Darobactin effective as an antibiotic against gram-negative bacteria
Darobactin is a promising lead structure for antibiotic development.
Many bacteria that cause serious infectious diseases have developed resistance to common antibiotics, so that antibiotics are no longer effective. These include in particular the Gram-negative bacteria with their stable outer membrane.
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Darobactin is now a promising candidate for a new class of drugs with a new mechanism of action. It binds to the protein BamA, which is localised in the outer membrane of Gram-negative bacteria. This disrupts the formation of a functional outer membrane and the bacteria die.
- New active substance candidate against antibiotic-resistant Gram-negative bacteria such as Pseudomonas aeruginosa, Escherichia coli Acinetobacter baumannii, Neisseria gonorrhoeae, Chlamydia trachomatis, Shigella sonnei, Salmonella enterica Typhimurium LT2, Enterobacter cloacae, Bifidobacterium longum, Bacteroides fragilis, Lactobacillus reuteri, Enterococcus faecalis, Yersinia pestis and Klebsiella pneumoniae.
- Darobactin can be easily administered and shows reliable efficacy against infections with wild-type or antibiotic-resistant Gram-negative bacteria.
- The good efficacy is shown in vivo in mice, where no cell toxicity and no development of resistance was found.
Scope of application
First preclinical experiments are available.
In Germany, most antibiotics are prescribed in the outpatient sector (85%), the share of clinic consumption is only 15%. In medical practices, about 39 million antibiotic prescriptions were issued in 2014, which corresponds to 374 million mean daily doses (DDD) and a turnover of 699 million euros. Consumption has been relatively constant over the last few years, but reserve antibiotics are being prescribed more and more frequently. In Europe, the situation is similar: most antibiotics (90%) are consumed outside hospitals. In the outpatient sector, the average is 21.5 DDD per 1,000 inhabitants per day, compared to 2.0 DDD in hospitals. Broad-spectrum antibiotics, which are effective against many different types of bacteria, are used most frequently. The top countries for antibiotic consumption are Greece (31.9 DDD per 1,000 inhabitants and day), as well as Belgium, France and Hungary. In terms of consumption in hospitals, Finland is the frontrunner. Global antibiotic consumption increased by 36% between 2000 and 2010, with South Africa and the BRIC countries accounting for three quarters of the increase: Brazil, Russia, India and China, as they experience huge population growth. This trend has roughly continued until today.
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- EP pending
- DE pending
- DE pending
KeywordsNew drug candidate for antibiotic therapy of patients
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