Pharmacological approaches to overcome antimicrobial resistance in gram-negative bacterial infections: current practice and future directions

Identifying proper strategies allowing to minimize the risk of resistance emergence among Gram-negative pathogens represents a compelling unmet clinical need. From a pharmacological perspective, optimizing the use of novel beta-lactams and beta-lactam/beta-lactamase inhibitor combinations based on PK/PD principles may represent a valuable approach for overcoming antimicrobial resistance. Both preclinical and clinical evidence suggested that attaining an aggressive PK/PD target may allow to prevent resistance emergence to beta-lactams. Delivering beta-lactams by prolonged or continuous infusion and optimizing plasma exposure by means of a therapeutic drug monitoring-guided approach could be helpful tools for maximizing the likelihood of attaining aggressive PK/PD targets with beta-lactams.