Shionogi data presented at IDWeek 2026 demonstrated a 76.7% clinical response with cefiderocol in carbapenem-resistant respiratory infections and high in vitro activity against resistant P aeruginosa VAP isolates.
Cefiderocol (Fetroja; Shionogi) achieved a 76.7% clinical response rate in critically ill US patients with Gram-negative respiratory tract infections, most of them carbapenem resistant, according to a PROVE subgroup analysis presented at
Christine Slover, vice president, Infectious Diseases US Medical Affairs, Shionogi, said the PROVE analysis focused on respiratory infections because highly resistant Gram-negative respiratory infections carry higher morbidity and mortality and poorer clinical outcomes. The pathogens studied, including P aeruginosa, Acinetobacter baumannii, S maltophilia, and Enterobacterales, are common in critically ill patients, she noted.
PROVE is an international, retrospective, observational chart review of more than 1,000 patients in the US and Europe treated between November 2020 and July 2024.¹ The subgroup analysis evaluated 266 US patients receiving cefiderocol for Gram-negative respiratory tract infections, of which 89.5% (n = 238) were carbapenem resistant.¹ Nearly all patients (96.6%) had at least one risk factor for carbapenem-resistant Gram-negative infection, and 35% (n = 93) had chronic pulmonary disease.¹
Patients were critically ill, with a median hospital stay of 42.0 days.¹ Overall, 74.8% were in the intensive care unit, 65.4% received organ support, and 66.2% required mechanical ventilation.¹ Most infections were monomicrobial (66.5%), and the most common pathogens were P aeruginosa (34.2%; n = 91) and A baumannii (19.2%; n = 51).¹
Cefiderocol was given for a median of 9.0 days (IQR, 7.0-14.0), and 72.9% of patients started therapy once pathogen and susceptibility data were known.¹ Clinical response reached 78.9% (153 of 194) with targeted therapy and 80.0% (24 of 30) with empiric therapy.¹ Response was 63.4% (26 of 41) when cefiderocol followed a failed prior regimen.¹
Slover cautioned against drawing comparative conclusions from the subgroups.
“It was a retrospective observational study. All of the analyses out of this study are descriptive only. It was not designed to establish causality or to have comparative treatments prospectively,” said Slover.
She added clinicians should follow up on microbiologic and susceptibility data to reassess therapy. Acuity of illness, prior cultures and antibiotic exposure, local surveillance patterns, and institutional stewardship practices should all inform the initial choice, she said.
The SENTRY Antimicrobial Surveillance Program analysis evaluated cefiderocol against 1,400 P aeruginosa isolates collected from patients with VAP in the US and Europe between 2020 and 2024.² Investigators compared cefiderocol with four commonly prescribed β-lactam/β-lactamase inhibitor (BL/BLI) combinations.² Cefiderocol susceptibility was 99.5% by CLSI, 98.9% by EUCAST, and 97.9% by FDA breakpoints.²
Among BL/BLI-nonsusceptible isolates, 91.4% to 96.0% remained susceptible to cefiderocol by CLSI criteria.² Cefiderocol also retained activity against isolates carrying VIM, NDM, and IMP metallo-β-lactamases, while BL/BLI combinations showed low susceptibility of 30.4% to 41.8% by CLSI criteria.² The investigators observed cross-resistance among the comparator BL/BLI agents in highly resistant phenotypes.²
Slover emphasized these are in vitro findings and said empiric decisions should still reflect patient factors and local epidemiology.
“It still depends on how severe the patient’s illness is, what the local susceptibility patterns are, and again, what the stewardship practices are within an institution when making decisions about which antibiotics to start with, before full susceptibility is known,” said Slover.
The systematic literature review included 45 published case reports and cohort studies of cefiderocol for S maltophilia, an opportunistic Gram-negative pathogen intrinsically resistant to many antibiotics.³ Clinical response occurred in 71.4% (35 of 49) of patients described in case reports.³ Favorable microbiologic and clinical outcomes were reported across a range of invasive infections.³
The IDSA 2026 AMR guidance lists cefiderocol as the preferred agent for invasive S maltophilia infections and notes the preference rests largely on animal model data.⁴ Slover said the review aimed to add to this limited clinical evidence base.
“What we were trying to undertake by doing this systematic literature review was to really look at the available published literature, which is mostly case reports and cohort studies,” said Slover.
Slover also pointed to the Fetroja label, which notes higher all-cause mortality with cefiderocol than with best available therapy in a pathogen-focused trial. She said clinicians should weigh the label alongside published data and IDSA guidance, particularly since patients with S maltophilia infections are often critically ill, have multiple comorbidities, and frequently have polymicrobial infections.
