Repurposing FDA-approved drugs to combat drug-resistant Acinetobacter baumannii

被引:43
作者
Chopra, Sidharth [2 ]
Torres-Ortiz, Maria [2 ]
Hokama, Leslie [2 ]
Madrid, Peter [2 ]
Tanga, Mary [2 ]
Mortelmans, Kristien [2 ]
Kodukula, Krishna [1 ]
Galande, Amit K. [1 ]
机构
[1] SRI Int, Ctr Adv Drug Res, Harrisonburg, VA USA
[2] SRI Int, Ctr Infect Dis & Biodef Res, Menlo Pk, CA 94025 USA
关键词
Gram-negative infections; cyclic peptides; tyrothricin;
D O I
10.1093/jac/dkq353
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
The rising occurrence of drug-resistant pathogens accentuates the need to identify novel antibiotics. We wanted to identify new scaffolds for drug discovery by repurposing FDA-approved drugs against Acinetobacter baumannii, an emerging Gram-negative nosocomial drug-resistant pathogen. In this study, we screened 1040 FDA-approved drugs against drug-susceptible A. baumannii ATCC 17978 and drug-resistant A. baumannii BAA-1605. Twenty compounds exhibited significant antimicrobial activity (MIC < 8 mg/L) against ATCC 17978 while only five compounds showed such activity against BAA-1605. Among the most notable results, tyrothricin, a bactericidal antibiotic typically active only against Gram-positive bacteria, exhibited equipotent activity against both strains. The paucity of identified compounds active against drug-resistant A. baumannii exemplifies its ability to resist antimicrobials as well as the resilience of drug-resistant Gram-negative pathogens. Repurposing of approved drugs is a viable alternative to de novo drug discovery and development.
引用
收藏
页码:2598 / 2601
页数:4
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