What is the utility of prolonged infusion versus short infusion of beta-lactam antibiotics in pediatric patients?

From the Guidelines

Prolonging all beta-lactam antibiotic infusions is not necessary for pediatric patients, as the benefits of prolonged infusions are smaller in pediatric patients compared to adults. When presenting to the pediatric department staff, you can explain that while prolonged infusions of beta-lactams have shown significant benefits in adult populations, particularly for treating resistant organisms, these benefits are not as pronounced in children. The pharmacokinetic and pharmacodynamic properties of beta-lactams differ between pediatric and adult patients due to differences in drug distribution, metabolism, and elimination. Children often achieve adequate drug concentrations with standard short infusions because they typically have better renal function and different volume of distribution compared to adults. Some key points to consider include:

• Pediatric patients generally have lower rates of multidrug-resistant infections than adults in many clinical settings, reducing the need for optimization strategies like prolonged infusions 1.
• The probability of target attainment (PTA) with prolonged infusion is worse than with short infusion when treating multidrug-resistant organisms in pediatric patients.
• Numerous studies of the pharmacokinetics of beta-lactam antibiotics in children and simulations in this patient population support the use of standard short infusions in pediatric patients 1.
• Therapeutic drug monitoring (TDM) of antibiotics is recommended in intensive care unit adults and pediatric patients to account for large unpredictable pharmacokinetic variability 1. This doesn't mean prolonged infusions have no role in pediatrics, but rather that a universal approach of prolonging all beta-lactam infusions is not necessary for pediatric patients based on current evidence. Key considerations for the use of prolonged-infusion beta-lactam antibiotics in pediatric patients include:
• The severity of the infection and the susceptibility of the causative organism to the antibiotic.
• The patient's renal function and volume of distribution.
• The potential for drug toxicity and the need for therapeutic drug monitoring. In general, the decision to use prolonged-infusion beta-lactam antibiotics in pediatric patients should be made on a case-by-case basis, taking into account the individual patient's needs and circumstances.

From the Research

Comparative Data on Prolonged Infusion and Short Infusion for Beta-Lactam Antibiotics

• The pediatric department staff requested comparative data on the utility of prolonged infusion and short infusion for beta-lactam antibiotics in pediatric patients.
• Based on the available data, it was concluded that prolonging all beta-lactam antibiotic infusions is not necessary for pediatric patients.
• The following explanations support this conclusion:
  • Numerous studies of the pharmacokinetics of beta-lactam antibiotics in children and simulations in this patient population show that the probability of target attainment (PTA) with prolonged infusion is worse than with short infusion when treating multidrug-resistant organisms 2.
  • The magnitude of the benefit for use of prolonged-infusion beta-lactam antibiotics is smaller in pediatric patients than in adults.
  • More data are available for prolonged-infusion beta-lactam antibiotics in pediatric patients compared with adult patients, especially for treating infections caused by gram-positive organisms.
  • There is no evidence to suggest that prolonged-infusion beta-lactams have fewer toxicities than short infusions in pediatric patients.

Evidence from Studies

• A study published in 2019 evaluated the use and clinical efficacy of extended-infusion (EI) beta-lactam antibiotics, including piperacillin-tazobactam, meropenem, and cefepime 2.
• Another study published in 2007 discussed the broad spectrum of antibacterial activity of piperacillin-tazobactam, a beta-lactam/beta-lactamase inhibitor combination 3.
• A 2022 study compared the pharmacodynamic activity of piperacillin-tazobactam and amikacin as mono and combination therapy versus meropenem monotherapy against extended-spectrum β-lactamase (ESBL)-producing E. coli 4.
• A 2024 systematic review and meta-analysis compared the clinical and microbiological outcomes of patients treated with piperacillin/tazobactam, cefepime, or carbapenems for bloodstream infections due to chromosomal AmpC beta-lactamase-producing Enterobacterales 5.
• A 2017 case-control study assessed the clinical effectiveness of piperacillin-tazobactam compared to cefepime or meropenem for treatment of bloodstream infections due to AmpC β-lactamase-producing Enterobacteriaceae 6.