{"doi":"10.1128/aac.00725-24","title":"Polymyxins retain <i>in vitro</i> activity and <i>in vivo</i> efficacy against “resistant” <i>Acinetobacter baumannii</i> strains when tested in physiological conditions","abstract":"ABSTRACT The emergence of plasmid-mediated resistance threatens the efficacy of polymyxins as the last line of defense against pan-drug-resistant infections. However, we have found that using Mueller-Hinton II (MHII), the standard minimum inhibitory concentration (MIC) medium, results in MIC data that are disconnected from in vivo treatment outcomes. We found that culturing putative colistin-resistant Acinetobacter baumannii clinical isolates, as defined by MICs of &gt;2 mg/L in standard MHII testing conditions, in bicarbonate-containing media reduced MICs to the susceptible range by preventing colistin resistance-conferring lipopolysaccharide modifications from occurring. Furthermore, the lower MICs in bicarbonate-containing media accurately predicted in vivo efficacy of a human-simulated dosing strategy of colistin and polymyxin B in a lethal murine infection model for some polymyxin-resistant A. baumannii strains. Thus, current polymyxin susceptibility testing methods overestimate the contribution of polymyxin resistance-conferring mutations and incorrectly predict antibiotic activity in vivo . Polymyxins may remain a viable therapeutic option against Acinetobacter baumannii strains heretofore determined to be “pan-resistant.”","journal":"Antimicrobial Agents and Chemotherapy","year":2024,"id":447434,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9549,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":634724,"name":"Jun Yan","orcid":"0000-0001-7509-2067","position":1,"is_corresponding":false},{"id":1265065,"name":"Sarah Miller","orcid":"0000-0002-1441-4015","position":2,"is_corresponding":false},{"id":1265066,"name":"Jiaqi Cheng","orcid":"0000-0002-8951-2410","position":3,"is_corresponding":false},{"id":488372,"name":"Rachel Li","orcid":"0000-0001-7053-7928","position":4,"is_corresponding":false},{"id":1265504,"name":"Zac Builta","orcid":null,"position":5,"is_corresponding":false},{"id":714031,"name":"Kari L. Aoyagi","orcid":"0009-0007-8330-9415","position":6,"is_corresponding":false},{"id":714032,"name":"Mark Fisher","orcid":"0000-0003-3422-454X","position":7,"is_corresponding":false},{"id":1265067,"name":"Rosemary C. She","orcid":"0000-0002-8773-1687","position":8,"is_corresponding":false},{"id":420771,"name":"Brad Spellberg","orcid":"0000-0002-3632-1709","position":9,"is_corresponding":false},{"id":634726,"name":"Brian Luna","orcid":"0000-0001-6718-4551","position":10,"is_corresponding":false},{"id":1265064,"name":"Jennifer S. Rubio","orcid":"0009-0006-3789-6551","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-19T02:01:59.101070Z","pmid":"39240097","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":[]}