A Review of Extended and Continuous Infusion Beta-Lactams in Pediatric Patients

Abstract

Intravenous beta-lactam antibiotics are the most prescribed antibiotic class in US hospitalized patients of all ages; therefore, optimizing their dosing is crucial. Bactericidal killing is best predicted by the time in which beta-lactam drug concentrations are maintained above the organism's minimum inhibitory concentration (MIC), rather than achievement of a high peak concentration. As such, administration of beta-lactam antibiotics via extended or continuous infusions over a minimum of 3 hours, rather than standard infusions over approximately 30 minutes, has been associated with improved achievement of pharmacodynamic targets and improved clinical outcomes in adult medical literature. This review summarizes the pediatric medical literature. Applicable studies include pharmacodynamic models, case series, retrospective analyses, and prospective studies on the use of extended infusion and continuous infusion penicillins, cephalosporins, carbapenems, and monobactams in neonates, infants, children, and adolescents. Specialized patient populations with unique pharmacokinetics and high-risk infections (neonates, critically ill, febrile neutropenia, cystic fibrosis) are also reviewed. While more studies are needed to confirm prospective clinical outcomes, the current body of evidence suggests extended and continuous infusions of beta-lactam antibiotics are well tolerated in children and improve achievement of pharmacokineticpharmacodynamic targets with similar or superior clinical outcomes, particularly in infections associated with high MICs.

Extended Infusion of Beta-Lactams and Glycopeptides: A New Era in Pediatric Care? A Systematic Review and Meta-Analysis

“…COI of beta-lactams and glycopeptides aligns better with the PK/PD profile than IA [49,52]. Our findings, demonstrating safety and efficacy benefits in pediatric patients, are supported by a review on COI use in the pediatric population [7,49,53,54]. Cheng et al also reported that COI of meropenem was more effective in treating sepsis than IA [55].…”

Appropriate Use of Antibiotic and Principles of Antimicrobial Stewardship in Children

“…If intravenous administration is started, the ideal schedule, currently under evaluation for many parenteral molecules (piperacillin–tazobactam, vancomycin, etc.) provides a loading dose to reach the effective concentration above the MIC, which is followed by continuous infusion to ensure T > MIC is maintained as long as possible [ 44 , 45 ] ( Figure 2 ). If antibiotics are administered orally, multiple daily doses should be preferred ( Figure 3 ): i.e., for amoxicillin, administration every 8 h is better than every 12 h [ 29 ].…”

Uso appropriato degli antibiotici e stewardship in pediatria

“…In termini pratici, gli antibiotici tempo-dipendenti (penicilline, cefalosporine, carbapenemi, vancomicina, clindamicina) hanno bisogno di mantenere concentrazioni plasmatiche stabili oltre la MIC, senza che sia necessario raggiungere picchi plasmatici elevati. La somministrazione ideale, attualmente in valutazione per molte molecole parenterali di questo tipo, prevede una dose di carico che serve a raggiungere rapidamente la concentrazione efficace sopra la MIC, seguita dall'infusione continua per garantire che il T>MIC sia mantenuto il più a lungo possibile [19][20].…”