Children's Continuous Infusion of Vancomycin
Vancomycin is a glycopeptide antibiotic used to treat a wide variety of systemic Gram-positive infections, including methicillin resistantStaphylococcus aureus(MRSA) and methicillin resistant coagulase-negativeStaphylococcus(MRCNS) in adult and pediatric populations. Vancomycin exhibits time-dependent bactericidal activity, meaning that the time in which the concentration of the drug in the body is above the minimum inhibitory concentration (MIC) affects antimicrobial efficacy.
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In adults, the vancomycin area under the plasma concentration-time curve (AUC) to MIC ratio (AUC/MIC) > 400 has long been the best predictor of clinical and bacteriological efficacy for patients with severe infections caused by MRSA . Recently, a revised consensus guideline developed by different scientific associations has been published, recommending a target of an AUC/MIC ratio of 400 to 600 (assuming a MIC of 1 mg/L) for empiric dosing in both adult and pediatric patients to maximize clinical efficacy and minimize nephrotoxicity . However, there is a lack of evidence for this parameter in children due to the complexity of vancomycin clearance in the various pediatric age groups, and the differences in tissue site-of-infection drug exposure as a consequence of higher pharmacokinetic variability . Due to the impracticalities of calculating the AUC, target trough concentrations of 15 to 20 mg/L are used as a surrogate marker in adults with normal renal function when MIC is ≤1 mg/mL . For the pediatric population, there is more controversy in establishing a target trough concentration. The majority of studies suggest a trough concentration between 6–11 mg/L to achieve AUC/MIC > 400, however no consensus has been reached .
In adults, continuous infusion of vancomycin (CIV) has been evaluated as an alternative to intermittent infusion of vancomycin (IIV) with potential advantages including: earlier concentration target attainment, less variability in serum concentrations, ease of drug level monitoring, and lower risk of nephrotoxicity . When compared to adults, achieving therapeutic serum vancomycin concentrations (SVCs) with IIV in children requires higher doses and shorter intervals given their increased renal clearance . However, higher doses have also been associated with increased nephrotoxicity in pediatrics .
This systematic review aims to provide efficacy and safety evidence for CIV within the pediatric population
2. Clinical Efficacy
- Hwang, D.; Chiu, N.C.; Chang, L.; Peng, C.C.; Huang, D.T.; Huang, F.Y.; Chi, H. Vancomycin dosing and target attainment in children. J. Microbiol. Immunol. Infect. 2017, 50, 494–499.
- Rybak, M.J.; Le, J.; Lodise, T.P.; Levine, D.P.; Bradley, J.S.; Liu, C.; Mueller, B.A.; Pai, M.P.; Wong-Beringer, A.; Rotschafer, J.C.; et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am. J. Health Pharm. 2020, 77, 835–864.
- Fiorito, T.; Luther, M.K.; Dennehy, P.H.; LaPlante, K.; Matson, K.L. Nephrotoxicity with Vancomycin in the Pediatric Population: A Systematic Review and Meta-Analysis. Pediatr. Infect. Dis. J. 2018, 37, 654–661.
- Liu, C.; Bayer, A.; Cosgrove, S.E.; Daum, R.S.; Fridkin, S.K.; Gorwitz, R.J.; Kaplan, S.L.; Karchmer, A.W.; Levine, D.P.; Murray, B.E.; 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, 285–292.
- Rybak, M.; Lomaestro, B.; Rotschafer, J.C.; Moellering, R.; Craig, W.; Billeter, M.; Dalovisio, J.R.; Levine, D.P. 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 Diseases Pharmacists. Am. J. Health Pharm. 2009, 66, 82–98.
- Tkachuk, S.; Collins, K.; Ensom, M.H.H. The Relationship Between Vancomycin Trough Concentrations and AUC/MIC Ratios in Pediatric Patients: A Qualitative Systematic Review. Pediatr. Drugs 2018, 20, 153–164.
- Kishk, O.A.; Lardieri, A.B.; Heil, E.L.; Morgan, J.A. Vancomycin AUC/MIC and Corresponding Troughs in a Pediatric Population. J. Pediatr. Pharmacol. Ther. 2017, 22, 41–47.
- Frymoyer, A.; Guglielmo, B.J.; Hersh, A.L. Desired Vancomycin Trough Serum Concentration for Treating Invasive Methicillin-resistant Staphylococcal Infections. Pediatr. Infect. Dis. J. 2013, 32, 1077–1079.
- Chu, Y.; Luo, Y.; Quan, X.; Jiang, M.; Zhou, B. Intermittent vs. continuous vancomycin infusion for gram-positive infections: A systematic review and meta-analysis. J. Infect. Public Health 2020, 13, 591–597.
- Van Maarseveen, E.M.; Gipmans, S.G.H.; Van Zanten, A.R.H. Exposure Variability and Target Attainment of Vancomycin: A Systematic Review Comparing Intermittent and Continuous Infusion. Ther. Drug Monit. 2020, 42, 381–391.
- Hurst, A.L.; Baumgartner, C.; MacBrayne, C.E.; Child, J. Experience with Continuous Infusion Vancomycin Dosing in a Large Pediatric Hospital. J. Pediatr. Infect. Dis. Soc. 2018, 8, 174–179.
- Veluzat, S.; Pauquet, E.; Sarlangue, J. Practice survey on the use of vancomycin in pediatrics in the New Aquitaine region and guidelines of learned societies. Arch. Pédiatr. 2020, 27, 176–182.
- Genuini, M.; Oualha, M.; Bouazza, N.; Moulin, F.; Treluyer, J.-M.; Lesage, F.; Renolleau, S.; Benaboud, S. Achievement of Therapeutic Vancomycin Exposure with Continuous Infusion in Critically Ill Children. Pediatr. Crit. Care Med. 2018, 19, e263–e269.
- Berthaud, R.; Benaboud, S.; Hirt, D.; Genuini, M.; Oualha, M.; Castelle, M.; Briand, C.; Artru, S.; Norsa, L.; Boyer, O.; et al. Early Bayesian Dose Adjustment of Vancomycin Continuous Infusion in Children in a Randomized Controlled Trial. Antimicrob. Agents Chemother. 2019, 63.
- Fung, L. Continuous Infusion Vancomycin for Treatment of Methicillin-Resistant Staphylococcus aureus in Cystic Fibrosis Patients. Ann. Pharmacother. 2012, 46, 1437.
- Zylbersztajn, B.L.; Chicco, P.; Vega, L.; Centeno, M.; Filippini, S.; Ruvinsky, S. Continuous infusion of vancomycin in pediatric critical care. Arch. Argent. Pediatr. 2013, 111, e31-4.
- Hoegy, D.; Goutelle, S.; Garnier, N.; Rénard, C.; Faure-Conter, C.; Bergeron, C.; Bertrand, Y.; Bleyzac, N. Continuous intravenous vancomycin in children with normal renal function hospitalized in hematology-oncology: Prospective validation of a dosing regimen optimizing steady-state concentration. Fundam. Clin. Pharmacol. 2018, 32, 323–329.
- McKamy, S.; Chen, T.; Lee, M.; Ambrose, P.J. Evaluation of a pediatric continuous-infusion vancomycin therapy guideline. Am. J. Health-Syst. Pharm. 2012, 69, 2066–2071.
- Lopes, J.A.; Jorge, S. The RIFLE and AKIN classifications for acute kidney injury: A critical and comprehensive review. Clin. Kidney J. 2013, 6, 8–14.
- Murphy, J.E. Clinical Pharmacokinetics, 6th ed.; American Society of Health–System Pharmacists: Bethesda, MD, USA, 2016.
- Madigan, T.; Sieve, R.M.; Graner, K.K.; Banerjee, R. The Effect of Age and Weight on Vancomycin Serum Trough Concentrations in Pediatric Patients. Pharmacother. J. Hum. Pharmacol. Drug Ther. 2013, 33, 1264–1272.
- Le, J.; Bradley, J.S.; Murray, W.; Romanowski, G.L.; Tran, T.T.; Nguyen, N.; Cho, S.; Natale, S.; Bui, I.; Tran, T.M.; et al. Improved Vancomycin Dosing in Children Using Area Under the Curve Exposure. Pediatr. Infect. Dis. J. 2013, 32, e155–e163.
- Girand, H.L. Continuous Infusion Vancomycin in Pediatric Patients: A Critical Review of the Evidence. J. Pediatr. Pharmacol. Ther. JPPT Off. J. PPAG 2020, 25, 198–214.
- Waineo, M.F.; Kuhn, T.C.; Brown, D.L. The pharmacokinetic/pharmacodynamic rationale for administering vancomycin via continuous infusion. J. Clin. Pharm. Ther. 2015, 40, 259–265.
- Hao, J.-J.; Chen, H.; Zhou, J.-X. Continuous versus intermittent infusion of vancomycin in adult patients: A systematic review and meta-analysis. Int. J. Antimicrob. Agents 2016, 47, 28–35.
- Cataldo, M.A.; 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. 2011, 67, 17–24.