New data by Japanese drugmaker Shionogi highlight the real-world effectiveness of cefiderocol in patients with serious infections caused by gram-negative (GN) bacteria, while GSK announced promising data for an experimental oral antibiotic for complicated urinary tract infections (cUTIs).
The presentations were made at the recent IDWeek 2025 – the joint annual meeting of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, the Paediatric Infectious Diseases Society and the Society of Infectious Diseases Pharmacists – took place last week in Atlanta, Georgia, reports CIDRAP.
Sold under the brand name Fetroja, cefiderocol is a siderophore cephalosporin antibiotic that was approved by the US Food and Drug Administration (FDA) in 2019 for treating seriously ill patients with cUTIs and hospital-acquired and ventilator-associated bacterial pneumonia caused by GN pathogens.
It was added to the World Health Organisation’s Essential Medicines List in 2022.
The yet-to-be published data are from the five-year PROVE study, an international retrospective study that assessed the effectiveness and safety of cefiderocol in more than 1 000 US and European patients with serious respiratory tract, skin and skin-structure, and bloodstream infections (BSIs), most of which were multidrug-resistant.
The study ran from November 2020 to July 2024.
More effective when used empirically
Analysis of the US cohort, which included 508 patients, showed that the overall clinical cure rate across different infection sites was 70.1%, with a cure rate of 73.7% in patients who received cefiderocol empirically and 54.3% when it was used as salvage therapy.
More than half of the patients (57.3%) were in the intensive care unit, and 47.6% were receiving organ support. The most frequent causative pathogens were Pseudomonas aeruginosa (29.9%), Acinetobacter baumannii (21.7%), Enterobacterales (11.4%), and Stenotrophomonas maltophilia (4.9%).
“Real-world studies like PROVE build on the insights of controlled clinical trials by showing how therapies perform in real-life clinical settings against the difficult-to-treat infections patients currently face in the US,” said Neil Clancy, MD, a Professor of Medicine at the University of Pittsburgh, in a news release.
“These results demonstrate that cefiderocol effectively treated seriously ill patients with a range of GN pathogens across multiple infection sites, particularly when used earlier in the treatment course – even before identifying the causative bacteria when appropriate risk factors exist.”
In a separate analysis of US and European BSI patients, the overall clinical cure rate was 63.7%, with a cure rate of 72.0% when cefiderocol was used empirically.
Shionogi also released in vitro data from the SENTRY Antimicrobial Surveillance Programme, which monitors pathogen prevalence and antimicrobial susceptibility patterns worldwide. The data showed cefiderocol is highly active against bacteria that’s not susceptible to newer beta-lactam/beta-lactamase inhibitor combinations and was one of the few agents that demonstrated activity against metallo-beta-lactamase–carrying A baumannii.
Positive results for oral carbapenem
In other positive antibiotic news announced at IDWeek, GSK and Spero Therapeutics released the topline results from a phase 3 trial of tebipenem hydrobromide (HBr), an investigational oral antibiotic for cUTIs.
The results from the PIVOT-PO trial, which was stopped early for efficacy in May, showed that tebipenem HBr was non-inferior to intravenous (IV) imipenem-cilastatin in hospitalised patients with cUTIs, including pyelonephritis, based on the overall response at the test-of-cure visit.
Tebipenem HBr’s overall success rate (a composite of clinical cure plus microbiologic eradication of the causative bacteria) was 58.5%, compared with 60.2% for imipenem-cilastatin, for an adjusted treatment difference of –1.3%. The safety profile was similar to that of imipenem-cilastatin and other carbapenems.
An estimated 2.9m cUTI cases are treated each year in the United States. IV carbapenems are the current standard of care when the infection is caused by multidrug-resistant pathogens or progresses to sepsis. If approved by the FDA, tebipenem HBr would be the first oral carbapenem in the US for cUTI patients.
“Complicated UTIs can have serious consequences for patients, including organ failure and sepsis, and oral options for drug-resistant infections are limited,” said GSK Chief Scientific Officer Tony Wood, PhD in a release. “These ground-breaking data show for the first time that cUTIs, including pyelonephritis, can be treated with an oral carbapenem antibiotic as effectively as with an intravenous one.”
In 2022, the FDA declined Spero’s initial new drug application (NDA) for tebipenem HBr, telling the company there weren’t enough data to support approval. The FDA later said that data from an additional phase 3 trial, supported by non-clinical evidence of efficacy, could be sufficient for approval.
In September 2022, GSK signed a licensing agreement with Spero to develop and commercialise the drug in all markets except Asia.
GSK says it plans to file another NDA for tebipenem HBr by the end of the year.
CIDRAP article – Drugmakers announce encouraging new antibiotic data at IDWeek (Open access)
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