New "Trojan horse" antibiotic offers hope in battle against superbugs
Promising results from a phase 2 human trial into the efficacy of a novel new antibiotic is giving hope to scientists desperate to find a new weapon against the growing global threat of antibiotic-resistant superbugs.
Called cefiderocol, this new antibiotic employs an incredibly novel technique to bypass the defenses of unwitting bacteria. In order to grow, bacteria needs iron molecules, and cefiderocol exploits that need by binding to iron so it can sneak past a bacterium's outer membrane.
"Cefiderocol acts as a trojan horse," says Simon Portsmouth, lead researcher on the project. "The drug uses a novel mechanism of cell entry that takes advantage of the bacteria's need for iron to survive."
The latest human trial gathered 448 subjects with complicated urinary tract infections and pitted cefiderocol against the current standard antibiotic, imipenem-cilastatin. The results were extremely positive with cefiderocol displaying equal efficacy compared to the conventionally used antibiotic. Safety profiles were also promising with cefiderocol demonstrating slightly less adverse effects than imipenem-cilastatin.
Phase 3 studies are currently underway and hopefully they can address the significant limitation of these earlier trials. While the new antibiotic has proved safe, and at least as effective as current treatments, it is unclear how effective cefiderocol is against bacteria known to have developed a resistance to conventional antibiotic treatments.
It is hypothesized that cefiderocol's unique mechanism of action may make it more effective in sneaking past the defenses of antibiotic-resistant bacteria, but until this has been clearly studied we will not know exactly how beneficial a future weapon it could be.
Graham Cooke, from Imperial College London, didn't work on this new research but has been following the development of cefiderocol closely in his role as Chair of the WHO Essential Medicines List Antibiotics Working group. Cooke is cautiously optimistic regarding cefiderocol's future as a new antibiotic.
"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," explains Cooke. "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)."
Cefiderocol is one of several investigational antibiotics being offered fast-track approval by the Food and Drug Administration (FDA). In an effort to help speed up development of new antibiotics the FDA created a designation called Qualified Infectious Disease Product (QIDP). This allows the agency to assist in moving certain drugs, deemed important and necessary, more rapidly through the development and approval system. Cefiderocol still has to prove itself as an effective agent against resistant superbugs, but if all goes well clinicians may have a new drug in their arsenal within a few short years.
The new study was published in the journal The Lancet Infectious Diseases.