Smart antibiotic kills dangerous bacteria while sparing the beneficial bacteria your gut needs

Smart antibiotic kills dangerous bacteria while sparing the beneficial bacteria your gut needs
The bacteria that causes syphilis.

Gram-negative bacteria can cause a host of ailments, such as salmonella, pneumonia, bloodstream infections, and peritonitis. Now, scientists are coming up with an antibiotic that kills them without wiping out your beneficial gut bacteria. Previously, the only antibiotics that had any effect on them would wipe out your gut microbiome, potentially exposing you to deadly pathogens. Nature reports:

They are the stuff of medical nightmares. Pathogens classified as Gram-negative bacteria are often hardy, virulent and quick to evolve resistance to antibiotics. Only a few drugs can knock them out, and these also destroy beneficial gut bacteria.

Now scientists have developed an antibiotic that kills pathogenic Gram-negative bacteria — even those resistant to many other drugs — without impairing the gut microbiome. So far, it has been studied only in mice, but if the compound works in humans, “it could help us dramatically”…However, there is a caveat….the compound’s usefulness “depends on whether bacteria will develop resistance to it in the long run”.

Gram-negative bacteria include public-health villains such as Escherichia coli and Klebsiella pneumoniae. They cause diseases ranging from salmonella to cholera, and can trigger sepsis, a potentially lethal immune-system response to infection.

The bacteria have “multiple barriers that prevent antibiotic penetration”, says molecular biologist Zemer Gitai at Princeton University in New Jersey, who was not involved in the research. As a result, there are almost no antibiotics that specifically target Gram-negative bacteria. The few drugs that do also wreak havoc with the gut microbiome, allowing potentially deadly pathogens such as Clostridioides difficile to take over.

To find a way around the bacteria’s defenses, the study’s authors started with compounds that don’t kill the bacteria but are known to inhibit the ‘Lol system’, a group of proteins that is exclusive to Gram-negative bacteria. Tinkering with those compounds produced one that the researchers called lolamicin, which “selectively kills pathogenic bacteria over non-pathogenic bacteria based on differences in Lol proteins between these bacteria”, says study co-author Paul Hergenrother, a chemist at the University of Illinois at Urbana-Champaign.

Lolamicin had anti-microbial effects against more than 130 multidrug-resistant strains of bacteria growing in laboratory dishes. Mice that developed blood stream infections after exposure to antibiotic-resistant bacteria all survived after being given lolamicin, whereas 87% of those that didn’t receive the compound died within three days.

The team also found that common antibiotics such as amoxicillin severely disrupted the animals’ gut microbiome, which led to infections with C. difficile. By contrast, lolamicin treatment did not cause observable changes in the gut microbiome and spared mice from C. difficile infection….

But this antibiotic will not be approved anytime soon, partly due to government red tape. Biologist Sebastian Hiller notes that “there is a long road from showing efficacy in mice to developing a drug for human use.” The time from an antibiotic’s discovery to its approval for clinical use can be more than two decades, “and there is not much money to be made with a novel antibiotic.” He points out that “ten to twenty new Gram-negative antibiotics have been discovered in the last ten years,” but none has been approved yet by the Food and Drug Administration.

The FDA is a huge impediment to approving such needed drugs. FDA employees commonly take years to approve life-saving drugs. That results in the deaths of hundreds of thousands of people who could have been saved by earlier approval of those drugs. For example, at least a hundred thousand people died waiting for the FDA to approve beta blockers. One of the FDA officials involved in delaying their approval was John Nestor. Nestor was notorious for following rules in ways designed to frustrate and inconvenience other people. As the Journal of American Physicians and Surgeons notes:

Nestor had the unique habit of getting into the leftmost lane [on the highway] with his cruise control set at 55 mph, the posted speed limit. He would drive at this speed regardless of what came up behind him. Cars would zoom up close to his rear bumper; drivers would flash their lights and blast their horns,some swerving around him on the right while giving him the finger—none of this fazed Nestor in the least. As he explained it, 55 mph was the law, and he had a right to drive in whichever lane he chose: “Why should I inconvenience myself for someone who wants to speed?”

Nestor followed this rigid mindset in his work at the FDA. He was very good at using agency red tape, and minor risks or side effects of drugs, as an excuse to avoid approving life-saving drugs.

The FDA didn’t approve a home test for HIV until 24 years after it first received an application. According to an FDA advisory committee, the test “holds the potential to prevent the transmission of more than 4,000 new HIV infections in its first year of use alone.” That means thousands of people likely got infected with AIDS as a result of the delay in approving it. As Roger Parloff of Fortune notes, the FDA’s delay in approving the home HIV test is a “scandal.” It likely caused the deaths of thousands of people, given the mortality rate from AIDS.  It may also have caused billions of dollars in additional costs for taxpayers, given that AIDS is a costly and debilitating disease to treat, resulting in treatment costs of perhaps $600,000 per AIDS sufferer.

In light of the countless people killed by the FDA’s deadly delays in approving life-saving drugs and medical devices, drugs and devices should not have to be approved by the FDA before they can be sold. Instead, the FDA should only be able to remove drugs and devices from the market once it has evidence that they should be banned based on their ineffectiveness or dangerousness. The FDA should also be allowed to place warning labels on drugs and devices based on their risks, even when the quantum of evidence is not sufficient to prove the need for a ban. Originally, the FDA did not have premarket approval powers, even when it had enforcement authority to take action against quackery and unsafe drugs and devices.

LU Staff

LU Staff

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