Cefiderocol, a late-stage investigational, novel siderophore cephalosporin, shows a high potential for treating infections caused by the most difficult to treat Gram-negative (GN)) bacterial collected from across Europe, according to new data from Shionogi.
The in vitro activity of cefiderocol was evaluated against GN bacteria collected from across Europe and the activity was compared with comparator agents in a multi-national surveillance study.
The study demonstrated not only the potent activity of cefiderocol against carbapenem-resistant isolates of Enterobacteriaceae, but also against the more difficult-to-treat carbapenem-resistant non-fermentative bacteria, A. baumannii and P. aeruginosa.
In separate studies, the susceptibility profile of cefiderocol was evaluated against a global collection of only carbapenem-resistant GN bacteria.
In these studies, the in vitro activity against the European isolates and the presence of carbapenemase genes were evaluated.
Cefiderocol showed antibacterial activity against 95.5% of carbapenem-resistant GN isolates at ≤4 mg/L. The study also evaluated regional differences in carbapenemase gene distribution.
Significant differences were seen in carbapenemase gene profile across bacterial species between regions and especially between EU countries; yet cefiderocol showed the potential to be effective against Enterobacteriaceae, A. baumannii, and P. aeruginosa regardless of the presence of serine- and metallo-carbapenemase-encoding genes.
Similar results were seen at a national level in a study conducted in the UK, with cefiderocol demonstrating activity at low concentrations against multi-drug-resistant carbapenemase-producing P. aeruginosa and A. baumannii. The relevance of in vitro to clinical efficacy has yet to be determined.
“Increasing resistance in Gram-negative bacteria complicates treatment, especially where it compromises carbapenems, which are the ‘go-to’ antibiotics for difficult infections. The enzymes responsible for this resistance – carbapenemases – are diverse. Different types predominate in different countries and species, adding to the challenge,” said Professor David Livermore, Professor of Medical Microbiology, University of East Anglia.
“In the lab, cefiderocol stays active against Enterobacteriaceae with any of the common carbapenemases. What’s more it’s also active against Pseudomonas and Acinetobacter with carbapenemases.
“Pseudomonas is inherently difficult as most antibiotics are not effective against this critical pathogen, and Acinetobacter has unique carbapenemases that evade all the inhibitors available so far. We found cefiderocol to be almost universally active.”