Clinical Pharmacokinetics of Vancomycin in Critically Ill Children
- 10 Downloads
Background and Objective
Critically ill children exhibit altered pharmacokinetic parameters of vancomycin, mainly due to altered renal excretion and volume of distribution (as a result of altered plasma protein concentrations). We assessed the pharmacokinetic parameters of vancomycin in this subpopulation.
Vancomycin trough concentrations in critically ill children were obtained following first dose and at steady state. Using a one-compartment model, clearance (CL), volume of distribution (Vd), elimination half-life (t1/2), and area under the time–concentration curve for 24 h (AUC0–24) were estimated. Subgroup analyses were carried out, with patients differentiated based on age, renal clearance, outcome, and renal dysfunction. Protein-free vancomycin concentrations were calculated using a previously reported formula.
Twenty-two samples were evaluated for first-dose and 182 for steady-state pharmacokinetics, and similar pharmacokinetic parameter values were observed at first dose and at steady state. Only 36.4% and 47.3% of the samples attained the recommended AUC0–24 (mg·hr/L) of > 400 at first dose and at steady state, while 62.5% of the patients with renal dysfunction achieved this target. Nearly 40% of the patients had augmented renal clearance (ARC), which was associated with higher CL, shorter t1/2, and lower AUC values. Amongst the patients with ARC, none had AUC0–24 (mg·hr/L) > 400 at first dose, while 16% achieved this target at steady state. Volume of distribution was significantly higher in infants and a decreasing trend was observed in toddlers, children, and older children at steady state. Children with renal dysfunction had lower CL, prolonged t1/2, and higher AUC values than patients with normal renal clearance at first dose. A good correlation was observed between trough concentration and AUC0–24, as corroborated by the area under the receiver operating characteristic curve. The median fraction of protein-free vancomycin was around 77%.
Vancomycin dosing strategies in younger children should be revisited, and increased doses should be considered for critically ill children with ARC in order to achieve therapeutic concentrations of AUC0–24.
Compliance with Ethical Standards
No funding was received to conduct this study.
Conflict of Interest
The authors have no conflict of interest.
The study was carried out after obtaining approval from the relevant ethics committees.
Since it was a retrospective study using anonymised data consent from patients was not required.
- 3.Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, Rybak JM, Talan DA, Chambers HF. Infectious Diseases Society of America. 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;52:e18–55.Google Scholar
- 5.Van Der Heggen T, Dhont E, Peperstraete H, Delanghe JR, Vande Walle J, De Paepe P, De Cock PA. Augmented renal clearance: a common condition in critically ill children. Pediatr Nephrol. 2019;34(6):1099–106. https://doi.org/10.1007/s00467-019-04205-x.
- 13.Shull BC, Haughey D, Koup JR, Baliah T, Li PK. A useful method for predicting creatinine clearance in children. Clin Chem. 1978;24:1167–9.Google Scholar
- 15.Matzke GR, Kovarik JM, et al. Evaluation of the vancomycin-clearance: creatinine-clearance relationship for predicting vancomycin dosage. Clin Pharm. 1985;4:311–5.Google Scholar
- 16.RxKinetics. Pharmacokinetic modeling of vancomycin. Plattsburg: RxKinetics; 2017. http://www.rxkinetics.com/vanmodel.html. Accessed on 3 May 2019.
- 17.Gawronski KM, Goff DA, Brown J, Khadem TM, Bauer KA. A stewardship program’s retrospective evaluation of vancomycin AUC24/MIC and time to microbiological clearance in patients with methicillin-resistant Staphylococcus aureus bacteremia and osteomyelitis. Clin Ther. 2013;35:772–9.Google Scholar
- 18.De Cock PA, Desmet S, De Jaeger A, Biarent D, Dhont E, Herck I, Vens D, Colman S, Stove V, Commeyne S, Vande Walle J, De Paepe P. Impact of vancomycin protein binding on target attainment in critically ill children: back to the drawing board? J Antimicrob Chemother. 2017;72:801–4.Google Scholar
- 20.Martin JH, Norris R, Barras M, Roberts J, Morris R, Doogue M, Jones GR. 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. Clin Biochem Rev. 2010;31:21–4.Google Scholar
- 25.Albrecht LM, Rybak MJ, Warbasse LH, Edwards DJ. Vancomycin protein binding in patients with infections caused by Staphylococcus aureus. DICP. 1991;25:713–5.Google Scholar
- 26.Rybak M, Lomaestro B, Rotschafer JC, Moellering R Jr, Craig W, Billeter M, Dalovisio JR, Levine DP. 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 Syst Pharm. 2009;66:82–98.Google Scholar
- 28.Delicourt A, Bussières JF, Lebel D. Pediatric pharmacokinetics of vancomycin: a Canadian perspective. Can J Hosp Pharm. 2011;64:156–7.Google Scholar
- 30.Arun A, Swamy S, Jacob K, Sharma R, Kohlhoff SA, Hammerschlag MR. Evaluation of clinical outcome in children and adolescents receiving vancomycin for invasive infections due to methicillin-resistant Staphylococcus aureus: impact of increasing vancomycin MICs. Minerva Pediatr. 2018;70:207–11.Google Scholar
- 37.Kishk OA, Lardieri AB, Heil EL, Morgan JA. Vancomycin AUC/MIC and corresponding troughs in a pediatric population. J Pediatr Pharmacol Ther. 2017;22:41–7.Google Scholar
- 39.Tkachuk S, Collins K, Ensom MHH. The relationship between vancomycin trough concentrations and AUC/MIC ratios in pediatric patients: a qualitative systematic review. Paediatr Drugs. 2018;20:153–64.Google Scholar