International Journal of Clinical Pharmacy

, Volume 40, Issue 5, pp 1328–1334 | Cite as

Evaluation of risk factors for vancomycin-induced nephrotoxicity

  • So Jin Park
  • Na Ri Lim
  • Hyo Jung ParkEmail author
  • Jae Wook Yang
  • Min-Ji Kim
  • Kyunga Kim
  • Yong Won In
  • Young Mee Lee
Research Article


Background Vancomycin is a glycopeptide antibiotic of choice for the treatment of serious infections caused by multi-resistant Gram-positive bacteria. However, vancomycin-associated nephrotoxicity (VAN) often limits its use. Previous data suggested a few risk factors of VAN, including higher mean vancomycin trough level, higher daily doses, old age, long duration of vancomycin therapy, and concomitant nephrotoxins. Objective To evaluate the incidence and risk factors of VAN and determine whether higher vancomycin trough concentrations were associated with a greater risk for VAN. Settings A retrospective, observational, single-center study at the 1960-bed university-affiliated tertiary care hospital (Samsung Medical Center), Seoul, Korea. Method A retrospective analysis of adult patients who received vancomycin parenterally in a tertiary care medical center from March 1, 2013 to June 30, 2013 was performed. We excluded patients with a baseline serum creatinine level > 2 mg/dL and those who had a history of end-stage renal disease and dialysis at baseline. The clinical characteristics were compared between patients with nephrotoxicity and those without nephrotoxicity to identify the risk factors associated with VAN. Main outcome measure Incidence of VAN and VAN-associated risk factors were analyzed. Results Of the 315 vancomycin-treated patients, nephrotoxicity occurred in 15.2% of the patients. In multivariate analysis, higher vancomycin trough concentrations of > 20 mg∕L (OR 9.57, 95% CI 2.49–36.83, p < 0.01) and intensive care unit (ICU) residence (OR 2.86, 95% CI 1.41–5.82, p < 0.01) were independently associated with VAN. Conclusion Our findings suggest that higher vancomycin trough levels and ICU residence might be associated with a greater risk for VAN. More careful monitoring of vancomycin serum trough levels and patient status might facilitate the timely prevention of VAN.


Nephrotoxicity Risk factors Trough level Vancomycin 



This study has no specific funding sources.

Conflicts of interest

The authors declare that they have no conflicts of interest with regard to this paper.


  1. 1.
    Cook FV, Farrar WE Jr. Vancomycin revisited. Ann Intern Med. 1978;88:813–8.CrossRefGoogle Scholar
  2. 2.
    Stevens DL. The role of vancomycin in the treatment paradigm. Clin Infect Dis. 2006;42(Suppl 1):S51–7.CrossRefGoogle Scholar
  3. 3.
    Bailie GR, Neal D. Vancomycin ototoxicity and nephrotoxicity. A review. Med Toxicol Adverse Drug Exp. 1988;3:376–86.PubMedGoogle Scholar
  4. 4.
    Rybak MJ, Albrecht LM, Boike SC, Chandrasekar PH. Nephrotoxicity of vancomycin, alone and with an aminoglycoside. J Antimicrob Chemother. 1990;25:679–87.CrossRefGoogle Scholar
  5. 5.
    Gupta A, Biyani M, Khaira A. Vancomycin nephrotoxicity: myths and facts. Neth J Med. 2011;69:379–83.PubMedGoogle Scholar
  6. 6.
    Carreno JJ, Kenney RM, Lomaestro B. Vancomycin-associated renal dysfunction: where are we now? Pharmacotherapy. 2014;34:1259–68.CrossRefGoogle Scholar
  7. 7.
    Elyasi S, Khalili H, Dashti-Khavidaki S, Mohammadpour A. Vancomycin-induced nephrotoxicity: mechanism, incidence, risk factors and special populations. A literature review. Eur J Clin Pharmacol. 2012;68:1243–55.CrossRefGoogle Scholar
  8. 8.
    Lodise TP, Lomaestro B, Graves J, Drusano GL. Larger vancomycin doses (at least four grams per day) are associated with an increased incidence of nephrotoxicity. Antimicrob Agents Chemother. 2008;52:1330–6.CrossRefGoogle Scholar
  9. 9.
    Hazlewood KA, Brouse SD, Pitcher WD, Hall RG. Vancomycin-associated nephrotoxicity: grave concern or death by character assassination? Am J Med. 2010;123(182):e1–7.Google Scholar
  10. 10.
    Hidayat LK, Hsu DI, Quist R, Shriner KA, Wong-Beringer A. High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity. Arch Intern Med. 2006;166:2138–44.CrossRefGoogle Scholar
  11. 11.
    Meaney CJ, Hynicka LM, Tsoukleris MG. Vancomycin-associated nephrotoxicity in adult medicine patients: incidence, outcomes, and risk factors. Pharmacotherapy. 2014;34:653–61.CrossRefGoogle Scholar
  12. 12.
    Hermsen ED, Hanson M, Sankaranarayanan J, Stoner JA, Florescu MC, Rupp ME. Clinical outcomes and nephrotoxicity associated with vancomycin trough concentrations during treatment of deep-seated infections. Expert Opin Drug Saf. 2010;9:9–14.CrossRefGoogle Scholar
  13. 13.
    Geraci JE. Vancomycin. Mayo Clin Proc. 1977;52:631–4.PubMedGoogle Scholar
  14. 14.
    Soriano A, Marco F, Martinez JA, Pisos E, Almela M, Dimova VP, et al. Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis. 2008;46:193–200.CrossRefGoogle Scholar
  15. 15.
    Lodise TP, Graves J, Evans A, Graffunder E, Helmecke M, Lomaestro BM, et al. Relationship between vancomycin MIC and failure among patients with methicillin-resistant Staphylococcus aureus bacteremia treated with vancomycin. Antimicrob Agents Chemother. 2008;52:3315–20.CrossRefGoogle Scholar
  16. 16.
    Rybak M, Lomaestro B, Rotschafer JC, Moellering R Jr, Craig W, Billeter M, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2009;66:82–98.CrossRefGoogle Scholar
  17. 17.
    Bosso JA, Nappi J, Rudisill C, Wellein M, Bookstaver PB, Swindler J, et al. Relationship between vancomycin trough concentrations and nephrotoxicity: a prospective multicenter trial. Antimicrob Agents Chemother. 2011;55:5475–9.CrossRefGoogle Scholar
  18. 18.
    Jeffres MN, Isakow W, Doherty JA, Micek ST, Kollef MH. A retrospective analysis of possible renal toxicity associated with vancomycin in patients with health care-associated methicillin-resistant Staphylococcus aureus pneumonia. Clin Ther. 2007;29:1107–15.CrossRefGoogle Scholar
  19. 19.
    Hal SJ, Paterson DL, Lodise TP. Systematic review and meta-analysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter. Antimicrob Agents Chemother. 2013;57:734–44.CrossRefGoogle Scholar
  20. 20.
    Cano EL, Haque NZ, Welch VL, Cely CM, Peyrani P, Scerpella EG, et al. Improving Medicine through Pathway Assessment of Critical Therapy of Hospital-Acquired Pneumonia(IMPACT-HAP) Study Group. Incidence of nephrotoxicity and association with vancomycin use in intensive care unit patients with pneumonia: retrospective analysis of the IMPACT-HAP Database. Clin Ther. 2012;34:149–57.CrossRefGoogle Scholar
  21. 21.
    Lodise TP, Patel N, Lomaestro BM, Rodvold KA, Drusano GL. Relationship between initial vancomycin concentration-time profile and nephrotoxicity among hospitalized patients. Clin Infect Dis. 2009;49:507–14.CrossRefGoogle Scholar
  22. 22.
    Prabaker KK, Tran TP, Pratummas T, Goetz MB, Graber CJ. Elevated vancomycin trough is not associated with nephrotoxicity among inpatient veterans. J Hosp Med. 2012;7:91–7.CrossRefGoogle Scholar
  23. 23.
    Carreno JJ, Jaworski A, Kenney RM, Davis SL. Comparative incidence of nephrotoxicity by age group among adult patients receiving vancomycin. Infect Dis Ther. 2013;2:201–8.CrossRefGoogle Scholar
  24. 24.
    Barriere SL, Stryjewski ME, Corey GR, Genter FC, Rubinstein E. Effect of vancomycin serum trough levels on outcomes in patients with nosocomial pneumonia due to Staphylococcus aureus: a retrospective, post hoc, subgroup analysis of the Phase 3 ATTAIN studies. BMC Infect Dis. 2014;14:183.CrossRefGoogle Scholar
  25. 25.
    Steinmetz T, Eliakim-Raz N, Goldberg E, Leibovici L, Yahav D. Association of vancomycin serum concentrations with efficacy in patients with MRSA infections: a systematic review and meta-analysis. Clin Microbiol Infect. 2015;21:665–73.CrossRefGoogle Scholar
  26. 26.
    Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, et al. Beginning, Ending Supportive Therapy for the Kidney I(BEST Kidney Investigators). Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294:813–8.CrossRefGoogle Scholar
  27. 27.
    Roberts JA, Abdul-Aziz MH, Lipman J, Mouton JW, Vinks AA, Felton TW, et al. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis. 2014;14:498–509.CrossRefGoogle Scholar
  28. 28.
    Roberts JA, Lipman J. Pharmacokinetic issues for antibiotics in the critically ill patient. Crit Care Med. 2009;37:840–51.CrossRefGoogle Scholar
  29. 29.
    Pannu N, Nadim MK. An overview of drug-induced acute kidney injury. Crit Care Med. 2008;36(Suppl 4):S216–23.CrossRefGoogle Scholar
  30. 30.
    Pritchard L, Baker C, Leggett J, Sehdev P, Brown A, Bayley KB. Increasing vancomycin serum trough concentrations and incidence of nephrotoxicity. Am J Med. 2010;123:1143–9.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • So Jin Park
    • 1
  • Na Ri Lim
    • 1
  • Hyo Jung Park
    • 1
    Email author
  • Jae Wook Yang
    • 1
    • 2
  • Min-Ji Kim
    • 1
    • 3
  • Kyunga Kim
    • 1
    • 3
  • Yong Won In
    • 1
  • Young Mee Lee
    • 1
  1. 1.Samsung Medical CenterGangnam-gu, SeoulRepublic of Korea
  2. 2.Department of Pharmaceutical SciencesSahmyook UniversitySeoulKorea
  3. 3.Statistics and Data center, Research Institute for Future MedicineSamsung Medical CenterSeoulKorea

Personalised recommendations