Drug tag team clobbers antibiotic-resistant bacteria

Drug tag team clobbers antibiotic-resistant bacteria
In the battle against superbugs, two specific antibiotics are better than one
In the battle against superbugs, two specific antibiotics are better than one
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In the battle against superbugs, two specific antibiotics are better than one
In the battle against superbugs, two specific antibiotics are better than one

Penicillin has been around since 1928, which means the bugs it's meant to fight have had almost 100 years to develop strategies to survive its effects. As more and more bacterial infections become impervious to penicillin and the other antibiotics that belong to the penicillin group, finding alternative ways to beat down deadly infections is becoming more critical than ever. Now researchers have found what all good combat specialists have long known – getting each other's back in a fight can be a winning strategy.

The bacteria that are immune to penicillins like amoxicillin and ampicillin release enzymes called beta-lactamases that shred the antibiotics, rendering them useless. Some bacteria can defeat even newly developed penicillins by putting out a group of bacterial beta-lactamases called metallo-beta-lactamases (MBLs). One such group of bacteria are those called carbapenem-resistant enterobacteriaceae or CRE, which cause infections that, according to the CDC can kill up to half of their victims.

In a study led by Robert A. Bonomo from Case Western Reserve University School of Medicine in Cleveland, Ohio, it was discovered that combining two antibiotics eliminated 81 percent of CRE specimens tested.

The first antibiotic is called ceftazidime/avibactam and it falls prey to the effects of MBLs, but not other debilitating enzymes released by the harmful bacteria. The second is called aztreonam, and it can withstand MBLs but is vulnerable to the other enzymes. Together, they run interference for each other and deliver an effective one-two punch to the CREs. Once the aztreonam gets by the MBLs with the help of the ceftazidime/avibactam, it binds to the infectious bugs and keeps them from building effective cell walls, leading to their death.

Although the regimen was shown to work in the lab and has yet to go through clinical trials, it was put into practice by necessity. A young recipient of a kidney transplant at Nationwide Children's Hospital in Columbus, and an elderly woman who had just received a new hip at University Hospitals in Cleveland were both given the drugs because they weren't responding to standard courses of treatment and were at risk of dying. They both survived.

Further clinical testing and more research is slated before the drug combo can be released for common use.

Antibiotic-resistant bacteria is quickly becoming a major global concern. Just last month, the World Health Organization issued its first-ever hit list of hard-to-kill bacteria, adding its voice to the the European Centre for Disease Control and Prevention(ECDC), the American Centers for Disease Control (CDC) and the British government in drawing global attention to the issue.

"If we understand the fundamental mechanisms by which bacteria become resistant to antibiotics, we can use what we know to help design better therapies," said Bonomo.

The findings have been reported in the journal Antimicrobial Agents and Chemotherapy.

Source: Case Western Reserve University via EurekAlert

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