patients enrolled in the Transplant-Associated Infection Surveillance Network

Abstract

We analyzed antifungal susceptibilities of 274 clinical Aspergillus isolates from transplant recipients with proven or probable invasive aspergillosis collected as part of the Transplant-Associated Infection Surveillance Network (TRANSNET) and examined the relationship between MIC and mortality at 6 or 12 weeks. Antifungal susceptibility testing was performed by the Clinical and Laboratory Standards Institute (CLSI) M38-A2 broth dilution method for amphotericin B (AMB), itraconazole (ITR), voriconazole (VOR), posaconazole (POS), and ravuconazole (RAV). The isolate collection included 181 Aspergillus fumigatus, 28 Aspergillus niger, 27 Aspergillus flavus, 22 Aspergillus terreus, seven Aspergillus versicolor, five Aspergillus calidoustus, and two Aspergillus nidulans isolates and two isolates identified as Aspergillus spp. Triazole susceptibilities were < or = 4 microg/ml for most isolates (POS, 97.6%; ITR, 96.3%; VOR, 95.9%; RAV, 93.5%). The triazoles were not active against the five A. calidoustus isolates, for which MICs were > or = 4 microg/ml. AMB inhibited 93.3% of isolates at an MIC of < or = 1 microg/ml. The exception was A. terreus, for which 15 (68%) of 22 isolates had MICs of >1 microg/ml. One of 181 isolates of A. fumigatus showed resistance (MIC > or = 4 microg/ml) to two of three azoles tested. Although there appeared to be a correlation of higher VOR MICs with increased mortality at 6 weeks, the relationship was not statistically significant (R2 = 0.61; P = 0.065). Significant relationships of in vitro MIC to all-cause mortality at 6 and 12 weeks for VOR or AMB were not found.

FIG. 1.

All-cause mortality based on Aspergillus MIC among 115 patients who received VOR therapy. Regression lines for the association of MIC with mortality at 6 weeks (R² = 0.61; P = 0.065) and 12 weeks (R² = 0.18; P = 0.40) are shown.

FIG. 2.

All-cause mortality based on Aspergillus MIC among 111 patients who received AMB therapy. Regression lines for the association of MIC with mortality at 6 weeks (R² = 0.70; P = 0.04) and 12 weeks (R² = 0.39; P = 0.18) are shown.