Linezolid does not improve bactericidal activity of rifampin-containing first-line regimens in animal models of TB meningitis

Tucker, Elizabeth W.; Ruiz-Bedoya, Camilo A.; Mota, Filipa; Erice, Clara; Kim, John; de Jesus, Patricia; Jahdav, Ravindra; Bahr, Melissa; Flavahan, Kelly; Chen, Xueyi; Peloquin, Charles A.; Freundlich, Joel S.; Jain, Sanjay K.

doi:10.1016/j.ijantimicag.2023.107048

International Journal of Antimicrobial Agents

2024

DOI: 10.1016/j.ijantimicag.2023.107048

|View full text |Cite

Linezolid does not improve bactericidal activity of rifampin-containing first-line regimens in animal models of TB meningitis

Elizabeth W. Tucker,

Camilo A. Ruiz-Bedoya,

Filipa Mota

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2024

Publication Types

Select...

Article1

Relationship

Self Cite0

Independent1

Authors

Journals

Cited by 1 publication

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Dynamic PET reveals compartmentalized brain and lung tissue antibiotic exposures of tuberculosis drugs

Chen,

Arun,

Nino-Meza

et al. 2024

Nat Commun

View full text Add to dashboard Cite

Tuberculosis (TB) remains a leading cause of death, but antibiotic treatments for tuberculous meningitis, the deadliest form of TB, are based on those developed for pulmonary TB and not optimized for brain penetration. Here, we perform first-in-human dynamic 18 F-pretomanid positron emission tomography (PET) in eight human subjects to visualize 18 F-pretomanid biodistribution as concentration-time exposures in multiple compartments (NCT05609552), demonstrating preferential brain versus lung tissue partitioning. Preferential, antibiotic-specific partitioning into brain or lung tissues of several antibiotics, active against multidrug resistant (MDR) Mycobacterium tuberculosis strains, are confirmed in experimentally-infected mice and rabbits, using dynamic PET with chemically identical antibiotic radioanalogs, and postmortem mass spectrometry measurements. PET-facilitated pharmacokinetic modeling predicts human dosing necessary to attain therapeutic brain exposures. These data are used to design optimized, pretomanid-based regimens which are evaluated at human equipotent dosing in a mouse model of TB meningitis, demonstrating excellent bactericidal activity without an increase in intracerebral inflammation or brain injury. Importantly, several antibiotic regimens demonstrate discordant activities in brain and lung tissues in the same animal, correlating with tissue antibiotic exposures. These data provide a mechanistic basis for the compartmentalized activities of antibiotic regimens, with important implications for developing treatments for meningitis and other infections in compartments with unique antibiotic penetration.

show abstract

Dynamic PET reveals compartmentalized brain and lung tissue antibiotic exposures of tuberculosis drugs

Chen,

Arun,

Nino-Meza

et al. 2024

Nat Commun

View full text Add to dashboard Cite

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Linezolid does not improve bactericidal activity of rifampin-containing first-line regimens in animal models of TB meningitis

Cited by 1 publication

References 44 publications

Dynamic PET reveals compartmentalized brain and lung tissue antibiotic exposures of tuberculosis drugs

Dynamic PET reveals compartmentalized brain and lung tissue antibiotic exposures of tuberculosis drugs

Contact Info

Product

Resources

About