Research Leads to Promising New Therapies for Treating and Preventing UTIs

Henri R. Ford, M.D., MHA, dean and chief academic officer of the University of Miami Miller School of Medicine, hosted a lecture on October 31 by renowned molecular microbiologist Scott J. Hultgren, Ph.D., whose groundbreaking contributions to understanding urinary tract infections (UTIs) are helping pave the way for promising new therapies.

Dr. Hultgren, the Helen L. Stoever Professor of Molecular Microbiology and director of the Center for Women’s Infectious Disease Research at Washington University School of Medicine, was introduced by Dr. Ford as “one of the preeminent scientists of our time.”

In 2017, Dr. Hultgren was elected to the National Academy of Medicine, one of the highest honors in the fields of health and medicine in the United States. He was elected to the National Academy of Sciences in 2011. In 1998, he received the Eli Lilly Award, the preeminent award granted in microbiology to those younger than 40. He also has been recognized as a Nobel Fellow and was awarded a merit grant from the National Institutes of Health.

Addressing more than 60 physicians and researchers gathered at the Lois Pope LIFE Center, Dr. Hultgren offered an in-depth look at the research he has been leading on UTIs. He and his team have focused on the molecular mechanisms of susceptibility, establishment, and progression of disease; epidemiology; and determination of factors that influence disease outcomes and sequelae. Their findings are opening the door to new UTI therapies that don’t require the use of antibiotics.

“UTIs are among the most common infectious diseases, afflicting more than 18 million women a year and accounting for up to 15 percent of all antibiotics prescribed in the U.S.,” Dr. Hultgren said.

Roughly half of all women will contract a UTI at some point in their lives. Many suffer recurrent infections that require preventive antibiotic regimens consisting of daily doses for months or even years. In these cases, Dr. Hultgren noted, breakthrough UTIs do occur and are often caused by antibiotic-resistant bacteria. While taking antibiotics for a UTI is typically effective in the short term, it increases the risk of getting one again, he added.

“In mice, we’ve discovered that an infection actually leaves a molecular imprint on the bladder, which may explain why some patients are predisposed to a lifetime of recurrent UTIs,” Dr. Hultgren said.

Another problem for UTI patients is that the proliferation of antibiotic-resistant pathogens is rendering many conventional therapies obsolete. This makes new, antibiotic-sparing therapies — such as those being developed as a result of Dr. Hultgren’s research — an essential tool in fighting these infections.

A strain of E. coli, uropathogenic Escherichia coli (UPEC), is the causative agent in the vast majority of UTIs, Dr. Hultgren explained. The bacteria establish themselves in the urinary tract and evade the body’s innate defenses by zipping onto the bladder walls like molecular Velcro, leading to an infection.

Dr. Hultgren and his team’s research has led to the development of a vaccine and, separately, a class of small molecule compounds, called mannosides, as new ways to treat and prevent UTIs.

“By simply preventing the bacteria from being able to stick to the walls of the bladder, mannosides allow the body to naturally eliminate the infection,” Dr. Hultgren said.

Thomas Hooton, M.D., professor of clinical medicine at the Miller School and an infectious diseases specialist, is a principal investigator studying the investigational vaccine under a Phase 1B clinical study in patients who have recurrent UTIs caused by multidrug-resistant bacteria.

“This investigational vaccine against the part of the E. coli bacterium that is critical for infection looks very promising in early human trials,” Dr. Hooton said. “We are very excited that it may offer an effective antibiotic-sparing strategy to help patients who suffer from recurrent UTIs.”

Gary Eldridge, CEO of Sequoia Sciences, who works with Drs. Hultgren and Hooton, said that the Phase 1 clinical study has already yielded encouraging results, and Phase 2 clinical studies will begin in about a year. The investigational vaccine has received Fast Track designation from the Food and Drug Administration and has also been allowed for compassionate use.

One patient in the study had about 20 UTIs over the two years before enrolling. But in the year since being treated with the vaccine, she has had only two.

“The results we’ve seen so far are very encouraging,” Eldridge said. “Reducing the use of antibiotics to treat UTIs represents one of the greatest opportunities to reduce overall antibiotic consumption.”

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