Summary
Vancomycin has been in clinical use as a potent antistaphylococcal antibiotic for over 30 years. Most reports of ototoxicity and nephrotoxicity have been associated with early, relatively impure, formulations of vancomycin. This paper reviews the literature concerning vancomycin otoxocity and nephrotoxicity and the evidence for their correlation with the therapeutic serum concentration range.
There have been 28 reports of vancomycin-associated ototoxicity published in the medical literature since 1958. It remains unclear whether any diminution in hearing is permanent or reversible. Few patients in the literature had follow-up audiometry and the hearing impairment tends to be at higher frequencies. Several authors reported peak serum vancomycin concentrations, but the exact time these were drawn with respect to the last dose is mostly unclear. In other reports, the ‘peak’ concentrations noted 3 to 6 hours after the last dose are probably indicative of much higher concentrations because of vancomycin’s rapid phase of distribution.
More than half the 57 cases of reported nephrotoxicity due to vancomycin occurred within the first 6 years of the drug’s use. Many of these patients also had pre-existing renal dysfunction or were concomitantly receiving other nephrotoxic agents. It is unclear whether the coadministration of aminoglycosides produces a synergistic toxicity. The exact incidence of nephrotoxicity is uncertain, but is probably less with the current, relatively pure, product. The correlation of nephrotoxicity with certain serum vancomycin concentrations remains to be clarified.
Other aspects also require clarification, such as when to draw samples to determine peak serum concentrations and whether or not routine measurements are necessary at all.
In the absence of better guidelines, efforts should be made to tailor individual patient’s regimens to produce peak and trough serum vancomycin concentrations to within the widely accepted ranges of 30 to 40 and 5 to 10 mg/L, respectively. In addition, the concomitant use of other potentially nephrotoxic and ototoxic agents should be avoided.
Similar content being viewed by others
References
Ahmad R, Raichura N, Kilbane V, Whitfield E. Vancomycin: a reappraisal. Correspondence. British Medical Journal 284: 1953–1954, 1982
Aronoff GR, Sloan RS, Dinwiddle CB, et al. Effects of vancomycin on renal function in rats. Antimicrobial Agents and Chemotherapy 19: 306–308, 1981
Bailie GR, Ackerman BH, Fischer J, et al. Increased vancomycin dosage requirements in young burn patients. Journal of Burn Care and Rehabilitation 5: 376–378; 1984
Bailie GR, Yu R, Morton R, Waldek S. Vancomycin, red-neck syndrome and fits. Lancet 2: 279–280, 1985
Cafferkey MT, Hone R, Keane T. Severe staphylococcal infections treated with vancomycin. Journal of Antimicrobial Chemotherapy 9: 69–74; 1982
Cheung RPF, DiPiro JT. Vancomycin: an update. Pharmacotherapy 6: 153–169, 1986
Craven DE, Kollisch NR, Hsieh CR, Connolly Jr MG, McCabe WR. Vancomycin treatment of bacteraemia caused by oxacillin-resistant Staphylococcus aureus: comparisons with B-lactam antibiotic treatment of bacteraemia caused by oxacillin-sensitive Staphylococcus aureus. Journal of Infectious Diseases 147: 137–143, 1983
Cunha BA, Ristuccia AM. Clinical usefulness of vancomycin. Clinical Pharmacy 2: 417–424, 1983
Dangerfield HC, Hewitt WL, Monzon OT, et al. Clinical use of vancomycin. Antimicrobial Agents Annual: 428-438, 1960
D’Arcy PF, Griffon JP (Eds). Iatrogenic diseases, 2nd ed. pp. 393–400, Oxford University Press, Oxford, 1979
Dean RP, Wagner DJ, Tolpin MD. Vancomycin/aminoglycoside toxicity. Journal of Paediatrics 106: 861–862, 1985
Dutton AAC, Elmes PC. Vancomycin: report on treatment of patients with severe staphylococcal infections. British Medical Journal 1: 1144–1149, 1959
Edwards DJ, Pancorbo S. Routine monitoring of serum vancomycin concentrations: waiting for proof of its value. Clinical Pharmacy 6: 652–654, 1987
Eisenberg ES, Robbins N, Lenci M. Vancomycin and interstitial nephritis. Annals of Internal Medicine 95: 658, 1981
Farber BF, Moellering RC. Retrospective study of the toxicity of preparations of vancomycin from 1974–1981. Antimicrobial Agents and Chemotherapy 23: 138–141, 1983
Fekety R. Vancomycin. Medical Clinics of North America 66: 175–181, 1982
Friedlander IR. Ototoxic drugs and the detection of ototoxicity. New England Journal of Medicine 301: 213–214, 1979
Geraci JE, Heilman FR, Nichols DR, Wellman WE. Antibiotic therapy of bacterial endocarditis (VII): vancomycin for acute micrococcal endocarditis. Proceedings of the Staff Meetings of the Mayo Clinic 33: 172–181, 1958
Geraci JE. Vancomycin. Mayo Clinic Proceedings 52: 631–634, 1977
Healy DP, Polk RE, Garson ML, et al. Comparison of steady state pharmacokinetics of two dosing regimens of vancomycin in normal volunteers. Antimicrobial Agents and Chemotherapy 31: 393–397, 1987
Hekster YA, Vree TB, Weemaes CMR, Rotteveel JJ. Toxicologic and pharmacokinetic evaluation of a case of vancomycin intoxication during continuous ambulatory peritoneal dialysis. Pharmaceutisch Weekblad — Scientific Edition 8: 293–297, 1986
Hook EW, Johnson WD. Vancomycin therapy of bacterial endocarditis. American Journal of Medicine 65: 411–415, 1978
Kavanagh KT, McCabe BF. Ototoxicity of oral neomycin and vancomycin. Laryngoscope 93: 649–653, 1983
Keller H. Cited in Dukes (Ed.) Meyler’s Side effects of drugs, 10th ed., p. 512, Elsevier, Amsterdam, 1984
Kirby WMM, Divelbiss CL. Vancomycin: clinical and laboratory studies. Antibiotics Annual: 107-117, 1956-1957 Kirby WMM, Perry DM, Bauer AW. Treatment of staphylococcal septicaemia with vancomycin. New England Journal of Medicine 162: 49–55, 1960
Koo KB, Bachand RL, Chow AW. Vancomycin-induced neutropenia. Drug Intelligence and Clinical Pharmacy 20: 780–782, 1986
Lake KD, Peterson CD. A simplified dosing method for initiating vancomycin therapy. Pharmacotherapy 5: 340–344, 1985
Louria DB, Kaminski T, Buchman J. Vancomycin in severe staphylococcal infections. Archives of Internal Medicine 107: 125–140, 1961
Masur H, Francioli P, Ruddy M, Murray HW, Vancomycin serum levels and toxicity in chronic haemodialysis patients with Staphylococcus aureusbacteremia. Clinical Nephrology 20: 85–88, 1983
Matzke GR, McGory RW, Halstenson CE, Keane WF. Pharmacokinetics of vancomycin in patients with various degrees of renal function. Antimicrobal Agents and Chemotherapy 25: 433–437, 1984
Matzke GR, Zhanel GG, Guay DRP. Clinical pharmacokinetics of vancomycin. Clinical Pharmacokinetics 11: 257–282, 1986
Mayhew JF, Deutsch S. Cardiac arrest following administration of vancomycin. Canadian Anaesthetists Society Journal 32: 65–66, 1985
Mellor JA, Kingdom J, Cafferkey M, Keane CT. Vancomycin ototoxicity in patients with normal renal function. British Journal of Audiology 18: 179–180, 1984
Mellor JA, Kingdom J, Cafferkey M, Keane CT. Vancomycin toxicity: a prospective study. Journal of Antimicrobial Chemotherapy 15: 773–780, 1985
Moellering RC, Krogstad DJ, Greenblatt DJ. Pharmacokinetics of vancomycin in normal subjects and in patients with reduced renal function, Reviews of Infectious Disease 3 (Suppl.): 230–235, 1981a
Moellering RC, Krogstad DJ, Greenblatt DJ. Vancomycin therapy in patients with impaired renal function: a nomogram for dosage. Annals of Internal Medicine 94: 343–346, 1981b
Morris AJ, Bilinsky RT. Prevention of staphylococcal shunt infections by continuous vancomycin prophylaxis. American Journal of the Medical Sciences 262: 87–92, 1971
Odio C, McCracken GH, Nelson JD. Nephrotoxicity associated with vancomycin/aminoglycoside therapy in four children. Journal of Paediatrics 105: 491–493, 1984
Pau AK, Khakoo R. “Red-neck syndrome” with slow infusion of vancomycin. New England Journal of Medicine 313: 756–757, 1983
Reynolds JEF (Ed). Martindale, the extra pharmacopoeia, 28th ed., The Pharmaceutical Press, London, 1982
Rodvold KA, Zokufa H, Rotschafer JC. Routine monitoring of serum vancomycin concentrations: can waiting be justified? Clinical Pharmacy 6: 655–658, 1987
Rotschafer JC, Crossley K, Zaske DE, et al. Pharmacokinetics of vancomycin; observations in 28 patients and dosage recommendations. Antimicrobial Agents and Chemotherapy 22: 391–394, 1982
Sayers JFB, Shimasaki R. Routine monitoring of serum vancomycin concentrations: the answer lies in the middle. Clinical Pharmacy 7: 18, 1988
Schaad UB, Nelson JD, McCracken GH. Pharmacology and efficacy of vancomycin for staphylococcal infections in children. Review of Infectious Diseases 3: S282–S288, 1981
Sorrell TC, Packham DR, Shanker S, Folds M, Munro R. Vancomycin therapy for methicillin-resistant Staphylococcus aureus. Annals of Internal Medicine 97: 344–350, 1982
Southorn PA, Plevak DJ, Wright AJ, Wilson WR. Adverse effects of vancomycin administered in the perioperative period. Mayo Clinic Proceedings 61: 721–724, 1986
Spears RL, Koch R. The use of vancomycin in paediatrics. Antibiotics Annual: 798-803, 1959-1960 Traber PG, Levine DP. Vancomycin ototoxicity in a patient with normal renal function. Annals of Internal Medicine 95: 458–460, 1981
Waisbren BA, Kleinerman L, Skemp J, et al. The comparative toxicity and clinical effectiveness of vancomycin, ristocetin and kanamycin. Antibiotics Annual: 497-515, 1959-1960
Wold JS, Turnipseed SA. Toxicology of vancomycin in laboratory animals. Reviews of Infectious Diseases 3 (Suppl): 224–229, 1981
Woodley DW, Hall WH. The treatment of severe staphylococcal infections with vancomycin. Annals of Internal Medicine 55: 235–249, 1961
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bailie, G.R., Neal, D. Vancomycin Ototoxicity and Nephrotoxicity. Med Toxicol Adverse Drug Exp 3, 376–386 (1988). https://doi.org/10.1007/BF03259891
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03259891