Skip to main content

Advertisement

SpringerLink
Log in

Development of acute kidney injury during continuous infusion of vancomycin in septic patients

  • Clinical and Epidemiological Study
  • Published:
Infection Aims and scope Submit manuscript

Abstract

Purpose

Few data are available on the occurrence of renal failure during continuous infusion of vancomycin in critically ill patients.

Methods

We reviewed the data of all patients admitted to the intensive care unit (ICU) between January 2008 and December 2009 in whom vancomycin was given as a continuous infusion for more than 48 h in the absence of renal replacement therapy. We collected data on the doses of vancomycin and blood concentrations during therapy. Acute kidney injury (AKI) was defined as a daily urine output <0.5 ml/kg/h and/or an increase in the serum creatinine of ≥0.3 mg/dl from baseline levels during vancomycin therapy or within 72 h after its discontinuation. Multivariable logistic regression analysis was performed to identify predictors of AKI.

Results

Of 207 patients who met the inclusion criteria, 50 (24 %) developed AKI. These patients were more severely ill, had lower creatinine clearance at admission, were more frequently exposed to other nephrotoxic agents, had a longer duration of therapy, and had higher concentrations of vancomycin during the first 3 days of treatment (C mean). The C mean was independently associated with early AKI (within 48 h from the onset of therapy) and the duration of vancomycin administration with late AKI.

Conclusions

AKI occurred in almost 25 % of critically ill patients treated with a continuous infusion of vancomycin. Vancomycin concentrations and duration of therapy were the strongest variables associated with the development of early and late AKI during therapy, respectively.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Griffin AT, Peyrani P, Wiemken TL, Ramirez JA, Arnold FW. Empiric therapy directed against MRSA in patients admitted to the intensive care unit does not improve outcomes in community-acquired pneumonia. Infection. 2013;41:517–23.

    Article  PubMed  CAS  Google Scholar 

  2. Finfer S, Bellomo R, Lipman J, French C, Dobb G, Myburgh J. Adult-population incidence of severe sepsis in Australian and New Zealand intensive care units. Intensive Care Med. 2004;30:589–96.

    Article  PubMed  Google Scholar 

  3. Hanberger H, Walther S, Leone M, Barie PS, Rello J, Lipman J, et al. Increased mortality associated with methicillin-resistant Staphylococcus aureus (MRSA) infection in the intensive care unit: results from the EPIC II study. Int J Antimicrob Agents. 2011;38:331–5.

    Article  PubMed  CAS  Google Scholar 

  4. Rybak MJ, Lomaestro BM, Rotschafer JC, Moellering RC Jr, Craig WA, Billeter M, et al. Therapeutic monitoring of vancomycin in adults summary of consensus recommendations from the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Pharmacotherapy. 2009;29:1275–9.

    Article  PubMed  CAS  Google Scholar 

  5. van Hal SJ, Lodise TP, Paterson DL. The clinical significance of vancomycin minimum inhibitory concentration in Staphylococcus aureus infections: a systematic review and meta-analysis. Clin Infect Dis. 2012;54:755–71.

    Article  PubMed  Google Scholar 

  6. Gupta A, Biyani M, Khaira A. Vancomycin nephrotoxicity: myths and facts. Neth J Med. 2011;69:379–83.

    PubMed  CAS  Google Scholar 

  7. 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.

    Article  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  9. 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.

    Article  PubMed  CAS  Google Scholar 

  10. 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.

    Article  PubMed  CAS  Google Scholar 

  11. 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.

    Article  PubMed  CAS  Google Scholar 

  12. Wunderink RG, Niederman MS, Kollef MH, Shorr AF, Kunkel MJ, Baruch A, et al. Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study. Clin Infect Dis. 2012;54:621–9.

    Article  PubMed  CAS  Google Scholar 

  13. Ocampos-Martinez E, Penaccini L, Scolletta S, Abdelhadii A, Devigili A, Cianferoni S, et al. Determinants of early inadequate vancomycin concentrations during continuous infusion in septic patients. Int J Antimicrob Agents. 2012;39:332–7.

    Article  PubMed  CAS  Google Scholar 

  14. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11:R31.

    Article  PubMed  Google Scholar 

  15. Marsot A, Boulamery A, Bruguerolle B, Simon N. Vancomycin: a review of population pharmacokinetic analyses. Clin Pharmacokinet. 2012;51:1–13.

    Article  PubMed  CAS  Google Scholar 

  16. Wysocki M, Delatour F, Faurisson F, Rauss A, Pean Y, Misset B, et al. Continuous versus intermittent infusion of vancomycin in severe Staphylococcal infections: prospective multicenter randomized study. Antimicrob Agents Chemother. 2001;45:2460–7.

    Article  PubMed  CAS  Google Scholar 

  17. Cataldo MA, Tacconelli E, Grilli E, Pea F, Petrosillo N. Continuous versus intermittent infusion of vancomycin for the treatment of Gram-positive infections: systematic review and meta-analysis. J Antimicrob Chemother. 2012;67:17–24.

    Article  PubMed  CAS  Google Scholar 

  18. Spapen HD, Janssen van Doorn K, Diltoer M, Verbrugghe W, Jacobs R, Dobbeleir N, et al. Retrospective evaluation of possible renal toxicity associated with continuous infusion of vancomycin in critically ill patients. Ann Intensive Care. 2011;1:26.

    Article  PubMed  Google Scholar 

  19. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31:1250–6.

    Article  PubMed  Google Scholar 

  20. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13:818–29.

    Article  PubMed  CAS  Google Scholar 

  21. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22:707–10.

    Article  PubMed  CAS  Google Scholar 

  22. Nishino Y, Takemura S, Minamiyama Y, Hirohashi K, Ogino T, Inoue M, et al. Targeting superoxide dismutase to renal proximal tubule cells attenuates vancomycin-induced nephrotoxicity in rats. Free Radic Res. 2003;37:373–9.

    Article  PubMed  CAS  Google Scholar 

  23. Dieterich C, Puey A, Lin S, Swezey R, Furimsky A, Fairchild D, et al. Gene expression analysis reveals new possible mechanisms of vancomycin-induced nephrotoxicity and identifies gene markers candidates. Toxicol Sci. 2009;107:258–69.

    Article  PubMed  CAS  Google Scholar 

  24. Wong-Beringer A, Joo J, Tse E, Beringer P. Vancomycin-associated nephrotoxicity: a critical appraisal of risk with high-dose therapy. Int J Antimicrob Agents. 2011;37:95–101.

    Article  PubMed  CAS  Google Scholar 

  25. Wu CY, Wang JS, Chiou YH, Chen CY, Su YT. Biopsy proven acute tubular necrosis associated with vancomycin in a child: case report and literature review. Ren Fail. 2007;29:1059–61.

    Article  PubMed  Google Scholar 

  26. Ellis-Grosse EJ, Babinchak T, Dartois N, Rose G, Loh E; Tigecycline 300 cSSSI Study Group; Tigecycline 305 cSSSI Study Group. 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;41:S341–53.

    Article  PubMed  CAS  Google Scholar 

  27. Fowler VG Jr, Boucher HW, Corey GR, Abrutyn E, Karchmer AW, Rupp ME, et al. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med. 2006;355:653–65.

    Article  PubMed  CAS  Google Scholar 

  28. 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.

    Article  PubMed  CAS  Google Scholar 

  29. 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.

    Article  PubMed  Google Scholar 

  30. Minejima E, Choi J, Beringer P, Lou M, Tse E, Wong-Beringer A. Applying new diagnostic criteria for acute kidney injury to facilitate early identification of nephrotoxicity in vancomycin-treated patients. Antimicrob Agents Chemother. 2011;55:3278–83.

    Article  PubMed  CAS  Google Scholar 

  31. Zimmermann AE, Katona BG, Plaisance KI. Association of vancomycin serum concentrations with outcomes in patients with gram-positive bacteremia. Pharmacotherapy. 1995;15:85–91.

    PubMed  CAS  Google Scholar 

  32. Farber BF, Moellering RC Jr. Retrospective study of the toxicity of preparations of vancomycin from 1974 to 1981. Antimicrob Agents Chemother. 1983;23:138–41.

    Article  PubMed  CAS  Google Scholar 

  33. 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.

    Article  PubMed  CAS  Google Scholar 

  34. Rodriguez Colomo O, Álvarez Lerma F, González Pérez MI, Sirvent JM, García Simón M; Study Group of Infection in Critical Patients. Impact of administration of vancomycin or linezolid to critically ill patients with impaired renal function. Eur J Clin Microbiol Infect Dis. 2011;30:635–43.

    Article  PubMed  CAS  Google Scholar 

  35. Shen WC, Chiang YC, Chen HY, Chen TH, Yu FL, Tang CH, et al. Nephrotoxicity of vancomycin in patients with methicillin-resistant Staphylococcus aureus bacteraemia. Nephrology (Carlton). 2011;16:697–703.

    Article  CAS  Google Scholar 

  36. Eichhorn ME, Wolf H, Küchenhoff H, Joka M, Jauch KW, Hartl WH. Secular trends in severe renal failure associated with the use of new antimicrobial agents in critically ill surgical patients. Eur J Clin Microbiol Infect Dis. 2007;26:395–402.

    Article  PubMed  CAS  Google Scholar 

  37. Teng CB, Rezai K, Itokazu GS, Xamplas RC, Glowacki RC, Rodvold KA, et al. Continuation of high-dose vancomycin despite nephrotoxicity. Antimicrob Agents Chemother. 2012;56:3470–1.

    Article  PubMed  CAS  Google Scholar 

  38. Jeurissen A, Sluyts I, Rutsaert R. A higher dose of vancomycin in continuous infusion is needed in critically ill patients. Int J Antimicrob Agents. 2011;37:75–7.

    Article  PubMed  CAS  Google Scholar 

  39. Roberts JA, Taccone FS, Udy AA, Vincent JL, Jacobs F, Lipman J. Vancomycin dosing in critically ill patients: robust methods for improved continuous-infusion regimens. Antimicrob Agents Chemother. 2011;55:2704–9.

    Article  PubMed  CAS  Google Scholar 

  40. Downs NJ, Neihart RE, Dolezal JM, Hodges GR. Mild nephrotoxicity associated with vancomycin use. Arch Intern Med. 1989;149:1777–81.

    Article  PubMed  CAS  Google Scholar 

  41. Cano EL, Haque NZ, Welch VL, Cely CM, Peyrani P, Scerpella EG, et al. 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.

    Article  PubMed  CAS  Google Scholar 

  42. Colares VS, Oliveira RB, Abdulkader RC. Nephrotoxicity of vancomycin in patients with normal serum creatinine. Nephrol Dial Transpl. 2006;21:3608.

    Article  Google Scholar 

  43. Hutschala D, Kinstner C, Skhirdladze K, Thalhammer F, Müller M, Tschernko E. Influence of vancomycin on renal function in critically ill patients after cardiac surgery: continuous versus intermittent infusion. Anesthesiology. 2009;111:356–65.

    Article  PubMed  CAS  Google Scholar 

  44. Bossé D, Lemire C, Ruel J, Cantin AM, Ménard F, Valiquette L. Severe anaphylaxis caused by orally administered vancomycin to a patient with Clostridium difficile infection. Infection. 2013;41:579–82.

    Article  PubMed  Google Scholar 

  45. Rocha JL, Kondo W, Baptista MI, Da Cunha CA, Martins LT. Uncommon vancomycin-induced side effects. Braz J Infect Dis. 2002;6:196–200.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Mr. Hassane Njimi for his help with the statistical analysis. The study was supported by institutional funds only. It was not supported by any grants.

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Department of Intensive Care, Hôpital Erasme, Université Libre de Bruxelles (ULB), Route de Lennik, 808, 1070, Brussels, Belgium

    S. Cianferoni, A. Devigili, E. Ocampos-Martinez, L. Penaccini, S. Scolletta, A. Abdelhadii, D. De Backer, M. Beumier, J.-L. Vincent & F. S. Taccone

  2. Department of Infectious Diseases, Hôpital Erasme, Université Libre de Bruxelles (ULB), Route de Lennik, 808, 1070, Brussels, Belgium

    F. Jacobs

Authors
  1. S. Cianferoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Devigili
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Ocampos-Martinez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. Penaccini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Scolletta
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Abdelhadii
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. D. De Backer
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. Beumier
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. F. Jacobs
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J.-L. Vincent
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. F. S. Taccone
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F. S. Taccone.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cianferoni, S., Devigili, A., Ocampos-Martinez, E. et al. Development of acute kidney injury during continuous infusion of vancomycin in septic patients. Infection 41, 811–820 (2013). https://doi.org/10.1007/s15010-013-0460-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s15010-013-0460-9

Keywords

Search

Navigation