{"doi":"10.1093/jac/dkaa549","title":"Pragmatic options for dose optimization of ceftazidime/avibactam with aztreonam in complex patients","abstract":"BACKGROUND: Avibactam is a β-lactamase inhibitor that is combined with aztreonam against Enterobacterales co-expressing serine- and metallo-β-lactamases (MBL). Optimal dosing of aztreonam with avibactam is not well-defined in critically ill patients and contingent on ceftazidime/avibactam product labelling. OBJECTIVES: To identify a pragmatic dosing strategy for aztreonam with avibactam to maximize the probability of target attainment (PTA). METHODS: We conducted a prospective observational pharmacokinetic study. Five blood samples were collected around the fourth dose of aztreonam or ceftazidime/avibactam and assayed for all three drugs. Population pharmacokinetic (PK) analysis coupled with Monte Carlo simulations were used to create a dosing nomogram for aztreonam and ceftazidime/avibactam based on drug-specific pharmacodynamic (PD) targets. RESULTS: A total of 41 participants (59% male) median age of 75 years (IQR 63-79 years) were enrolled. They were critically ill (46%) with multiple comorbidities and complications including burns (20%). Population PK analysis identified higher volume of distribution and lower clearance (CL) compared with typical value expectations for aztreonam and ceftazidime/avibactam. Estimated glomerular filtration (eGFR) rate using the CKD-EPI equation predicted CL for all three drugs. The need for high doses of aztreonam and ceftazidime/avibactam above those in the existing product labels are not predicted by this analysis with the exception of ceftazidime/avibactam for patients with eGFR of 6-15 mL/min, in whom suboptimal PTA of ≤71% is predicted. CONCLUSIONS: Pragmatic and lower daily-dose options are predicted for aztreonam and ceftazidime/avibactam when the eGFR is <90 mL/min. These options should be tested prospectively.","journal":"Journal of Antimicrobial Chemotherapy","year":2020,"id":95670,"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":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9555,"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":475138,"name":"Francesco Menichetti","orcid":"0000-0003-0824-7166","position":1,"is_corresponding":false},{"id":475139,"name":"Dario Cattaneo","orcid":"0000-0003-1512-6530","position":2,"is_corresponding":false},{"id":475140,"name":"Giusy Tiseo","orcid":"0000-0002-3884-4933","position":3,"is_corresponding":false},{"id":475141,"name":"Sara Baldelli","orcid":"0000-0003-2389-7191","position":4,"is_corresponding":false},{"id":476101,"name":"Valentina Galfo","orcid":null,"position":5,"is_corresponding":false},{"id":476102,"name":"Alessandro Leonildi","orcid":null,"position":6,"is_corresponding":false},{"id":121301,"name":"Enrico Tagliaferri","orcid":null,"position":7,"is_corresponding":false},{"id":475142,"name":"Antonello Di Paolo","orcid":"0000-0002-2661-6183","position":8,"is_corresponding":false},{"id":302166,"name":"Manjunath P. Pai","orcid":"0000-0001-7119-5034","position":9,"is_corresponding":false},{"id":475137,"name":"Marco Falcone","orcid":"0000-0003-3813-8796","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-18T22:33:57.534608Z","pmid":"33378458","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":[]}