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NEW YORK — A team of US scientists have developed a novel antibiotic that can kill a drug-resistant superbug, known to kill about half of all patients who acquire it.
The antibiotic zosurabalpin was found to effectively treat highly drug-resistant isolates of the highly drug-resistant strains of Carbapenem-resistant Acinetobacter baumannii (Crab) both in vitro and in mouse models of infection, revealed two studies published in the journal Nature.
Antibiotic resistance has become an urgent threat to global public health in recent decades.
Crab is classified as a priority 1 critical pathogen by the World Health Organization, alongside two other drug-resistant forms of bacteria -- Pseudomonas aeruginosa and Enterobacteriaceae.
The US Centers for Disease Control and Prevention (CDC) also classified the Gram-negative bacteria as an urgent threat.
The bacteria, which causes conditions such as sepsis and pneumonia, thrives in hospitals due to its ease of transmission among patients weakened by other illnesses.
No new antibiotic chemical class with activity against A. baumannii has reached patients in over 50 years, said the researchers from Harvard University and the Swiss health care company Hoffmann-La Roche.
A. baumannii is a species of Gram-negative bacteria, which are extraordinarily difficult to kill because they are surrounded by an outer membrane which blocks the entry of most antibiotics. This outer membrane contains large molecules called lipopolysaccharide (LPS) -- resistant to penetration by several antibiotics.
Halting the working of LPS and its transport to the outer membrane reduces cell viability and can increase susceptibility to some antibiotics.
Zosurabalpin was found to inhibit the growth of Acinetobacter baumannii by preventing the movement of LPS to the outer membrane, where they’re needed to maintain the membrane’s integrity. This causes the molecules to accumulate inside the bacterial cell. Levels inside the cell become so toxic that the cell itself dies.
The research showed that Zosurabalpin was effective against more than 100 CRAB clinical samples that were tested.
Zosurabalpin defeated the existing antibiotic resistance mechanisms of the highly drug-resistant strains of Crab in mouse models of pneumonia and sepsis, and is also being tested in human trials.
“It represents a promising treatment paradigm for patients with invasive infections due to CRAB, for whom current treatment options are inadequate,” said Kenneth Bradley, global head of infectious disease discovery at Roche Pharma Research and Early Development.
“New antibiotics directed against the world's highest priority bacteria, like Acinetobacter baumannii, require novel development paths. Importantly, regulatory guidelines facilitate this, allowing us to use highly translatable animal model data to complement leaner clinical trials in support of registration,” added Michael Lobritz, global head of infectious diseases at Roche Pharma Research and Early Development.