- Title
- Flucloxacillin worsens while imipenem–cilastatin protects against vancomycin-induced kidney injury in a translational rat model
- Creator
- Pais, Gwendolyn M.; Marianski, Sylwia; Valdez, Kimberly; Melicor, Renz Paulo; Liu, Jiajun; Rohani, Roxane; Chang, Jack; Tong, Steven Y. C.; Davis, Joshua S.; Scheetz, Marc H.
- Relation
- British Journal of Pharmacology Vol. 181, Issue 5, p. 670-680
- Publisher Link
- http://dx.doi.org/10.1111/bph.16234
- Publisher
- John Wiley & Sons
- Resource Type
- journal article
- Date
- 2024
- Description
- 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.
- Subject
- acute kidney injury; biomarkers; drug-induced kidney injury; flucloxacillin; imipenem-cilastatin; nephrotoxicity
- Identifier
- http://hdl.handle.net/1959.13/1498971
- Identifier
- uon:54577
- Identifier
- ISSN:0007-1188
- Language
- eng
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