Responsible use of new antibiotics for critically ill patients suffering from infections due to carbapenem-resistant organisms—a narrative review for an enablement strategy

Abstract Infections caused by multidrug-resistant Gram-negative (MDR-GN) bacteria, particularly carbapenem-resistant organisms (CROs), constitute a significant burden in critically ill patients (CIPs). A multidisciplinary, collaborative approach is essential for responsible antibiotic use in CIPs, balancing the necessity for effective treatment with mitigation of antimicrobial resistance (AMR). While the efficacy of existing antibiotics against CROs is increasingly limited due to resistance development and suboptimal pharmacokinetic/pharmacodynamic properties, several barriers impede the widespread adoption of new agents, including selective susceptibility testing, limited availability, high costs, and concerns regarding the fostering of resistance. Antimicrobial stewardship (AMS) strategies aim to optimize antibiotic use; however, there is an ongoing debate between restrictive and enabling approaches for new antibiotics in CIPs with CRO infections. While restrictive strategies focus on limiting antibiotic use to mitigate resistance, they may delay necessary treatment and negatively impact professional culture. Enablement strategies promote informed decision-making and accessibility when needed but require substantial workforce and expertise. In this narrative review and expert opinion, we propose an algorithm supporting a coordinated AMS approach in CIPs, emphasizing the importance of early diagnosis and appropriate therapy. We advocate for an enablement strategy for new antibiotics in CIPs with MDR-GN infections, aiming to reduce mortality and toxicity associated with older agents. This strategy should be integrated into local AMS programmes under the guidance of experienced clinicians.