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Risk Factors for Non-Therapeutic Initial Steady-State Vancomycin Trough Concentrations in Children and Adolescents Receiving High Empiric Doses of Intravenous Vancomycin

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Abstract

Background

Achieving vancomycin troughs of 15–20 μg/mL remains challenging in children. Our objective was to identify risk factors associated with non-therapeutic initial vancomycin troughs in children.

Methods

We conducted a retrospective cohort study of children who received intravenous vancomycin with at least one initial steady-state trough obtained. Patients who achieved therapeutic troughs (15–20 μg/mL in the 20-mg/kg/dose sub-cohort and 10–15 μg/mL in the 15-mg/kg/dose sub-cohort) were compared with those with subtherapeutic troughs (<15 and <10 μg/mL, respectively) and supratherapeutic troughs (>20 and >15 μg/mL, respectively) separately to determine risk factors associated with non-therapeutic troughs.

Results

A total of 153 vancomycin courses in 140 patients met study eligibility criteria. Of 45 patients who received 20 mg/kg/dose of empiric vancomycin, 60, 16, and 24% were subtherapeutic, therapeutic, and supratherapeutic, respectively. Each 10-mL/min/1.73 m2 increase in initial creatinine clearance (CrCl) was associated with a 47% increase in the odds of an initial subtherapeutic trough (adjusted odds ratio [aOR] 1.47; 95% CI 0.98–2.22). Of 108 patients who received 15 mg/kg/dose of empiric vancomycin, 62, 19, and 19% were subtherapeutic, therapeutic, and supratherapeutic, respectively. Each 10-mL/min/1.73 m2 increase in initial CrCl was associated with an 18% increase in the odds of an initial subtherapeutic trough (aOR 1.18; 95% CI 1.02–1.37).

Conclusion

Achieving vancomycin troughs of 15–20 μg/mL for severe Gram-positive infections continues to be challenging in children, even at higher empiric doses of 20 mg/kg/dose IV every 6–8 h. Children with higher initial CrCls are particularly susceptible to subtherapeutic initial steady-state vancomycin troughs.

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References

  1. Rybak MJ, Lomaestro BM, Rotschafer JC, 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;11:1275–9.

    Article  Google Scholar 

  2. Moise-Broder PA, Forrest A, Birmingham MC, Schentag JJ. Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections. Clin Pharmacokinet. 2004;13:925–42.

    Article  Google Scholar 

  3. Kullar R, Davis SL, Levine DP, Rybak MJ. Impact of vancomycin exposure on outcomes in patients with methicillin-resistant Staphylococcus aureus bacteremia: support for consensus guidelines suggested targets. Clin Infect Dis. 2011;8:975–81.

    Article  Google Scholar 

  4. Kullar R, Davis SL, Taylor TN, Kaye KS, Rybak MJ. Effects of targeting higher vancomycin trough levels on clinical outcomes and costs in a matched patient cohort. Pharmacotherapy. 2012;3:195–201.

    Article  Google Scholar 

  5. Holmes NE, Turnidge JD, Munckhof WJ, et al. Vancomycin minimum inhibitory concentration, host comorbidities and mortality in Staphylococcus aureus bacteraemia. Clin Microbiol Infect. 2013;12:1163–8.

    Article  Google Scholar 

  6. Jung Y, Song KH, Cho J, et al. Area under the concentration-time curve to minimum inhibitory concentration ratio as a predictor of vancomycin treatment outcome in methicillin-resistant Staphylococcus aureus bacteraemia. Int J Antimicrob Agents. 2014;2:179–83.

    Article  Google Scholar 

  7. Zelenitsky S, Rubinstein E, Ariano R, et al. Vancomycin pharmacodynamics and survival in patients with methicillin-resistant Staphylococcus aureus-associated septic shock. Int J Antimicrob Agents. 2013;3:255–60.

    Article  Google Scholar 

  8. Sakoulas G, Eliopoulos GM, Moellering RC Jr, 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;6:929–38.

    Article  Google Scholar 

  9. Tsuji BT, Rybak MJ, Lau KL, Sakoulas G. Evaluation of accessory gene regulator (agr) group and function in the proclivity towards vancomycin intermediate resistance in Staphylococcus aureus. Antimicrob Agents Chemother. 2007;3:1089–91.

    Article  Google Scholar 

  10. Sakoulas G, Gold HS, Cohen RA, Venkataraman L, Moellering RC, Eliopoulos GM. Effects of prolonged vancomycin administration on methicillin-resistant Staphylococcus aureus (MRSA) in a patient with recurrent bacteraemia. J Antimicrob Chemother. 2006;4:699–704.

    Article  Google Scholar 

  11. 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. Clin Infect Dis. 2011;3:e18–55.

    Article  Google Scholar 

  12. Benner KW, Worthington MA, Kimberlin DW, Hill K, Buckley K, Tofil NM. Correlation of vancomycin dosing to serum concentrations in pediatric patients: a retrospective database review. J Pediatr Pharmacol Ther. 2009;2:86–93.

    Google Scholar 

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

    Article  Google Scholar 

  14. Casapao AM, Lodise TP, Davis SL, et al. Association between vancomycin day 1 exposure profile and outcomes among patients with methicillin-resistant Staphylococcus aureus infective endocarditis. Antimicrob Agents Chemother. 2015;59:2978–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Schwartz GJ, Munoz A, Schneider MF, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009;3:629–37.

    Article  Google Scholar 

  16. Kim DI, Im MS, Choi JH, Lee J, Choi EH, Lee HJ. Therapeutic monitoring of vancomycin according to initial dosing regimen in pediatric patients. Korean J Pediatr. 2010;12:1000–5.

    Article  Google Scholar 

  17. 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 Pediatric Infect Dis Soc. 2013;3:292.

    Article  Google Scholar 

  18. Eiland LS, English TM, Eiland EH 3rd. Assessment of vancomycin dosing and subsequent serum concentrations in pediatric patients. Ann Pharmacother. 2011;5:582–9.

    Article  Google Scholar 

  19. Broome L, So TY. An evaluation of initial vancomycin dosing in infants, children, and adolescents. Int J Pediatr 2011;2011:470364. doi:10.1155/2011/470364.

  20. Geerlof LM, Boucher J. Evaluation of vancomycin dosing and corresponding drug concentrations in pediatric patients. Hosp Pediatr. 2014;6:342–7.

    Article  Google Scholar 

  21. Frymoyer A, Guglielmo BJ, Wilson SD, Scarpace SB, Benet LZ, Hersh AL. Impact of a hospitalwide increase in empiric pediatric vancomycin dosing on initial trough concentrations. Pharmacotherapy. 2011;9:871–6.

    Article  Google Scholar 

  22. Rainkie D, Ensom MH, Carr R. Pediatric assessment of vancomycin empiric dosing (PAVED): a retrospective review. Paediatr Drugs. 2015;3:245–53.

    Article  Google Scholar 

  23. Hoang J, Dersch-Mills D, Bresee L, Kraft T, Vanderkooi OG. Achieving therapeutic vancomycin levels in pediatric patients. Can J Hosp Pharm. 2014;6:416–22.

    Google Scholar 

  24. Goutelle S, Neely M, Bleyzac N. Comment: assessment of vancomycin dosing and subsequent serum concentrations in pediatric patients. Ann Pharmacother. 2011;9:1171–2.

    Article  Google Scholar 

  25. McCabe T, Davis G, Iocono J, Nelson C, Kunh R. Evaluating the empiric dose of vancomycin in pediatric patients. J Pediatr Pharmacol Ther. 2009;3:154–92.

    Google Scholar 

  26. 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;3:422–6.

    Article  Google Scholar 

  27. Le J, Ny P, Capparelli E, et al. Pharmacodynamic characteristics of nephrotoxicity associated with vancomycin use in children. J Pediatric Infect Dis Soc. 2015;4(4):e109–16.

    Article  PubMed  Google Scholar 

  28. Knoderer CA, Nichols KR, Lyon KC, Veverka MM, Wilson AC. Are elevated vancomycin serum trough concentrations achieved within the first 7 days of therapy associated with acute kidney injury in children? J Pediatric Infect Dis Soc. 2014;2:127–31.

    Article  Google Scholar 

  29. Sinclair EA, Yenokyan G, McMunn A, Fadrowski JJ, Milstone AM, Lee CK. Factors associated with acute kidney injury in children receiving vancomycin. Ann Pharmacother. 2014;12:1555–62.

    Article  Google Scholar 

  30. Mohr JF, Murray BE. Point: vancomycin is not obsolete for the treatment of infection caused by methicillin-resistant Staphylococcus aureus. Clin Infect Dis. 2007;12:1536–42.

    Article  Google Scholar 

  31. Frymoyer A, Guglielmo BJ, Hersh AL. Desired vancomycin trough serum concentration for treating invasive methicillin-resistant Staphylococcal infections. Pediatr Infect Dis J. 2013;10:1077–9.

    Article  Google Scholar 

  32. Le J, Bradley JS, Murray W, et al. Improved vancomycin dosing in children using area under the curve exposure. Pediatr Infect Dis J. 2013;4:e155–63.

    Article  Google Scholar 

  33. Silva DC, Seixas GT, Araujo OR, Arduini RG, Carlesse FA, Petrilli AS. Vancomycin serum concentrations in pediatric oncologic/hematologic intensive care patients. Braz J Infect Dis. 2012;4:361–5.

    Google Scholar 

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Acknowledgements

The authors would like to thank Janet Lee, Pharm.D., Jamie Rouch, Pharm.D., and Mercedes Vilasoa for their contribution to data collection. This study was presented in part at the American Society of Health-System Pharmacists Midyear Clinical Meeting and United Health-System Consortium; New Orleans, LA, USA, December 2011.

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    Authors and Affiliations

    1. Department of Pharmacy, Intermountain Medical Center, Murray, UT, USA

      Whitney R. Buckel

    2. Division of Pediatric Pharmacy, Department of Pharmacy, The Johns Hopkins Hospital, 600 N. Wolfe Street, Carnegie 180, Baltimore, MD, 21287, USA

      Shahira Ghobrial & Alice J. Hsu

    3. Division of Pediatric Infectious Diseases, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

      Pranita D. Tamma, Aaron M. Milstone & Yuan Zhao

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    1. Whitney R. Buckel
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    2. Shahira Ghobrial
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    Correspondence to Alice J. Hsu.

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    No funding was received by any of the authors for the preparation of this manuscript.

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    WRB, SG, PDT, AMM, YZ, and AJH do not have any conflicts of interests to disclose.

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    W. R. Buckel and S. Ghobrial contributed equally.

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    Buckel, W.R., Ghobrial, S., Tamma, P.D. et al. Risk Factors for Non-Therapeutic Initial Steady-State Vancomycin Trough Concentrations in Children and Adolescents Receiving High Empiric Doses of Intravenous Vancomycin. Pediatr Drugs 19, 43–51 (2017). https://doi.org/10.1007/s40272-016-0202-4

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