Evaluation of studies on extended versus standard infusion of beta-lactam antibiotics

Abstract

Purpose: To summarize the current literature on the use and clinical efficacy of extended-infusion (EI) beta-lactam antibiotics, including piperacillin-tazobactam, meropenem, and cefepime.

Summary: Gram-negative infections are a serious concern among hospitalized patients and require innovative pharmacokinetic dosing strategies to achieve clinical success, especially as the emergence of resistant gram-negative pathogens has outpaced the development of new antibiotics. Beta-lactam antibiotics exhibit time-dependent activity, which means that optimal efficacy is achieved when free drug concentrations stay above the minimum inhibitory concentration for an extended duration of the recommended dosage interval. EI piperacillin-tazobactam therapy has demonstrated improved clinical outcomes and decrease mortality in critically ill patients with gram-negative infections, particularly Pseudomonas aeruginosa infections. EI meropenem has shown higher therapeutic success rates for patients with febrile neutropenia and shorter intensive care unit (ICU) length of stay (LOS) with a reduction in ventilator days in patients with multidrug-resistant ventilator-associated pneumonia. However, a larger study showed no difference in clinical outcomes between standard-infusion and EI meropenem. EI cefepime has been associated with decreased mortality and shorter ICU LOS in patients with Pseudomonas aeruginosa infections. Common challenges associated with EI beta-lactam antibiotics include Y-site incompatibilities, lack of intravenous access, and tubing residuals. It is important to note that factors such as diverse patient populations and study methodology, along with various antibiotic dose regimens, may have contributed to conflicting data on EI beta-lactam therapy.

Conclusion: Based on most published literature, there appears to be a favorable trend toward use of EI beta-lactam therapy in clinical practice, particularly in critically ill patients with gram-negative infections.

Keywords: beta-lactam antibiotics; cefepime; extended infusion; meropenem; piperacillin–tazobactam.