PHARMACOLOGICAL PRINCIPLES OF PYELONEPHRITIS TREATMENT - DISTRIBUTION, EFFICIENCY AND RENAL TOXICITY OF ANTIBIOTICS

Although antibiotics have been used for more than sixty years, no rati onal and standard approaches have been defined for the treatment of ur inary tract infections. Antibiotics given for the treatment of pyelone phritis 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 sh ow that the efficacy of an antibiotic for the treatment of pyelonephri tis is proportional to its capacity to concentrate in high concentrati on not only in the urine but also in the renal parenchyma as serum and urine levels of antibiotics are poor predictors of the intrarenal lev els. Our experimental studies have shown that antibiotics behaved diff erently within the kidney and that the intrarenal pharmacokinetic of a ntibiotic was a determinant factor of efficacy ill pyelonephritis. Ami noglycosides and quinolones which penetrate well renal tissue were sho wn effective agents for the treatment of pyelonephritis, We have also shown that multiple factors such as renal infection, septicemia, endot oxemia, age, and starvation could significantly modify the intrarenal pharmacokinetic and toxicity of antibiotics. Drug interactions between aminoglycosides and other antimicrobial agents have also been shown t o influence the renal accumulation and toxicity of aminoglycosides. In general, factors increasing the renal levels of aminoglycoside also i ncrease their toxicity while those decreasing their accumulation decre ase their toxicity. Several studies on the subcellular distribution of antibiotics have contributed to a better understanding of the mechani sms of toxicity and how they interact with other drugs. A better under standing of the factors modulating the pharmacodynamic and the toxicit y of antibiotics used in pyelonephritis should contribute to a more ra tional use of these drugs while limiting their toxicity.