Elsevier

The American Journal of Medicine

Volume 123, Issue 2, February 2010, Pages 182.e1-182.e7
The American Journal of Medicine

AJM online
Review
Vancomycin-Associated Nephrotoxicity: Grave Concern or Death by Character Assassination?

https://doi.org/10.1016/j.amjmed.2009.05.031Get rights and content

Abstract

Vancomycin-associated nephrotoxicity was reported in 0% to 5% of patients in the 1980s. This has been confirmed by numerous clinical trials comparing novel anti–methicillin-resistant Staphylococcus aureus agents with vancomycin at the Food and Drug Administration-approved dosage of 1 g every 12 hours. Treatment failures of vancomycin in patients with methicillin-resistant S. aureus infections have been reported despite in vitro susceptibility. These failures have led to the use of vancomycin doses higher than those approved by the Food and Drug Administration. Higher doses are being administered to achieve goal vancomycin trough concentrations of 10 to 20 μg/mL recommended by several clinical practice guidelines endorsed by the Infectious Diseases Society of America. Recent studies suggest that increased rates of nephrotoxicity are associated with aggressive vancomycin dosing. These increased rates are confounded by concomitant nephrotoxins, renal insufficiency, or changing hemodynamics. These studies also have demonstrated that vancomycin's nephrotoxicity risk is minimal in patients without risk factors for nephrotoxicity. Clinicians unwilling to dose vancomycin in accordance with clinical practice guidelines should use an alternative agent because inadequate dosing increases the likelihood of selecting heteroresistant methicillin-resistant S. aureus isolates.

Section snippets

Vancomycin Nephrotoxicity in Recent Prospective Studies

Numerous clinical trials of anti–methicillin-resistant S. aureus medications have used vancomycin 1 g every 12 hours as the comparator (Table).14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 Most studies did not state a target vancomycin trough concentration and allowed vancomycin dosing adjustments according to the local standard of care. Two studies evaluating nosocomial pneumonia targeted vancomycin trough concentrations of 5 to 10 μg/mL.25 These clinical trials confirm that nephrotoxicity occurs

Retrospective Studies of Vancomycin Nephrotoxicity

Greater emphasis has been placed on retrospective data because of the deficit of prospective studies evaluating nephrotoxicity with vancomycin dosages greater than 2 g per day (Table 1).12, 13 The following studies defined nephrotoxicity as an increase in serum creatinine of 0.5 mg/dL or a more than 50% increase from baseline serum creatinine. This definition is based on a retrospective study that noted increases in serum creatinine of 0.5 mg/dL or more in hospitalized patients to be associated

Discussion

Although vancomycin-associated nephrotoxicity has been studied in humans and animals, its exact mechanism remains to be elucidated. Le Moyec et al30 assessed aminoglycoside and glycopeptide renal toxicity in intensive care patients. The study concluded that toxicity from vancomycin and aminoglycosides are not confined to the proximal tubules but might involve the medullary region of the nephron. However, the authors did not specify which patients were receiving concomitant or monotherapy. A

Conclusions

Increased vancomycin trough concentrations have been recommended based on expert opinion by several Infectious Diseases Society of America-endorsed guidelines. Three published studies have suggested that there is a significant association between increased vancomycin trough concentrations and nephrotoxicity. There are currently insufficient data to identify the true incidence of nephrotoxicity associated with aggressive vancomycin dosing. Limitations of the existing data include the following:

References (42)

  • G. Sakoulas et al.

    Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcus aureus bacteremia

    J Clin Microbiol.

    (2004)
  • L.K. Hidayat et al.

    High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity

    Arch Intern Med.

    (2006)
  • L.M. Baddour et al.

    Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America

    Circulation

    (2005)
  • Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia

    Am J Respir Crit Care Med.

    (2005)
  • M. Rybak 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)
  • G. Sakoulas et al.

    Staphylococcus aureus accessory gene regulator (agr) group II: is there a relationship to the development of intermediate-level glycopeptide resistance?

    J Infect Dis.

    (2003)
  • T.P. Lodise et al.

    Larger vancomycin doses (at least four grams per day) are associated with an increased incidence of nephrotoxicity

    Antimicrob Agents Chemother.

    (2008)
  • D.L. Stevens et al.

    Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections

    Clin Infect Dis.

    (2002)
  • R.D. Arbeit et al.

    The safety and efficacy of daptomycin for the treatment of complicated skin and skin-structure infections

    Clin Infect Dis.

    (2004)
  • E.J. Ellis-Grosse et al.

    The efficacy and safety of tigecycline in the treatment of skin and skin-structure infections: results of 2 double-blind phase 3 comparison studies with vancomycin-aztreonam

    Clin Infect Dis.

    (2005)
  • J. Weigelt et al.

    Linezolid versus vancomycin in treatment of complicated skin and soft tissue infections

    Antimicrob Agents Chemother.

    (2005)
  • Cited by (0)

    Funding: Dr Hall's involvement in this publication was supported by Grant Number KL2RR024983, titled, “North and Central Texas Clinical and Translational Science Initiative” (Milton Packer, MD, PI) from the National Center for Research Resources, a component of the National Institutes of Health, and National Institutes of Health Roadmap for Medical Research, and its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Research Resources or National Institutes of Health. Information on National Center for Research Resources is available at http://www.ncrr.nih.gov/. Information on Re-engineering the Clinical Research Enterprise can be obtained from http://nihroadmap.nih.gov/clinicalresearch/overview-translational.asp.

    Conflict of Interest: None of the authors have any conflicts of interest associated with the work presented in this manuscript.

    Authorship: All authors had access to the data and played a role in writing this manuscript.

    View full text