美国约翰·霍普金斯大学医学院Sanjay K. Jain研究团队通过肺结核患者的动态成像揭示出肺部病变药物暴露的异质性。这一研究成果2020年2月17日在线发表在国际学术期刊《自然—医学》上。
Author: Alvaro A. Ordonez, Hechuan Wang, Gesham Magombedze, Camilo A. Ruiz-Bedoya, Shashikant Srivastava, Allen Chen, Elizabeth W. Tucker, Michael E. Urbanowski, Lisa Pieterse, E. Fabian Cardozo, Martin A. Lodge, Maunank R. Shah, Daniel P. Holt, William B. Mathews, Robert F. Dannals, Jogarao V. S. Gobburu, Charles A. Peloquin, Steven P. Rowe, Tawanda Gumbo, Vijay D. Ivaturi, Sanjay K. Jain
Issue&Volume: 2020-02-17
Abstract: Tuberculosis (TB) is the leading cause of death from a single infectious agent, requiring at least 6 months of multidrug treatment to achieve cure1. However, the lack of reliable data on antimicrobial pharmacokinetics (PK) at infection sites hinders efforts to optimize antimicrobial dosing and shorten TB treatments2. In this study, we applied a new tool to perform unbiased, noninvasive and multicompartment measurements of antimicrobial concentration–time profiles in humans3. Newly identified patients with rifampin-susceptible pulmonary TB were enrolled in a first-in-human study4 using dynamic [11C]rifampin (administered as a microdose) positron emission tomography (PET) and computed tomography (CT). [11C]rifampin PET–CT was safe and demonstrated spatially compartmentalized rifampin exposures in pathologically distinct TB lesions within the same patients, with low cavity wall rifampin exposures. Repeat PET–CT measurements demonstrated independent temporal evolution of rifampin exposure trajectories in different lesions within the same patients. Similar findings were recapitulated by PET–CT in experimentally infected rabbits with cavitary TB and confirmed using postmortem mass spectrometry. Integrated modeling of the PET-captured concentration–time profiles in hollow-fiber bacterial kill curve experiments provided estimates on the rifampin dosing required to achieve cure in 4 months. These data, capturing the spatial and temporal heterogeneity of intralesional drug PK, have major implications for antimicrobial drug development.
DOI: 10.1038/s41591-020-0770-2
Source: https://www.nature.com/articles/s41591-020-0770-2
Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex