Modern antibiotics have a design flaw, and it’s contributing to millions of resistant bacterial infections each year. That calculation is courtesy of the Wellcome Leap program, which just invested $50 million to develop reformulated antibiotics that could fix that flaw—and dramatically cut the odds of future resistance.1
Until now, the design flaw was often impossible to avoid. More than 85 percent of bacterial infections are local, affecting a single part of the body, such as the bladder, skin, middle ear, or lungs. Yet patients typically are given antibiotics as tablets or injections.
This means the antibiotic reaches the infection site, but also circulates through the rest of the body, including the gut, home to an entire microbial ecosystem with trillions of bacteria, most of them either important to wellness or innocuous.
Exposure to the antibiotic creates selection pressure, which can lead resistant microbes of all sorts to multiply, altering the ecosystem known as the gut microbiome. Those resistant microbes often persist or pass genes that confer that ability to other microbes, both of which increase the odds of a future resistant infection. That’s the design flaw at work.
The logical fix was clear for years—kill the disease-causing microbes but leave innocuous and beneficial microbes alone. That’s the goal of narrow-spectrum antibiotics, which kill pathogens but spare more of the microbiome. But those are still often given systemically. The goal of the $50 million Wellcome Leap Focused Antibiotics program, which funded 16 academic researchers on five continents, is to target treatment even more.
If the work succeeds and scales globally, program leaders write, it could reduce antibiotic-driven resistant infections by up to 40 percent in its first decade of use.1
Three Targeted Approaches
The funded researchers are taking one of three approaches, each enabled by recent technological advances.
One is to develop drug carriers, such as nanoparticles or peptides, that release or activate the antibiotic at the infection site. In animal models, the experimental medicines would have to be safe for the gut microbiome while retaining the same efficacy against bacterial infections.
A second approach is to keep the antibiotic away from the large intestine. This would mimic an existing antibiotic called nitrofurantoin that consists of a microbe-killing part of the antibiotic molecule attached to a sugar molecule through a process called glycosylation. This allows the antibiotic to be absorbed into the bloodstream in the small intestine, so little reaches the large intestine, where most of the gut microbiome lives.
A third approach involves delivering the antibiotic directly to the infection site. For example, an antibiotic formulation could be delivered directly to the ear of a child suffering an ear infection.
Ultimately, the program aims to develop successful approaches to first-line antibiotics that offer manufacturers more potential revenue than a new class of reserve antibiotics and are therefore more likely to be manufactured and delivered to patients. Learn more about Wellcome Leap’s program and discover the program’s awardees.
