New investigational effective antibiotic against drug-resistant bacteria in phase 2 trial

The findings, published in The Lancet Infectious Diseases, commented that patients treated with the siderophore-based drug, cefiderocol, had a higher and more sustained level of pathogenesis and similar clinical outcomes to those treated with the current standard of care, imipenem-cilastatin.

This antibiotic is used in antibiotics, antibiotics, antibiotics, antibiotics, antibiotics, antibiotics, antibiotics, and antibiotics. 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. "In the case of an acute infection, an increase in the amount of iron intake in the immune system, it is necessary to These molecules may also be transported through the bacterium's own outer membrane by the bacterium's own iron-transport system.

The findings highlight the potential of cefiderocol as an important new treatment option for highly resistant Gram-negative bacteria, once approved. Cefiderocol's effect on carbapenem-resistant strains-which causes some of the hardest-to-treat infections in health-care settings, and for which there is no alternative antibiotic that does not have serious side effects or other complications the drug imipenem-cilastatin carbapenem was used as the active control treatment.

The US Centers for Disease Control and Prevention (CDC) estimates that antibiotic-resistant microorganisms cause more than two million infections in the United States each year, resulting in at least 23,000 deaths. A 2014 Review on Antimicrobial Resistance predicted that by 2050, the overall cost of antibiotic resistance will be as high as 100 trillion pounds 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 is effective, new antibiotics with novel modes of action are urgently needed. This group includes carbapenem-resistant, Gram-negative pathogens including Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae as the highest priority for the development of new antibiotics. Previous studies have shown that cefiderocol is active against all three multidrug-resistant pathogens.

As part of the US Food and Drug Administration (FDA) approach to fast-tracking antibiotic development, this randomized study 448 adults (aged 18 or older) who had been hospitalized with a complicated UTI or uncomplicated pyelonephritis (inflammation of the kidney hard to a bacterial infection) to receive three daily infusions of cefiderocol (300 patients) or imipenem-cilastatin (148 patients) for seven to 14 days. In total, 252 patients treated with cefiderocol and 119 with imipenem-cilastatin had a Gram-negative uropathogen and were included in the efficacy analysis. The majority of participants had Escherichia coli, Klebsiella pneumoniae, or P aeruginosa infections (Figure 2).

Results suggest that 73% of patients (183/252 patients) and 55% (65/119 patients) were treated with the same effect. This difference was mainly driven by the sustained antibacterial activity of cefiderocol while the clinical responses were highly similar (90% vs 87%).

Overall, cefiderocol was well tolerated with similar numbers of adverse events to that of imipenem-cilastatin (41% [122/300 patients] vs 51% [76/148 patients]). Gastrointestinal disorders (ie, diarrhoea, constipation, nausea, vomiting, and abdominal pain) were the most common adverse events in both groups (35 [12%] patients in the cefiderocol group and 27 [18%] patients in the imipenem-cilastatin group). Fourteen (5%) participants in the cefiderocol group and 12 (8%) in the imipenem-cilastatin group reported at least one serious adverse event, with C difficile colitis the most common.

Dr. Portsmouth says: "Cefiderocol was found to be both safe and tolerable in a population of older patients who were very ill with complex comorbid conditions and a wide range of multidrug-resistant pathogens. used to overcome Gram-negative resistance. "

"Ongoing clinical trials of pneumonia, including hospital-acquired pneumonia and ventilator-associated pneumonia, and a study in patients with carbapenem-resistant infections, will provide additional important information about cefiderocol."

The authors note that an important limitation of the study was the exclusion of patients with carbapenem-resistant infections because the comparator was a carbapenem.

Writing in a linked Comment, Dr. Angela Huttner, Geneva University Hospitals, Switzerland, discusses the importance of assessing the post-market clinical experience of the drug: "The FDA's new guidance on complicated urinary tract infection endpoints, issued in June 2018, calls for complete clinical resolution and changed the cutoff for microbiological response to bacterial counts of less than 1 × 10³ CFU / mL. An accelerated process to get new antibiotics to market was urgently needed, and But it's not going to be any more than four months ago (including an ongoing phase 3 cefiderocol trial, NCT02714595) There is still no guidance on measuring baseline or emerging resistance; this too will fall to post-market development. Although these results are promising with regard to increasing immunotherapy and increasing resistance to antimicrobial resistance, this finding is still available. Cefiderocol remains on the fast track to approval. This is welcome news, as well as those in post-market clinical medicine understand the deal we have made: it will be necessary to continue the drug's clinical development, while managing its appropriate use and conservation, and thus take its true measure. "

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More information:
The Lancet Infectious Diseases (2018). www.thelancet.com/journals/lan … (18) 30554-1 / fulltext