Cefiderocol Shows Activity Against Difficult-to-Treat Pathogens

At this year’s IDWeek, Shionogi presented data around the SENTRY Antimicrobial Surveillance Program, which examined the company’s antibiotic, cefiderocol, and in vitro activity against more than 60,000 high-priority Gram-negative clinical isolates collected in the US and Europe. Christine Slover, PharmD, executive medical director, Anti-Infectives, Shionogi, discussed findings from Sentry and beyond the program.

For example, the company did an analysis looking at cross-resistance among beta-lactam (BL)-beta-lactamase inhibitor (BLI) combinations in Enterobacterales.

“The BL-BLI no susceptibility really is a public health threat, and these are difficult to treat organisms that many times, don't have other options for treatment,” Slover said. "And so, even though this is an in vitro analysis and that does not necessarily correlate to clinical outcomes, it's really important to evaluate this to see how our antibiotics are performing. And when you look at how cefiderocol continues to perform, it really does maintain its susceptibility and have a robust activity against a lot of these difficult-to-treat isolates.”

“In the analysis we did for Enterobacterales, approximately 84% of isolates that were nonsusceptible to a particular beta-lactam-beta-lactamase inhibitor combination were also nonsusceptible to other BL-BLI combinations. Then when we looked at the cefiderocol susceptibilities in those same Enterobacterales isolates, cefiderocol was susceptible in up to 90% of those isolates from that study,” Slover said.

Separately, cefiderocol has shown activity against New Delhi metallo-β-lactamase (NDM)-producing carbapenem-resistant Enterobacterales (NDM-CRE). This is significant as the Centers for Disease Control and Prevention (CDC) recently reported US infections caused by NDM-CRE increased by more than 460% from 2019 to 2023. NDM-CRE cause pneumonia, bloodstream, urinary tract, and wound infections and are resistant to many available antibiotics, leaving limited treatment options. Detection is frequently delayed because many clinical laboratories do not routinely perform carbapenemase testing, complicating targeted therapy and control measures.^1,2

“We actually just did a separate in vitro analysis from a different surveillance database, and we found that cefiderocol maintained activity up to about 85% in many MBL-producing CRE,” Slover said.

CDC advises clinicians to stay informed about local CRE epidemiology; test promptly to identify the carbapenemase mechanism when CRE is detected; select therapy based on the resistance mechanism; and strengthen infection-prevention practices. Facilities should coordinate with state and local HAI/AR programs to enhance detection and limit spread.¹

In light of the recent CDC news on NDM-CRE, as well as the World Antimicrobial Resistance Awareness Week that just ended on Monday, these frontline resistance issues remind everyone for the continued need for antimicrobial development.

“There are hundreds of bacterial and fungal pathogens out there that we care about, and there are really a lack of options, so investment is really important—and that's one of the reasons I am very proud to work for Shionogi. We continue to invest in this space, and we've committed to that future through the acquisition with Qpex over the last few years, and then just this year, we actually increased our research capacity when Qpex and Shionogi opened new research facilities here in the United States.”

References

1.CDC Report Finds Sharp Rise in Dangerous Drug-Resistant Bacteria. September 23, 2025. Accessed September 24, 2025. https://www.cdc.gov/media/releases/2025/2025-cdc-report-finds-sharp-rise-in-dangerous-drug-resistant-bacteria.html

2.Danielle A. Rankin, Anna Stahl, Sarah Sabour, et al. Changes in Carbapenemase-Producing Carbapenem-Resistant Enterobacterales, 2019 to 2023. Ann Intern Med. [Epub 23 September 2025]. doi:10.7326/ANNALS-25-02404