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利福布汀对脓肿分枝杆菌复合群有活性。

Rifabutin Is Active against Mycobacterium abscessus Complex.

作者信息

Aziz Dinah Binte, Low Jian Liang, Wu Mu-Lu, Gengenbacher Martin, Teo Jeanette W P, Dartois Véronique, Dick Thomas

机构信息

Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Department of Laboratory Medicine, National University Hospital, Singapore.

出版信息

Antimicrob Agents Chemother. 2017 May 24;61(6). doi: 10.1128/AAC.00155-17. Print 2017 Jun.

Abstract

Lung infections caused by are emerging as a global threat to individuals with cystic fibrosis and to other patient groups. Recent evidence for human-to-human transmission worsens the situation. is an intrinsically multidrug-resistant pathogen showing resistance to even standard antituberculosis drugs, such as rifampin. Here, our objective was to identify existing drugs that may be employed for the treatment of lung disease. A collection of more than 2,700 approved drugs was screened at a single-point concentration against an clinical isolate. Hits were confirmed with fresh solids in dose-response experiments. For the most attractive hit, growth inhibition and bactericidal activities against reference strains of the three subspecies and a collection of clinical isolates were determined. Surprisingly, the rifampin derivative rifabutin had MICs of 3 ± 2 μM (3 μg/ml) against the screening strain, the reference strains subsp. ATCC 19977, subsp. CCUG 50184-T, and subsp. CCUG 48898-T, as well as against a collection of clinical isolates. Furthermore, rifabutin was active against clarithromycin-resistant strains. In conclusion, rifabutin, in contrast to rifampin, is active against the complex bacteria and may be considered for treatment of lung disease.

摘要

由[病原体名称未给出]引起的肺部感染正成为对囊性纤维化患者及其他患者群体的全球性威胁。最近人际传播的证据使情况更加恶化。[病原体名称未给出]是一种具有内在多重耐药性的病原体,甚至对标准抗结核药物如利福平也有耐药性。在此,我们的目标是确定可用于治疗[病原体名称未给出]肺部疾病的现有药物。针对一种[病原体名称未给出]临床分离株,在单点浓度下对2700多种已批准药物的集合进行了筛选。在剂量反应实验中用新鲜固体确认了命中结果。对于最有吸引力的命中药物,测定了其对[病原体名称未给出]三个亚种的参考菌株和一组临床分离株的生长抑制和杀菌活性。令人惊讶的是,利福布汀对筛选菌株、参考菌株[亚种名称未给出]ATCC 19977、[亚种名称未给出]CCUG 50184 - T和[亚种名称未给出]CCUG 48898 - T以及一组临床分离株的最低抑菌浓度(MIC)为3±2μM(3μg/ml)。此外,利福布汀对克拉霉素耐药菌株也有活性。总之,与利福平不同,利福布汀对[病原体名称未给出]复合菌有活性,可考虑用于治疗[病原体名称未给出]肺部疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd87/5444174/61bca02e1439/zac0061762430001.jpg

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