Shionogi's Cefiderocol Shows 68% Clinical Cure Rate Against Highly Resistant MBL-Producing Enterobacterales in Real-World Study
核心洞察
The CIRCE study demonstrated that cefiderocol achieved a 68% clinical cure rate at day 14 and 83% overall survival at day 28 in 232 patients with MBL-producing Enterobacterales infections (搜索).
MBL (搜索)-producing Enterobacterales inactivate almost all beta-lactam antibiotics including carbapenems (搜索), representing critical priority pathogens with limited treatment options.
Additional surveillance data showed sustained cefiderocol activity against Stenotrophomonas maltophilia (搜索) over a 10-year period with no significant resistance development.
Shionogi (搜索) presented compelling real-world evidence at ESCMID Global 2026 demonstrating the clinical effectiveness of cefiderocol (Fetroja/Fetcroja) against metallo-beta-lactamase (搜索) (MBL (搜索))-producing Enterobacterales infections, a class of pathogens considered among the most critical health threats by the World Health Organization.
CIRCE Study Results Show Strong Clinical Outcomes
The CIRCE study, a retrospective, observational, multicenter chart review conducted in Spain between January 2023 and April 2025, evaluated real-world cefiderocol use in 232 adult patients with infections caused by MBL (搜索)-producing Enterobacterales. The analysis revealed that 68% of patients who received cefiderocol were considered clinically cured at day 14, with 82% achieving clinical response at the same timepoint.
Survival outcomes were particularly encouraging, with overall survival rates of 90% at day 14 and 83% at day 28. These results are notable given the severity of the patient population, where 29% were immunosuppressed, 27% were in intensive care, and 13% presented with septic shock (搜索) at baseline.
"MBL-producing Enterobacterales infections (搜索) represent a significant and growing clinical challenge worldwide, particularly in critically ill patients where treatment options are limited," said Dr. Ricard Ferrer, Head of the Intensive Care Department at Vall d'Hebron Hospital (搜索) in Barcelona, Spain. "These data support the clinical effectiveness of cefiderocol in adult patients with these infections, contributing further real-world evidence to inform future treatment considerations in practice."
Addressing Critical Antimicrobial Resistance Challenge
MBL (搜索)-producing Enterobacterales pose a significant therapeutic challenge as they inactivate almost all beta-lactam antibiotics, including carbapenems (搜索)—agents typically reserved for severe or high-risk infections. In the CIRCE study, the most frequently identified pathogens were carbapenem-resistant Klebsiella pneumoniae and Enterobacter species (搜索), both classified by the WHO as critical priority pathogens due to their high levels of resistance to currently available therapies.
Among patients with available follow-up cultures, microbiological eradication rates were reported as 85% in bloodstream infections (搜索) and 82% in urinary tract infections. Approximately half of patients received cefiderocol based on susceptibility testing, highlighting the importance of targeted antimicrobial therapy.
Sustained Activity Against Stenotrophomonas maltophilia
Additional data presented at ESCMID 2026 evaluated cefiderocol's in vitro activity against more than 4,000 Stenotrophomonas maltophilia (搜索) clinical isolates collected through the multinational SIDERO-WT (2014-2019) and SENTRY (2020-2024) surveillance programs. Across this 10-year period, there was no significant change in cefiderocol susceptibility observed before or after market introduction.
Stenotrophomonas maltophilia (搜索) is an opportunistic pathogen with high intrinsic resistance to multiple antimicrobial classes, often limiting treatment options in high-risk patients. Supporting these surveillance findings, a subgroup analysis of 119 patients from the PROVE study demonstrated clinical cure in approximately two-thirds of patients treated with cefiderocol for Stenotrophomonas infections, with the majority being critically ill patients receiving care in intensive care units.
Safety Profile Consistent with Established Data
Drug-associated adverse events were collected through routine chart review in the CIRCE study, with no new identified safety signals beyond the established safety profile of cefiderocol. This finding supports the drug's known safety profile in real-world clinical practice.
"Antimicrobial resistance continues to threaten effective treatment of serious Gram-negative infections globally," said Mark Hill, Global Head of Medical Affairs, Shionogi (搜索) & Co. Ltd. "These data add to the growing body of evidence supporting cefiderocol in resistant pathogens and underscores the importance of sustained investment in innovation and evidence generation in antimicrobials."
Clinical Implications for Resistant Infections
Cefiderocol represents an innovative siderophore cephalosporin designed to overcome resistance mechanisms that render many existing antibiotics ineffective. The drug is indicated for treatment of complicated urinary tract infections (搜索) and hospital-acquired bacterial pneumonia (搜索)/ventilator-associated bacterial pneumonia (搜索) caused by certain Gram-negative bacterial infections in adults.
The real-world evidence from the CIRCE study provides clinicians with valuable data on cefiderocol's effectiveness in treating some of the most challenging bacterial infections, particularly in critically ill patient populations where treatment options are severely limited. These findings support the drug's role in addressing the growing threat of antimicrobial resistance in clinical practice.