Sterilizing Activity of Second-Line Regimens Containing TMC207 in a Murine Model of Tuberculosis
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{"title"=>"Sterilizing activity of second-line regimens containing TMC207 in a murine model of tuberculosis", "type"=>"journal", "authors"=>[{"first_name"=>"Nicolas", "last_name"=>"Veziris", "scopus_author_id"=>"6602331312"}, {"first_name"=>"Murad", "last_name"=>"Ibrahim", "scopus_author_id"=>"15022210800"}, {"first_name"=>"Nacer", "last_name"=>"Lounis", "scopus_author_id"=>"6604091254"}, {"first_name"=>"Koen", "last_name"=>"Andries", "scopus_author_id"=>"7003290210"}, {"first_name"=>"Vincent", "last_name"=>"Jarlier", "scopus_author_id"=>"7005338388"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"79952422865", "pmid"=>"21408613", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pui"=>"361391746", "issn"=>"19326203", "scopus"=>"2-s2.0-79952422865", "doi"=>"10.1371/journal.pone.0017556"}, "id"=>"c43447b5-43e5-3780-9c5c-7dabd3a4ef11", "abstract"=>"RATIONALE The sterilizing activity of the regimen used to treat multidrug resistant tuberculosis (MDR TB) has not been studied in a mouse model. OBJECTIVE AND METHODS Swiss mice were intravenously inoculated with 6 log10 of Mycobacterium tuberculosis (TB) strain H37Rv, treated with second-line drug combinations with or without the diarylquinoline TMC207, and then followed without treatment for 3 more months to determine relapse rates (modified Cornell model). MEASUREMENTS Bactericidal efficacy was assessed by quantitative lung colony-forming unit (CFU) counts. Sterilizing efficacy was assessed by measuring bacteriological relapse rates 3 months after the end of treatment. MAIN RESULTS The relapse rate observed after 12 months treatment with the WHO recommended MDR TB regimen (amikacin, ethionamide, pyrazinamide and moxifloxacin) was equivalent to the relapse rate observed after 6 months treatment with the recommended drug susceptible TB regimen (rifampin, isoniazid and pyrazinamide). When TMC207 was added to this MDR TB regimen, the treatment duration needed to reach the same relapse rate dropped to 6 months. A similar relapse rate was also obtained with a 6-month completely oral regimen including TMC207, moxifloxacin and pyrazinamide but excluding both amikacin and ethionamide. CONCLUSIONS In this murine model the duration of the WHO MDR TB treatment could be reduced to 12 months instead of the recommended 18-24 months. The inclusion of TMC207 in the WHO MDR TB treatment regimen has the potential to further shorten the treatment duration and at the same time to simplify treatment by eliminating the need to include an injectable aminoglycoside.", "link"=>"http://www.mendeley.com/research/sterilizing-activity-secondline-regimens-containing-tmc207-murine-model-tuberculosis", "reader_count"=>43, "reader_count_by_academic_status"=>{"Researcher"=>11, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>3, "Other"=>6, "Student > Master"=>5, "Student > Bachelor"=>3, "Lecturer"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>11, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>3, "Other"=>6, "Student > Master"=>5, "Student > Bachelor"=>3, "Lecturer"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>18, "Medicine and Dentistry"=>17, "Pharmacology, Toxicology and Pharmaceutical Science"=>2, "Chemistry"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>17}, "Chemistry"=>{"Chemistry"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>18}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "reader_count_by_country"=>{"Sweden"=>1}, "group_count"=>3}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/793336"], "description"=>"<p>Definition of abbreviations: J = TMC 207, R = Rifampin, M = Moxifloxacin, H = Isoniazid, Z = Pyrazinamide, A = amikacin, Et = ethionamide.</p><p>Mice were infected intravenously with 1.1×10<sup>6</sup> of <i>M. tuberculosis</i> H37Rv.</p><p>Day -18: the day after infection, Day 0: start of treatment.</p><p>*Mice kept untreated for mortality assessment.</p><p>All drugs were given 5 times per week at the following doses: J, 25 mg/kg; R, 10 mg/kg; M, 100 mg/kg; H, 25 mg/kg; Z, 150 mg/kg; A, 150 mg/kg; Et, 50 mg/kg.</p>", "links"=>[], "tags"=>["Infectious diseases", "Non-clinical medicine"], "article_id"=>463705, "categories"=>["Medicine", "Infectious Diseases"], "users"=>["Nicolas Veziris", "Murad Ibrahim", "Nacer Lounis", "Koen Andries", "Vincent Jarlier"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0017556.t001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Experiment_Design_/463705", "title"=>"Experiment Design.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 20:05:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/793364"], "description"=>"<p>*Lung CFU count at start of treatment (D0): 7.1 log10 CFU.</p><p>Definition of abbreviations: J = TMC 207, R = Rifampin, M = Moxifloxacin, H = Isoniazid, Z = Pyrazinamide, A = amikacin, Et = ethionamide.</p>a<p>significantly more relapses than RHZ (p<0.05).</p>b<p>not significantly different from RHZ (p>0.05).</p>", "links"=>[], "tags"=>["mice", "months", "completion"], "article_id"=>463733, "categories"=>["Medicine", "Infectious Diseases"], "users"=>["Nicolas Veziris", "Murad Ibrahim", "Nacer Lounis", "Koen Andries", "Vincent Jarlier"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0017556.t002", "stats"=>{"downloads"=>3, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Proportion_of_mice_with_positive_culture_of_lung_3_months_after_treatment_completion_relapse_/463733", "title"=>"Proportion of mice with positive culture of lung 3 months after treatment completion (relapse).<sup>*</sup>", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 20:06:00"}

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  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
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  • {"unique-ip"=>"9", "full-text"=>"902", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
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Relative Metric

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