Carbapenem-resistant Acinetobacter baumanni (CRAB) has been categorised by the World Health Organization and the US Centers for Disease Control and Prevention as a ‘priority 1 pathogen’.
It is therefore ranked among a group of antibiotic-resistant bacteria that is considered to be of the highest priority for new antibiotic drug development owing to the threat it poses to human health.
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While no new antibiotic class with activity against A. baumanni has been launched in the last 50 years, a recent article published in the Nature scientific journal has verified that zosurabalpin, a novel antibiotic currently in Phase I development by Roche, effectively treats highly drug-resistant contemporary isolates of CRAB in vitro and in mouse models of infection.
CRAB is known to be a very difficult bacterium to defeat, particularly because of its double lipopolysaccharide (LPS) outer membrane which provides a protective layer against antibiotic treatment.
Consequently, invasive CRAB infections can lead to mortality in up to 60% of cases, demonstrating the high level of unmet need in this indication.
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The aforementioned novel drug candidate, zosurabalpin, functions by inhibiting a bacterial protein complex called LptB2FGC.
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By GlobalDataThis blocks the LPS from being transported to the surface of the bacterium. Instead, the LPS builds up to toxic levels within the microbe, which leads to its eventual death.
A study assessing the efficiency of zosurabalpin by screening approximately 45,000 small molecules with possible antibiotic properties showed that the compound worked against more than 100 CRAB samples from infected humans, destroying the organism’s ability to create its protective double membrane.
Additionally, the compound reduced the levels of bacteria in mice with CRAB-induced pneumonia, preventing the deaths of mice with bacteria-triggered sepsis.
Zosurabalpin is a new molecular entity that has the potential to treat lethal hospital-associated infections through its unique mechanism of action.
It is also possible that this method could be utilised for the treatment of various other bacterial infections.
Aside from zosurabalpin, there are nine other drugs currently in clinical development for the treatment of Acinetobacter infections, according to GlobalData, a leading data and analytics company.
One example is Fetroja, which is already marketed for the treatment of urinary tract infections and hospital-acquired pneumonia, among other infections, and is currently in late-stage development for acinetobacter infections in the US, EU, and Japan.
However, the overall pipeline is small, and with only eight clinical trials currently ongoing or planned for this indication, there is limited activity in the CRAB space, particularly considering the very high level of unmet need.
Antibiotic-resistant bacterial infections are an urgent global threat to public health.
The effective treatment of bacterial infections is a foundation of modern healthcare, and hence the rise of antibiotic-resistant bacteria represents a silent pandemic, eroding the safety of basic medical interventions, and is an increasing cause of mortality globally.
In general, the number of novel antibiotics in development is lacking, although various novel approaches have been utilised to find alternative options to treat bacterial infections.
For example, the Massachusetts Institute of Technology has used AI to discover another class of antibiotics with the potential to treat methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus.
These recent discoveries could help in the fight against antimicrobial resistance, with the possibility of saving countless lives upon their success in clinical trials.
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