Characterization of mouse models of Mycobacterium avium complex infection and evaluation of drug combinations
The Mycobacterium avium complex is the most common cause of nontuberculous mycobacterial lung disease worldwide; yet, an optimal treatment regimen for M. avium complex infection has not been established. Clarithromycin is accepted as the cornerstone drug for treatment of M. avium lung disease; howev...
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| Veröffentlicht in: | Antimicrobial agents and chemotherapy Jg. 59; H. 4; S. 2129 |
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| Abstract | The Mycobacterium avium complex is the most common cause of nontuberculous mycobacterial lung disease worldwide; yet, an optimal treatment regimen for M. avium complex infection has not been established. Clarithromycin is accepted as the cornerstone drug for treatment of M. avium lung disease; however, good model systems, especially animal models, are needed to evaluate the most effective companion drugs. We performed a series of experiments to evaluate and use different mouse models (comparing BALB/c, C57BL/6, nude, and beige mice) of M. avium infection and to assess the anti-M. avium activity of single and combination drug regimens, in vitro, ex vivo, and in mice. In vitro, clarithromycin and moxifloxacin were most active against M. avium, and no antagonism was observed between these two drugs. Nude mice were more susceptible to M. avium infection than the other mouse strains tested, but the impact of treatment was most clearly seen in M. avium-infected BALB/c mice. The combination of clarithromycin-ethambutol-rifampin was more effective in all infected mice than moxifloxacin-ethambutol-rifampin; the addition of moxifloxacin to the clarithromycin-containing regimen did not increase treatment efficacy. Clarithromycin-containing regimens are the most effective for M. avium infection; substitution of moxifloxacin for clarithromycin had a negative impact on treatment efficacy. |
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| AbstractList | The Mycobacterium avium complex is the most common cause of nontuberculous mycobacterial lung disease worldwide; yet, an optimal treatment regimen for M. avium complex infection has not been established. Clarithromycin is accepted as the cornerstone drug for treatment of M. avium lung disease; however, good model systems, especially animal models, are needed to evaluate the most effective companion drugs. We performed a series of experiments to evaluate and use different mouse models (comparing BALB/c, C57BL/6, nude, and beige mice) of M. avium infection and to assess the anti-M. avium activity of single and combination drug regimens, in vitro, ex vivo, and in mice. In vitro, clarithromycin and moxifloxacin were most active against M. avium, and no antagonism was observed between these two drugs. Nude mice were more susceptible to M. avium infection than the other mouse strains tested, but the impact of treatment was most clearly seen in M. avium-infected BALB/c mice. The combination of clarithromycin-ethambutol-rifampin was more effective in all infected mice than moxifloxacin-ethambutol-rifampin; the addition of moxifloxacin to the clarithromycin-containing regimen did not increase treatment efficacy. Clarithromycin-containing regimens are the most effective for M. avium infection; substitution of moxifloxacin for clarithromycin had a negative impact on treatment efficacy. The Mycobacterium avium complex is the most common cause of nontuberculous mycobacterial lung disease worldwide; yet, an optimal treatment regimen for M. avium complex infection has not been established. Clarithromycin is accepted as the cornerstone drug for treatment of M. avium lung disease; however, good model systems, especially animal models, are needed to evaluate the most effective companion drugs. We performed a series of experiments to evaluate and use different mouse models (comparing BALB/c, C57BL/6, nude, and beige mice) of M. avium infection and to assess the anti-M. avium activity of single and combination drug regimens, in vitro, ex vivo, and in mice. In vitro, clarithromycin and moxifloxacin were most active against M. avium, and no antagonism was observed between these two drugs. Nude mice were more susceptible to M. avium infection than the other mouse strains tested, but the impact of treatment was most clearly seen in M. avium-infected BALB/c mice. The combination of clarithromycin-ethambutol-rifampin was more effective in all infected mice than moxifloxacin-ethambutol-rifampin; the addition of moxifloxacin to the clarithromycin-containing regimen did not increase treatment efficacy. Clarithromycin-containing regimens are the most effective for M. avium infection; substitution of moxifloxacin for clarithromycin had a negative impact on treatment efficacy.The Mycobacterium avium complex is the most common cause of nontuberculous mycobacterial lung disease worldwide; yet, an optimal treatment regimen for M. avium complex infection has not been established. Clarithromycin is accepted as the cornerstone drug for treatment of M. avium lung disease; however, good model systems, especially animal models, are needed to evaluate the most effective companion drugs. We performed a series of experiments to evaluate and use different mouse models (comparing BALB/c, C57BL/6, nude, and beige mice) of M. avium infection and to assess the anti-M. avium activity of single and combination drug regimens, in vitro, ex vivo, and in mice. In vitro, clarithromycin and moxifloxacin were most active against M. avium, and no antagonism was observed between these two drugs. Nude mice were more susceptible to M. avium infection than the other mouse strains tested, but the impact of treatment was most clearly seen in M. avium-infected BALB/c mice. The combination of clarithromycin-ethambutol-rifampin was more effective in all infected mice than moxifloxacin-ethambutol-rifampin; the addition of moxifloxacin to the clarithromycin-containing regimen did not increase treatment efficacy. Clarithromycin-containing regimens are the most effective for M. avium infection; substitution of moxifloxacin for clarithromycin had a negative impact on treatment efficacy. |
| Author | Converse, Paul J Ammerman, Nicole C Tyagi, Sandeep Andréjak, Claire Almeida, Deepak V Grosset, Jacques H |
| Author_xml | – sequence: 1 givenname: Claire surname: Andréjak fullname: Andréjak, Claire email: clandrejak@gmail.com organization: Johns Hopkins University School of Medicine, Center for Tuberculosis Research, Baltimore, Maryland, USA Unité INSERM U 1088, Picardie Jules Verne, Amiens, France Respiratory Disease Unit, University Hospital, Amiens, France clandrejak@gmail.com – sequence: 2 givenname: Deepak V surname: Almeida fullname: Almeida, Deepak V organization: Johns Hopkins University School of Medicine, Center for Tuberculosis Research, Baltimore, Maryland, USA KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandel School of Medicine, University of KwaZulu-Natal, Durban, South Africa – sequence: 3 givenname: Sandeep surname: Tyagi fullname: Tyagi, Sandeep organization: Johns Hopkins University School of Medicine, Center for Tuberculosis Research, Baltimore, Maryland, USA – sequence: 4 givenname: Paul J surname: Converse fullname: Converse, Paul J organization: Johns Hopkins University School of Medicine, Center for Tuberculosis Research, Baltimore, Maryland, USA – sequence: 5 givenname: Nicole C surname: Ammerman fullname: Ammerman, Nicole C organization: Johns Hopkins University School of Medicine, Center for Tuberculosis Research, Baltimore, Maryland, USA KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandel School of Medicine, University of KwaZulu-Natal, Durban, South Africa – sequence: 6 givenname: Jacques H surname: Grosset fullname: Grosset, Jacques H organization: Johns Hopkins University School of Medicine, Center for Tuberculosis Research, Baltimore, Maryland, USA KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandel School of Medicine, University of KwaZulu-Natal, Durban, South Africa |
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| SubjectTerms | Animals Anti-Bacterial Agents - pharmacology Anti-Bacterial Agents - therapeutic use Colony Count, Microbial Drug Combinations Drug Synergism Female Lung - pathology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Nude Microbial Sensitivity Tests Mycobacterium avium Complex - drug effects Mycobacterium avium-intracellulare Infection - drug therapy Mycobacterium avium-intracellulare Infection - microbiology Mycobacterium avium-intracellulare Infection - pathology Species Specificity |
| Title | Characterization of mouse models of Mycobacterium avium complex infection and evaluation of drug combinations |
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