Next-Generation Diarylquinolines Improve Sterilizing Activity of Regimens with Pretomanid and the Novel Oxazolidinone TBI-223 in a Mouse Tuberculosis Model
Antimicrob Agents Chemother. 2023 Mar 15:e0003523. doi: 10.1128/aac.00035-23. Online ahead of print.ABSTRACTA regimen comprised of bedaquiline (BDQ, or B), pretomanid, and linezolid (BPaL) is the first oral 6-month regimen approved by the U.S. Food and Drug Administration and recommended by the World Health Organization for the treatment of extensively drug-resistant tuberculosis. We used a well-established BALB/c mouse model of tuberculosis to evaluate the treatment-shortening potential of replacing bedaquiline with either of two new, more potent diarylquinolines, TBAJ-587 and TBAJ-876, in early clinical trials. We also e...
Source: Antimicrobial Agents and Chemotherapy - March 15, 2023 Category: Microbiology Authors: Si-Yang Li Paul J Converse Fabrice Betoudji Jin Lee Khisimuzi Mdluli Anna Upton Nader Fotouhi Eric L Nuermberger Source Type: research
Next-Generation Diarylquinolines Improve Sterilizing Activity of Regimens with Pretomanid and the Novel Oxazolidinone TBI-223 in a Mouse Tuberculosis Model
Antimicrob Agents Chemother. 2023 Mar 15:e0003523. doi: 10.1128/aac.00035-23. Online ahead of print.ABSTRACTA regimen comprised of bedaquiline (BDQ, or B), pretomanid, and linezolid (BPaL) is the first oral 6-month regimen approved by the U.S. Food and Drug Administration and recommended by the World Health Organization for the treatment of extensively drug-resistant tuberculosis. We used a well-established BALB/c mouse model of tuberculosis to evaluate the treatment-shortening potential of replacing bedaquiline with either of two new, more potent diarylquinolines, TBAJ-587 and TBAJ-876, in early clinical trials. We also e...
Source: Antimicrobial Agents and Chemotherapy - March 15, 2023 Category: Microbiology Authors: Si-Yang Li Paul J Converse Fabrice Betoudji Jin Lee Khisimuzi Mdluli Anna Upton Nader Fotouhi Eric L Nuermberger Source Type: research
Next-Generation Diarylquinolines Improve Sterilizing Activity of Regimens with Pretomanid and the Novel Oxazolidinone TBI-223 in a Mouse Tuberculosis Model
Antimicrob Agents Chemother. 2023 Mar 15:e0003523. doi: 10.1128/aac.00035-23. Online ahead of print.ABSTRACTA regimen comprised of bedaquiline (BDQ, or B), pretomanid, and linezolid (BPaL) is the first oral 6-month regimen approved by the U.S. Food and Drug Administration and recommended by the World Health Organization for the treatment of extensively drug-resistant tuberculosis. We used a well-established BALB/c mouse model of tuberculosis to evaluate the treatment-shortening potential of replacing bedaquiline with either of two new, more potent diarylquinolines, TBAJ-587 and TBAJ-876, in early clinical trials. We also e...
Source: Antimicrobial Agents and Chemotherapy - March 15, 2023 Category: Microbiology Authors: Si-Yang Li Paul J Converse Fabrice Betoudji Jin Lee Khisimuzi Mdluli Anna Upton Nader Fotouhi Eric L Nuermberger Source Type: research
Next-Generation Diarylquinolines Improve Sterilizing Activity of Regimens with Pretomanid and the Novel Oxazolidinone TBI-223 in a Mouse Tuberculosis Model
Antimicrob Agents Chemother. 2023 Mar 15:e0003523. doi: 10.1128/aac.00035-23. Online ahead of print.ABSTRACTA regimen comprised of bedaquiline (BDQ, or B), pretomanid, and linezolid (BPaL) is the first oral 6-month regimen approved by the U.S. Food and Drug Administration and recommended by the World Health Organization for the treatment of extensively drug-resistant tuberculosis. We used a well-established BALB/c mouse model of tuberculosis to evaluate the treatment-shortening potential of replacing bedaquiline with either of two new, more potent diarylquinolines, TBAJ-587 and TBAJ-876, in early clinical trials. We also e...
Source: Antimicrobial Agents and Chemotherapy - March 15, 2023 Category: Microbiology Authors: Si-Yang Li Paul J Converse Fabrice Betoudji Jin Lee Khisimuzi Mdluli Anna Upton Nader Fotouhi Eric L Nuermberger Source Type: research
Emergence of Canonical and Noncanonical Genomic Variants following < em > In Vitro < /em > Exposure of Clinical Mycobacterium tuberculosis Strains to Bedaquiline or Clofazimine
Antimicrob Agents Chemother. 2023 Mar 9:e0136822. doi: 10.1128/aac.01368-22. Online ahead of print.ABSTRACTIn Mycobacterium tuberculosis, bedaquiline and clofazimine resistance occurs primarily through Rv0678 variants, a gene encoding a repressor protein that regulates mmpS5/mmpL5 efflux pump gene expression. Despite the shared effect of both drugs on efflux, little else is known about other pathways affected. We hypothesized that in vitro generation of bedaquiline- or clofazimine-resistant mutants could provide insight into additional mechanisms of action. We performed whole-genome sequencing and determined phenotypic MIC...
Source: Antimicrobial Agents and Chemotherapy - March 9, 2023 Category: Microbiology Authors: N Ismail A Dippenaar R M Warren R P H Peters S V Omar Source Type: research
Bedaquiline and Delamanid: Salvage Therapy in Mycobacterium avium Infection With Treatment Failure
Arch Bronconeumol. 2023 Feb 25:S0300-2896(23)00041-8. doi: 10.1016/j.arbres.2023.02.014. Online ahead of print.NO ABSTRACTPMID:36894473 | DOI:10.1016/j.arbres.2023.02.014 (Source: Archivos de Bronconeumologia)
Source: Archivos de Bronconeumologia - March 9, 2023 Category: Respiratory Medicine Authors: Helena Albend ín-Iglesias Jos é Antonio Caminero Carlos Galera Pe ñaranda Source Type: research
Emergence of Canonical and Noncanonical Genomic Variants following < em > In Vitro < /em > Exposure of Clinical Mycobacterium tuberculosis Strains to Bedaquiline or Clofazimine
Antimicrob Agents Chemother. 2023 Mar 9:e0136822. doi: 10.1128/aac.01368-22. Online ahead of print.ABSTRACTIn Mycobacterium tuberculosis, bedaquiline and clofazimine resistance occurs primarily through Rv0678 variants, a gene encoding a repressor protein that regulates mmpS5/mmpL5 efflux pump gene expression. Despite the shared effect of both drugs on efflux, little else is known about other pathways affected. We hypothesized that in vitro generation of bedaquiline- or clofazimine-resistant mutants could provide insight into additional mechanisms of action. We performed whole-genome sequencing and determined phenotypic MIC...
Source: Antimicrobial Agents and Chemotherapy - March 9, 2023 Category: Microbiology Authors: N Ismail A Dippenaar R M Warren R P H Peters S V Omar Source Type: research
Bedaquiline and Delamanid: Salvage Therapy in Mycobacterium avium Infection With Treatment Failure
Arch Bronconeumol. 2023 Feb 25:S0300-2896(23)00041-8. doi: 10.1016/j.arbres.2023.02.014. Online ahead of print.NO ABSTRACTPMID:36894473 | DOI:10.1016/j.arbres.2023.02.014 (Source: Archivos de Bronconeumologia)
Source: Archivos de Bronconeumologia - March 9, 2023 Category: Respiratory Medicine Authors: Helena Albend ín-Iglesias Jos é Antonio Caminero Carlos Galera Pe ñaranda Source Type: research
Emergence of Canonical and Noncanonical Genomic Variants following < em > In Vitro < /em > Exposure of Clinical Mycobacterium tuberculosis Strains to Bedaquiline or Clofazimine
Antimicrob Agents Chemother. 2023 Mar 9:e0136822. doi: 10.1128/aac.01368-22. Online ahead of print.ABSTRACTIn Mycobacterium tuberculosis, bedaquiline and clofazimine resistance occurs primarily through Rv0678 variants, a gene encoding a repressor protein that regulates mmpS5/mmpL5 efflux pump gene expression. Despite the shared effect of both drugs on efflux, little else is known about other pathways affected. We hypothesized that in vitro generation of bedaquiline- or clofazimine-resistant mutants could provide insight into additional mechanisms of action. We performed whole-genome sequencing and determined phenotypic MIC...
Source: Antimicrobial Agents and Chemotherapy - March 9, 2023 Category: Microbiology Authors: N Ismail A Dippenaar R M Warren R P H Peters S V Omar Source Type: research
Bedaquiline and Delamanid: Salvage Therapy in Mycobacterium avium Infection With Treatment Failure
Arch Bronconeumol. 2023 Feb 25:S0300-2896(23)00041-8. doi: 10.1016/j.arbres.2023.02.014. Online ahead of print.NO ABSTRACTPMID:36894473 | DOI:10.1016/j.arbres.2023.02.014 (Source: Archivos de Bronconeumologia)
Source: Archivos de Bronconeumologia - March 9, 2023 Category: Respiratory Medicine Authors: Helena Albend ín-Iglesias Jos é Antonio Caminero Carlos Galera Pe ñaranda Source Type: research
Emergence of Canonical and Noncanonical Genomic Variants following < em > In Vitro < /em > Exposure of Clinical Mycobacterium tuberculosis Strains to Bedaquiline or Clofazimine
Antimicrob Agents Chemother. 2023 Mar 9:e0136822. doi: 10.1128/aac.01368-22. Online ahead of print.ABSTRACTIn Mycobacterium tuberculosis, bedaquiline and clofazimine resistance occurs primarily through Rv0678 variants, a gene encoding a repressor protein that regulates mmpS5/mmpL5 efflux pump gene expression. Despite the shared effect of both drugs on efflux, little else is known about other pathways affected. We hypothesized that in vitro generation of bedaquiline- or clofazimine-resistant mutants could provide insight into additional mechanisms of action. We performed whole-genome sequencing and determined phenotypic MIC...
Source: Antimicrobial Agents and Chemotherapy - March 9, 2023 Category: Microbiology Authors: N Ismail A Dippenaar R M Warren R P H Peters S V Omar Source Type: research
Bedaquiline and Delamanid: Salvage Therapy in Mycobacterium avium Infection With Treatment Failure
Arch Bronconeumol. 2023 Feb 25:S0300-2896(23)00041-8. doi: 10.1016/j.arbres.2023.02.014. Online ahead of print.NO ABSTRACTPMID:36894473 | DOI:10.1016/j.arbres.2023.02.014 (Source: Archivos de Bronconeumologia)
Source: Archivos de Bronconeumologia - March 9, 2023 Category: Respiratory Medicine Authors: Helena Albend ín-Iglesias Jos é Antonio Caminero Carlos Galera Pe ñaranda Source Type: research
Bedaquiline and Delamanid: Salvage Therapy in Mycobacterium avium Infection With Treatment Failure
Arch Bronconeumol. 2023 Feb 25:S0300-2896(23)00041-8. doi: 10.1016/j.arbres.2023.02.014. Online ahead of print.NO ABSTRACTPMID:36894473 | DOI:10.1016/j.arbres.2023.02.014 (Source: Archivos de Bronconeumologia)
Source: Archivos de Bronconeumologia - March 9, 2023 Category: Respiratory Medicine Authors: Helena Albend ín-Iglesias Jos é Antonio Caminero Carlos Galera Pe ñaranda Source Type: research
Bedaquiline and Delamanid: Salvage Therapy in Mycobacterium avium Infection With Treatment Failure
Arch Bronconeumol. 2023 Feb 25:S0300-2896(23)00041-8. doi: 10.1016/j.arbres.2023.02.014. Online ahead of print.NO ABSTRACTPMID:36894473 | DOI:10.1016/j.arbres.2023.02.014 (Source: Archivos de Bronconeumologia)
Source: Archivos de Bronconeumologia - March 9, 2023 Category: Respiratory Medicine Authors: Helena Albend ín-Iglesias Jos é Antonio Caminero Carlos Galera Pe ñaranda Source Type: research
Bedaquiline and Delamanid: Salvage Therapy in Mycobacterium avium Infection With Treatment Failure
Arch Bronconeumol. 2023 Feb 25:S0300-2896(23)00041-8. doi: 10.1016/j.arbres.2023.02.014. Online ahead of print.NO ABSTRACTPMID:36894473 | DOI:10.1016/j.arbres.2023.02.014 (Source: Archivos de Bronconeumologia)
Source: Archivos de Bronconeumologia - March 9, 2023 Category: Respiratory Medicine Authors: Helena Albend ín-Iglesias Jos é Antonio Caminero Carlos Galera Pe ñaranda Source Type: research
