MORTALITY rates in difficult-to-treat resistant (DTR) infections have not improved despite the introduction of newer antibiotics, according to a large US study, raising concerns about delays in appropriate treatment.
DTR Gram-negative infections are resistant to key first-line antibiotics, including β-lactams and fluoroquinolones, and are associated with around 40% higher mortality than susceptible infections.
Impact of New Antibiotics on Drug-Resistant Infection Mortality
The study analysed over 8 million hospital encounters between 2016 and 2023, identifying more than 5,000 patients with confirmed DTR Gram-negative infections caused by organisms such as Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii. While newer antibiotics with activity against these pathogens have become increasingly available, their real-world impact on patient outcomes has remained uncertain.
Limited Uptake and Ongoing Treatment Mismatch
Use of newer DTR-active antibiotics rose during the study period, with initial prescribing increasing from 4% in 2016 to 15% in 2023. However, most patients, 84% even in 2023, still received initial antibiotic therapy that was not active against the infecting organism based on laboratory susceptibility testing.
This mismatch, known as in-vitro discordant therapy, is a key clinical concern as delays in effective treatment are known to worsen outcomes in severe infections. The findings suggest that simply having access to newer drugs is not enough if they are not used promptly and appropriately.
No Overall Improvement in Mortality
After adjusting for patient, hospital, and pandemic-related factors, researchers found no meaningful change in mortality over time for most infections caused by Enterobacterales, Pseudomonas aeruginosa, or Acinetobacter baumannii.
An exception was seen in bloodstream infections caused by Pseudomonas aeruginosa, where mortality showed a modest decline over time. However, researchers caution that this finding is based on a relatively small number of cases and should be interpreted carefully.
Implications for Clinical Practice
For clinicians, the study highlights a critical gap between antibiotic availability and effective use. Rapid identification of both the pathogen and its resistance profile appears essential to guide timely, targeted therapy.
Improving diagnostic turnaround times and antimicrobial stewardship may be as important as developing new drugs in reducing deaths from DTR infections. Without faster, more accurate treatment decisions, mortality rates are likely to remain high despite advances in antimicrobial therapy.
Reference
Walker MK et al; NIH Antimicrobial Resistance Outcomes Research Initiative (NIH-ARORI). Survival trends in patients with difficult-to-treat, antibiotic-resistant, Gram-negative infections in the era of next-generation antibiotics in the USA: a retrospective cohort study. Lancet Infect Dis. 2026; DOI:10.1016/S1473-3099(26)00020-4.
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