THE EFFECT OF VANCOMYCIN DOSES GREATER THAN 2 GRAMS ON SERUM CREATININE AND VANCOMYCIN TROUGH LEVELS
Objective: To assess the effect of vancomycin doses greater than 2 grams on renal function and vancomycin trough levels
Methods: This is a retrospective, pharmacokinetic study performed in a tertiary care level II trauma center. 3579 electronic charts of patients who received vancomcyin at the medical facility between January 2010 and December 2011 were reviewed. Only 30 patients met the inclusion criteria of the study. Included patients were those who were at least 18 years of age who received doses greater than 2 grams of vancomycin for at least 48 hours. Patients in the intensive care units, pregnant or on hemodialysis and were not included in the study. The mean weight for the participants was 154.67 kg.
Results: Patients were dosed based on the institutionâ€™s vancomycin dosing protocol such as 15-20 mg/kg per dose where the frequency was determined based on the estimated creatinine clearance using cockroft gault equation. A loading dose of 25-30 mg/kg was administered in few cases. Two out of thirty subjects had shown an increase of serum creatinine of â‰¥ 0.3mg/dL when receiving maintenance doses greater than 2 grams of vancomycin. A Z approximation test was used where a standard error of 0.043 with an Î± error equal to 0.05 and a 95% confidence interval of (-0.024-0.144) were found. The use of doses greater than 2 grams of IV vancomycin did not show a statistically significance increase in serum creatinine. The two subjects who did have a significant increase in serum creatinine were receiving concomitant nephrotoxins.
Conclusion: The use of doses greater than 2 grams of IV vancomycin did not show a statistically significant increase in serum creatinine. Patients whom serum creatinine increased were on other nephrotoxin agents that could have contributed to the acute kidney injury that was seen in these patients.
2. Lodise TP, Lomaestro B, Graves J, Drusano GL. Larger vancomycin doses (â‰¥4 grams/day) are associated with an increased incidence of nephrotoxicity. Antimicrob Agents Chemother 2008;52:1330-6.
3. 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(12):5475-9.
4. Hodoshima N, Masuda S, Inui K. Decreased renal accumulation and toxicity of a new VCM formulation in rats with chronic renal failure. Drug Metab Pharmacokinet 2007;22:419-27.
5. Bailie GR, Neal D. Vancomycin ototoxicity and nephrotoxicity, a review. Med Toxicol 1998;3:376-86.
6. Lodise TP, Patel N, Lomestro BM, Rodvold KA, Drusano GL. Relationship between Initial Vancomycin Concetnration-Time Profile and Nephrotoxicity among Hospitalized Patients. Clinical Infectious Disease 2009;49:507-14.
7. Elting LS, Rubenstein EB, Kurtin D. Mississippi mud in the 1990s:risks and outcomes of vancomycin-associated toxicity in general oncology practice. Cancer 1998;83:2597-607.
8. Am J. American Thoracic Society and the Infectious Diseases Society of America. Guidelines for the management of adults with hospitalacquired ventilatorassociated health care associated pneumonia respire. Crit Care Med 2005;171:388-416.
9. Lui C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al. Clinical practice guidelines by the Infectious Disease Society of America for the treatment of methicillin-resistant Staphylococcus aureus infectious in adults and children. Clin Infect Dis 2011;52:e18-e55.
10. Jeffres MN, Isakow W, Doherty JA, Micek ST, Kollef MH. A retrospective analysis of possible renal toxicity associated with vancomcyin in patients with health care â€“associated methicillin-resistant Staphylococcus aureus pneumonia. Clin ther 2007;29:1107-15.
11. Hermsen ED, Hanson M, Sankaranarayanan J, Stoner JA, Florescu MC, Rupp ME. Clinical outcomes and nephrotoxicity associated with vancomycin trough concentrations during treatment of deap-seated infections. J Expert Opin Drug Safe 2010;9:9-14.
12. Mckamy S, Hernandez E, Jahng M, Moriwaki T, Deveikis A, Le J. Incidence and risk factors influencing the development of vancomycin nephrotoxicity in children. J Pediatr. 2011;158:422-9.
13. Nguyen M, Wong J, Lee C, Nguyen L, Quist R, Hirokawa C, et al. Nephrotoxicity associated with high dose vs standard dose vancomycin therapy. Presented at:47th Interscience Conference on Antimicrobial Agents and Chemotherapy. September 17-20,2007:Chicago, Ill. Abstract K-1096
14. Prabaker K, Tran T, Pratummas T, Goetz M, Graber C. Association of vancomycin trough levels with nephrotoxicity. Abstract presented at 47th Annual Meeting of Infectious diseases Society of America IDSA October 29 to November 1 Philadelphia Penn Abstract 192;2009.
15. Sorrell TC, Collignon PJ. A prospective study of adverse reactions associated with vancomycin therapy. J Antimicrob Chemother 1985:16:235-41.
16. Celik I, Cihangiroglu M, Ilhan N, Akpolat N, Akbulut HH. Protective effects of different anti-oxidants and amrinonr on vancomycin-induced nephrotoxicity. Basic Clin Pharmacol Toxicol 2005;97:325-32.
17. Kidney disease:Improving Global Outcomes. Clinical practice guidelines on acute kidney injury. Kidney disease:improving Global Outcomes, National Kidney Foundation, New York, NY. http://www. kdigo. org/clinical_practice_guidelines_3. php. Accessed March 5, 2013
18. Waikar SS, Bonventre JV. Kinetics and the Definition of Acute Kidney Injury. J Am Soc Nephrol 2009;20:672â€“9.
19. Review Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults-The Evidence Report. National Institutes of Health Obes Res 1998:6:2:51S-209S.
20. 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". Critical Care 2007;11:R31.
21. Wong-Beringer A, Joo J, Tse E, Beringer P. Vancomycin-associated Nephrotoxicity:A Critical appraisal of Risk with high dose therapy. International J of Antimicrobial Agents 2011 37:95-101.
22. 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.
23. Bauer LA, Black JS. Vancomycin Dosing in Morbidly Obese Patients. Eur J of Clinical Pharmacology 1998:54:621-5.