{"doi":"10.1093/jac/dkac416","title":"Relationship between piperacillin concentrations, clinical factors and piperacillin/tazobactam-associated acute kidney injury","abstract":"BACKGROUND: Piperacillin/tazobactam, a commonly used antibiotic, is associated with acute kidney injury (AKI). The relationship between piperacillin concentrations and AKI remains unknown. OBJECTIVE: Estimate piperacillin exposures in critically ill children and young adults administered piperacillin/tazobactam to identify concentrations and clinical factors associated with piperacillin-associated AKI. PATIENTS AND METHODS: We assessed piperacillin pharmacokinetics in 107 patients admitted to the paediatric ICU who received at least one dose of piperacillin/tazobactam. Piperacillin AUC, highest peak (Cmax) and highest trough (Cmin) in the first 24 hours of therapy were estimated. Piperacillin-associated AKI was defined as Kidney Disease: Improving Global Outcomes (KDIGO) Stage 2/3 AKI present >24 hours after initial piperacillin/tazobactam dose. Likelihood of piperacillin-associated AKI was rated using the Naranjo Adverse Drug Reaction Probability Scale. Multivariable logistic regression was performed to identify patient and clinical predictors of piperacillin-associated AKI. RESULTS: Out of 107 patients, 16 (15%) were rated as possibly or probably having piperacillin-associated AKI. Estimated AUC and highest Cmin in the first 24 hours were higher in patients with piperacillin-associated AKI (2042 versus 1445 mg*h/L, P = 0.03; 50.1 versus 10.7 mg/L, P < 0.001). Logistic regression showed predictors of piperacillin-associated AKI included higher Cmin (OR: 5.4, 95% CI: 1.7-23) and age (OR: 1.13, 95% CI: 1.05-1.25). CONCLUSIONS: We show a relationship between estimated piperacillin AUC and highest Cmin in the first 24 hours of piperacillin/tazobactam therapy and piperacillin-associated AKI, suggesting total piperacillin exposure early in the course is associated with AKI development. These data could serve as the foundation for implementation of model-informed precision dosing to reduce AKI incidence in patients given piperacillin/tazobactam.","journal":"Journal of Antimicrobial Chemotherapy","year":2022,"id":255979,"datarank":0.7876272550678434,"base_score":3.044522437723423,"endowment":3.044522437723423,"self_citation_contribution":0.4566783656585135,"citation_network_contribution":0.3309488894093299,"self_endowment_contribution":0.4566783656585135,"citer_contribution":0.3309488894093299,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":16,"citers_with_citation_signal":12,"citers_with_endowment":12,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9569,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":895208,"name":"Denise Hasson","orcid":"0000-0001-6172-4756","position":1,"is_corresponding":false},{"id":904793,"name":"J. Timothy Caldwell","orcid":"0000-0003-0807-4664","position":2,"is_corresponding":false},{"id":904794,"name":"Cara Slagle","orcid":"0000-0003-4880-9792","position":3,"is_corresponding":false},{"id":904795,"name":"Shun Dong","orcid":"0009-0001-0099-4485","position":4,"is_corresponding":false},{"id":328242,"name":"Lin Fei","orcid":"0000-0002-8187-6295","position":5,"is_corresponding":false},{"id":708179,"name":"Peter Tang","orcid":null,"position":6,"is_corresponding":false},{"id":295601,"name":"Alexander A. Vinks","orcid":"0000-0003-4224-2967","position":7,"is_corresponding":false},{"id":707533,"name":"Jennifer Kaplan","orcid":"0000-0001-7020-2394","position":8,"is_corresponding":false},{"id":108942,"name":"Stuart L. Goldstein","orcid":"0000-0003-3711-8785","position":9,"is_corresponding":false},{"id":707531,"name":"Sonya Tang Girdwood","orcid":"0000-0001-7737-8499","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:25:21.336200Z","pmid":"36545869","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":[]}