Increasing natural immunity may prevent recurrent urinary tract infections

Vaccine may become an alternative to a lifetime on antibiotics, but critics charge that the research has a long way to go.

By Victoria Stagg Elliott, amednews staff. Jan. 14, 2002.

A vaccine is showing promise in phase II clinical trials as a possible treatment for recurrent urinary tract infections in women.

The vaccine, composed of the heat-killed bacteria that cause most UTIs, appears to provoke an immune response that creates resistance to infection, according to a paper presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy last month.

Making the break from antibiotics
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Researchers with the University of Wisconsin in Madison followed 54 women for five months. All were taking daily antibiotics because of a history of as many as 20 infections per year. All were taken off their medication. One-third were given monthly placebo vaginal suppository vaccines while another third were given three weekly doses of the vaccine. The last third were given the initial set of three treatments with "boosters" at six, 10 and 14 weeks.

Of those who received all six treatments, 55% did not experience a new infection while 89% of those on placebo did.

"We wanted to increase the natural immunity of the women by using a vaccine," said Walter J. Hopkins, PhD, lead author of the study and a University of Wisconsin distinguished scientist. "The bacteria that are causing infections in the bladder are infecting mucosal surfaces so we wanted to increase immunity at mucosal sites. That's much better achieved through a mucosal vaccine than an injectable vaccine."

Unlike most currently available vaccines, this one does not appear to provide long-lasting immunity, but researchers say it could be an alternative to prophylactic antibiotic use for the women who have repeated UTIs. It could decrease antibiotic use overall and be one step to reducing antibiotic resistance.

"A lot of women who have these infections are on prophylactic antibiotics for months or years at a time," said Dr. Hopkins. "The bacteria develop resistance, and patients have to switch to the next one. Some women run out of options. Some develop an allergic reaction."

Researchers speculate that a self-administered vaccine has the potential to be cheaper and reduce physician visits. A periodic suppository could also mean increased compliance with treatment as well as being more convenient for the patient than a daily antibiotic.

Still not the easy answer

Critics say the research is interesting, but maintain that it does not yet have the adequate data to take it to the next step. In other words, more study is needed with more subjects over a longer period of time.

"I don't think it's a bad idea. It would be nice to have another modality," said Nancy Church, MD, an obstetrician-gynecologist with Wellness Connection, based in Chicago. "But why would this be in any way superior to suppressive therapy?"

Researchers are now seeking funding from the National Institutes of Health to conduct a larger multicenter trial and are setting up an open label trial for their current subjects.

There is also a question of how effective this could be if used more broadly. In this trial, quite a few women who received the full course of the vaccine -- 45% -- still developed infections. Researchers speculate that this may be due to genetics or the lack of inclusion in the vaccine of the bacteria a patient is infected with, although this aspect is unclear.

"There are many different pathogens that cause UTI," said Dr. Church. "Can a vaccine cover them all?"

Those who treat recurrent UTIs also say that antibiotic resistance is not a problem. They sometimes have to switch their patients to other medications, but none of their patients are close to running out of options.

"There are still many antibiotics available that will be effective for resistant bacteria. We haven't run out yet, but that could ultimately happen," said Lee W. Riley, MD, professor of epidemiology and infectious disease at the University of California, Berkeley.

Other issues involved

One school of thought, however, suggests that the antibiotics that humans take is not the problem. Instead, the ones taken by animals are.

A study authored by Dr. Riley and published in the New England Journal of Medicine in October 2001, suggested that a source of the Escherichia coli bacteria that cause many urinary tract infections may be tainted food. In addition, the bacteria may be resistant to common antibiotics because of its original host animal's previous exposure to the same medication.

"From a public health perspective, we need to prevent women from ingesting resistant E. coli to begin with," said Dr. Riley. "We're never going to prevent the ingesting of the bacteria, but we can certainly prevent the development of resistance. We know that farm animals on antibiotics has led to drug-resistant Salmonella. This can certainly happen with E. coli."

ADDITIONAL INFORMATION:

Making the break from antibiotics

Study question: Can a vaginal mucosal vaccine be effective in increasing resistance to recurrent urinary tract infections in women?
Method: 54 women with a history of frequent UTIs were recruited for a double-blind, placebo-controlled phase II trial to test a vaccine containing heat-killed bacteria as a vaginal suppository. All were taken off their prophylactic antibiotics and randomly assigned to receive placebo, three weeks of the vaccine or three weeks and boosters at weeks six, 10, and 14. Women were followed for five months total.
Results: 55% of patients receiving the initial vaccination plus boosters were UTI free; 89% of those who received placebo developed an infection.
Conclusion: The vaccine is safe and well-tolerated. Initial and booster immunizations given over a 14-week span increased resistance to UTIs.

Source: Walter J. Hopkins, PhD, at the Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago, December 2001.

Weblink

Interscience Conference on Antimicrobial Agents and Chemotherapy (http://www.icaac.org/)

Urinary tract infection information from the National Kidney and Urologic Diseases Information Clearinghouse (http://www.niddk.nih.gov/health/urolog/pubs/utiadult/utiadult.htm)

Abstract, "Widespread Distribution of Urinary Tract Infections Caused by a Multidrug-Resistant Escherichia coli Clonal Group," New England Journal Of Medicine, Oct. 4, 2001 (vol. 345, issue 14) (http://content.nejm.org/cgi/content/abstract/345/14/1007)