{"doi":"10.1038/s42003-020-01313-5","title":"Carbapenems drive the collateral resistance to ceftaroline in cystic fibrosis patients with MRSA","abstract":"Chronic airways infection with methicillin-resistant Staphylococcus aureus (MRSA) is associated with worse respiratory disease cystic fibrosis (CF) patients. Ceftaroline is a cephalosporin that inhibits the penicillin-binding protein (PBP2a) uniquely produced by MRSA. We analyzed 335 S. aureus isolates from CF sputum samples collected at three US centers between 2015-2018. Molecular relationships demonstrated that high-level resistance of preceding isolates to carbapenems were associated with subsequent isolation of ceftaroline resistant CF MRSA. In vitro evolution experiments showed that pre-exposure of CF MRSA to meropenem with further selection with ceftaroline implied mutations in mecA and additional mutations in pbp1 and pbp2, targets of carbapenems; no effects were achieved by other β-lactams. An in vivo pneumonia mouse model showed the potential therapeutic efficacy of ceftaroline/meropenem combination against ceftaroline-resistant CF MRSA infections. Thus, the present findings highlight risk factors and potential therapeutic strategies offering an opportunity to both prevent and address antibiotic resistance in this patient population.","journal":"Communications Biology","year":2020,"id":71773,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9487,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":378975,"name":"Mélanie Roch","orcid":"0000-0001-6485-8434","position":1,"is_corresponding":false},{"id":378976,"name":"Agustina Taglialegna","orcid":"0000-0003-4844-8720","position":2,"is_corresponding":false},{"id":245823,"name":"S. Wesley Long","orcid":"0000-0003-3043-5307","position":3,"is_corresponding":false},{"id":235709,"name":"Matthew Ojeda Saavedra","orcid":"0000-0002-2044-4560","position":4,"is_corresponding":false},{"id":270150,"name":"Warren E. Rose","orcid":"0000-0001-5012-5993","position":5,"is_corresponding":false},{"id":262642,"name":"James J. Davis","orcid":"0000-0003-0104-5852","position":6,"is_corresponding":false},{"id":277198,"name":"Lucas R. Hoffman","orcid":"0000-0001-8864-6751","position":7,"is_corresponding":false},{"id":378977,"name":"Rafael E. Hernandez","orcid":"0000-0003-4408-7411","position":8,"is_corresponding":false},{"id":378978,"name":"Roberto R. Rosato","orcid":"0000-0002-7885-5127","position":9,"is_corresponding":false},{"id":378979,"name":"Adriana E. Rosato","orcid":"0000-0001-6115-6955","position":10,"is_corresponding":false},{"id":379950,"name":"Maria Celeste Varela","orcid":null,"position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-18T21:44:25.469842Z","pmid":"33093601","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":[]}