{"doi":"10.1183/13993003.02502-2019","title":"Fully weekly antituberculosis regimen: a proof-of-concept study","abstract":"<jats:sec><jats:title>Background</jats:title><jats:p>The World Health Organization recommends supervising the treatment of tuberculosis. Intermittent regimens have the potential to simplify the supervision and improve compliance. Our objective was to analyse the sterilising activity of once-weekly regimens based on drugs with a long half-life, bedaquiline and rifapentine, in a murine model of tuberculosis.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>300 Swiss mice were infected intravenously infected with ×10<jats:sup>−6</jats:sup> CFU<jats:italic>Mycobacterium tuberculosis</jats:italic>H37Rv. Mice were treated once weekly with regimens containing: 1) bedaquiline, rifapentine and pyrazinamide (BPZ); 2) BPZ plus moxifloxacin (BPZM); 3) BPZM plus clofazimine (BPZMC); 4) the standard daily regimen of tuberculosis. All regimens were given for 4 or 6 months. Bactericidal and sterilising activity were assessed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>After 2 months of treatment, the mean count in lungs was 0.76±0.60 log<jats:sub>10</jats:sub>CFU in mice treated with the daily control regimen and negative in all mice treated with once-weekly regimens (p&lt;0.05 compared to the daily control). All mice had negative lung cultures on completion of either 4 or 6 months of treatment, whereas 3 months after 4 and 6 months of treatment, respectively, the relapse rate was 64% and 13% in the standard daily regimen, 5% and 0% in BPZ, 0% and 0% in BPMZ and 0% and 5% in BPMZC (p&lt;0.05 for all once-weekly regimens<jats:italic>versus</jats:italic>4-month daily control; p&gt;0.05 for all once-weekly regimens<jats:italic>versus</jats:italic>6-month daily control).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>BPZ-based once-weekly regimens have higher sterilising activity than the standard daily regimen and could greatly simplify treatment administration and possibly shorten the duration of tuberculosis treatment.</jats:p></jats:sec>","journal":"European Respiratory Journal","year":2020,"id":649615,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":885062,"name":"Laure Fournier Le Ray","orcid":null,"position":1,"is_corresponding":false},{"id":398093,"name":"Aurélie Chauffour","orcid":"0000-0002-8846-5069","position":2,"is_corresponding":false},{"id":398098,"name":"Vincent Jarlier","orcid":"0000-0003-0957-0002","position":3,"is_corresponding":false},{"id":1548841,"name":"Nacer Lounis","orcid":null,"position":4,"is_corresponding":false},{"id":1548837,"name":"Koen Andries","orcid":null,"position":5,"is_corresponding":false},{"id":884296,"name":"Alexandra Aubry","orcid":"0000-0003-4230-4793","position":6,"is_corresponding":false},{"id":108183,"name":"Lorenzo Guglielmetti","orcid":"0000-0003-0886-9635","position":7,"is_corresponding":false},{"id":1021414,"name":"Nicolas Véziris","orcid":"0000-0001-5660-6544","position":8,"is_corresponding":false},{"id":1693548,"name":"Fatma Kort","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Fully weekly antituberculosis regimen: a proof-of-concept study","abstract":"<jats:sec><jats:title>Background</jats:title><jats:p>The World Health Organization recommends supervising the treatment of tuberculosis. Intermittent regimens have the potential to simplify the supervision and improve compliance. Our objective was to analyse the sterilising activity of once-weekly regimens based on drugs with a long half-life, bedaquiline and rifapentine, in a murine model of tuberculosis.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>300 Swiss mice were infected intravenously infected with ×10<jats:sup>−6</jats:sup> CFU<jats:italic>Mycobacterium tuberculosis</jats:italic>H37Rv. Mice were treated once weekly with regimens containing: 1) bedaquiline, rifapentine and pyrazinamide (BPZ); 2) BPZ plus moxifloxacin (BPZM); 3) BPZM plus clofazimine (BPZMC); 4) the standard daily regimen of tuberculosis. All regimens were given for 4 or 6 months. Bactericidal and sterilising activity were assessed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>After 2 months of treatment, the mean count in lungs was 0.76±0.60 log<jats:sub>10</jats:sub>CFU in mice treated with the daily control regimen and negative in all mice treated with once-weekly regimens (p&lt;0.05 compared to the daily control). All mice had negative lung cultures on completion of either 4 or 6 months of treatment, whereas 3 months after 4 and 6 months of treatment, respectively, the relapse rate was 64% and 13% in the standard daily regimen, 5% and 0% in BPZ, 0% and 0% in BPMZ and 0% and 5% in BPMZC (p&lt;0.05 for all once-weekly regimens<jats:italic>versus</jats:italic>4-month daily control; p&gt;0.05 for all once-weekly regimens<jats:italic>versus</jats:italic>6-month daily control).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>BPZ-based once-weekly regimens have higher sterilising activity than the standard daily regimen and could greatly simplify treatment administration and possibly shorten the duration of tuberculosis treatment.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"32430417","pmcid":null,"openalex_id":"https://openalex.org/W3028553049","authors":[],"funders":[{"funder_name":"Janssen Research and Development","grant_id":"","title":null},{"funder_name":"Fonds de Recherche en Santé Respiratoire","grant_id":"","title":null}],"total_grants":2,"fwci":0.0726,"citation_percentile":0.48429177,"influential_citations":0,"citation_trend":[{"year":2020,"count":1},{"year":2021,"count":2},{"year":2025,"count":1}],"oa_status":"bronze","license":"https://www.ersjournals.com/user-licence","oa_locations":[{"url":"https://erj.ersjournals.com/content/erj/56/3/1902502.full.pdf","host_type":"journal"},{"url":"https://erj.ersjournals.com/content/erj/56/3/1902502.full.pdf","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1183/13993003.02502-2019","host_type":"publisher"},{"url":"https://doi.org/10.1183/13993003.02502-2019","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/32430417","host_type":"repository"},{"url":"https://hal.sorbonne-universite.fr/hal-02962259","host_type":"repository"}],"fields_of_study":["Tuberculosis Research and Epidemiology","Antibiotics Pharmacokinetics and Efficacy","Pharmaceutical Quality and Counterfeiting"],"mesh_terms":["Animals","Antitubercular Agents","Drug Administration Schedule","Drug Therapy, Combination","Isoniazid","Mycobacterium tuberculosis","Pyrazinamide","Tuberculosis","Mice"],"keywords":["Medicine","Regimen","Rifapentine","Bedaquiline","Clofazimine","Pyrazinamide","Moxifloxacin","Tuberculosis","Internal medicine","Surgery","Isoniazid","Mycobacterium tuberculosis","Antibiotics","Immunology","Leprosy","Pathology","Latent tuberculosis"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T04:01:27.375502Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}