Investigational agent for chronic UTI successful in early study

An experimental treatment for urinary tract infections has passed its first test in animals, alleviating weeks-long infections in mice in as little as 6 hours, according to a recent study.

"This drug can block the spread of the bacteria that cause urinary tract infections far better than any other previously reported compound," said senior author Scott J. Hultgren, PhD, of Washington University School of Medicine in St. Louis. "If it has similar effects in humans, the potential applications would be very exciting."

The compound is a novel derivative of the natural sugar called mannose, making it unlikely to be toxic. Because the body normally directs excess sugars to the kidney for disposal in the urine, the new drug is naturally sent to exactly where it needs to be to treat infections of the urinary tract, researchers say.

Co-author James W. Janetka, PhD, designed a group of investigational drugs, called mannosides, based on information from Dr. Hultgren’s research. The researchers designed and tested a number of these compounds and chose one finalist from among the top six candidates.

When scientists fed the most promising drug to mice with chronic UTIs, bacteria levels in their bladders declined much more quickly than in a second group of mice given antibiotics. The mannoside also prevented new infections.

"In other tests, when we gave infected mice the mannoside first, the bacteria became much more vulnerable to treatment with antibiotics," Dr. Janetka said. "But we produced our most exciting results when we used the mannoside and the antibiotics simultaneously. This created a synergistic effect in the mice that could rapidly eliminate even infections by antibiotic-resistant bacterial strains."

Dr. Hultgren and Dr. Janetka are continuing to develop more potent mannosides. They hope to begin human toxicity tests for the drugs late in 2012. If those tests are successful, clinical trials may follow.Findings from the study were published in Science Translational Medicine (2011; 3:109ra115).

Washington University holds a patent on the mannoside compounds reported in this study.

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