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Repurposed Heart and Flu Drugs May Help Body Fight Sepsis
The author:Go Top Peptide Biotech    Released in:2021年04月08日
摘要:Higher platelet counts linked to better outcomes for patients with staph sepsis; repurposed drugs that protect platelets improve survival of septic mice

Despite continued improvements in antibiotics and hospital intensive care, staph sepsis — a bloodstream infection caused by Staphylococcus aureus bacteria — still causes severe illness or death in 20 to 30 percent of patients who contract it.

Rather than continue to throw more antibiotics at the problem, University of California San Diego researchers want to boost the other side of the equation: the patient’s own immune system.

The team recently discovered a battle that occurs between staph 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 (FDA) for other uses, protect platelets and improve survival in mouse models of staph sepsis. The two repurposed drugs were ticagrelor (Brilinta), a blood thinner commonly prescribed to prevent heart attack recurrence, and oseltamivir (Tamiflu), prescribed to treat the flu.

The study is published March 24, 2021 in Science Translational Medicine.

Repurposed Heart and Flu Drugs May Help Body Fight Sepsis

“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 Victor Nizet, MD, Distinguished Professor at UC San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences. “If we can reduce mortality in staph sepsis by 10 or 20 percent 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.”

Repurposed Heart and Flu Drugs May Help Body Fight Sepsis

The study started with a group of 49 University of Wisconsin patients with staph sepsis. The team collected the patients’ blood, bacteria samples, and demographic and health information. To their surprise, it wasn’t white blood cell counts (immune cells) that correlated with patient outcomes — it was the platelet count. Low platelet counts, defined in this case as fewer than 100,000 per mm3 blood, were associated with increased risk of death from staph sepsis. Approximately 31 percent of patients with low platelet counts died from the infection, compared to less than 6 percent 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 bacteria’s alpha-toxin convinces the blood cells to produce an enzyme that trims off sugar molecules that decorate their own surfaces. The platelet’s new look is recognized by another molecule in the liver called the Ashwell-Morell receptor, which pulls “bald” platelets out of circulation.

Original source:UC San Diego News Center


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