Improving the Drug Development Pipeline for Mycobacteria: Modelling Antibiotic Exposure in the Hollow Fibre Infection Model.
Improving the Drug Development Pipeline for Mycobacteria: Modelling Antibiotic Exposure in the Hollow Fibre Infection Model.
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DOI：
10.3390/antibiotics10121515
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发表时间：
2021-12-10
期刊：
影响因子：
--
通讯作者：
Kloprogge F
中科院分区：
文献类型：
--
作者：
Maitra A;Solanki P;Sadouki Z;McHugh TD;Kloprogge F
分枝杆菌感染很难治疗，需要联合用药和漫长的治疗时间，从而给全世界的患者和卫生服务带来了巨大的负担。由于病原体出现抗生素耐药性，有限的治疗方案受到威胁，因此需要开发新的治疗方案。药物开发过程漫长，资源密集，风险高，这导致了市场失灵，制药公司限制了他们的抗菌药物发现计划。评估可以模拟体内PK/PD属性的治疗方案的临床前方案可以支持药物开发过程。中空纤维感染模型（HSP 70）允许将病原体暴露于体内（血浆中或感染部位）达到浓度的单一或组合试剂。根据所进行的分析，从受阻碍地区采集的样本提供了关于细菌杀灭率和抗药性出现的信息。因此，阻滞剂是研究药物组合疗效的有效手段。虽然适用于各种各样的感染，抗分枝杆菌药物的发现的复杂性，使信息提供的阻碍无价的探讨，在这方面的审查。
Mycobacterial infections are difficult to treat, requiring a combination of drugs and lengthy treatment times, thereby presenting a substantial burden to both the patient and health services worldwide. The limited treatment options available are under threat due to the emergence of antibiotic resistance in the pathogen, hence necessitating the development of new treatment regimens. Drug development processes are lengthy, resource intensive, and high-risk, which have contributed to market failure as demonstrated by pharmaceutical companies limiting their antimicrobial drug discovery programmes. Pre-clinical protocols evaluating treatment regimens that can mimic in vivo PK/PD attributes can underpin the drug development process. The hollow fibre infection model (HFIM) allows for the pathogen to be exposed to a single or a combination of agents at concentrations achieved in vivo–in plasma or at infection sites. Samples taken from the HFIM, depending on the analyses performed, provide information on the rate of bacterial killing and the emergence of resistance. Thereby, the HFIM is an effective means to investigate the efficacy of a drug combination. Although applicable to a wide variety of infections, the complexity of anti-mycobacterial drug discovery makes the information available from the HFIM invaluable as explored in this review.
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影响因子：
13.6
作者：
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