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Balancing Vancomycin Efficacy and Nephrotoxicity: Should We Be Aiming for Trough or AUC/MIC?

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Abstract

Sixty years later, the question that still remains is how to appropriately utilize vancomycin in the pediatric population. The Infectious Diseases Society of America published guidelines in 2011 that provide guidance for dosing and monitoring of vancomycin in adults and pediatrics. However, goal vancomycin trough concentrations of 15–20 μg/mL for invasive infections caused by methicillin-resistant Staphylococcus aureus were based primarily on adult pharmacokinetic and pharmacodynamic data that achieved an area under the curve to minimum inhibitory concentration ratio (AUC/MIC) of ≥400. Recent pediatric literature shows that vancomycin trough concentrations needed to achieve the target AUC/MIC are different than the adult goal troughs cited in the guidelines. This paper addresses several thoughts, including the role of vancomycin AUC/MIC in dosing strategies and safety monitoring, consistency in laboratory reporting, and future directions for calculating AUC/MIC in pediatrics.

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References

  1. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis. 2011;52(3):285–92.

    Article  PubMed  Google Scholar 

  2. Rybak M, Lomaestro B, Rotschafer JC, 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 Disease Pharmacists. Am J Health Syst Pharm. 2009;66:82–98.

    Article  CAS  PubMed  Google Scholar 

  3. Gonzalez BE, Hulten KG, Dishop MK, et al. Pulmonary manifestations in children with invasive community-acquired Staphylococcus aureus infection. Clin Infect Dis. 2005;41:583–90.

    Article  PubMed  Google Scholar 

  4. Gonzalez BE, Teruya J, Mahoney DH Jr, et al. Venous thrombosis associated with staphylococcal osteomyelitis in children. Pediatrics. 2006;117:1673–9.

    Article  PubMed  Google Scholar 

  5. Frymoyer A, Hersh AL, Benet LZ. Current recommended dosing of vancomycin for children with invasive methicillin-resistant Staphylococcus aureus infections is inadequate. Pediatr Infect Dis J. 2009;28(5):398–402.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Moise-Broder PA, Forrest A, Birmingham MC, et al. Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections. Clin Pharmacokinet. 2004;43(13):925–42.

    Article  CAS  PubMed  Google Scholar 

  7. Patel N. Vancomycin: we can’t get there from here. Clin Infect Dis. 2011;52:969–74.

    Article  CAS  PubMed  Google Scholar 

  8. Pai MP, Neely M, Rodvold KA, et al. Innovative approaches to optimizing the delivery of vancomycin in individual patients. Adv Drug Deliv Rev. 2014. doi:10.1016/j.addr.2014.05.016.

  9. Chhim RF, Arnold SR, Lee KR. Vancomycin dosing practices, trough concentrations, and predicted area under the curve in children with suspected invasive staphylococcal infections. J Ped Infect Dis. 2013;2(3):259–62.

    Google Scholar 

  10. Bourguignon da Silva DC, Seixas GT, de Araujo DR, et al. Vancomycin serum concentrations in pediatric oncologic/hematologic intensive care patients. Braz J Infect Dis. 2012;16:361–5.

    Article  CAS  Google Scholar 

  11. Fuchs A, Csajka C, Thoma Y, et al. Benchmarking therapeutic drug monitoring software: a review of available computer tools. Clin Pharmacokinet. 2013;52(1):9–22.

    Article  CAS  PubMed  Google Scholar 

  12. Frymoyer A, Guglielmo BJ, Hersh AL. Desired vancomycin trough serum concentration for treating invasive methicillin-resistant Staphylococcal infections. Pediatr Infect Dis J. 2013;32:1077–9.

    Article  PubMed  Google Scholar 

  13. Le J, Bradley JS, Murray W, et al. Improved vancomycin dosing in children using area under the curve exposure. Pediatr Infect Dis J. 2013;32:e155–63.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Frymoyer A, Guglielmo BJ, Wilson SD, et al. Impact of a hospital wide increase in empiric pediatric vancomycin dosing on initial trough concentrations. Pharmacotherapy. 2011;31:871–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Eiland LS, English TM, Eiland EH 3rd. Assessment of vancomycin dosing and subsequent serum concentrations in pediatric patients. Ann Pharmacother. 2011;45:582–9.

    Article  CAS  PubMed  Google Scholar 

  16. Madigan T, Sieve RM, Graner KK, et al. The effect of age and weight on vancomycin serum trough concentrations in pediatric patients. Pharmacotherapy. 2013;33(12):1264–72.

    Article  CAS  PubMed  Google Scholar 

  17. Gordon CL, Thompson C, Carapetis JR, et al. Trough concentrations of vancomycin: adult therapeutic targets are not appropriate for children. Pediatr Infect Dis J. 2012;31:1269–71.

    Article  PubMed  Google Scholar 

  18. Heble DE, McPherson C, Nelson MP, et al. Vancomycin trough concentrations in overweight or obese pediatric patients. Pharmacotherapy. 2013;33(12):1273–7.

    Article  CAS  PubMed  Google Scholar 

  19. van Hal SJ, Lodise TP. DL Paterson. 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 

  20. Cole TS, Riordan A. Vancomycin dosing in children: what is the question? Arch Dis Child. 2013;98(12):994–7.

    Article  PubMed  Google Scholar 

  21. Rose L, Chan S, Hossain J, et al. Effects of aggregate and individual antibiotic exposure on vancomycin MICs for Staphylococcus aureus isolates recovered from pediatric patients. J Clin Microbiol. 2013;51(9):2837–42.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Goldman JL, Harrison CJ, Myers AL, et al. No evidence of vancomycin minimal inhibitory concentration creep or heteroresistance identified in pediatric Staphylococcus aureus blood isolates. Pediatr Infect Dis J. 2014;33(2):216–8.

    Article  PubMed  Google Scholar 

  23. Zheng X, Qi C, Arrieta M, et al. Lack of increase in vancomycin resistance of pediatric methicillin-resistant Staphylococcus aureus isolates from 2000 to 2007. Pediatr Infect Dis J. 2010;29(9):882–4.

    Article  PubMed  Google Scholar 

  24. McKamy S, Hernandez E, Jahng M, et al. Incidence and risk factors influencing the development of vancomycin nephrotoxicity in children. J Pediatr. 2011;158(3):422–6.

    Article  CAS  PubMed  Google Scholar 

  25. Wu CY, Wang JS, Chiou YH, et al. Biopsy proven acute tubular necrosis associated with vancomycin in a child: case report and literature review. Ren Fail. 2007;29(8):1059–61.

    Article  PubMed  Google Scholar 

  26. Oktem 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(3):227–33.

    Article  PubMed  Google Scholar 

  27. Nishino Y, Takemura S, Minamiyama Y, et al. Targeting superoxide dismutase to renal proximal tubule cells attenuates vancomycin-induced nephrotoxicity in rats. Free Radic Res. 2003;37(4):373–9.

    Article  CAS  PubMed  Google Scholar 

  28. 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(9):1243–55.

    Article  CAS  PubMed  Google Scholar 

  29. van 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(2):734–44.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Knoderer CA, Nichols KR, Lyon K, et al. Are elevated vancomycin serum trough concentrations achieved within the first 7 days of therapy associated with acute kidney injury in children? J Pediatr Infect Dis Soc. 2014;3(2):127–31.

    Article  Google Scholar 

  31. Ragab AR, Al-Mazroua MK, Al-Harony MA. Incidence and predisposing factors of vancomycin-induced nephrotoxicity in children. Infect Dis Ther. 2013;2:37–46.

    Article  PubMed Central  PubMed  Google Scholar 

  32. Totapally BR, Machado J, Lee H, et al. Acute kidney injury during vancomycin therapy in critically ill children. Pharmacother. 2013;33(6):598–602.

    Article  CAS  Google Scholar 

  33. Cies JJ, Shankar VS. Nephrotoxicity in patients with vancomycin trough concentrations of 15–20 μg/ml in a pediatric intensive care unit. Pharmacotherapy. 2013;33(4):392–400.

    Article  CAS  PubMed  Google Scholar 

  34. Moffett BS, Hilvers PS, Dinh K, et al. Vancomycin-associated acute kidney injury in pediatric cardiac intensive care patients. Congenit Heart Dis. Epub 17 Jun 2014. doi:10.1111/chd.12187.

  35. Cano EL, Haque NZ, Welch VL, et al. Improving medicine through pathway assessment of critical therapy of hospital-acquired pneumonia (IMPACT-HAP) study group. Clin Ther. 2012;34:149–57.

    Article  CAS  PubMed  Google Scholar 

  36. Pritchard L, Baker C, Leggett J, et al. Increasing vancomycin serum concentrations and incidence of nephrotoxicity. Am J Med. 2010;123:1143–9.

    Article  CAS  PubMed  Google Scholar 

  37. Lodise TP, Patel N, Lomaestro BM, et al. Relationship between initial vancomycin concentration-time profile and nephrotoxicity among hospitalized patients. Clin Infect Dis. 2009;49:507–14.

    Article  CAS  PubMed  Google Scholar 

  38. Kuller R, Davis SL, Levine DP, et al. Impact of vancomycin exposure on outcomes in patients with methicillin-resistant Staphylococcus aureus bacteremia: support for consensus guidelines suggested targets. Clin Infect Dis. 2011;52:975–81.

    Article  Google Scholar 

  39. Neely MN, Youn G, Jones B, et al. Are vancomycin trough concentrations adequate for optimal dosing? Antimicrob Agents Chemother. 2014;58(1):309–16.

    Article  PubMed Central  PubMed  Google Scholar 

  40. 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 Chemother. 2012;67:17–24.

    Article  CAS  PubMed  Google Scholar 

  41. Akcan-Arikan A, Zappitelli M, Loftis LL, et al. Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int. 2007;71:1028–35.

    Article  CAS  PubMed  Google Scholar 

  42. Neuman G, Nulman I, Adeli K, et al. Implications of serum creatinine measurements on GFR estimation and vancomycin dosing in children. J Clin Pharmacol. 2014;54(7):785–91.

    Article  CAS  PubMed  Google Scholar 

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Conflicts of interest

K Patel, AS Crumby and HD Maples have no conflicts of interest.

Author information

Authors and Affiliations

  1. Infectious Diseases, Children’s Mercy Hospital, 2401 Gillham Rd, Kansas City, MO, 64108, USA

    Karisma Patel

  2. Department of Pharmacy Administration, University of Mississippi School of Pharmacy, P.O. Box 1848, University, MS, 38677-1848, USA

    Ashley S. Crumby

  3. Jeff and Kathy Lewis Sanders College of Pharmacy Chair in Pediatrics, Department of Pharmacy Practice, University of Arkansas for Medical Sciences College of Pharmacy, 4301 W Markham St #522, Little Rock, AR, 72205, USA

    Holly D. Maples

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  1. Karisma Patel
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  2. Ashley S. Crumby
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  3. Holly D. Maples
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Correspondence to Holly D. Maples.

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Patel, K., Crumby, A.S. & Maples, H.D. Balancing Vancomycin Efficacy and Nephrotoxicity: Should We Be Aiming for Trough or AUC/MIC?. Pediatr Drugs 17, 97–103 (2015). https://doi.org/10.1007/s40272-015-0117-5

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  • DOI: https://doi.org/10.1007/s40272-015-0117-5

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