Optimizing Betalactam Clinical Response by Using a Continuous Infusion: A Comprehensive Review

Abstract

Introduction: Antimicrobial resistance is a major healthcare issue responsible for a large number of deaths. Many reviews identified that PKPD data are in favor of the use of continuous infusion, and we wanted to review clinical data results in order to optimize our clinical practice. Methodology: We reviewed Medline for existing literature comparing continuous or extended infusion to intermittent infusion of betalactams. Results: In clinical studies, continuous infusion is as good as intermittent infusion. In the subset group of critically ill patients or those with an infection due to an organism with high MIC, a continuous infusion was associated with better clinical response. Conclusions: Clinical data appear to confirm those of PK/PD to use a continuous infusion in severely ill patients or those infected by an organism with an elevated MIC, as it is associated with higher survival rates. In other cases, it may allow for a decrease in antibiotic daily dosage, thereby contributing to a decrease in overall costs.

Population Pharmacokinetic and Pharmacodynamic Analysis for Maximizing the Effectiveness of Ceftobiprole in the Treatment of Severe Methicillin-Resistant Staphylococcal Infections

“…A paradigm shift in the concept of desired PK/PD target attainment with beta-lactam is currently occurring nowadays [25] from the traditional 50-100% t > MIC up to the aggressive PK/PD target of 100% t > 4-8 × MIC, which was considered optimal since it was recently shown to minimize the risks of microbiological failure and of resistance development [13,14,16,26]. Unfortunately, attainment of this aggressive target is never checked during drug development as it is not a requirement of the regulatory authorities.…”

“…However, this PK/PD target may be insufficient when treating severe MRSA infections, and more aggressive PK/PD targets up to 100% t > 4-8 × MIC are recommended nowadays for maximizing treatment with 24-continuous infusion (CI) beta-lactams among critically ill patients [13][14][15]. Attaining aggressive PK/PD target could be especially challenging in patients with augmented renal clearance (ARC), a condition occurring in at least one-third of critically ill patients, which may fasten renal elimination of ceftobiprole [16].…”