{"doi":"10.1128/aac.01766-25","title":"Critical threshold target attainment rates for tazobactam combined with piperacillin among patients admitted to the ICU with hospital-acquired pneumonia","abstract":"Optimizing antibiotic exposures in hospital-acquired pneumonia (HAP) is crucial; however, dosing decisions often overlook target levels for the beta-lactamase inhibitor tazobactam (TAZ), and the impact of renal dysfunction and renal replacement therapy on TAZ pharmacokinetics (PK) remains poorly described. We developed a population PK model of TAZ using 162 plasma samples from 35 ICU patients with HAP, including those receiving continuous renal replacement therapy (CRRT). TAZ concentrations were quantified using validated LC-MS/MS methods. A one-compartment model was fit using Monolix, with clearance modeled as a function of creatinine clearance, CRRT effluent flow rate, and intermittent hemodialysis. Monte Carlo simulations assessed the probability of unbound TAZ concentrations exceeding 1, 2, or 4 mg/L for 100% of the interval between 24 and 48 h across intermittent, extended, and continuous infusion (CI) regimens, stratified by renal function and CRRT. TAZ clearance was driven by renal function and CRRT flow rate. All regimens achieved ≥90% probability of target attainment (PTA) at thresholds of 1-2 mg/L. At 4 mg/L, PTA fell below 90% in patients with creatinine clearance ≥150 mL/min for all regimens, with low-dose CI performing the worst. High-dose CI improved PTA at this higher threshold but may increase the risk of piperacillin overexposure. TAZ exposures sufficient for enzymatic beta-lactamase inhibition are generally achieved with standard dosing for lower thresholds but not for more aggressive targets (e.g., high extended-spectrum β-lactamase expression), particularly in patients with preserved or augmented renal function, who may require therapeutic drug monitoring or alternative therapy.","journal":"Antimicrobial Agents and Chemotherapy","year":2025,"id":554571,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9494,"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":1451891,"name":"Marta Zurawska","orcid":"0000-0001-5990-5451","position":1,"is_corresponding":false},{"id":1145173,"name":"Adrian Valadez","orcid":"0009-0003-4192-5229","position":2,"is_corresponding":false},{"id":1434810,"name":"Emma Harlan","orcid":null,"position":3,"is_corresponding":false},{"id":339323,"name":"Marc H. Scheetz","orcid":"0000-0002-1091-6130","position":4,"is_corresponding":false},{"id":364681,"name":"Michael Neely","orcid":"0000-0002-1675-8276","position":5,"is_corresponding":false},{"id":490062,"name":"Paul R. Yarnold","orcid":"0000-0002-1648-739X","position":6,"is_corresponding":false},{"id":553695,"name":"Mengjia Kang","orcid":"0000-0002-1679-9473","position":7,"is_corresponding":false},{"id":470112,"name":"Helen K. Donnelly","orcid":"0000-0001-8827-8581","position":8,"is_corresponding":false},{"id":1452402,"name":"Franciso Martinez","orcid":null,"position":9,"is_corresponding":false},{"id":965833,"name":"Erin Korth","orcid":"0000-0003-3853-3219","position":10,"is_corresponding":false},{"id":1119971,"name":"Rachel L. Medernach","orcid":"0000-0001-8015-3581","position":11,"is_corresponding":false},{"id":809216,"name":"Sophia Nozick","orcid":"0000-0002-0791-6340","position":12,"is_corresponding":false},{"id":274090,"name":"Alan R. Hauser","orcid":"0000-0003-4596-7939","position":13,"is_corresponding":false},{"id":283133,"name":"Egon A. Ozer","orcid":"0000-0002-7131-3691","position":14,"is_corresponding":false},{"id":965828,"name":"Estefani Diaz","orcid":"0000-0003-4146-0276","position":15,"is_corresponding":false},{"id":1699,"name":"Alexander V. Misharin","orcid":"0000-0003-2879-3789","position":16,"is_corresponding":false},{"id":266702,"name":"Richard G. Wunderink","orcid":"0000-0002-8527-4195","position":17,"is_corresponding":false},{"id":339322,"name":"Nathaniel J. Rhodes","orcid":"0000-0002-0018-5434","position":18,"is_corresponding":false},{"id":898403,"name":"Ryan H. 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