Introducing new antibiotics for multidrug-resistant bacteria: obstacles and the way forward.

Background: Following intense efforts to revive the dry antibiotic research and development pipeline, a few highly awaited antibiotics with activity against multidrug-resistant (MDR) bacteria were recently approved.

Objectives: We aim to highlight gaps in the evidence generated for new antibiotics by the time of their approval and to review the consequent limitations of treatment guidelines for priority MDR bacteria. We also report on the availability of the new antibiotics, reimbursement strategies allowing the use of these antibiotics in hospitals, and antibiotic stewardship efforts.

Sources: We searched PubMed for phase 3 randomized controlled trials, guidelines, and publications on access, usage, regulatory aspects and antimicrobial stewardship of antibiotics approved for use against MDR bacteria between 2013 and 2023. Other sources included governmental and professional documents regarding policies for reimbursement and use of the new antibiotics.

Content: Several gaps in the evidence available regarding the new antibiotics are described related to the trials' target populations, comparators, management algorithm within the trial, non-inferiority hypotheses, and assessment of resistance development within the studies. We highlight the risk of current guidelines to increase the usage of new antibiotics and consequently accelerate resistance development. Updated mapping of antibiotic availability reveals critical inequality in access to the new antibiotics. Finally, strategies used nationally in Europe to provide access to the new antibiotics are not sufficiently balanced by antibiotic stewardship efforts to calibrate the judicious use of the new antibiotics.

Implications: Antibiotic resistance is an immediate threat. The present review highlights areas where more systematic and uniform strategies across countries and geographical regions are warranted to improve evidence, availability, and use of new broad-spectrum antibiotics.