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UCSD researchers find promising results treating staph with existing drugs

Posted at 1:42 PM, Mar 24, 2021
and last updated 2021-03-24 16:42:55-04

SAN DIEGO (CNS) - A team of UC San Diego researchers found that repurposing heart and flu drugs may bolster a patient's immune system enough to fight more effectively against staph sepsis, a bloodstream infection, it was announced Wednesday.

The UCSD scientists, whose findings were published Wednesday in Science Translational Medicine, found that despite continued improvements in antibiotics and hospital intensive care, staph sepsis still causes severe illness or death in 20 to 30% of patients who contract it.

The team discovered a battle that occurs between Staphylococcus aureus bacteria and platelets -- blood cells known better for their role in clotting than in immune defense. In some sepsis cases, they found, the bacteria win out and platelet levels plummet. Patients with fewer platelets were more likely to die of staph sepsis than patients with higher platelet counts.

The researchers also determined that two currently available prescription medications approved by the U.S. Food and Drug Administration for other uses can protect platelets and improve survival in mouse models of staph sepsis. The two repurposed drugs were ticagrelor or Brilinta, a blood thinner commonly prescribed to prevent heart attack recurrence, and oseltamivir or Tamiflu, prescribed to treat influenza.

"In many cases, the antibiotics we give these patients should be able to kill the bacteria, based on lab tests, yet a significant number of patients are not pulling through," said senior author Dr. Victor Nizet, a professor at the UCSD School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences. "If we can reduce mortality in staph sepsis by 10 or 20% by arming or protecting the immune system, we can likely save more lives than discovering an additional new antibiotic that may still not cure the sickest patients."

Around 31% of patients with low platelet counts died from the infection, compared to fewer than 6% of patients with platelets above the threshold.

In laboratory experiments, the researchers worked out what's likely happening. Platelets secrete antimicrobial peptides that help the immune system destroy staph bacteria. At the same time, staph release an alpha-toxin that's detrimental to platelets. In addition to poking holes in platelets, the toxin convinces the blood cells to produce an enzyme that trims off sugar molecules that decorate their own surfaces.

Once Nizet and his team had an idea of what might be happening in the patients who are less likely to survive staph sepsis, they turned to mouse models of the disease to find ways to tip the balance of what they call the "toxin-platelet-receptor" axis back in favor of the human patient.

Mice with staph sepsis and treated with either ticagrelor or oseltamivir maintained more platelets and had less bacteria in their blood. Ultimately, around 60% of treated mice survived 10 days following infection, compared to 20% of untreated mice.

"Discovering a new drug is tremendously expensive and takes many, many years," said Nizet, who is also faculty lead for the Collaborative to Halt Antibiotic-Resistant Microbes at UCSD. "But if we look around at what we already have, what we already know to be safe, we may find many opportunities to improve patient outcomes."

According to the U.S. Centers for Disease Control and Prevention, each year at least 1.7 million adults in the U.S. develop sepsis and nearly 270,000 die as a result. One in three patients who die in a hospital has sepsis.

It's also one of the costliest diseases. In 2013, for example, the Department of Health and Human Services reported that sepsis management added up to more than $24 billion in hospital expenses, or 13% of total U.S. hospital costs.