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[Nephrotoxicity and drug interaction of vancomycin (2)]
1Department of Pharmacy, Yamagata University Hospital, Japan.
Summary
Vancomycin (VCM) can cause kidney damage. Combining VCM with imipenem-cilastatin, flomoxef, or fosfomycin in rabbits reduced VCM
Area of Science:
- Pharmacology
- Nephrology
- Infectious Diseases
Background:
- Vancomycin hydrochloride (VCM) is crucial for treating Gram-positive bacterial infections, including Methicillin-resistant Staphylococcus aureus (MRSA).
- Clinical scenarios often involve mixed infections with Gram-negative bacteria, necessitating combination antibiotic therapy.
- VCM's nephrotoxicity is a significant concern, especially when co-administered with other drugs, potentially exacerbating kidney damage.
Purpose of the Study:
- To investigate the nephrotoxic effects of Vancomycin (VCM) when administered alone versus in combination with other antibiotics.
- To evaluate the impact of VCM combination therapy on VCM pharmacokinetics and renal drug concentrations.
- To identify antibiotic combinations that may mitigate VCM-induced nephrotoxicity.
Main Methods:
- A rabbit model was used to assess nephrotoxicity and pharmacokinetics.
- Rabbits received a single intravenous injection of VCM (300 mg/kg) alone or in combination with imipenem-cilastatin sodium (IPM-CS), flomoxef sodium (FMOX), fosfomycin sodium (FOM), ceftazidime, cefpimizole sodium (CPIZ), or cefoperazone sodium.
- Nephrotoxicity was evaluated by monitoring serum creatinine, BUN levels, and kidney morphology. VCM clearance and renal concentrations were also measured.
Main Results:
- Single VCM injection induced nephrotoxicity, evidenced by elevated serum creatinine, BUN, and kidney morphological changes.
- Combinations of VCM with IPM-CS, FMOX, or FOM did not result in nephrotoxicity and increased VCM clearance.
- Conversely, VCM combined with ceftazidime, CPIZ, or cefoperazone showed no protective effect against nephrotoxicity.
Conclusions:
- Certain antibiotic combinations, specifically IPM-CS, FMOX, and FOM, may reduce VCM nephrotoxicity.
- This protective effect appears to be mediated by decreased renal VCM concentrations, possibly due to inhibited uptake into kidney tissues.
- These findings suggest that careful selection of combination antibiotics can help manage VCM-induced nephrotoxicity in mixed infections.