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Gentamicin nephrotoxicity: failure of three cephalosporins to potentiate injury in rats
Abstract:
The possibility that gentamicin and cephalosporin antibiotics may act synergistically to produce nephrotoxicity was evaluated in an experimental model. Necrosis of the proximal tubules occurred when rats were treated with 60 to 120 mg/kg of gentamicin for 5 days but not when 15 to 20 mg/kg per day was given for up to 4 weeks. In all gentamicin-treated animals lysosomes of proximal tubules were increased in size and number and the lumens of many tubules contained a granular deposit. Examination by electron microscopy revealed that the abnormal lysosomes contained membranous whorls. The luminal deposits consisted of similar material; identical bodies were also present in the urinary sediment. To determine whether concurrent administration of a cephalosporin would augment the nephrotoxic potential of gentamicin, additional rats were treated for 4 weeks with daily injections of gentamicin (20 mg/kg) and either cephaloridine, cephalothin, or cefazolin (500 mg/kg). None of the combination regimens produced any more injury than did gentamicin alone.
Insights
Gentamicin and cephalosporin antibiotics were studied for combined kidney toxicity. Results showed that combining these antibiotics did not increase nephrotoxicity compared to gentamicin alone in rats.
Area of Science:
- Pharmacology
- Toxicology
- Nephrology
Background:
- Gentamicin is an aminoglycoside antibiotic with known nephrotoxic potential.
- Cephalosporins are a class of beta-lactam antibiotics.
- The potential for synergistic nephrotoxicity between gentamicin and cephalosporins requires investigation.
Purpose of the Study:
- To evaluate the synergistic nephrotoxic potential of combining gentamicin with cephalosporin antibiotics in an experimental model.
- To determine if concurrent administration of cephalosporins augments gentamicin-induced kidney injury.
Main Methods:
- Rats were treated with varying doses of gentamicin to establish dose-dependent nephrotoxicity.
- Electron microscopy was used to examine cellular changes in proximal tubules.
- Rats received daily injections of gentamicin concurrently with cephaloridine, cephalothin, or cefazolin for 4 weeks.
Main Results:
- Gentamicin treatment at high doses (60-120 mg/kg) for 5 days caused proximal tubule necrosis.
- Lower gentamicin doses (15-20 mg/kg) for 4 weeks induced lysosomal changes and luminal deposits but not necrosis.
- Concurrent administration of cephaloridine, cephalothin, or cefazolin with gentamicin did not result in increased kidney injury compared to gentamicin alone.
Conclusions:
- Gentamicin alone can cause dose-dependent nephrotoxicity, characterized by lysosomal abnormalities and luminal deposits.
- Concurrent administration of commonly used cephalosporins does not appear to potentiate gentamicin-induced nephrotoxicity in this rat model.
- These findings suggest that the combination of gentamicin with these cephalosporins may be safe regarding nephrotoxicity at the tested dosages.