Lu Mengjiao, Yang Xinmei, Yu Cuixiang, Gong Ying, Yuan Lei, Hao Lina, Sun Shujuan
School of Pharmaceutical Sciences, Shandong University, Ji'nan, China.
Department of Pharmacy, Baodi People's Hospital, Tianjin, China.
Front Microbiol. 2019 Jan 31;9:3142. doi: 10.3389/fmicb.2018.03142. eCollection 2018.
The incidence of resistant isolates has increased continuously in recent decades, especially . To overcome this resistance, research on antifungal sensitizers has attracted considerable attention. Linezolid was found to inhibit the growth of and synergize with amphotericin B against . The objective of this study was to determine the interactions of linezolid and azoles against and . , linezolid combined with azoles induced synergistic effects not only against some susceptible isolates, but also against all tested resistant isolates. For all resistant isolates, exposure to the combination of linezolid with azoles induced a significant decrease in the minimum inhibitory concentrations (MIC) of azoles, from >512 to 0.5-1 μg/mL for fluconazole, from >16 to 0.25-1 μg/mL for itraconazole, and from >16 to 0.03-0.25 μg/mL for voriconazole. Additionally, linezolid synergized with fluconazole against biofilms that were preformed for ≤ 12 h from both susceptible and resistant , and the sessile MIC of fluconazole decreased from >1024 to 1-4 μg/mL. , linezolid plus azoles prolonged the survival rate of infected larvae twofold compared with the azole monotherapy group, significantly decreased the fungal burden of the infected larvae, and reduced the damage of resistant to the larval tissue. These findings will contribute to antifungal agent discovery and new approaches for the treatment of candidiasis caused by .
近几十年来，耐药菌株的发生率持续上升，尤其是……。为克服这种耐药性，抗真菌增敏剂的研究备受关注。发现利奈唑胺可抑制……的生长，并与两性霉素B协同作用对抗……。本研究的目的是确定利奈唑胺与唑类药物对……和……的相互作用。结果表明，利奈唑胺与唑类药物联合使用不仅对一些敏感的……菌株产生协同作用，而且对所有测试的耐药……菌株也有协同作用。对于所有耐药菌株，暴露于利奈唑胺与唑类药物的组合后，唑类药物的最低抑菌浓度（MIC）显著降低，氟康唑从>512降至0.5 - 1μg/mL，伊曲康唑从>16降至0.25 - 1μg/mL，伏立康唑从>16降至0.03 - 0.25μg/mL。此外，利奈唑胺与氟康唑协同作用对抗由敏感和耐药……形成≤12小时的生物膜，氟康唑的静息MIC从>1024降至1 - 4μg/mL。结果还表明，与唑类单药治疗组相比，利奈唑胺加唑类药物使感染……幼虫的存活率提高了两倍，显著降低了感染幼虫的真菌负荷，并减少了耐药……对幼虫组织的损伤。这些发现将有助于抗真菌药物的发现以及治疗由……引起的念珠菌病的新方法。
