{"doi":"10.1111/bph.16234","title":"Flucloxacillin worsens while imipenem–cilastatin protects against vancomycin‐induced kidney injury in a translational rat model","abstract":"BACKGROUND AND PURPOSE: Vancomycin is one of the most common clinical antibiotics, yet acute kidney injury is a major limiting factor. Common combinations of antibiotics with vancomycin have been reported to worsen and improve vancomycin-induced kidney injury. We aimed to study the impact of flucloxacillin and imipenem-cilastatin on kidney injury when combined with vancomycin in our translational rat model. EXPERIMENTAL APPROACH: Male Sprague-Dawley rats received allometrically scaled (1) vancomycin, (2) flucloxacillin, (3) vancomycin + flucloxacillin, (4) vancomycin + imipenem-cilastatin or (5) saline for 4 days. Kidney injury was evaluated via drug accumulation and urinary biomarkers including urinary output, kidney injury molecule-1 (KIM-1), clusterin and osteopontin. Relationships between vancomycin accumulation in the kidney and urinary kidney injury biomarkers were explored. KEY RESULTS: Urinary output increased every study day for vancomycin + flucloxacillin, but after the first dose only in the vancomycin group. In the vancomycin + flucloxacillin group, urinary KIM-1 increased on all days compared with vancomycin. In the vancomycin + imipenem-cilastatin group, urinary KIM-1 was decreased on Days 1 and 2 compared with vancomycin. Similar trends were observed for clusterin. More vancomycin accumulated in the kidney with vancomycin + flucloxacillin compared with vancomycin and vancomycin + imipenem-cilastatin. The accumulation of vancomycin in the kidney tissue correlated with increasing urinary KIM-1. CONCLUSIONS AND IMPLICATIONS: Vancomycin + flucloxacillin caused more kidney injury compared with vancomycin alone and vancomycin + imipenem-cilastatin in a translational rat model. The combination of vancomycin + imipenem-cilastatin was nephroprotective.","journal":"British Journal of Pharmacology","year":2023,"id":359753,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":832480,"name":"Sylwia Marianski","orcid":null,"position":1,"is_corresponding":false},{"id":832479,"name":"Kimberly Valdez","orcid":null,"position":2,"is_corresponding":false},{"id":1111245,"name":"Renz Paulo Melicor","orcid":null,"position":3,"is_corresponding":false},{"id":339321,"name":"Jiajun Liu","orcid":"0000-0002-4330-2098","position":4,"is_corresponding":false},{"id":965827,"name":"Roxane Rohani","orcid":"0000-0003-2343-8198","position":5,"is_corresponding":false},{"id":536554,"name":"Jack Chang","orcid":"0000-0002-5645-0014","position":6,"is_corresponding":false},{"id":64821,"name":"Steven Y. C. Tong","orcid":"0000-0002-1368-8356","position":7,"is_corresponding":false},{"id":236389,"name":"Joshua S. Davis","orcid":"0000-0001-9864-5699","position":8,"is_corresponding":false},{"id":339323,"name":"Marc H. Scheetz","orcid":"0000-0002-1091-6130","position":9,"is_corresponding":false},{"id":565595,"name":"Gwendolyn Pais","orcid":null,"position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T01:13:57.361401Z","pmid":"37696768","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":[]}