Bayesian Estimation of Vancomycin Pharmacokinetics in Obese Children: Matched Case-Control Study

Abstract

Purpose The study objective was to compare different body size descriptors that best estimate vancomycin Vd and clearance (CL). Methods Patients between 3 months and 21 years old who received vancomycin for ≥48 hours from 2003 to 2011 were evaluated in this matched case-control study. Cases had body mass index in the ≥85th percentile; controls were nonobese individuals who were matched by age and baseline serum creatinine (SCr). Using a 1-compartment model with first-order kinetics, Bayesian post hoc individual Vd and CL were estimated. Findings Analysis included 87 matched pairs with 389 vancomycin serum concentrations. Median ages were 10.0 (interquartile range [IQR], 4.8–15.2) years for cases (overweight and obese children) and 10.2 (IQR, 4.5–14.8) years for controls (normal-weight children). Median weights were 44.0 (IQR, 23.4–78.1) kg for cases and 31.3 (IQR, 16.8–47.1) kg for controls. Mean (SD) for the baseline SCr values were also similar between the groups: 0.51 (0.22) (IQR, 0.34–0.67) mg/dL and 0.48 (0.20) (IQR, 0.30–0.60) mg/dL for the cases and controls, respectively. Actual weight and allometric weight (ie, weight0.75) were used in the final model to estimate Vd and CL, respectively. The mean Vd and CL, based on weight, for cases were lower than controls by 0.012 L/kg and 0.014 L/kg/h, respectively. Implications In obese children, actual weight and allometric weight are reasonable, convenient estimations of body fat to use for estimating vancomycin Vd and CL, respectively. However, these pharmacokinetic differences between obese children and those with normal weights are small and may not likely to be clinically relevant in dose variation.

Continuous intravenous vancomycin in children with normal renal function hospitalized in hematology–oncology: prospective validation of a dosing regimen optimizing steady‐state concentration

“…BMI did not influence vancomycin target Css achievement. This is also consistent with previous studies showing that vancomycin clearance was similar in both obese and normal-weight children [35,36]. This may be due to the distribution characteristics of vancomycin, which mainly diffuses into extracellular fluids.…”

Review of vancomycin-induced renal toxicity: an update

“…Apparently influenced by the retrospective design, the results of such studies are inconsistent. Few studies showed higher vancomycin trough concentration in the absence of weight adjustment but most data found no difference in comparison with the controls [Heble et al 2013;Le et al 2015;Eiland and Sonawane, 2014]. Because sample sizes of the studies are often small, there may be a lack of adequate power to detect a significant difference.…”

Childhood obesity: Pharmacokinetics considerations for drugs used in the Intensive Care Unit

“…Vancomycin is one of the most studied antibiotics in obese children. [71][72][73][74][75] It is widely distributed in fluids and body tissues and is mostly excreted by glomerular filtration. Pharmacokinetic studies in adults show a strong correlation between TBW and the Vd and clearance.…”

“…On the contrary, in the pediatric population, no differences between obese and normal weight children have been demonstrated. 74 Three retrospective cohort studies conducted in the pediatric population 71,72,75 concluded that obese children had higher vancomycin levels (trough level) than normal weight children at a similar dose of mg/kg of TBW.…”

“…76 At present, the recommendation is to use a 60 mg/kg/day maintenance dose (divided in doses every 8 hours) adjusted by TBW accompanied by monitoring of therapeutic levels. 74 For patients with severe infections, a 25-30 mg/kg initial loading dose adjusted by TBW is recommended so that trough levels are achieved rapidly (15-20 mcg/mL). 77,78…”