{"doi":"10.1128/aac.02068-15","title":"Activity of Tobramycin against Cystic Fibrosis Isolates of Burkholderia cepacia Complex Grown as Biofilms","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            Pulmonary infection with\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Burkholderia cepacia</jats:named-content>\n            complex in cystic fibrosis (CF) patients is associated with more-rapid lung function decline and earlier death than in CF patients without this infection. In this study, we used confocal microscopy to visualize the effects of various concentrations of tobramycin, achievable with systemic and aerosolized drug administration, on mature\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. cepacia</jats:named-content>\n            complex biofilms, both in the presence and absence of CF sputum. After 24 h of growth, biofilm thickness was significantly reduced by exposure to 2,000 μg/ml of tobramycin for\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Burkholderia cepacia</jats:named-content>\n            ,\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Burkholderia multivorans</jats:named-content>\n            , and\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Burkholderia vietnamiensis</jats:named-content>\n            ; 200 μg/ml of tobramycin was sufficient to reduce the thickness of\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Burkholderia dolosa</jats:named-content>\n            biofilm. With a more mature 48-h biofilm, significant reductions in thickness were seen with tobramycin at concentrations of ≥100 μg/ml for all\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Burkholderia</jats:named-content>\n            species. In addition, an increased ratio of dead to live cells was observed in comparison to control with tobramycin concentrations of ≥200 μg/ml for\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. cepacia</jats:named-content>\n            and\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. dolosa</jats:named-content>\n            (24 h) and ≥100 μg/ml for\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Burkholderia cenocepacia</jats:named-content>\n            and\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. dolosa</jats:named-content>\n            (48 h). Although sputum significantly increased biofilm thickness, tobramycin concentrations of 1,000 μg/ml were still able to significantly reduce biofilm thickness of all\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. cepacia</jats:named-content>\n            complex species with the exception of\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. vietnamiensis</jats:named-content>\n            . In the presence of sputum, 1,000 μg/ml of tobramycin significantly increased the dead-to-live ratio only for\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. multivorans</jats:named-content>\n            compared to control. In summary, although killing is attenuated, high-dose tobramycin can effectively decrease the thickness of\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. cepacia</jats:named-content>\n            complex biofilms, even in the presence of sputum, suggesting a possible role as a suppressive therapy in CF.\n          </jats:p>","journal":"Antimicrobial Agents and Chemotherapy","year":2016,"id":622862,"datarank":0.44166584687496613,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"self_citation_contribution":0.44166584687496613,"citation_network_contribution":0.0,"self_endowment_contribution":0.44166584687496613,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"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":685947,"name":"Trevor Beaudoin","orcid":null,"position":1,"is_corresponding":false},{"id":1609536,"name":"Yvonne C. W. Yau","orcid":null,"position":2,"is_corresponding":false},{"id":1609537,"name":"Emma Caraher","orcid":null,"position":3,"is_corresponding":false},{"id":1600808,"name":"James E. A. Zlosnik","orcid":null,"position":4,"is_corresponding":false},{"id":1609538,"name":"David P. Speert","orcid":null,"position":5,"is_corresponding":false},{"id":347642,"name":"John J. LiPuma","orcid":"0000-0003-4033-7794","position":6,"is_corresponding":false},{"id":622099,"name":"Elizabeth Tullis","orcid":null,"position":7,"is_corresponding":false},{"id":491417,"name":"Valerie Waters","orcid":null,"position":8,"is_corresponding":false},{"id":610139,"name":"Sarah Kennedy","orcid":"0000-0003-1421-3704","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Activity of Tobramycin against Cystic Fibrosis Isolates of Burkholderia cepacia Complex Grown as Biofilms","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            Pulmonary infection with\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Burkholderia cepacia</jats:named-content>\n            complex in cystic fibrosis (CF) patients is associated with more-rapid lung function decline and earlier death than in CF patients without this infection. In this study, we used confocal microscopy to visualize the effects of various concentrations of tobramycin, achievable with systemic and aerosolized drug administration, on mature\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. cepacia</jats:named-content>\n            complex biofilms, both in the presence and absence of CF sputum. After 24 h of growth, biofilm thickness was significantly reduced by exposure to 2,000 μg/ml of tobramycin for\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Burkholderia cepacia</jats:named-content>\n            ,\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Burkholderia multivorans</jats:named-content>\n            , and\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Burkholderia vietnamiensis</jats:named-content>\n            ; 200 μg/ml of tobramycin was sufficient to reduce the thickness of\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Burkholderia dolosa</jats:named-content>\n            biofilm. With a more mature 48-h biofilm, significant reductions in thickness were seen with tobramycin at concentrations of ≥100 μg/ml for all\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Burkholderia</jats:named-content>\n            species. In addition, an increased ratio of dead to live cells was observed in comparison to control with tobramycin concentrations of ≥200 μg/ml for\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. cepacia</jats:named-content>\n            and\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. dolosa</jats:named-content>\n            (24 h) and ≥100 μg/ml for\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Burkholderia cenocepacia</jats:named-content>\n            and\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. dolosa</jats:named-content>\n            (48 h). Although sputum significantly increased biofilm thickness, tobramycin concentrations of 1,000 μg/ml were still able to significantly reduce biofilm thickness of all\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. cepacia</jats:named-content>\n            complex species with the exception of\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. vietnamiensis</jats:named-content>\n            . In the presence of sputum, 1,000 μg/ml of tobramycin significantly increased the dead-to-live ratio only for\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. multivorans</jats:named-content>\n            compared to control. In summary, although killing is attenuated, high-dose tobramycin can effectively decrease the thickness of\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. cepacia</jats:named-content>\n            complex biofilms, even in the presence of sputum, suggesting a possible role as a suppressive therapy in CF.\n          </jats:p>","is_dataset_classified":null,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26503664","pmcid":"PMC4704152","openalex_id":"https://openalex.org/W1947394714","authors":[],"funders":[{"funder_name":"Canadian Institutes of Health Research","grant_id":"MT13337","title":null}],"total_grants":1,"fwci":1.8885,"citation_percentile":0.85894959,"influential_citations":0,"citation_trend":[{"year":2016,"count":3},{"year":2017,"count":2},{"year":2018,"count":3},{"year":2019,"count":1},{"year":2020,"count":3},{"year":2021,"count":2},{"year":2022,"count":2},{"year":2023,"count":1},{"year":2024,"count":1}],"oa_status":"green","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4704152","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4704152","host_type":"repository"},{"url":"https://journals.asm.org/doi/pdf/10.1128/AAC.02068-15","host_type":"publisher"},{"url":"https://doi.org/10.1128/aac.02068-15","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26503664","host_type":"repository"}],"fields_of_study":["Cystic Fibrosis Research Advances","Bacterial biofilms and quorum sensing"],"mesh_terms":["Anti-Bacterial Agents","Child","Cystic Fibrosis","Dose-Response Relationship, Drug","Humans","Microbial Sensitivity Tests","Species Specificity","Sputum","Tobramycin","Biofilms","Microscopy, Confocal","Burkholderia","Burkholderia cepacia complex"],"keywords":["Tobramycin","Burkholderia cepacia complex","Burkholderia","Burkholderia cenocepacia","Microbiology","Sputum","Biofilm","Cystic fibrosis","Biology","Pseudomonas aeruginosa","Antibiotics","Chemistry","Bacteria","Medicine","Gentamicin","Pathology"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T21:20:17.744716Z","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":[]}