Background: Bis(methylthio)gliotoxin(bmGT) has been proposed as a diagnostic biomarker of invasive aspergillosis(IA). Its clearance from serum of patients with probable/proven IA treated with antifungals could correlate with a better outcome. In order to assess this question, we have analyzed the effect of Voriconazole(VCZ) on bmGT production by Aspergillus spp. cultures in vitro and during antifungal therapy in patients at-risk of IA.
Material/methods: In vitro: 9-Aspergillus fumitatus strains were cultured in Sabouraud agar for 3-5days. A 12McF conidial suspension was made in sterile water. 1ml of this suspension was added to 9ml of liquid medium with a 0-0.125-0.25-0.5 and 1μg/ml VCZ final concentration. Cultures were incubated at 37ºC for 96h. BmGT was quantified by HPTLC. Fungal growth was assessed by tetrazolium (XTT)-reduction-test. In vivo: Ten oncohematological patients at-risk of IA treated with VCZ were included in the study. Serum bmGT and VCZ levels were quantified by HPTLC.
Results: In vitro: bmGT and XTT-test results of the 9-A.fumigatus strains are summarized in Table 1. At high [VCZ], near to minimal inhibitory concentration, when the fungal strain growth is inhibited, bmGT is not detected. In vivo: Four of the ten patients treated with VCZ had detectable bmGT. The effect of VCZ on bmGT detection is shown in Graphic 1. Patients 1-3 showed high [bmGT]serum, but it decreased when high [VCZ]serum was detected. In Patient-4, where [VCZ]serum was below therapeutic range, bmGT was clearly detected in serum.
Conclusions: The presence of bmGT correlates with the VCZ efficacy against Aspergillus during in vitro cultures. This effect is also observed in vivo in patients at-risk of IA suggesting the potential utility of bmGT to monitor the efficacy of VCZ treatment. At present larger studies are being performed to confirm the correlation between serum bmGT and VCZ efficacy.
Full conference title:
- ECCMID 26th (2016)