{"doi":"10.1093/jac/dkae329","title":"Cefepime–taniborbactam activity against antimicrobial-resistant clinical isolates of Enterobacterales and <i>Pseudomonas aeruginosa</i>: GEARS global surveillance programme 2018–22","abstract":"OBJECTIVES: Taniborbactam is a boronate-based β-lactamase inhibitor in clinical development in combination with cefepime. METHODS: Cefepime-taniborbactam and comparator broth microdilution MICs were determined for patient isolates of Enterobacterales (n = 20 725) and Pseudomonas aeruginosa (n = 7919) collected in 59 countries from 2018 to 2022. Taniborbactam was tested at a fixed concentration of 4 mg/L. Isolates with cefepime-taniborbactam MICs ≥ 16 mg/L underwent WGS. β-Lactamase genes were identified in additional meropenem-resistant isolates by PCR/Sanger sequencing. RESULTS: Taniborbactam reduced the cefepime MIC90 value for all Enterobacterales from >16 to 0.25 mg/L (>64-fold). At ≤16 mg/L, cefepime-taniborbactam inhibited 99.5% of all Enterobacterales isolates; >95% of isolates with MDR and ceftolozane-tazobactam-resistant phenotypes; ≥ 89% of isolates with meropenem-resistant and difficult-to-treat-resistant (DTR) phenotypes; >80% of isolates with meropenem-vaborbactam-resistant and ceftazidime-avibactam-resistant phenotypes; 100% of KPC-positive, 99% of OXA-48-like-positive, 99% of ESBL-positive, 97% of acquired AmpC-positive, 95% of VIM-positive and 76% of NDM-positive isolates. Against P. aeruginosa, taniborbactam reduced the cefepime MIC90 value from 32 to 8 mg/L (4-fold). At ≤16 mg/L, cefepime-taniborbactam inhibited 96.5% of all P. aeruginosa isolates; 85% of meropenem-resistant phenotype isolates; 80% of isolates with MDR and meropenem-vaborbactam-resistant phenotypes; >70% of isolates with DTR, ceftazidime-avibactam-resistant and ceftolozane-tazobactam-resistant phenotypes; and 82% of VIM-positive isolates. Multiple potential mechanisms of resistance, including carriage of IMP, or alterations in PBP3 (ftsI), porins (decreased permeability) and efflux (up-regulation) were present in most isolates with cefepime-taniborbactam MICs ≥ 16 mg/L. CONCLUSIONS: Cefepime-taniborbactam exhibited potent in vitro activity against Enterobacterales and P. aeruginosa, and inhibited most carbapenem-resistant isolates, including those carrying serine carbapenemases or NDM/VIM MBLs.","journal":"Journal of Antimicrobial Chemotherapy","year":2024,"id":423449,"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":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8443,"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":1218565,"name":"Mark G. Wise","orcid":"0000-0001-7356-1851","position":1,"is_corresponding":false},{"id":1218566,"name":"Meredith Hackel","orcid":"0000-0003-3339-2701","position":2,"is_corresponding":false},{"id":887202,"name":"David A. Six","orcid":"0000-0002-9013-1711","position":3,"is_corresponding":false},{"id":1218567,"name":"Tsuyoshi Uehara","orcid":"0000-0001-6994-4286","position":4,"is_corresponding":false},{"id":666472,"name":"Denis M. Daigle","orcid":"0000-0001-9287-2997","position":5,"is_corresponding":false},{"id":667269,"name":"Daniel C. Pevear","orcid":null,"position":6,"is_corresponding":false},{"id":666474,"name":"Greg Moeck","orcid":"0000-0001-7827-7227","position":7,"is_corresponding":false},{"id":1219145,"name":"Daniel F. Sahm","orcid":null,"position":8,"is_corresponding":false},{"id":651707,"name":"James A. Karlowsky","orcid":"0000-0002-1939-464X","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T01:57:56.814994Z","pmid":"39287999","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":[]}