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The heme oxygenase-1 metalloporphyrin inhibitor stannsoporfin enhances the bactericidal activity of a novel regimen for multidrug-resistant tuberculosis in a murine model
Antimicrob Agents Chemother. 2023 Dec 22:e0104323. doi: 10.1128/aac.01043-23. Online ahead of print.ABSTRACTMultidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) poses significant challenges to global tuberculosis (TB) control efforts. Host-directed therapies (HDTs) offer a novel approach to TB treatment by enhancing immune-mediated clearance of Mtb. Prior preclinical studies found that the inhibition of heme oxygenase-1 (HO-1), an enzyme involved in heme metabolism, with tin-protoporphyrin IX (SnPP) significantly reduced mouse lung bacillary burden when co-administered with the first-line antitubercular regimen. Here...
Source: Antimicrobial Agents and Chemotherapy - December 22, 2023 Category: Microbiology Authors: Jennie Ruelas Castillo Pranita Neupane Styliani Karanika Stefanie Krug Darla Quijada Andrew Garcia Samuel Ayeh Addis Yilma Diego L Costa Alan Sher Nader Fotouhi Natalya Serbina Petros C Karakousis Source Type: research

Omadacycline pharmacokinetics/pharmacodynamics and efficacy against multidrug-resistant < em > Mycobacterium tuberculosis < /em > in the hollow fiber system model
Antimicrob Agents Chemother. 2023 Dec 22:e0108023. doi: 10.1128/aac.01080-23. Online ahead of print.ABSTRACTSeventy-five years ago, first-generation tetracyclines demonstrated limited efficacy in the treatment of tuberculosis but were more toxic than efficacious. We performed a series of pharmacokinetic/pharmacodynamic (PK/PD) experiments with a potentially safer third-generation tetracycline, omadacycline, for the treatment of multidrug-resistant tuberculosis (MDR-TB). Mycobacterium tuberculosis (Mtb) H37Rv and an MDR-TB clinical strain (16D) were used in the minimum inhibitory concentration (MIC) and static concentration...
Source: Antimicrobial Agents and Chemotherapy - December 22, 2023 Category: Microbiology Authors: Sanjay Singh Tawanda Gumbo Gunavanthi D Boorgula Tania A Thomas Julie V Philley Shashikant Srivastava Source Type: research

Pharmacokinetics and cardiac safety of clofazimine in children with rifampicin-resistant tuberculosis
Antimicrob Agents Chemother. 2023 Dec 19:e0079423. doi: 10.1128/aac.00794-23. Online ahead of print.ABSTRACTClofazimine is recommended for the treatment of rifampicin-resistant tuberculosis (RR-TB), but there is currently no verified dosing guideline for its use in children. There is only limited safety and no pharmacokinetic (PK) data available for children. We aimed to characterize clofazimine PK and its relationship with QT-interval prolongation in children. An observational cohort study of South African children <18 years old routinely treated for RR-TB with a clofazimine-containing regimen was analyzed. Clofazimine...
Source: Antimicrobial Agents and Chemotherapy - December 19, 2023 Category: Microbiology Authors: Ali Mohamed Ali Bel én P Solans Anneke C Hesseling Jana Winckler H Simon Schaaf Heather R Draper Louvina van der Laan Jennifer Hughes Barend Fourie James Nielsen Lubbe Wiesner Anthony J Garcia-Prats Radojka M Savic Source Type: research

Phase I study, and dosing regimen selection for a pivotal COVID-19 trial of GST-HG171
This study is aimed to evaluate the safety, tolerability, and pharmacokinetics (PK), as well as to select an appropriate dosing regimen for the pivotal clinical trial of GST-HG171, an orally bioavailable, potent, and selective 3CL protease inhibitor by a randomized, double-blind, and placebo-controlled phase I trial in healthy subjects. We conducted a Ph1 study involving 78 healthy subjects to assess the safety, tolerability, and PK of single ascending doses (150-900 mg) as well as multiple ascending doses (MADs) (150 and 300 mg) of GST-HG171. Additionally, we examined the food effect and drug-drug interaction of GST-HG171...
Source: Antimicrobial Agents and Chemotherapy - December 15, 2023 Category: Microbiology Authors: Hong Zhang Jing Zhou Hong Chen John Mao Yanan Tang Wenhao Yan Tianxiang Zhang Chuanjing Li Shikui Chen Guoping Li George Zhang Yanhua Ding Li Liu Source Type: research