ArticleBritish journal of pharmacology2024
Flucloxacillin worsens while imipenem-cilastatin protects against vancomycin-induced kidney injury in a translational rat model.
Article in British journal of pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 9 citations in OpenAlex.
- Protamine protects against vancomycin-induced kidney injury.Antimicrobial agents and chemotherapy · 2025Article
- Elucidating the function of clusterin in the progression of diabetic kidney disease.Frontiers in pharmacology · 2025Review
- Impact of humanized vancomycin infusion on kidney function and kidney injury in a translational rat model.International journal of antimicrobial agents · 2024Article
- Nut Cracked? Does the ACORN Trial End the Debate Surrounding Vancomycin and Piperacillin-Tazobactam Combination Therapy and Increased Risk for Acute Kidney Injury?Open forum infectious diseases · 2024Article
- Adjunctive β-lactams forTherapeutic advances in infectious diseaseReview
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
background and purposeVancomycin 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
resultsUrinary 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.
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