Question

1. The dose of aminoglycoside should be decreased in patients with poor renal function. Since this patient’s creatinine clearance is unknown, what initial dose should he be started on?
2. How is a maintenance dose determined?
3. What are the clinical symptoms of ototoxicity with aminoglycosides?
4. How should aminoglycosides be monitored to avoid ototoxicity?

Answer 1

1)Aminoglycosides are the mainstay in the treatment of serious gram negative infections including catheter-associated infections. They are not metabolized and are rapidly excreted as such by glomerular filtration. Aminoglycosides are usually excreted within two hours of intake in patients with normal renal function. However it will take around 30 hours to eliminate in renal failure patients. Because of the nephrotoxicity of this medicine, the physician may advise to take a 5-10mg/l for those who have renal failure.

2)The traditional approach to parenteral aminoglycoside dosing in adults involves the administration of a weight-based dose divided two to three times daily in patients with normal renal function. The dose is reduced and/or dosing interval extended in patients with decreased renal function or as indicated by measured serum drug concentration.For aminoglycoside the ideal dosing regimen would maximize concentration, because the higher the concentration, the more extensive and the faster is the degree of bacteriocide. Therefore, the Peak/MIC ratio is an important predictor of efficacy. It has been shown that aminoglycosides eradicate bacteria best when they achieve a Peak/MIC ratio of at least 8-10. Therefore it is important to give a large enough dose to produce a peak level 8 to 10 times greater than the MIC.

3)It has long been known that the major irreversible toxicity of aminoglycosides is ototoxicity.Cochlear damage can produce permanent hearing loss, and damage to the vestibular apparatus results in dizziness, ataxia, and/or nystagmus. Aminoglycosides appear to generate free radicals within the inner ear, with subsequent permanent damage to sensory cells and neurons, resulting in permanent hearing loss.

4)Your audiologist may be able to detect early signs of ototoxicity. Depending on the type and dose of the medication it may be necessary to test your hearing weekly in order to detect ototoxicity. Testing of the balance system (vestibular testing) may also be used to assess possible effects on balance. Monitoring of serum drug levels and renal function as well as hearing evaluations before, during, and after therapy. Measure baseline audiometric function before therapy. These are the best measure to monitor the aminoglycosides ototoxicity.