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Flucloxacillin worsens while imipenem-cilastatin protects against vancomycin-induced kidney injury in a translational rat model.
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.
Afiliación
  • Pais GM; Department of Pharmacy Practice, Midwestern University-Downers Grove Campus, Downers Grove, Illinois, USA.
  • Marianski S; Pharmacometrics Center of Excellence, Midwestern University-Downers Grove Campus, Downers Grove, Illinois, USA.
  • Valdez K; Department of Pharmacy Practice, Midwestern University-Downers Grove Campus, Downers Grove, Illinois, USA.
  • Melicor RP; Department of Pharmacy Practice, Midwestern University-Downers Grove Campus, Downers Grove, Illinois, USA.
  • Liu J; Department of Pharmacy Practice, Midwestern University-Downers Grove Campus, Downers Grove, Illinois, USA.
  • Rohani R; Midwestern University College of Pharmacy, Downers Grove, Illinois, USA.
  • Chang J; Department of Pharmacy Practice, Midwestern University-Downers Grove Campus, Downers Grove, Illinois, USA.
  • Tong SYC; Pharmacometrics Center of Excellence, Midwestern University-Downers Grove Campus, Downers Grove, Illinois, USA.
  • Davis JS; Department of Pharmacy Practice, Midwestern University-Downers Grove Campus, Downers Grove, Illinois, USA.
  • Scheetz MH; Pharmacometrics Center of Excellence, Midwestern University-Downers Grove Campus, Downers Grove, Illinois, USA.
Br J Pharmacol ; 181(5): 670-680, 2024 03.
Article en En | MEDLINE | ID: mdl-37696768
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vancomicina / Floxacilina Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Br J Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vancomicina / Floxacilina Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Br J Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido