Efficacy and Safety of Continuous Infusion of Vancomycin in Children: A Systematic Review

Abstract

Vancomycin is used to treat a wide variety of infections within the pediatric population. In adults, continuous infusion of vancomycin (CIV) has been evaluated as an alternative to intermittent infusion of vancomycin (IIV) with potential advantages. In children, the use of CIV is increasing; however, data is currently limited. The objective is to provide efficacy and safety evidence for CIV within this population. The review was carried out following PRISMA guidelines. A bibliographic search was performed for studies on PubMed and EMBASE. Clinical trials and observational studies that reported clinical efficacy and/or target attainment of CIV in pediatrics were included. Articles were reviewed to assess their design and target population, characteristics of vancomycin treatment and the main findings in terms of safety and efficacy. A total of 359 articles were identified, of which seven met the inclusion criteria. All of them evaluated the target attainment, six assessed safety but only three assessed clinical efficacy. The best administration method for this antibiotic within the pediatric population is still unknown due to limited evidence. However, studies conducted thus far suggest pharmacokinetic advantages for CIV. Further investigation is required, in particular for studies comparing IIV with CIV for clinical efficacy and toxicity outcomes.

Evaluation of Continuous Infusion Vancomycin in a Pediatric Hematology/Oncology Population

“…Literature from both adult and pediatric patients has not shown an increased incidence of nephrotoxicity using CIV. 29 Consistent with these previously published studies, utilization of CIV did not elevate this risk in our patient population. An additional benefit of CIV is the ability to provide additional hydration with the CIV infusion itself, eliminating the need for an additional bag of IV fluids.…”

“…1 These findings are consistent with other recently published institutional cohort studies that also displayed lower TDD associated with continuous administration versus intermittent dosing. [28][29][30] Overall, lower TDD may be beneficial as higher daily doses of vancomycin have been shown to be associated with increased risk of nephrotoxicity. 28 Nephrotoxicity is a significant historical concern when using vancomycin, which requires vigilant monitoring of renal function throughout therapy.…”

The OBTAINS study: A nationwide cross-sectional survey on the implementation of extended or continuous infusion of β-lactams and vancomycin among neonatal sepsis patients in China

“…The potential barriers to its implementation might be mainly attributed to the lack of pharmacological knowledge, the absence of an MDT team, and the lack of confidence in clinical practice owing to limited efficacy and safety evidence in pediatrics. Recent published systematic reviews have demonstrated that EI/CI had generally improved clinical outcomes and safety profiles compared with intermittent infusion strategy, with a greater probability of achieving the target ( Costenaro et al, 2020 ; Alonso-Moreno et al, 2021 ; Zhou et al, 2021 ). It is undeniable that the EI/CI strategy has emerged as a promising option ( De Waele et al, 2014 ), even though PK of antibiotics may be affected in critically ill neonates undergoing significant physiological alterations and the appropriateness of EI/CI administration remains further PK/PD or clinical evaluation data ( Wang et al, 2020 ; Saito et al, 2021 ; Yonwises et al, 2021 ).…”

“…As time-dependent antibiotics, extended infusion (EI) or continuous infusion (CI) administration of β-lactams could theoretically lead to improved PK/PD profiles when the concentration remains above the minimum inhibitory concentration (MIC) of the causative pathogen (fT > MIC) for a longer duration ( Rizk et al, 2017 ; Veiga and Paiva, 2018 ). Vancomycin could also theoretically better meet PD targets when provided as prolonged administration ( DiMondi and Rafferty, 2013 ; Gwee et al, 2014 ; Alonso-Moreno et al, 2021 ). Although EI/CI administration for critically ill patients has been suggested by clinical practice guidelines ( Bretonnière et al, 2015 ; Egi et al, 2021 ; Evans et al, 2021 ), there lacks convincing evidence demonstrating its superiority compared with a short-term infusion or bolus dosing in children ( Zhou et al, 2021 ), and pediatricians seem to be not knowledgeable of it or to apply it frequently in clinical practice.…”

Comparison of the Areas Under the Curve of Vancomycin Continuous vs. Intermittent Infusion in Critically Ill Pediatrics: A Randomized Clinical Trial

“…Continuous infusions of vancomycin (CIV) is proposed as one method to achieve the desired AUC 24 /MIC. Continuous infusions of vancomycin delivers the desired serum concentration faster than the IIV method, reduces subtherapeutic episodes, and may decrease drug toxicity (1,4,19).…”