“Antibiotic resistance is a growing problem, directly causing the deaths of around 750,000 people globally each year,” Dr. Matthew Avison, reader in molecular bacteriology at the University of Bristol and senior author of both studies, told Seeker. “β-lactam antibiotics are the most commonly used class, about 60 percent of all prescriptions, and they are particularly important for serious infections of patients in hospitals.”
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The use of β-lactam enzymes is one important mechanism that bacteria use to resist antibiotics, by using them to destroy the medication once it enters a cell. Avison’s team was searching for a β-lactam enzyme inhibitor that would protect antibiotics in the body, allowing them to effectively fight infection.
They examined two inhibitors, one known as avibactam that is already being used in clinical trials, and another that is a bicyclic boronate inhibitor. On their own, both inhibitors failed to protect the antibiotic, known as ceftazidime. When paired with another antibiotic called aztreonam, however, they both worked extremely well, killing some of the most resistant bacteria the lab has ever observed.
“This discovery adds significantly to what we already know about β-lactam inhibitors,” Avison said. “We’ve shown that different combinations of β-lactamase inhibitors and β-lactam antibiotics work better than others, and most importantly, we have identified the biological explanation of this difference. We hope it will give clinicians the confidence to use these combinations in the treatment of serious infections where all other antimicrobials have failed.”
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Earlier this year, the combination of avibactam and aztreonam helped save the lives of two patients in the US. Each case involved antibiotic-resistant illnesses, and the novel combination of the β-lactamase inhibitor with the β-lactam antibiotic cleared the infections.
“This would only be used on very seriously ill patients in hospitals,” Avidon noted, “and so would only be given intravenously, usually via an infusion pump.”
Studies on β-lactamase enzymes continue to aid in the discovery of many more β-lactamase inhibitors, like the bicyclic boronate inhibitor that this study found to be effective. According to Avison, this is the first time in 10 years that scientists are hopeful about reversing β-lactam antibiotic resistance.
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“The combination we identified as the best is already in clinical trials, and it is likely that, if licensing is successful, it will be commercially available in 18 months in the US,” he said.
Looking toward the future, Avison is optimistic about the life-saving potential of this discovery.
“As resistance to other antibiotics increases,” he said, “there is every reason to believe that this combination would be used more and more widely, and would help in the cure of tens of thousands of potentially fatal infections.”
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