Gentamicin and gram-negative bacteremia. A synergism for the development of experimental nephrotoxic acute renal failure.
To explore whether bacteremia potentiates gentamicin nephrotoxicity, we injected rats with either 1 X 10(9) Escherichia coli (E. coli), Pseudomonas aeruginosa, or Staphylococcus aureus, and then gave them gentamicin, 100 mg/kg. Renal injury was assessed over the next 24-48 h. Staphylococcus/gentamicin or gentamicin alone induced no renal injury. However, E. coli/gentamicin and Pseudomonas/gentamicin caused acute renal failure (severe azotemia; tubular necrosis; cast formation). This effect was not due to acute reductions in arterial blood pressure or renal blood flow, it could be reproduced by substituting nonviable for viable gram-negative organisms, and it was associated with increased renal gentamicin uptake. E. coli without gentamicin induced only mild azotemia and no tubular necrosis. Endotoxin-tolerant rats were significantly protected against the E. coli/gentamicin nephrotoxic interaction. We conclude that gram-negative bacteremia and gentamicin exert synergistic nephrotoxicities; and that this effect is mediated, at least in part, by endotoxin and in part by increased renal gentamicin uptake.
D058186:Acute Kidney Injury / Q000150:complications*; D000818:Animals; D001794:Blood Pressure; D004357:Drug Synergism; D004731:Endotoxins / Q000494:pharmacology; D004926:Escherichia coli; D005260:Female; D005839:Gentamicins / Q000633:toxicity*; D006090:Gram-Negative Bacteria; D007114:Immunization; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D008826:Microbial Sensitivity Tests; D009336:Necrosis; D011550:Pseudomonas aeruginosa; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow; D018805:Sepsis / Q000150:complications*; D013211:Staphylococcus aureus; D014511:Uremia / Q000150:complications
D004731:Endotoxins; D005839:Gentamicins