A novel index that helps clinicians monitor difficult-to-treat resistance may offer a practical solution to gauge the effects of new antibiotics and regional differences in antibiotic access, according to new research from the National Institutes of Health.
“Its incorporation might help quantify efforts to improve global antibiotic access,” wrote the authors of a poster presented at the IDWeek 2025 meeting, in Atlanta (P211). Due to the government shutdown, they were not permitted to speak directly with Infectious Disease Special Edition.
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A DTR Index
Global disparities in antibiotic access complicate analyses of antibiotic resistance burdens, they wrote. “Difficult-to-treat [DTR] resistance, or resistance to all highly safe and effective antibiotics, has clinical relevance and prognostic utility but assumes these antibiotics are accessible.”
For the study, the investigators proposed a DTR index, which for a pathogen is defined as the percentage of isolates with no accessible safe and effective antibiotic options in a region over a denominator of total isolates with available antibiotic susceptibility data. They tested how a DTR index changed over time with emergence of newer antibiotics in a real-world cohort of U.S. hospitals and across regions with simulated degrees of antibiotic access.
The scientists identified clinical cultures with Enterobacterales, Pseudomonas aeruginosa, or Acinetobacter baumannii and susceptibility testing to at least one carbapenem, extended-spectrum cephalosporin, and fluoroquinolone, using data from 339 U.S. hospitals in the PINC AI healthcare database between 2017 and 2023.
They plotted quarterly pathogen-specific trends in DTR proportion and DTR index with the introduction of ceftazidime-avibactam (CZA; Avycaz, AbbVie), ceftolozane-tazobactam (C/T; Zerbaxa, Merck), and cefiderocol (Fetroja, Shionogi). Using microbiologic data in the cohort, the investigators developed three hypothetical scenarios to determine changes in the DTR index for Enterobacterales as antibiotic access decreased.
The DTR index for Enterobacterales and P. aeruginosa remained substantially lower than the estimated DTR proportion between 2017 and 2023, given the availability of C/T and CZA. In contrast, the DTR index for A. baumannii, which assumed the value of the estimated DTR proportion until cefiderocol became available at reporting hospitals in 2020, decreased from 35% to nearly 0%. They also demonstrated an increase in the Enterobacterales DTR index in three hypothetical scenarios with varying levels of antibiotic accessibility.
A Tool for the Developing World
An index like this could help shine a light on medications needed in developing countries, commented Athena Hobbs, PharmD, BCIDP, a clinical pharmacy manager with Cardinal Health, who was not directly involved in the research. For example, she said, if there were a developing country where only 10% of Pseudomonas isolates were resistant to everything, their DTR rate wouldn’t look terrible, and they might not qualify for aid. However, if this country did not have access to CZA and C/T, and 80% of isolates were resistant to all agents except one of these two, their DTR index would be much higher and would give a more real-world picture of the types of patient outcomes expected there. This could potentially help identify countries most in need of direct humanitarian aid.
U.S. hospitals potentially could use it as a way to help manage their formularies, Dr. Hobbs said. If they were only able to stock one, a hospital could evaluate their different projected DTR indexes with CZA and C/T and choose the agent with the lower index for the greatest number of organisms.
“I think it could be helpful in the U.S. but would probably make a bigger impact in developing countries,” she said.
The study authors and Dr. Hobbs reported no relevant financial disclosures.