{"doi":"10.1128/aac.00584-11","title":"Daptomycin, Fosfomycin, or Both for Treatment of Methicillin-Resistant Staphylococcus aureus Osteomyelitis in an Experimental Rat Model","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            The\n            <jats:italic>in vivo</jats:italic>\n            activities of daptomycin, fosfomycin, and a combination of both antibiotics against a clinical isolate of methicillin-resistant\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus</jats:named-content>\n            (daptomycin MIC, 0.25 μg/ml; fosfomycin MIC, 0.5 μg/ml) were evaluated in a rat model of osteomyelitis. A total of 37 rats with experimental osteomyelitis were treated for 4 weeks with either 60 mg/kg of body weight of daptomycin subcutaneously once daily, 75 mg/kg fosfomycin intraperitoneally once daily, a combination of both drugs, or a saline placebo. After the completion of treatment, animals were euthanized, and the infected tibiae were processed for quantitative bacterial culture. Bone cultures were found to be positive for methicillin-resistant\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus</jats:named-content>\n            in 9 of 9 (100%) animals of the placebo group, in 9 of 9 (100%) animals treated with daptomycin, in 1 of 10 (10%) fosfomycin-treated rats, and in 1 of 9 (22.2%) rats comprising the combination group. Results of bacterial counts in the bone samples were expressed as log\n            <jats:sub>10</jats:sub>\n            CFU/g of bone and analyzed by using the Mann-Whitney U test followed by Bonferroni's multiple-comparison test. Based on bacterial counts, treatment with daptomycin was significantly superior to placebo, although it remained inferior to treatment with fosfomycin. No synergistic or antagonistic effect was observed for the combination therapy. No development of resistance against daptomycin or fosfomycin was observed after the 4-week treatment period.\n          </jats:p>","journal":"Antimicrobial Agents and Chemotherapy","year":2011,"id":680158,"datarank":0.5709993734655481,"base_score":3.8066624897703196,"endowment":3.8066624897703196,"self_citation_contribution":0.5709993734655481,"citation_network_contribution":0.0,"self_endowment_contribution":0.5709993734655481,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":44,"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":1777081,"name":"S. Tobudic","orcid":null,"position":1,"is_corresponding":false},{"id":1777082,"name":"T. Lingscheid","orcid":null,"position":2,"is_corresponding":false},{"id":1777083,"name":"R. Plasenzotti","orcid":null,"position":3,"is_corresponding":false},{"id":1777084,"name":"N. Kozakowski","orcid":null,"position":4,"is_corresponding":false},{"id":1777085,"name":"H. Lagler","orcid":null,"position":5,"is_corresponding":false},{"id":1510422,"name":"A. Georgopoulos","orcid":null,"position":6,"is_corresponding":false},{"id":1777086,"name":"H. Burgmann","orcid":null,"position":7,"is_corresponding":false},{"id":1777080,"name":"W. Poeppl","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Daptomycin, Fosfomycin, or Both for Treatment of Methicillin-Resistant Staphylococcus aureus Osteomyelitis in an Experimental Rat Model","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            The\n            <jats:italic>in vivo</jats:italic>\n            activities of daptomycin, fosfomycin, and a combination of both antibiotics against a clinical isolate of methicillin-resistant\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus</jats:named-content>\n            (daptomycin MIC, 0.25 μg/ml; fosfomycin MIC, 0.5 μg/ml) were evaluated in a rat model of osteomyelitis. A total of 37 rats with experimental osteomyelitis were treated for 4 weeks with either 60 mg/kg of body weight of daptomycin subcutaneously once daily, 75 mg/kg fosfomycin intraperitoneally once daily, a combination of both drugs, or a saline placebo. After the completion of treatment, animals were euthanized, and the infected tibiae were processed for quantitative bacterial culture. Bone cultures were found to be positive for methicillin-resistant\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus</jats:named-content>\n            in 9 of 9 (100%) animals of the placebo group, in 9 of 9 (100%) animals treated with daptomycin, in 1 of 10 (10%) fosfomycin-treated rats, and in 1 of 9 (22.2%) rats comprising the combination group. Results of bacterial counts in the bone samples were expressed as log\n            <jats:sub>10</jats:sub>\n            CFU/g of bone and analyzed by using the Mann-Whitney U test followed by Bonferroni's multiple-comparison test. Based on bacterial counts, treatment with daptomycin was significantly superior to placebo, although it remained inferior to treatment with fosfomycin. No synergistic or antagonistic effect was observed for the combination therapy. No development of resistance against daptomycin or fosfomycin was observed after the 4-week treatment period.\n          </jats:p>","is_dataset_classified":null,"base_score":3.8066624897703196,"endowment":3.8066624897703196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21859942","pmcid":"PMC3194995","openalex_id":"https://openalex.org/W2169291267","authors":[],"funders":[],"total_grants":0,"fwci":2.6698,"citation_percentile":0.89939445,"influential_citations":0,"citation_trend":[{"year":2012,"count":5},{"year":2013,"count":6},{"year":2014,"count":6},{"year":2015,"count":3},{"year":2016,"count":1},{"year":2017,"count":1},{"year":2018,"count":2},{"year":2019,"count":3},{"year":2020,"count":3},{"year":2021,"count":3},{"year":2022,"count":3},{"year":2023,"count":2},{"year":2024,"count":2},{"year":2025,"count":3},{"year":2026,"count":1}],"oa_status":"bronze","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://aac.asm.org/content/aac/55/11/4999.full.pdf","host_type":"journal"},{"url":"https://aac.asm.org/content/aac/55/11/4999.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/AAC.00584-11","host_type":"publisher"},{"url":"https://doi.org/10.1128/aac.00584-11","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/21859942","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3194995","host_type":"repository"}],"fields_of_study":["Antimicrobial Resistance in Staphylococcus","Orthopedic Infections and Treatments","Infective Endocarditis Diagnosis and Management"],"mesh_terms":["Animals","Anti-Bacterial Agents","Disease Models, Animal","Fosfomycin","Male","Osteomyelitis","Rats, Sprague-Dawley","Daptomycin","Rats","Methicillin-Resistant Staphylococcus aureus"],"keywords":["Daptomycin","Fosfomycin","Staphylococcus aureus","Osteomyelitis","Antibiotics","Medicine","Placebo","Microbiology","Methicillin-resistant Staphylococcus aureus","Pharmacodynamics","Pharmacology","Internal medicine","Surgery","Vancomycin","Pharmacokinetics","Biology","Bacteria","Pathology"],"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":"2026-08-17T14:32:05.294645Z","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":[]}