Original Article

Incidence and Predictors of Vancomycin-Associated Nephrotoxicity

Authors: Hamzah Moh’d, MD, MS, Fayez Kheir, MD, Lan Kong, PhD, Ping Du, MD, PhD, Hosam Farag, MD, Ahmad Mohamad, MD, John J. Zurlo, MD

Abstract

Objectives: Earlier studies reported a low incidence of vancomycin-associated nephrotoxicity (VAN); however, recent studies have reported higher incidences exceeding 30%. Predictors of nephrotoxicity are not well defined. In this study we aimed to better estimate the incidence and evaluate predictors of VAN in a cohort of patients predominated by long treatment courses.

Methods: We conducted a retrospective study on patients treated with vancomycin while in the hospital and who were observed closely through the Outpatient Parenteral Antibiotic Therapy program. Nephrotoxicity was defined as an increase in the serum creatinine level of 0.5 mg/dL or 50% from baseline on at least two consecutive readings while taking vancomycin. We compared the patients who developed nephrotoxicity with those who did not with regard to vancomycin dosing, trough levels, baseline serum creatinine, underlying infection, residence in the critical care unit, comorbid conditions, concurrent nephrotoxic treatments, and baseline characteristics.

Results: Of 579 patients, 154 (26.6%) developed nephrotoxicity. Ninety patients developed VAN within the first 14 days of treatment, whereas 64 patients developed nephrotoxicity after 14 days of treatment. The median time to development of nephrotoxicity was 9 days. Admission to the intensive care unit, concurrent use of loop diuretics, and comorbidity with cirrhosis were independently associated with nephrotoxicity. A higher baseline creatinine value was unexpectedly associated with a lower incidence of nephrotoxicity ( P = 0.0016).

Conclusions: VAN is not an uncommon outcome in both short- and long-term treatment courses. Admission to the intensive care unit while receiving treatment, concurrent treatment with a loop diuretic, an underlying diagnosis of cirrhosis, and the initial trough level appear to be the main risk factors for nephrotoxicity. Unexpectedly, elevated baseline creatinine levels appeared to be protective and this could be the result of careful use of vancomycin among individuals with relatively higher baseline creatinine values.

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

1. Newton P. The role of monitoring serum vancomycin concentrations. Phatol 2004;2:1-2.
 
2. Ingram PR, Lye DC, Tambyah PA, et al. Risk factors for nephrotoxicity associated with continuous vancomycin infusion in outpatient parenteral antibiotic therapy. J Antimicrob Chemother 2008;62:168-171.
 
3. Shah-Khan F, Scheetz MH, Ghossein C. Biopsy-proven acute tubular necrosis due to vancomycin toxicity. Int J Nephrol 2011;2011:436856.
 
4. Öktem F, Arslan MK, Ozguner F, et al. In vivo evidences suggesting the role of oxidative stress in pathogenesis of vancomycin-induced nephrotoxicity: protection by erdosteine. Toxicology 2005;215:227-233.
 
5. Dieterich C, Puey A, Lin S, et al. Gene expression analysis reveals new possible mechanisms of vancomycin-induced nephrotoxicity and identifies gene markers candidates. Toxicol Sci 2009;107:258-269.
 
6. Elyasi S, Khalili H, Dashti-Khavidaki S, et al. Vancomycin-induced nephrotoxicity: mechanism, incidence, risk factors and special populations. A literature review. Eur J Clin Pharmacol 2012;68:1243-1255.
 
7. Bailie GR, Neal D. Vancomycin ototoxicity and nephrotoxicity, a review. Med Toxicol 1998;3:376-386.
 
8. Lodise TP, Patel N, Lomaestro BM, et al. Relationship between initial vancomycin concentration time profile and nephrotoxicity. Clin Infect Dis 2009;49:507-514.
 
9. Lodise TP, Lomaestro B, Graves J, et al. Larger vancomycin doses (at least four grams per day) are associated with an increased incidence of nephrotoxicity. Antimicrob Agents Chemother 2008;52:1330-1336.
 
10. Elting LS, Rubenstein EB, Kurtin D. Mississippi mud in the 1990s: risks and outcomes of vancomycin-associated toxicity in general oncology practice. Cancer 1998;83:2597-2607.
 
11. Rybak MJ, Lomaestro BM, Rotschafer JC, et al. Vancomycin therapeutic guidelines: a summary of consensus recommendations from the infectious diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists. Clin Infect Dis 2009;49:325-327.
 
12. Pritchard L, Baker C, Leggett J, et al. Increasing vancomycin serum trough concentrations and incidence of nephrotoxicity. Am J Med 2010;123:1143-1149.
 
13. Huanga LY, Wanga CY, Jangb TN, et al. Nephrotoxicity of vancomycin and teicoplanin alone and in combination with an aminoglycoside. Taiwan Pharm J 2007;59:1-8.
 
14. Hazlewood KA, Brouse SD, Pitcher WD, et al. Vancomycin-associated nephrotoxicity: grave concern or death by character assassination? Am J Med 2010;123:182.e1-182.e7.
 
15. Minejima E, Choi J, Beringer P, et al. Applying new diagnostic criteria for acute kidney injury to facilitate early identification of nephrotoxicity in vancomycin treated patients. Antimicrob Agents Chemother 2011;55:3278-3283.
 
16. Shen WC, Chiang YC, Chen HY, et al. Nephrotoxicity of vancomycin in patients with methicillin-resistant Staphylococcus aureus bacteremia. Nephrology (Carlton) 2011;16:697-703.
 
17. Hidayat LK, Hsu DI, Quist R, et al. High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections. Arch Intern Med 2006;166:2138-2144.
 
18. Malacarne P, Bergamasco S, Donadio C. Nephrotoxicity due to combination antibiotic therapy with vancomycin and aminoglycosides in septic critically ill patients. Chemotherapy 2006;52:178-184.
 
19. Colares VS, Oliveira RB, Abdulkader R. Nephrotoxicity of vancomycin in patients with normal serum creatinine. Nephrol Dial Transplant 2006;21:3608.
 
20. Lodise TP, Patel N, Lomaestro BM, et al. Relationship between initial vancomycin concentration-time profile and nephrotoxicity among hospitalized patients. Clin Infect Dis 2009;49:507-514.
 
21. Wong-Beringer A, Joo J, Tse E, et al. Vancomycin-associated nephrotoxicity: a critical appraisal of risk with high dose therapy. Int J Antimicrob Agents 2011;37:95-101.
 
22. Housman ST, Kopcza K, Cross J, et al. Incidence and risk factors of developing nephrotoxicity in adult non-intensive care unit patients receiving vancomycin for greater than 48 hours. Paper presented at: Infectious Diseases Society of America 48th Annual Meeting; Vancouver, Canada; October 21-October 24, 2010.
 
23. Prabaker KK, Tran TP, Pratummas T, et al. Elevated vancomycin trough is not associated with nephrotoxicity among inpatient veterans. J Hosp Med 2012;7:91-97.
 
24. Bosso JA, Nappi J, Rudisill C, et al. Relationship between vancomycin trough concentrations and nephrotoxicity: a prospective multicenter trial. Antimicrob Agents Chemother 2011;55:5475-5479.
 
25. Gasparovic GV. Vancomycin nephrotoxicity in ICU and risk factors for acute renal failure. Electronic poster no. 1037. Presented at: 22nd European Society of Intensive Care Medicine Annual Congress; Vienna, Austria; 2009.
 
26. Cano EL, Haque NZ, Welch VL, 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;34:149-157.
 
27. Hutschala D, Kinstner C, Skhirdladze K, et al. Influence of vancomycin on renal function in critically ill patients after cardiac surgery. Anesthesiology 2009;111:356-365.
 
28. Cataldo MA, Tacconelli E, Grilli E, et al. Continuous versus intermittent infusion of vancomycin for the treatment of Gram-positive infections: systematic review and meta-analysis. J Antimicrob Chemother2012;67:17-24.
 
29. Yi F, Qing H, Jing X, et al. Evaluation of nephrotoxicity in 25 elderly patients treated with vancomycin. China Pharm 2010;7:123-125.
 
30. Bellomo R, Ronco C, Kellum JA, et al. Acute renal failureVdefinition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group.Crit Care 2004;8:R204-R212.
 
31. Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007;11:R31.
 
32. Jeffres MN, Isakow W, Doherty JA, et al. A retrospective analysis of possible renal toxicity associated with vancomycin in patients with health care-associated methicillin-resistant Staphylococcus aureus pneumonia. Clin Ther 2007;29:1107-1115.
 
33. Kralovicová K, Spanik S, Halko J, et al. Do vancomycin serum levels predict failures of vancomycin therapy or nephrotoxicity in cancer patients? J Chemother 1997;9:420-426.
 
34. Davies SW, Guidry CA, Petroze RT, et al. Vancomycin and nephrotoxicity: just another myth? J Trauma Acute Care Surg 2013;75:830-835.