Vancomycin Ototoxicity

Timothy C. Hain, MD Page last modified: October 31, 2010

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)

Reports of toxicity

There were only 28 reports of vancomycin ototoxicity published between 1958 and 1988 (Baile and Neal, 1988). Vancomycin is not especially toxic in CAPD (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)

Vancomycin has a somewhat complex pharmacokinetics. It is 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.

References:

• Bailie, G. R. and D. Neal (1988). "Vancomycin ototoxicity and nephrotoxicity. A review." Med Toxicol Adverse Drug Exp 3(5): 376-386.
• Brummett, R. E., K. E. Fox, et al. (1990). "Augmented gentamicin ototoxicity induced by vancomycin in guinea pigs." Arch Otolaryngol Head Neck Surg 116(1): 61-64.
• Buckingham, S. C., J. A. McCullers, et al. (2006). "Early vancomycin therapy and adverse outcomes in children with pneumococcal meningitis." Pediatrics 117(5): 1688-1694.
• Cantu, T. G., N. A. Yamanaka-Yuen, et al. (1994). "Serum vancomycin concentrations: reappraisal of their clinical value." Clin Infect Dis 18(4): 533-543.
• Cheung, R. P. and J. T. DiPiro (1986). "Vancomycin: an update." Pharmacotherapy 6(4): 153-169.
• Elting, L. S., E. B. Rubenstein, et al. (1998). "Mississippi mud in the 1990s: risks and outcomes of vancomycin- associated toxicity in general oncology practice." Cancer 83(12): 2597-2607.
• Forouzesh, A., P. A. Moise, et al. (2009). "Vancomycin ototoxicity: a reevaluation in an era of increasing doses." Antimicrob Agents Chemother 53(2): 483-486.
• Gendeh, B. S., A. G. Gibb, et al. (1998). "Vancomycin administration in continuous ambulatory peritoneal dialysis: the risk of ototoxicity." Otolaryngol Head Neck Surg 118(4): 551-558.
• Hermans, P. E. and M. P. Wilhelm (1987). "Vancomycin." Mayo Clin Proc 62(10): 901-905.
• Herzstein, J., J. L. Ryan, et al. (1984). "Optimal therapy for enterococcal endocarditis." Am J Med 76(2): 186-191.
• Kavanagh, K. T. and B. F. McCabe (1983). "Ototoxicity of oral neomycin and vancomycin." Laryngoscope 93(5): 649-653.
• Klibanov, O. M., J. E. Filicko, et al. (2003). "Sensorineural hearing loss associated with intrathecal vancomycin." Ann Pharmacother 37(1): 61-65.
• Mellor, J. A., J. Kingdom, et al. (1985). "Vancomycin toxicity: a prospective study." J Antimicrob Chemother 15(6): 773-780.
• Miner, L. J. and R. G. Faix (2004). "Large vancomycin overdose in two premature infants with minimal toxicity." Am J Perinatol 21(8): 433-438.
• Reyes, M. P., E. M. Ostrea, Jr., et al. (1989). "Vancomycin during pregnancy: does it cause hearing loss or nephrotoxicity in the infant?" Am J Obstet Gynecol 161(4): 977-981.
• Walczyk, M. H., D. Hill, et al. (1988). "Acute renal failure owing to inadvertent vancomycin overdose. Vancomycin removal by continuous arteriovenous hemofiltration." Ann Clin Lab Sci 18(6): 440-443.