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Fungi can be friend or foe and they're getting smarter (6/17/97)

We eat them, we breathe them, we act as host for colonies inside of our bodies. Sometimes the colonies grow uncontrollably and can kill us if our immune systems are not working properly.

The "them" are fungi, a kingdom of organisms that includes moulds, rusts, mushrooms, toadstools, and yeasts.

Fungus expert Michael Rinaldi, PhD, who supervises two world-renowned fungus testing laboratories in San Antonio, is working with scientists and caregivers around the globe to help identify and control fungi in the body and develop drugs to combat the increasing resistance fungi are showing to existing medications.

"Largely because of the AIDS epidemic and the development of organ transplantation, following which patients' immune systems are suppressed to keep them from rejecting organs, we are experiencing what I believe is a golden age of mycology and antifungal therapy," Dr. Rinaldi says. Mycology is the study of fungi.

"Patients with suppressed or damaged immune systems are living petri dishes (dishes in which scientists grow cultures in the lab) who can develop a wide array of fungal infections that clinicians may never have had to treat in patients before," he says. Thanks to laboratories like Dr. Rinaldi's at The University of Texas Health Science Center at San Antonio and the Audie L. Murphy Memorial Veterans Hospital, development of antifungal medications is proceeding very rapidly.

The laboratories examine between 30 and 40 thousand specimens each year. Staff has grown from one--Dr. Rinaldi--in 1985, to 12 at present.

The yeast fungus *Candida albicans* alone has spawned numerous studies. "Spencer Redding in the Health Science Center's Dental School has studied *Candida albicans* resistance to the drug fluconazole and he published what has been considered a landmark paper on the subject several years ago," Dr. Rinaldi said.

Dr. Redding works with other faculty including Drs. Jean Smith and Thomas Patterson of the division of infectious diseases in the department of medicine to treat HIV-positive patients for thrush, a condition in the mouth caused by *Candida albicans*.

Says Dr. Redding, "*Candida* is part of the normal flora in the human body. More than half the population has *Candida* living in their mouths. But in patients who have an impaired immune system, it can multiply uncontrollably. In 1993, Dr. Smith and I published a paper tracking resistance of *Candida albicans* to fluconazole in a patient with AIDS. He required progressively higher doses of the drug to keep down the infection and even after 12 treatment regimens over a two-year period, the fungus was still present." Adds Dr. Rinaldi, "Dr. Redding was also one of the first to notice that fungi in a patient's blood traveled to the mouth and vice versa."

That paper in the journal *Clinical Infectious Diseases* drew attention to the problem of drug resistance in patients with fungal infections and pointed the way for future treatment. "With support from the National Institute of Dental Research, Dr. Patterson and I are still looking at *Candida* and at fluconazole," Dr. Redding reports. "In the absence of safer, more effective drugs, we are trying to find treatment regimens that will be effective, depending on the relapse rate of patients. For example, if a patient relapses quickly, it appears that a low dose all the time is more effective than an intermittent high dose of the drug."

Dr. Redding and Dr. Patterson are looking at oral *Candida* in patients who have had head and neck radiation. "These patients sometimes have a problem with *Candida* multiplying, probably because the radiation affects their salivary glands. The mouth isn't getting enough saliva to stay healthy."

Thrush infections caused by *Candida* are now also being influenced positively because of treatment of AIDS patients with protease inhibitors -- new drugs that may restore some immune function in this patient population.

Says Dr. Patterson, "In some patients, increasing doses of standard therapy are required to treat oral thrush, particularly in patients with advanced AIDS." Dr. Patterson, who is also staff physician at the Audie L. Murphy Memorial Veterans Hospital, is leading a 3-year study to determine optimal strategies for treating patients with oral yeast infections. "In some patients, even high doses of standard antifungal therapies are not effective, so understanding ways that yeasts develop resistance is important. That's where collaboration with an epidemiologist is especially critical."

Epidemiologist Dr. Jan Evans Patterson tracks factors associated with increased risk for fungal infections. In addition to being associate professor of medicine at the Health Science Center, she is epidemiologist for San Antonio's University Health System, including University Hospital, and for the South Texas Veterans Health Care System, including the Audie L. Murphy Memorial Veterans Hospital. "Resistant yeasts are like antibiotic-resistant bacteria in that they are increasingly common and can rapidly be spread from one patient to another," she says. "We are assessing patterns of resistance in AIDS patients with oral thrush and in hospitalized patients in intensive care units so that spread of these strains can be understood and controlled."

Says Dr. Rinaldi, "I would say that fungi are among the most critical problems in health care right now. Drug companies are constantly submitting new drugs for testing. We help them perform tests both in the lab and in animal and human subjects."

The labs help identify unknown samples from throughout the world and the VA labs are the central facility for the Department of Veterans Affairs and the Federal Government, including the National Institutes of Health and the Food and Drug Administration.

"When the word 'fungus' used to come up in health care, it meant primarily athlete's foot and vaginal yeast infections," recalled Dr. Rinaldi. "Today, we are in a race against a wide array of fungal infectious that are attempting to keep one step ahead of us in their ability to develop resistance to available drugs. But we're making headway," he says, "as the interest in fungal infections and the development of new therapeutic approaches have never been so active."

Contact: Mike Lawrence (210) 567-2570