Extended and Continuous Infusion of Novel Protected β-Lactam Antibiotics: A Narrative Review

Consolidated data from pharmacokinetic and pharmacodynamic studies support the administration of β-lactam antibiotics in prolonged infusion (i.e., extended or continuous) to optimize therapeutic efficacy by increasing the probability of attaining maximal bactericidal activity. This is the longest possible time during which the free drug concentrations are approximately four-fold the minimum inhibitory concentration between dosing intervals. In the context of antimicrobial stewardship strategies, achieving aggressive pharmacokinetic and pharmacodynamic targets is an important tool in the management of multi-drug resistant (MDR) bacterial infections and in the attainment of mutant preventing concentrations. However, prolonged infusion remains an unexploited resource. Novel β-lactam/β-lactamase inhibitor (βL/βLI) combinations (ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-cilastatin-relebactam) have been released in recent years to face the emerging challenge of MDR Gram-negative bacteria. Pre-clinical and real-life evidence has confirmed the promising role of prolonged infusion of these molecules in specific settings and clinical populations. In this narrative review we have summarized available pharmacological and clinical data, future perspectives, and current limitations of prolonged infusion of the novel protected β-lactams, their application in hospital settings and in the context of outpatient parenteral antimicrobial therapy.