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Aminoglycosides exhibit a number of favorable pharmacokinetic and pharmacodynamic advantages, but a major doselimiting toxicity of the aminoglycosides remains the risk of drug-induced AKI.270 The risk of AKI attributable to aminoglycosides is sufficiently high (up to 25% in some series, depending upon the definition of AKI used and the population studied)271-276, 278 that they should no longer be used for standard empirical or directed treatment, unless no other suitable alternatives exist. The intrinsic risk of AKI with the administration of aminoglycosides has led some authors to recommend the elimination of aminoglycosides as a clinical treatment option.277 Certainly their use should be restricted to treat severe infections where aminoglycosides are the best, or only, therapeutic option.
Aminoglycosides should be used for as short a period of time as possible. Repeated administration of aminoglycosides over several days or weeks can result in accumulation of aminoglycosides within the renal interstitium and within the tubular epithelial cells.279 This can result in a higher incidence of nephrotoxicity with repeated exposure to aminoglycosides over time. Older patients ( > 65 years), patients with pre-existing renal dysfunction, and septic patients with intravascular volume depletion and rapid alterations in fluid dynamics may be at greater risk for aminoglycoside nephrotoxicity. Other risk factors for aminoglycoside-induced AKI are diabetes mellitus, concomitant use of other nephrotoxic drugs, prolonged use, excessive blood levels, or repeated exposure to separate courses of aminoglycoside therapy over a short time interval.267-279
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