In:
British Journal of Pharmacology, Wiley
Abstract:
Vancomycin is one of the most common antibiotics administered in the hospital setting, 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. Vancomycin was administered intravenously and flucloxacillin or imipenem‐cilastatin were administered intraperitoneally. 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; whereas in the vancomycin group it was elevated after the first dose only. In the vancomycin+flucloxacillin group, urinary KIM‐1/24h increased on all days compared to vancomycin. In the vancomycin+imipenem‐cilastatin group, urinary KIM‐1/24h was decreased on days 1 and 2 compared to vancomycin. Similar trends were observed for clusterin. More vancomycin accumulated in the kidney with vancomycin+flucloxacillin compared to vancomycin and vancomycin+imipenem‐cilastatin. The accumulation of vancomycin in the kidney tissue correlated with increasing urinary KIM‐1 (4‐parameter Hill Slope, R 2 =0.7985). Conclusion and Implications Vancomycin+flucloxacillin caused more kidney injury compared to vancomycin alone and vancomycin+imipenem‐cilastatin in a translational rat model as determined by multiple kidney injury biomarkers. The combination of vancomycin+imipenem‐cilastatin was nephroprotective.
Type of Medium:
Online Resource
ISSN:
0007-1188
,
1476-5381
Language:
English
Publisher:
Wiley
Publication Date:
2023
detail.hit.zdb_id:
2029728-2
SSG:
15,3
