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Researchers Explore Old Drugs as Options for Treating Sepsis

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Researchers | Image by Mongkolchon Akesin

Researchers are looking at new ways to use older drugs that have already been safety tested and approved. Two older drugs are showing promise in the treatment of sepsis, an illness affecting millions of people each year.

Researchers at the University of California San Diego (UC San Diego) studied two drugs, Brilinta and Tamiflu, which are already approved by the U.S. Food and Drug Administration (FDA), as a new way to fight sepsis.

Dr. Victor Nizet, a professor at UC San Diego’s School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, said in an interview with NBC DFW, “Sepsis is one of the most dangerous syndromes known in medicine. It is an uncontrolled inflammatory response to a severe bacterial infection that is spreading through your body.”

The inflammatory response can lead to tissue damage, organ failure, and death.

According to the Centers for Disease Control and Prevention (CDC), around 270,000 people in the United States die each year from sepsis, which is more deaths than those caused by opioid overdose, prostate cancer, and breast cancer combined.

Around 49 million people are diagnosed with sepsis around the world each year, including over 20 million children under the age of 5. In the U.S., someone is diagnosed with sepsis every 20 seconds.

One in three hospital deaths have sepsis listed as one of the culprits. In 2013, the Department of Health and Human Services reported that hospital expenses were over $24 billion for patients with sepsis, which is 13% of the total hospital costs in the United States.

The symptoms of sepsis are increased heart rate, confusion, rapid breathing, fever, and chills.

Although bacterial infections are the typical cause of sepsis, fungal infections and viral infections, such as COVID-19, can cause sepsis as well.

Sepsis is typically treated with antibiotics, although no specific drug has been discovered to target it directly.

Researchers at the University of Wisconsin studied blood and bacteria samples from forty-nine patients with staph sepsis, a bloodstream infection. The study concluded that patients with lower platelet counts have a higher chance of dying from sepsis. Platelets are blood cells that cause clotting to stop bleeding, but they also secrete antimicrobial peptides that bolster the immune system.

Based on that research, the team at the University of California began looking for ways to protect the platelet count in patients with sepsis.

Nizet said, “We are looking for new ideas in which we try to assist in the clearance of infection by boosting the immune system.”

According to a press release from UC San Diego, researchers focused on two medications currently on the market,  Brilinta and Tamiflu.

Brilinta (Ticagrelor) is a blood thinner typically prescribed to prevent heart attacks from reoccurring. Tamiflu (Oseltamivir) is prescribed to treat the flu. These two drugs were known to protect platelets.

The press release said, “Ticagrelor blocks staph’s alpha-toxin so it can’t injure platelets or stimulate its sugar-removing enzyme. Oseltamivir inhibits the platelet sugar-removing enzyme so the cells don’t go bald and aren’t cleared by the liver, even when staph’s alpha-toxin is around.”

Sixty percent of mice in the study treated with Brilinta and Tamiflu survived to the tenth day after the infection began. They had more platelets and less bacteria in their blood due to the drugs protecting the immune system. Only 20% of the untreated mice survived to the tenth day.

Nizet said, “Discovering a new drug is tremendously expensive and takes many, many years. 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.”

“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,” Nizet stated.

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