New drugs, old problems: a narrative review of antibiotic stewardship programme in the era of novel gram-negative antibiotics.

BACKGROUND

The global spread of multidrug-resistant 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 programmes (ASPs).

OBJECTIVES

This narrative review synthesizes current evidence on ASP interventions optimizing the use of recently approved antibiotics against multidrug-resistant gram-negative pathogens and identifies priorities for sustainable implementation.

SOURCES: A literature search (PubMed, Scopus, 2010-2025) identified interventional and quasiexperimental 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.