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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Published in:Antimicrobial agents and chemotherapy Vol. 59; no. 4; p. 2129
Main Authors: Andréjak, Claire, Almeida, Deepak V, Tyagi, Sandeep, Converse, Paul J, Ammerman, Nicole C, Grosset, Jacques H
Format: Journal Article
Language:English
Published: United States 01.04.2015
Subjects:
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
ISSN:1098-6596, 1098-6596
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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.
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
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  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
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  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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– reference: 16944258 - J Infect Chemother. 2006 Aug;12(4):195-202
– reference: 21673463 - Intern Med. 2011;50(12):1287-92
– reference: 22198962 - J Infect Dis. 2012 Feb 15;205(4):595-602
– reference: 11120969 - Antimicrob Agents Chemother. 2001 Jan;45(1):217-22
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– reference: 17277290 - Am J Respir Crit Care Med. 2007 Feb 15;175(4):367-416
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Snippet The Mycobacterium avium complex is the most common cause of nontuberculous mycobacterial lung disease worldwide; yet, an optimal treatment regimen for M. avium...
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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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