Furnica Dan-Tiberiu, Dittmer Silke, Sanders Maike Isabell, Steinmann Joerg, Rath Peter-Michael, Kirchhoff Lisa
Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany.
Institute of Clinical Hygiene, Medical Microbiology and Infectiology, Klinikum Nürnberg, Paracelsus Medical University, 90419 Nuremberg, Germany.
J Fungi (Basel). 2022 Mar 28;8(4):350. doi: 10.3390/jof8040350.
has become a significant threat in clinical settings. Cases of invasive infections with azole-resistant isolates (ARAF) increased recently. Developing strategies for dealing with ARAF has become crucial. We here investigated the in-vitro and in-vivo activity of the imidazole luliconazole (LLCZ) against clinical ARAF. In total, the LLCZ minimum inhibitory concentrations (MICs) were tested for 101 isolates (84 ARAF and 17 azole-susceptible as wild-type controls) according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Additionally, antifungal activity was assessed in vitro, including an XTT planktonic growth kinetics assay and biofilm assays (crystal violet and XTT assay). Further, a single-dose LLCZ treatment (152 mg/L) was tested for seven days in vivo in a infection model. LLCZ showed an MIC of 0.002 mg/L and no significant difference was found between triazole-resistant and wild-type isolates. Growth inhibition took place between 6 and 12 h after the start of incubation. LLCZ inhibited biofilm formation when added in the pre-adhesion stages. In vivo, single-dose LLCZ-treated larvae show a significantly higher survival percentage than the control group (20%). In conclusion, LLCZ has activity against planktonic cells and early biofilms of ARAF.
在临床环境中已成为一个重大威胁。近期，耐唑类分离株引起的侵袭性感染病例有所增加。制定应对耐唑类分离株的策略变得至关重要。我们在此研究了咪唑类卢立康唑（LLCZ）对临床耐唑类分离株的体外和体内活性。根据欧洲抗菌药物敏感性试验委员会（EUCAST）的标准，共对101株分离株（84株耐唑类分离株和17株作为野生型对照的唑类敏感株）进行了LLCZ最低抑菌浓度（MIC）测试。此外，还进行了体外抗真菌活性评估，包括XTT浮游生长动力学试验和生物膜试验（结晶紫和XTT试验）。进一步地，在感染模型中对单剂量LLCZ治疗（152 mg/L）进行了为期7天的体内试验。LLCZ的MIC为0.002 mg/L，耐三唑类分离株和野生型分离株之间未发现显著差异。孵育开始后6至12小时出现生长抑制。在预黏附阶段添加LLCZ可抑制生物膜形成。在体内，单剂量LLCZ治疗的幼虫存活率显著高于对照组（20%）。总之，LLCZ对耐唑类分离株的浮游细胞和早期生物膜具有活性。
