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Vancomycin Ototoxicity

Timothy C. Hain, MD Page last modified: September 21, 2014

Vancomycin is a useful antibotic which is sometimes combined with other agents to treat resistant infections. For example, Vancomcin is often used to treat MRSA, as well as enterococcal endocarditis (Herzstein et al., 1984).

Vancomycin, by itself, appears to have only minor ototoxicity, but it potentiates the ototoxicity of gentamicin as well as (probably) other aminoglycosides such as Tobramycin (Brummett et al, 1990). The majority of vancomycin ototoxicity appears to be cochlear (i.e. to hearing). This is dose dependent (Forouzesh et al, 2009), and rarely significant (Mellor et al. 1985). Infants have been overdosed without ill effects (Miner and Faix 2004), and neonates in utero do not appear to be sensitive (Reyes et al. 1989)

Occasional persons appear to have substantial vestibular toxicity from Vancomycin. The reason why occasional persons are more sensitive is not clear but might resemble the situation with gentamicin where there is a susceptibility mutation.

Vancomycin is also nephrotoxic, although again, this toxicity appears to be minor (Elting and Rubenstein, 1998).

Vancomycin "killing" activity, unlike the aminoglycsides, is poorly correlated with serum dose. Instead, it appears that the area under the curve (AUC) divided by the MIC is the best predictor of activity. (Rybak, 2006)

Reports of toxicity

Historically, toxicity of vancomycin was related to impurities in the manufactoring process. However, there is also good evidence that there is occasional kidney (nephrotoxicity) and ototoxicity. Vancomycin is often combined with aminoglycosides, such as gentamicin, and in this situation may greatly increase the nephrotoxicity of aminoglycosides (by 3-4 fold) (Rybak et al, 2006). It is very rare to encounter ototoxicity from vancomycin, given without another ototoxic drug (such as gentamicin).

There were only 28 reports of vancomycin ototoxicity published between 1958 and 1988 (Baile and Neal, 1988). Vancomycin is not especially toxic in peritoneal dialysis situations (Gendeh and Gibb, 1998).

Oral vancomycin has not been reported to cause ototoxicity (Kavanagh and McCabe, 1983)

Intrathecal vancomycin has been associated with toxicity (Klibanov, et al. 2003).

Levels

Peaks and troughs are generally set at 30 to 40 and 5 to 10 mg/L, respectively. However, some authors suggest that there is no clinical value to this monitoring (Cantu et al, 1994). Toxicity is thought to be more common in person with levels above 30 mg/L.( Hermans and Wilhelm, 1987). However, according to Rybak (2006), most clinicians have abandoned the routine practice of determining peak serum concentrations. This is reasonable given that vancomycin has such a long half-life.

Vancomycin has a very complex pharmacokinetics. It is mainly eliminated by the kidneys (Cheung and DiPiro, 1986), but it it has a complicated distribution, with an apparent volume of distribution greater than blood volume. The volume of distribution is much more variable than for aminoglycosides. The profile is characterized as either a 2 or 3 compartment model (Rybak, 2006). The drug is given intravenously with a standard infusion time of at least 1 hour. In persons with normal kidney function, vancomycin's elimination half-life is 6-12 hours, and the volume of distribution is between 0.4-1 L/Kg (Rybak, 2006). The long elimination half-life of vancomycin makes it very different from the aminoglycosides, such as gentamicin, that generally have a half-life of around 2 hours. In renal failure, the half-life is even longer.

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Gentamicin ototoxicity
Copyright August 3, 2016 , Timothy C. Hain, M.D. All rights reserved. Last saved on August 3, 2016