Treatment of multidrug-resistant Gram-negative infections: a stewardship imperative

Antimicrobial resistance (AMR) continues to drive high morbidity, mortality, and healthcare costs, despite the recent introduction of several new antibiotics targeting difficult-to-treat (DTR) Gram-negative infections. A large US study (2016–2023) shows that uptake of these newer agents has increased, yet inappropriate initial (empirical) therapy remains common and, overall, no significant reduction in mortality was observed—except for a small subgroup with Pseudomonas aeruginosa bloodstream infections. The findings highlight that simply having new antibiotics is insufficient; challenges in timely and appropriate use persist. Strengthened antibiotic stewardship, faster diagnostics, and better data-driven treatment decisions are essential to improve outcomes. Moreover, given the severity of illness in these patients, additional strategies—such as adjunctive non-antibiotic therapies—may be needed alongside antibiotics to meaningfully reduce mortality.