Principes pharmacologiques du traitement de la pyélonéphrite : distribution, efficacité et toxicité rénale des antibiotiques

Abstract

L'efficacité d'un antibiotique dans la pyélonéphrite est proportionnelle à sa capacité de se retrouver à des concentrations suffisantes non seulement dans l'urine mais aussi dans le parenchyme rénal. La cinétique intrarénale varie d'un antibiotique à l'autre et la distribution intrarénale est un facteur déterminant du succès dans la pyélonéphrite. Les aminosides sont la classe d'antibiotiques qui, avec les quinolones, pénètrent le mieux le parenchyme rénal et sont les plus e fficaces dans le traitement de la pyélonéphrite. L'infection rénale, la septicémie, l'endotoxémie, l'âge et le jeûne peuvent modifier de façon significative la pharmacocinétique intrarénale et la toxicité des aminosides. En outre, de nombreuses interactions médicamenteuses influencent l'accumulation intrarénale et la toxicité de ces antibiotiques. Les études de distribution subcellulaire ont grandement contribué à mettre à jour les mécanismes de la toxicité rénale des aminosides et leur interaction avec d'autres antibiotiques. En général, les facteurs qui augmentent leur accumulation intrarénale augmentent leur toxicité alors que ceux qui interfèrent avec cette accumulation la limitent.

Although antibiotics have been used for more than sixty years, no rational and standard approaches have been defined for the treatment of urinary tract infections. Antibiotics given for the treatment of pyelonephritis must kill bacteria embedded within the renal parenchyma. Up to now, investigators have considered that antibiotics must concentrate in sufficient amount in the urine of infected patients to be effective in treating pyelonephritis. Results presented in the present paper show that the efficacy of an antibiotic for the treatment of pyelonephritis is proportional to its capacity to concentrate in high concentration not only in the urine but also in the renal parenchyma as serum and urine levels of antibiotics are poor predictors of the intrarenal levels. Our experimental studies have shown that antibiotics behaved differently within the kidney and that the intrarenal pharmacokinetic of antibiotic was a determinant factor of efficacy in pyelonephritis. Aminoglycosides and quinolones which penetrate well renal tissue were shown effective agents for the treatment of pyelonephritis. We have also shown that multiple factors such as renal infection, septicemia, endotoxemia age, and starvation could significantly modify the intrarenal pharmaco kinetic and toxicity of aminoglycosides. In general, factors increasing the renal levels of aminoglycoside also increase their toxicity while those decreasing their accumulation decrease their toxicity. Several studies on the subcellular distribution of antibiotics have contributed to a better understanding of the mechanisms of toxicity and how they interact with other drugs. A better understanding of the factors modulating the pharmacodynamic and the toxicity of antibiotics used in pyelonephritis should contribute to a more rational use of these drugs while limiting their toxicity. [References: 50]