{"doi":"10.1093/jacamr/dlaf129","title":"Cefepime-zidebactam therapy for extensively drug-resistant <i>Pseudomonas aeruginosa</i> and <i>Klebsiella pneumoniae</i> infection as a bridge to liver transplantation","abstract":"Abstract Background Infections due to antimicrobial-resistant Gram-negative organisms present increasingly difficult therapeutic challenges, especially in the presence of metallo-β-lactamases. We present the case of a patient with cholangitis due to Pseudomonas aeruginosa and Klebsiella pneumoniae isolates that developed cefiderocol resistance on therapy treated successfully with cefepime-zidebactam. Methods Serial clinical isolates recovered from biliary fluid and ascitic fluid were tested for susceptibility to cefiderocol, aztreonam-avibactam, cefepime-taniborbactam, cefepime-zidebactam, and cefiderocol-xeruborbactam by broth microdilution. Whole-genome sequencing was performed to identify resistance determinants. An emergency investigational new drug application was authorized by the United States Food and Drug Administration for the compassionate use of cefepime-zidebactam based on susceptibility test results. Results Index isolates of P. aeruginosa (IMP positive) and K. pneumoniae (NDM-5, OXA-232 positive) tested susceptible to cefiderocol by disk diffusion in the clinical microbiology laboratory. The patient was treated with a regimen of cefiderocol and eravacycline, with persistent fever and development of hepatic microabscesses on imaging. Compassionate use cefepime-zidebactam therapy was initiated the day prior to liver transplantation and continued for a total of 14 days due to positive ascitic fluid cultures obtained during the operation. The K. pneumoniae and P. aeruginosa were cefiderocol resistant by broth microdilution. Cefepime-zidebactam remained active with MICs of 8/8 mg/L and 32/32 mg/L, respectively. The patient did well post-transplant and resumed chemotherapy. Conclusion Antimicrobial therapy with cefepime-zidebactam along with source control allowed successful liver transplantation in a patient with cefiderocol-resistant K. pneumoniae and P. aeruginosa. Cefepime-zidebactam may be a therapeutic option for extensively drug-resistant Gram-negative organisms.","journal":"JAC-Antimicrobial Resistance","year":2025,"id":513947,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9513,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":873813,"name":"Masayuki Nigo","orcid":"0000-0003-4898-1808","position":1,"is_corresponding":false},{"id":487178,"name":"Donghoon Kang","orcid":"0000-0001-5314-0961","position":2,"is_corresponding":false},{"id":356928,"name":"Rodrigo P. Baptista","orcid":"0000-0002-1806-8260","position":3,"is_corresponding":false},{"id":287739,"name":"Pranita D. Tamma","orcid":"0000-0002-4143-6324","position":4,"is_corresponding":false},{"id":680802,"name":"Emily Jacobs","orcid":null,"position":5,"is_corresponding":false},{"id":573746,"name":"Yehudit Bergman","orcid":"0000-0002-4262-7173","position":6,"is_corresponding":false},{"id":655149,"name":"David W. Victor","orcid":"0000-0003-1414-3128","position":7,"is_corresponding":false},{"id":13365,"name":"Ashton A. Connor","orcid":"0000-0002-7596-3771","position":8,"is_corresponding":false},{"id":1049590,"name":"Ashish Saharia","orcid":"0000-0001-5366-8432","position":9,"is_corresponding":false},{"id":509931,"name":"R. Mark Ghobrial","orcid":"0000-0001-6077-9595","position":10,"is_corresponding":false},{"id":232742,"name":"César A. Arias","orcid":"0000-0001-9054-9774","position":11,"is_corresponding":false},{"id":582538,"name":"William R. 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