Optimizing Antibiotic Treatment Strategies for Neonates and Children: Does Implementing Extended or Prolonged Infusion Provide any Advantage?

Paola Costenaro,Elisa Barbieri,Chiara Minotti,Carlo Giaquinto,Daniele Donà,Elena Cuppini

doi:10.3390/antibiotics9060329

Paola Costenaro, Elisa Barbieri + Show 4 more

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https://doi.org/10.3390/antibiotics9060329

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Abstract

Optimizing the use of antibiotics has become mandatory, particularly for the pediatric population where limited options are currently available. Selecting the dosing strategy may improve overall outcomes and limit the further development of antimicrobial resistance. Time-dependent antibiotics optimize their free concentration above the minimal inhibitory concentration (MIC) when administered by continuous infusion, however evidences from literature are still insufficient to recommend its widespread adoption. The aim of this review is to assess the state-of-the-art of intermittent versus prolonged intravenous administration of antibiotics in children and neonates with bacterial infections. We identified and reviewed relevant literature by searching PubMed, from 1 January 1 2000 to 15 April 2020. We included studies comparing intermittent versus prolonged/continuous antibiotic infusion, among the pediatric population. Nine relevant articles were selected, including RCTs, prospective and retrospective studies focusing on different infusion strategies of vancomycin, piperacillin/tazobactam, ceftazidime, cefepime and meropenem in the pediatric population. Prolonged and continuous infusions of antibiotics showed a greater probability of target attainment as compared to intermittent infusion regimens, with generally good clinical outcomes and safety profiles, however its impact in terms on efficacy, feasibility and toxicity is still open, with few studies led on children and adult data not being fully extendable.

Highlights

Infections acquired during hospitalization (HAIs) are challenging among vulnerable populations, neonates and children affected by chronic conditions such as immune deficiency or when admitted to the intensive care unit
This class of antibiotics exhibits time-dependent bactericidal activity against most gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus species; oral administration of glycopeptides is recommended for the management of Clostridium difficile infection [20]
The question whether time-dependent antibiotics should be administered in continuous or intermittent infusion is still open, with few studies led on children and adult data not being fully extendable

Summary

Introduction

Infections acquired during hospitalization (HAIs) are challenging among vulnerable populations, neonates and children affected by chronic conditions such as immune deficiency or when admitted to the intensive care unit. The emergency of multidrug resistant bacteria as a common cause of HAIs, with very limited treatment options available for pediatric use, increases the need of optimizing the use of currently employed antibiotics, focusing on the best dosing strategy to improve overall outcomes as well as to limit the further development of antimicrobial resistance. Composing the antimicrobial treatment puzzle is even more complex in neonates and children, due either to their age-related changes in physiological characteristics and to the limited antibiotic options that have already been approved for the pediatric population. Age-related differences in physiological characteristics have to be taken into account as they have an impact on the pharmacokinetic parameters of the administered drug, due to variations in absorption, distribution, metabolism and excretion [10]. Further variations in pharmacokinetics of mainly hydrophilic antimicrobials occur in critically ill neonates and children [11,12]

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