Cargando…
The Combination of Rifampin plus Moxifloxacin Is Synergistic for Suppression of Resistance but Antagonistic for Cell Kill of Mycobacterium tuberculosis as Determined in a Hollow-Fiber Infection Model
Moxifloxacin is under development for expanded use against Mycobacterium tuberculosis. Rifampin is a mainstay of therapy. We examined the interaction of moxifloxacin plus rifampin for log-phase and nonreplicating persister (NRP) organisms. For this evaluation, we employed our hollow-fiber infection...
Autores principales: | , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
American Society of Microbiology
2010
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925073/ https://www.ncbi.nlm.nih.gov/pubmed/20802826 http://dx.doi.org/10.1128/mBio.00139-10 |
_version_ | 1782185648217653248 |
---|---|
author | Drusano, G. L. Sgambati, Nicole Eichas, Adam Brown, David L. Kulawy, Robert Louie, Arnold |
author_facet | Drusano, G. L. Sgambati, Nicole Eichas, Adam Brown, David L. Kulawy, Robert Louie, Arnold |
author_sort | Drusano, G. L. |
collection | PubMed |
description | Moxifloxacin is under development for expanded use against Mycobacterium tuberculosis. Rifampin is a mainstay of therapy. We examined the interaction of moxifloxacin plus rifampin for log-phase and nonreplicating persister (NRP) organisms. For this evaluation, we employed our hollow-fiber infection model, in which organisms are exposed to clinically relevant drug concentration-time profiles and the impact on bacterial cell kill and resistant subpopulation amplification is determined. In log phase, resistance emergence was observed in all monotherapy regimens and in no combination therapy regimen. No difference was seen in time to a 3-log reduction in the bacterial burden; there was a significant difference in time to resistance emergence (P = 0.0006). In the NRP experiment, no resistance emergence was seen. There was a significant difference between the monotherapy and combination therapy regimens in time to a 3-log reduction in the bacterial burden (P = 0.042). The combination is efficacious for suppressing resistant organisms but is antagonistic for cell kill. |
format | Text |
id | pubmed-2925073 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | American Society of Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-29250732010-08-29 The Combination of Rifampin plus Moxifloxacin Is Synergistic for Suppression of Resistance but Antagonistic for Cell Kill of Mycobacterium tuberculosis as Determined in a Hollow-Fiber Infection Model Drusano, G. L. Sgambati, Nicole Eichas, Adam Brown, David L. Kulawy, Robert Louie, Arnold mBio Research Article Moxifloxacin is under development for expanded use against Mycobacterium tuberculosis. Rifampin is a mainstay of therapy. We examined the interaction of moxifloxacin plus rifampin for log-phase and nonreplicating persister (NRP) organisms. For this evaluation, we employed our hollow-fiber infection model, in which organisms are exposed to clinically relevant drug concentration-time profiles and the impact on bacterial cell kill and resistant subpopulation amplification is determined. In log phase, resistance emergence was observed in all monotherapy regimens and in no combination therapy regimen. No difference was seen in time to a 3-log reduction in the bacterial burden; there was a significant difference in time to resistance emergence (P = 0.0006). In the NRP experiment, no resistance emergence was seen. There was a significant difference between the monotherapy and combination therapy regimens in time to a 3-log reduction in the bacterial burden (P = 0.042). The combination is efficacious for suppressing resistant organisms but is antagonistic for cell kill. American Society of Microbiology 2010-08-10 /pmc/articles/PMC2925073/ /pubmed/20802826 http://dx.doi.org/10.1128/mBio.00139-10 Text en Copyright © 2010 Drusano et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Drusano, G. L. Sgambati, Nicole Eichas, Adam Brown, David L. Kulawy, Robert Louie, Arnold The Combination of Rifampin plus Moxifloxacin Is Synergistic for Suppression of Resistance but Antagonistic for Cell Kill of Mycobacterium tuberculosis as Determined in a Hollow-Fiber Infection Model |
title | The Combination of Rifampin plus Moxifloxacin Is Synergistic for Suppression of Resistance but Antagonistic for Cell Kill of Mycobacterium tuberculosis as Determined in a Hollow-Fiber Infection Model |
title_full | The Combination of Rifampin plus Moxifloxacin Is Synergistic for Suppression of Resistance but Antagonistic for Cell Kill of Mycobacterium tuberculosis as Determined in a Hollow-Fiber Infection Model |
title_fullStr | The Combination of Rifampin plus Moxifloxacin Is Synergistic for Suppression of Resistance but Antagonistic for Cell Kill of Mycobacterium tuberculosis as Determined in a Hollow-Fiber Infection Model |
title_full_unstemmed | The Combination of Rifampin plus Moxifloxacin Is Synergistic for Suppression of Resistance but Antagonistic for Cell Kill of Mycobacterium tuberculosis as Determined in a Hollow-Fiber Infection Model |
title_short | The Combination of Rifampin plus Moxifloxacin Is Synergistic for Suppression of Resistance but Antagonistic for Cell Kill of Mycobacterium tuberculosis as Determined in a Hollow-Fiber Infection Model |
title_sort | combination of rifampin plus moxifloxacin is synergistic for suppression of resistance but antagonistic for cell kill of mycobacterium tuberculosis as determined in a hollow-fiber infection model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925073/ https://www.ncbi.nlm.nih.gov/pubmed/20802826 http://dx.doi.org/10.1128/mBio.00139-10 |
work_keys_str_mv | AT drusanogl thecombinationofrifampinplusmoxifloxacinissynergisticforsuppressionofresistancebutantagonisticforcellkillofmycobacteriumtuberculosisasdeterminedinahollowfiberinfectionmodel AT sgambatinicole thecombinationofrifampinplusmoxifloxacinissynergisticforsuppressionofresistancebutantagonisticforcellkillofmycobacteriumtuberculosisasdeterminedinahollowfiberinfectionmodel AT eichasadam thecombinationofrifampinplusmoxifloxacinissynergisticforsuppressionofresistancebutantagonisticforcellkillofmycobacteriumtuberculosisasdeterminedinahollowfiberinfectionmodel AT browndavidl thecombinationofrifampinplusmoxifloxacinissynergisticforsuppressionofresistancebutantagonisticforcellkillofmycobacteriumtuberculosisasdeterminedinahollowfiberinfectionmodel AT kulawyrobert thecombinationofrifampinplusmoxifloxacinissynergisticforsuppressionofresistancebutantagonisticforcellkillofmycobacteriumtuberculosisasdeterminedinahollowfiberinfectionmodel AT louiearnold thecombinationofrifampinplusmoxifloxacinissynergisticforsuppressionofresistancebutantagonisticforcellkillofmycobacteriumtuberculosisasdeterminedinahollowfiberinfectionmodel AT drusanogl combinationofrifampinplusmoxifloxacinissynergisticforsuppressionofresistancebutantagonisticforcellkillofmycobacteriumtuberculosisasdeterminedinahollowfiberinfectionmodel AT sgambatinicole combinationofrifampinplusmoxifloxacinissynergisticforsuppressionofresistancebutantagonisticforcellkillofmycobacteriumtuberculosisasdeterminedinahollowfiberinfectionmodel AT eichasadam combinationofrifampinplusmoxifloxacinissynergisticforsuppressionofresistancebutantagonisticforcellkillofmycobacteriumtuberculosisasdeterminedinahollowfiberinfectionmodel AT browndavidl combinationofrifampinplusmoxifloxacinissynergisticforsuppressionofresistancebutantagonisticforcellkillofmycobacteriumtuberculosisasdeterminedinahollowfiberinfectionmodel AT kulawyrobert combinationofrifampinplusmoxifloxacinissynergisticforsuppressionofresistancebutantagonisticforcellkillofmycobacteriumtuberculosisasdeterminedinahollowfiberinfectionmodel AT louiearnold combinationofrifampinplusmoxifloxacinissynergisticforsuppressionofresistancebutantagonisticforcellkillofmycobacteriumtuberculosisasdeterminedinahollowfiberinfectionmodel |