New Delhi: For India and other countries faced with the grave problem of antimicrobial resistance (AMR), there is some good news. Scientists seem to have discovered a new class of antibiotics that appears capable of killing one of three superbugs that have emerged as a major challenge to public health due to their extensive drug-resistance.
According to a study published in the journal Nature this month, the new class of antibiotic — Zosurabalpin, developed by Swiss pharma giant Roche — has been found to kill drug-resistant strains of carbapenem-resistant Acinetobacter baumannii (CRAB), called a superbug because it is highly resistant to existing antibiotics.
The results are from animal studies, says the paper, adding that the drug is now being tested in humans.
Carbapenems are a class of very effective antibiotic agents most commonly used for treatment of severe bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections.
The World Health Organization (WHO) classifies CRAB as a priority-1 critical pathogen along with two other drug-resistant forms of bacteria — Pseudomonas aeruginosa and Enterobacteriaceae.
These pathogens belong to a class called ‘gram-negative bacteria’, which are particularly difficult to treat. No new antibiotic has been approved for gram-negative bacteria in more than 50 years.
CRAB is believed to be a significant cause of hospital-acquired infections, mainly in people who are on ventilators. It can cause acute infections of the blood, urinary tract, and lungs.
Since it is resistant to existing medicines, infections are hard to treat, which means an increased risk of disease spread, severe illness, and deaths in nearly 60 percent of people infected with it.
In response to a query from ThePrint, a Roche spokesperson said drug resistance to all existing classes of antibiotics has been on the rise in various gram-negative bacteria for several decades.
“Any new antibiotic class that has the ability to treat infections caused by multidrug-resistant (MDR) bacteria such as CRAB would be a significant breakthrough,” said the spokesperson, adding that Zosurabalpin has many features that position it to be a medical breakthrough.
The spokesperson said the human clinical trials will inform whether it has the potential to address a major gap in the fight against antimicrobial resistance.
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Growing burden of AMR
The WHO recognises AMR as one of the top threats to global public health. It is estimated that bacterial AMR was directly responsible for 1.27 million global deaths in 2019, and contributed to 4.95 million deaths.
The misuse and overuse of antimicrobials in humans, animals and plants are the main drivers in the development of drug-resistant pathogens, the world health body says.
India’s National Action Plan on AMR says that the country has among the highest burdens of bacterial infections — an estimated 410,000 children aged five years or less die from pneumonia in India annually, with pneumonia accounting for almost 25 percent of all child deaths.
Also, the crude mortality (a measure of deaths in proportion to population) from infectious diseases in India is 417 per 100,000 people.
“AMR is a major public health concern in India. The emergence of resistance is not only limited to the older and more frequently used classes of drugs but there has also been a rapid increase in resistance to the newer and more expensive drugs, like carbapenems,” the plan says.
A researcher working on an AMR-related project with the National Centre for Disease Control under the Union health ministry said the discovery of a new class of antibiotic that promises to treat superbug-related infection is astounding, “even though it might take a few years to show efficacy in human trials”.
Roche, meanwhile, maintained that phase 1 global trials of Zosurabalpin in humans is currently ongoing.
“These studies aim to test safety, tolerability, and pharmacokinetics (the concentration of Zosurabalpin in the human body over time). Once we have completed the currently ongoing phase 1 trials, we will evaluate this data and work with all our collaborating partners to determine the next appropriate step,” the spokesperson said.
How the drug works
Researchers tested Zosurabalpin against more than 100 CRAB samples from patients, and found that it was able to kill all of these bacterial strains.
The medicine, the paper says, could also kill the bacteria in the bloodstream of mice infected with CRAB, preventing them from developing sepsis.
The pathogen has the ability to produce a toxin called lipopolysaccharide that it uses for infecting people, and which is present on its outer cell wall.
The mechanism of this molecule class (Zosurabalpin) involves blocking the transport of bacterial lipopolysaccharide from the inner membrane to its destination on the outer membrane, through inhibition of the LptB2FGC complex — a lipopolysaccharide transporter.
This leads to a toxin build-up inside the bacteria, causing the CRAB cells to die.
(Edited by Sunanda Ranjan)
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