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[Modification of vancomycin nephrotoxicity by other antibiotics in rats]
1Developmental Research Laboratories, Shionogi Co., & Ltd.
Abstract:
Vancomycin (VCM) was intravenously administered to rats for 14 days at doses of 150 mg/kg/day and 250 mg/kg/day alone or in combination with 1,000 mg/kg/day of latamoxef (LMOX), flomoxef (FMOX) or cefpirome (CPR) or 250 mg/kg/day of fosfomycin (FOM), and the influences of combined antibiotics on the VCM-induced renal damage were studied. The renal impairment caused by VCM alone was, morphologically, demonstrated mainly as regeneration of tubular epithelium: slight regeneration was observed in a half of rats administered 150 mg/kg/day and slight to extensive regeneration in all the rats administered 250 mg/kg/day. Clinical examinations found apparent increases in urinary LDH and MDH activities in rats administered 250 mg/kg/day, thus showing a good correlation with renal pathological changes. In addition, increase in kidney weight and increase in urinary NAG activity were noted, while changes in plasma urea-N and creatinine were mild, and gamma-GTP activity and protein in urine could not be used as a parameter of the renal impairment. The slight renal impairment as noted in rats administered VCM 150 mg/kg/day alone was not observed at all when LMOX or FMOX was administered concomitantly, and less pronounced even when FOM was administered concomitantly. When CPR was administered concomitantly, the changes were the same as those observed with VCM alone. The renal impairment in rats administered VCM 250 mg/kg/day was apparently less severe when combined with LMOX, FMOX and FOM than that in rats administered VCM alone, and this was supported by apparent reduction of clinical examination values as the parameter of VCM-induced nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Certain antibiotics, latamoxef (LMOX), flomoxef (FMOX), and fosfomycin (FOM), can mitigate vancomycin (VCM)-induced kidney damage in rats. These combinations show reduced nephrotoxicity compared to VCM alone.
Area of Science:
- Pharmacology
- Nephrology
- Toxicology
Background:
- Vancomycin (VCM) is a critical antibiotic, but its use can be limited by nephrotoxicity.
- Understanding potential protective agents against VCM-induced renal damage is crucial for optimizing patient treatment.
Purpose of the Study:
- To investigate the protective effects of co-administered antibiotics against vancomycin-induced nephrotoxicity in a rat model.
- To evaluate the impact of latamoxef (LMOX), flomoxef (FMOX), cefpirome (CPR), and fosfomycin (FOM) on VCM-induced renal impairment.
Main Methods:
- Rats received intravenous vancomycin (150 or 250 mg/kg/day) alone or combined with other antibiotics for 14 days.
- Renal damage was assessed through morphological examination of tubular epithelium and clinical markers like urinary LDH, MDH, NAG, kidney weight, plasma urea-N, and creatinine.
Main Results:
- Vancomycin alone caused dose-dependent renal tubular regeneration, with increased urinary LDH and MDH activities at higher doses.
- Co-administration of LMOX or FMOX completely prevented VCM-induced renal impairment at the lower VCM dose.
- FOM reduced, while CPR did not alter, VCM-induced nephrotoxicity.
- At the higher VCM dose, LMOX, FMOX, and FOM significantly attenuated renal damage, evidenced by reduced clinical markers.
Conclusions:
- Latamoxef, flomoxef, and fosfomycin demonstrate nephroprotective potential against vancomycin-induced renal damage in rats.
- These findings suggest that specific antibiotic combinations may reduce the risk of vancomycin nephrotoxicity, warranting further clinical investigation.