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Multi-resistant bacteria at large
At least 56,000 people die in the US and European Economic area each year due to antibiotic-resistant bacteria. Up to half of the infections are caused by Gram-negative bacteria. Many life-threatening bacteremic Gram-negative infections arise from complicated urinary tract infections (cUTIs) which far outnumber the other Gram-negative infections altogether. Out of all the cUTIs treated in hospitals, 80% are caused by Escherichia coli and Klebsiella pneumoniae, and now they are turning multi-resistant at double-digit rates.
Comeback of polymyxins
Polymyxins (polymyxin B and colistin), both discovered in 1947, are highly active against most Gram-negative bacteria. However, they were abandoned in the 1960s because of nephrotoxicity. Long considered as “dinosaurs” from the bygone era, polymyxins are now, however, reinstated as the last-line therapy of infections caused by extremely drug-resistant strains. Northern Antibiotics has developed polymyxin derivatives that are more effective and less toxic in animal studies than polymyxin B (PMB).
40 years of experience in polymyxin R&D
Northern Antibiotics Oy (Ltd.), headquartered in Espoo, Finland, is a virtual antibiotic development company co-founded in 2003 by Prof. Martti Vaara, MD, PhD. Prof. Vaara is a broadly acknowledged expert in the research on the outer membrane (OM) of Gram-negative bacteria in general and on polymyxins and other agents damaging the OM in particular. He was the first to elucidate the mechanism of polymyxin resistance and in 1983 he developed polymyxin B nonapeptide (PMBN) which is today used as the gold standard for outer membrane permeabilizers.
NAB polymyxin derivatives
NAB polymyxin derivatives are the only polymyxins known to be actively excreted in to urine. In the mouse UTI model, NAB739 and NAB815 have been shown to be required at doses 10 times lower than those of PMB and, in addition, their nephrotoxicity is 2-3 times lower than that of polymyxin B, indicating a major improvement in safety potential. NAB741 (now SPR741) which has no direct activity but sensitizes target bacteria to other antibiotics, has been out-licensed to Spero Therapeutics (Cambridge, US) and it has already passed the clinical phase 1.
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