[Aminoglycoside-induced nephrotoxicity]

In severe gram-negative infections aminoglycosides generally remain the first-line antibiotic. Their use is limited by the high risk of side effects and, especially, nephrotoxicity. High peak levels are crucial for antibacterial activity, whereas toxic side effects are determined by the more prolonged trough levels. Thus, aminoglycosides should not be given by intramuscular injection because the peak levels achieved are inadequate, whilst long-lasting elevated plasma trough levels result. On administration of a daily single dose intravenously high antibacterial efficacy can be combined with low nephrotoxicity. Besides the dose-dependent bactericidal effect, the post-antibiotic effect of aminoglycosides is of importance. The main site of nephrotoxicity are the proximal tubule epithelial cells. Renal toxicity is usually reversible after discontinuation of drug therapy. Toxic acute renal failure is not uncommon (5-35%) and usually dependent on the underlying disease, preexisting renal function, hydration state, age, cumulative dose, additional medication, previous therapy with aminoglycosides and the choice of the specific aminoglycoside. By implementing a single daily dose regimen in conjunction with adequate hydration, alkalization therapy with bicarbonate, monitoring of plasma trough levels and minimization of the duration of therapy (5 days), development of renal impairment can be prevented in the large majority of patients. Hence, acute renal failure has become an avoidable, and much less frequently observed complication of aminoglycoside therapy due to these measures.