{"doi":"10.1093/ofid/ofab311","title":"Cefiderocol Activity Against Clinical<i>Pseudomonas aeruginosa</i>Isolates Exhibiting Ceftolozane-Tazobactam Resistance","abstract":"BACKGROUND: Mutations in the AmpC-AmpR region are associated with treatment-emergent ceftolozane-tazobactam (TOL-TAZ) and ceftazidime-avibactam (CAZ-AVI) resistance. We sought to determine if these mutations impact susceptibility to the novel cephalosporin-siderophore compound cefiderocol. METHODS: isolates available after TOL-TAZ exposure from January 2019 to December 2020 were included. TOL-TAZ, CAZ-AVI, imipenem-relebactam (IMI-REL), and cefiderocol minimum inhibitory concentrations (MICs) were determined using broth microdilution. Whole-genome sequencing of paired isolates was used to identify mechanisms of resistance to cefiderocol that emerged, focusing on putative mechanisms of resistance to cefiderocol or earlier siderophore-antibiotic conjugates based on the previously published literature. RESULTS: isolates, ≥4-fold increases in cefiderocol MICs occurred in 4 of 16 isolates. Cefiderocol nonsusceptibility criteria were met for only 1 of the 4 isolates, using Clinical and Laboratory Standards Institute criteria. Specific mechanisms identified included the following: AmpC E247K (2 isolates), MexR A66V and L57D (1 isolate each), and AmpD G116D (1 isolate) substitutions. For both isolates with AmpC E247K mutations, ≥4-fold MIC increases occurred for both TOL-TAZ and CAZ-AVI, while a ≥4-fold reduction in IMI-REL MICs was observed. CONCLUSIONS: -derived AmpC β-lactamases have the potential to reduce the activity of 3 of 4 novel β-lactams (ie, ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol) and potentially increase susceptibility to imipenem-relebactam. These findings are in need of validation in a larger cohort.","journal":"Open Forum Infectious Diseases","year":2021,"id":151779,"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":80,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9438,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":634111,"name":"Stephan Beisken","orcid":"0000-0002-2412-4118","position":1,"is_corresponding":false},{"id":573746,"name":"Yehudit Bergman","orcid":"0000-0002-4262-7173","position":2,"is_corresponding":false},{"id":644914,"name":"Andreas E. Posch","orcid":"0000-0003-3893-3562","position":3,"is_corresponding":false},{"id":246183,"name":"Sara E. Cosgrove","orcid":"0000-0001-9458-4331","position":4,"is_corresponding":false},{"id":287739,"name":"Pranita D. Tamma","orcid":"0000-0002-4143-6324","position":5,"is_corresponding":false},{"id":305631,"name":"Patricia J. Simner","orcid":"0000-0001-6134-151X","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-18T23:43:16.823357Z","pmid":"34262990","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":[]}