A new antibiotic is as effective as the current preferred option for treatment of complicated urinary tract infections
There may be a new weapon on the anvil against drug resistant bacteria, suggest results of a phase 2 randomised trial.
A new investigational antibiotic is as effective as the current preferred antibiotic for the treatment of complicated urinary tract infections (UTIs) caused by several multidrug resistant Gram-negative bacteria.
The findings, published in The Lancet Infectious Diseases, indicated that patients treated with the siderophore-based drug, cefiderocol, had a higher and more sustained level of pathogen eradication. The clinical outcomes were similar to those treated with the current standard of care, imipenem-cilastatin.
A 2014 Review on Antimicrobial Resistance predicted that by 2050, the global cost of antibiotic resistance will rise to as such as £100 trillion and account for 10 million deaths every year
Cefiderocol is novel in its approach to overcoming the three main mechanisms of antibiotic resistance used by Gram-negative bacteria–two outer membranes that make it hard for antibiotics to penetrate, porin channels which can adapt and change to block the antibiotic entry, and efflux pumps that expel antibiotics back out of the cell and make the drugs ineffective.
“Cefiderocol acts as a trojan horse,” explains Dr Simon Portsmouth, Shionogi Inc, USA, who led the research. “The drug uses a novel mechanism of cell entry that takes advantage of the bacteria’s need for iron to survive. During an acute infection, one of our innate immune responses is to create an iron-poor environment. In response, bacteria increase their iron intake. Cefiderocol binds to irons and is transported through the extra outer membrane by the bacterium’s own iron-transport system. These iron channels also enable the drug to bypass the bacteria’s porin channels and gain repeat entry even if the bacterium has evolved efflux pumps.”
The findings highlight the potential of cefiderocol as an important new option for treating highly resistant Gram-negative bacteria, once approved. Cefiderocol’s effect on carbapenem-resistant strains–which cause some of the hardest-to-treat infections in health-care settings, and for which there is no antibiotic alternative that does not have serious side effects or other complications–could not be properly evaluated because the carbapenem drug imipenem-cilastatin was used as the active control treatment.
The US Centers for Disease Control and Prevention (CDC) estimate that antibiotic-resistant microorganisms cause more than two million infections in the USA each year, resulting in at least 23,000 deaths. A 2014 Review on Antimicrobial Resistance predicted that by 2050, the global cost of antibiotic resistance will rise to as such as £100 trillion and account for 10 million deaths every year.
Antibiotic resistance has been identified as one of the biggest threats to human health globally. While the antibiotic arsenal dwindles in effectiveness, new antibiotics with novel modes of action are urgently needed. WHO considers carbapenem-resistant, Gram-negative pathogens including Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae as the highest priority and critical for development of new antibiotics. Previous studies have demonstrated that cefiderocol is active against all three multidrug-resistant pathogens.
