Vancomycin is commonly under‐dosed in critically ill children and neonates

Abstract

Aims Vancomycin is frequently used in critically ill children in whom the drug pharmacokinetics are significantly altered as a result of changes in renal clearance and volume of distribution. Therapeutic drug monitoring (TDM) is recommended to achieve vancomycin trough concentrations between 10 and 20 mg/L. In this study we reviewed vancomycin dosing, TDM and treatment outcomes in paediatric and neonatal intensive care unit patients. Methods We reviewed the medical records of all patients receiving intravenous vancomycin in a tertiary paediatric and neonatal intensive care unit over a 10‐month period. Demographic, vancomycin dosing, TDM and drug‐related adverse effects data were collected. Results In total, 115 children received 126 courses of vancomycin and had at least 1 TDM blood sample taken at steady state. In only 38/126 (30%) courses was the target concentration (10–20 mg/L) achieved at the initial steady state trough sample. Of the 88 courses that had initial trough concentrations outside the target range, the dose was adjusted in only 49 (56%). Overall, minimum doses of 30 mg/kg/day in neonates with a corrected gestational age of <35 weeks, and 50 mg/kg/day in older children, were required to achieve target vancomycin concentrations. Vancomycin‐attributable nephrotoxicity occurred in 10/126 (8%) courses and there were no episodes of red man syndrome. Conclusion In critically ill children, individualised dosing is needed. In the absence of Bayesian model‐based dosing, in children with normal renal function, empiric vancomycin doses of at least 30 mg/kg/day in neonates of <35 weeks corrected gestational age, and 50 mg/kg/day in older children, should be considered. Optimisation of TDM practices through the development of protocols, ideally built into electronic medical records, should be considered.

<p>Vancomycin Dosage and Its Association with Clinical Outcomes in Pediatric Patients with Gram-Positive Bacterial Infections</p>

“…As a result, insufficient vancomycin dosages and suboptimal trough levels have been frequently encountered among pediatric patients in real-world practice. Our findings regarding a high incidence of subtherapeutic levels in children are consistent with the data in previous studies that reported the issue of insufficient doses of vancomycin commonly administered to pediatric patients [9][10][11][12][13][14][15][16][17] and that also suggested a higher empiric dose of at least 50-60 mg/ kg/day in children with no renal impairment. [9][10][11]…”

“…7,8 This phenomenon leaves clinicians uncertain about optimal dosing and target troughs of vancomycin in this patient population. Some studies confirmed that vancomycin is frequently under-dosed, resulting in insufficient serum concentrations in pediatric patients, and suggested a higher empiric vancomycin dose of at least 50-60 mg/kg/day in critically ill children with no renal impairment [9][10][11] or a loading dose of 18-24 mg/kg in case of positive fluid balance. 12 Several other clinical studies also suggested a higher dose or an extended infusion of vancomycin in pediatric patients to improve target-attainment but without providing a dosing advice for these patients.…”

Early Life Antibiotics Influence In Vivo and In Vitro Mouse Intestinal Epithelium Maturation and Functioning

“…Recently, our group developed an in vitro model to study gut neonatal development using a prolonged culture of fetal mice gut organoids. We established that fetal organoids isolated from the intestine of mice at late fetal stage (embryonic day 19) undergo intrinsic maturation in vitro, recapitulate sucklingto-weaning transition, and that extrinsic factors can be applied to the culture to investigate whether they can modulate intestinal epithelial maturation. 80,81 Here, we combined 2 different approaches to study how ABs affect the neonatal intestinal epithelium.…”

“… 11 , 15 , 16 , 17 , 18 Upon onset of systemic or gastrointestinal infections with gram-positive bacteria, especially in the case of Staphylococcus aureus and Clostridium difficile , vancomycin is administered. 5 , 8 , 11 , 19 , 20 , 21 , 22 The combined use of the earlier-mentioned ABs is also common. 8 , 11 , 17 , 20 , 21 , 22 Although ABs have a crucial and beneficial role in treating bacterial infections, they also have several short- and long-term detrimental effects.…”

A Proof of Concept of the Role of TDM-Based Clinical Pharmacological Advices in Optimizing Antimicrobial Therapy on Real-Time in Different Paediatric Settings

“…Antimicrobial TDM may be very helpful in this challenging scenario, considering that in the newborns the relationship between drug dose and exposure is quite unpredictable, especially in the pre-terms, due to the abrupt developmental physiological changes that occur in this age period (Pauwels and Allegaert, 2016;De Rose et al, 2020). In this regard, several evidences support the potential role of TDM in the management of neonatal sepsis (Hoff et al, 2009;Touw et al, 2009;Sicard et al, 2015;Sosnin et al, 2019;Tauzin et al, 2019).…”