Caspofungin acetate

Caspofungin from two different sources was used to verify the consistency of our reported phenomena: caspofungin diacetate from Sigma-Aldrich (St. Louis, MO, USA) and caspofungin acetate from Merck (Rashway, NJ, USA). Micafungin sodium was provided by Astellas Pharma Inc. (Chuo-ku, Tokyo, Japan). Anidulafungin and amphotericin B were purchased from Sigma-Aldrich. Caspofungin and micafungin was dissolved in distilled water, amphotericin B and Anidulafungin was dissolved in 100% DMSO. Glucose [d-(+)-glucose] was purchased from FUJIFILM Wako Pure Chemical Corporation (Osaka, Japan). Three types of dH₂O were used in all experiments in order to verify the consistency of our reported phenomena: Invitrogen UltraPure DNase/RNase-free dH₂O, Otsuka dH₂O for 100% injection, and tap water purified using a Yamato Scientific Auto Still water purifier (WG250 with a 0.22 μm Sartolab RF filter; Sartorius, Göttingen, Germany).

Anti-fungal therapies for ACLF patients complicated with IPA have evolved in our Hepatology Unit. In the first few years (2011–2014), our patients were treated with echinocandins (Cancidas, caspofungin acetate, Merck) or standard voriconazole (voriconazole tablet, 50 milligrams/tablet; Huashen, Chendu, PR China) dosage (loading dose as 0.4 g, po, q12h, maintenance dose as 0.2 g, po, q12h, which was adjusted mainly based on overt clinical adverse effects).
In October 2014, plasma voriconazole concentrations monitoring tests became available in our hospital. We then began to explore an optimal voriconazole regimen based on the plasma drug level (Supplementary material: Voriconazole monitoring protocol). Finally, an optimal voriconazole regimen was established, which consisted of a lower loading dose (0.2 g, po, q12h) and a lower maintenance dose (0.1 g, po, qd), and this optimal regimen turned to be the preferred anti-fungal option for the majority of the subsequent IPA cases with underlying ACLF.