Aminoglycoside use in cystic fibrosis: therapeutic strategies and toxicity

Abstract

This review summarizes the recent literature regarding the uses for and toxicity of aminoglycosides in cystic fibrosis (CF). Aminoglycosides are indicated in the management of acute exacerbations of CF, to control chronic infection, and to eradicate Pseudomonas aeruginosa after recent acquisition. Intravenous gentamicin is associated with increased risk of acute kidney injury, whereas intravenous tobramycin is less so. Studies regarding chronic kidney disease related to cumulative aminoglycoside exposure are currently conflicting, but a prevalence of up to 42% has been reported. A single daily dose of intravenous tobramycin is as effective as a thrice-daily regimen and is less nephrotoxic. A large paediatric series has recently reported a prevalence of hearing impairment of 4.5%, and a small adult cohort has found a 30% rate of vestibulotoxicity. Neither appears to be related to cumulative exposure. In recent years, the well known toxicities of aminoglycosides have been investigated in CF populations. It appears that intravenous tobramycin is well tolerated in the kidneys compared with gentamicin, and that cumulative exposure may result in chronic kidney disease. Hearing loss and vestibulotoxicity are also prevalent. These important epidemiological studies lay the groundwork to design interventional studies to reduce toxicity.