New Drugs, Old Problems: A Narrative Review of Antibiotic Stewardship Program in the era of novel Gram-negative antibiotics

Background: The global spread of multidrug-resistant (MDR) Gram-negative bacteria has led to the introduction of several novel antibiotics. However, emerging resistance threatens their long-term utility, emphasizing the importance of antimicrobial stewardship programs (ASPs). Objectives: This narrative review synthesizes current evidence on ASP interventions optimizing the use of recently approved antibiotics against MDR Gram-negative pathogens and identifies priorities for sustainable implementation. Sources: A literature search (PubMed, Scopus, 2010-2025) identified interventional and quasi-experimental studies addressing stewardship strategies for novel agents such as ceftazidime/avibactam, ceftolozane/tazobactam, meropenem/vaborbactam, imipenem/relebactam, cefiderocol, sulbactam/durlobactam, eravacycline, and aztreonam/avibactam. Content: Seven studies were included, encompassing educational bundles, pharmacokinetic/pharmacodynamic optimization, decision-support tools, formulary restrictions, and multidisciplinary models. Most relied on enablement strategies-education, feedback, and therapeutic monitoring-often integrated with diagnostics or digital support. These interventions improved therapy appropriateness and microbiological outcomes, though evidence remains limited by small, single-centre, and heterogeneous studies. Implications: Effective stewardship of new Gram-negative antibiotics requires combining enablement, personalized pharmacology, and selective restriction within multidisciplinary ASPs. Strengthening real-world evidence, digital infrastructure, and standardized outcome measures is essential to guide equitable and sustainable implementation.