[ad_1]
Results from a phase 2 randomized trial suggests that a new investigational antibiotic is effective as standard antibiotic for the treatment of complicated urinary tract infections (UTIs) caused by multiple multidrug resistant Gram-negative bacteria.
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.
Antibiotic resistance, antibiotic resistance, antibiotic resistance, antibiotic resistance, antibiotic resistance, antibiotic resistance, antibiotic resistance, and efflux medications 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. "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. [1]
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 – could not be properly because the carbapenem drug imipenem-cilastatin has been 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 [2]This study randomized 448 adults (aged 18 or older) who had been hospitalized with a complicated UTI or uncomplicated pyelonephritis (inflammation of the kidney 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: "These are the two patients who have been treated with multiple drug-resistant pathogens. to overcome Gram-negative resistance. " [1]
"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." [1]
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 A new study of the effects of CFU / mL has been performed in the past. (Including an ongoing phase 3 cefiderocol trial, NCT02714595) This article is only available in French and English. to gain immunization and increase resistance to antimicrobial resistance, skepticism will persist ence is 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. "
###
NOTES TO EDITORS
This study was funded by Shionogi & Co. Ltd. and Shionogi Inc. It was conducted by Shionogi Inc., ID3C, Shionogi & Co. Ltd., and Jahn Ferenc Del-Pesti Hospital.
[1] Quotes direct from authors and can not be found in the text of the article. [2] Antibacterial Therapies for Patients with an Unmet Medical Need for the Treatment of Serious Bacterial Disease – https: /The labels have been added to this press release by the Academy of Medical Sciences. For more information, please see: http: // www.
IF YOU WISH TO PROVIDE A LINK FOR YOUR READERS, PLEASE USE THE FOLLOWING, WHICH WILL GO LIVE AT THE TIME THE EMBARGO LIFTS: http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30554 -1 / fulltext
Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.
Source link
