Goh Boon Chong, Larsson Simon, Dam Linh Chi, Ling Yan Han Sharon, Chua Wei Lin Patrina, Abirami R, Singh Samsher, Ong Jun Long Ernest, Teo Jeanette W P, Ho Peiying, Ingham Philip W, Pethe Kevin, Dedon Peter C
Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology Centre, Singapore, Singapore.
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
JAC Antimicrob Resist. 2023 May 8;5(3):dlad052. doi: 10.1093/jacamr/dlad052. eCollection 2023 Jun.
is a non-tuberculous mycobacterium (NTM) that causes chronic pulmonary infections. Because of its extensive innate resistance to numerous antibiotics, treatment options are limited, often resulting in poor clinical outcomes. Current treatment regimens usually involve a combination of antibiotics, with clarithromycin being the cornerstone of NTM treatments.
To identify drug candidates that exhibit synergistic activity with clarithromycin against .
We performed cell-based phenotypic screening of a compound library against induced to become resistant to clarithromycin. Furthermore, we evaluated the toxicity and efficacy of the top compound in a zebrafish embryo infection model.
The screen revealed rifaximin as a clarithromycin potentiator. The combination of rifaximin and clarithromycin was synergistic and bactericidal and potent in the zebrafish model.
The data indicate that the rifaximin/clarithromycin combination is promising to effectively treat pulmonary NTM infections.
是一种引起慢性肺部感染的非结核分枝杆菌(NTM)。由于其对多种抗生素具有广泛的固有抗性,治疗选择有限,常常导致临床预后不佳。当前的治疗方案通常涉及多种抗生素联合使用,其中克拉霉素是NTM治疗的基石。
鉴定与克拉霉素对具有协同活性的候选药物。
我们针对诱导对克拉霉素耐药的进行了基于细胞的化合物文库表型筛选。此外,我们在斑马鱼胚胎感染模型中评估了顶级化合物的毒性和疗效。
筛选显示利福昔明是克拉霉素增强剂。利福昔明和克拉霉素的组合具有协同作用且在斑马鱼模型中具有杀菌作用且效力强大。
数据表明利福昔明/克拉霉素组合有望有效治疗肺部NTM感染。