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expert reaction to trial on new investigational antibiotic, cefiderocol, in treating urinary tract infections

Research published in the The Lancet Infectious Diseases demonstrates that the use of cefiderocol was non-inferior compared with imipenem-cilastatin for the treatment of complicated urinary tract infection in people with multidrug-resistant infections.


Prof Serge Mostowy, Professor of Cellular Microbiology at the London School of Hygiene & Tropical Medicine, said:

“Antibiotic resistance is one of the greatest global health challenges we face. Infections from enterobacteria, such as pathogenic E. coli, are becoming harder and harder to treat. This important study offers hope for a new antibiotic that could potentially be an alternative to treating them, but we are not there yet.

“How cefiderocol kills bacteria is not new. From inside the bacterial cell the drug interferes with peptidoglycan, an important component of the bacterial cell wall. What is new is how the drug can enter the bacterial cell – highjacking a natural bacterial iron transport system. Exploiting this mechanism is a perfect example of modern medicine and should encourage novel research avenues aiming to fight antibiotic resistant infection.

“This is a phase 2 clinical trial and we await information on clinical improvement and treatment durability. However, it provides proof-of-principle for a novel method of therapeutic treatment, and will be of wider interest to researchers and physicians interested in future-antibiotics.”


Prof Graham Cooke, NIHR Research Professor Imperial College London, and Chair WHO EML Antibiotics Working group, said:

“It’s encouraging to see a new antibiotic coming through development. We urgently need new classes of drugs, not just new drugs from the same family as existing ones. This will give us treatment options for the increasing numbers of patients we see with resistant infections, particularly from Gram negative bacteria.

“These strong findings from Phase II should give us optimism that we may in future have another drug in the arsenal against resistant infection. However, the design of this study meant is wasn’t possible to test the drug’s role against perhaps the most important challenge we face – bacteria that are resistant to the carbapenem family of antibiotics, and that remains a key question. The results of the Phase III trial of cefiderocol which is underway will be important, exploring the role of the antibiotic in a range of severe clinical illnesses. Of fewer than 10 antibiotic drugs in Phase III development, cefiderocol probably has the broadest activity against Gram negative organisms (that are a particular challenge in terms of resistance).

“Understanding when and how to use any new antibiotic in practice (and when to hold it back for later) will be an important challenge, but this will be a good problem to have.”


* ‘Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: a phase 2, randomised, double-blind, non-inferiority trial’ by Simon Portsmouth et al. was published in The Lancet Infectious Diseases at 23:30 UK time on Thursday 25th  October.


All our previous output on this subject can be seen at this weblink:


Declared interests

 Prof Serge Mostowy: No conflicts of interest.


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