Asset Details
Do you wish to reserve the book?
Distribution of contezolid in different tissues of mice and human patients infected with Mycobacterium abscessus
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Distribution of contezolid in different tissues of mice and human patients infected with Mycobacterium abscessus
Do you wish to request the book?
Distribution of contezolid in different tissues of mice and human patients infected with Mycobacterium abscessus
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Paper
Distribution of contezolid in different tissues of mice and human patients infected with Mycobacterium abscessus
2024
Overview
Background: Linezolid (LZD), while effective against Mycobacterium abscessus (MAB), can cause myelosuppression and peripheral neuropathy. Contezolid (CZD) shares a similar antimicrobial profile with improved safety, but biodistribution data remain limited. This study evaluated CZD’s biodistribution in MAB-infected mice and humans and its therapeutic potential across infection sites. Methods: MICs of CZD and LZD against 32 clinical MAB isolates and three reference strains were determined. In MAB-infected mice, drug concentrations were quantified in plasma and pulmonary and cerebral tissues at 2, 4, and 8 hours post-administration. In MAB-infected patients, CZD concentrations in bone, plasma, and cerebrospinal fluid were measured at multiple time points and MAB counts in sputum cultures were assessed daily over 14 days. Results: Respective MIC50 and MIC90 values were 8 and 32 μg/mL (LZD) and 16 and 32 μg/mL (CZD). Pharmacokinetic CZD and LZD level comparisons revealed peak CZD plasma levels within 2 hours, higher systemic CZD levels, comparable pulmonary tissue concentrations, and slightly lower CZD cerebral tissue penetration. In patients, CZD levels in ankle joint effusion samples reached 2.0885 μg/mL at 6 hours, peaking in the posterior malleolus. Plasma CZD concentrations peaked at 8.2349 μg/mL at 3 hours and dropped to 6.1065 μg/mL by 6 hours, while CSF levels were 0.9295 and 0.792 μg/mL at 3 and 6 hours, respectively. Sputum bacterial burden decreased rapidly within 24 hours of CZD treatment, with near-complete clearance by day 4. Conclusion: CZD and LZD exhibit comparable tissue distribution but different site-specific penetration, supporting their potential for treating diverse MAB infections.
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
Subject
