Continuous and Extended Infusions of β-lactam Antibiotics in the Pediatric Population

Objective: To conduct a systematic review of available data on the use of extended or continuous infusion of β-lactam and monobactam therapy in the pediatric population (aged 0-18 years).

Data Sources: A literature search was performed using PubMed (1975-May 2012), International Pharmaceutical Abstracts (1970-May 2012), and Web of Science (1977-May 2012) to identify studies for inclusion. In addition, reference citations from identified publications were reviewed. The following search terms were used: pediatric, children, neonate, infant, adolescent, β-lactam, cephalosporin, carbapenem, penicillin, monobactam, continuous infusion, extended infusion, and/or prolonged infusion. Individual names of drugs in each class of antibiotics were also included in the search.

Study Selection And Data Extraction: Randomized controlled clinical trials, pharmacokinetic/pharmacodynamic studies, observational studies, and case reports involving pediatric patients who received extended or continuous infusion of β-lactam or monobactam antibiotics were reviewed. Only English-language publications were included.

Data Synthesis: One randomized controlled clinical trial, 5 pharmacokinetic studies, 2 pharmacodynamic studies using Monte Carlo simulation, 1 case series, and 7 case reports were included in the analysis. The cephalosporin class has been studied the most and currently represents the only clinical trial using a continuous infusion dosing strategy in pediatric patients. There is limited clinical evidence available to support the use of extended or continuous infusion of β-lactam antibiotics in the pediatric population. Pharmacodynamic studies conducted in this population mirror the current evidence in adults for cefepime and meropenem. The single prospective clinical trial using continuous infusion of ceftazidime failed to demonstrate any clinical benefit over traditional dosing; however, there was equal efficacy.

Conclusions: More well-designed prospective clinical trials are required to determine the role of extended or continuous infusion of β-lactam antibiotics in treatment of pediatric patients.