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Brain & Nervous System Health Center

Combo Therapy Helps Knock Out Fungal Meningitis

Study found 2-drug treatment reduced death risk from cryptococcal meningitis by 40 percent
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"Most of us have been exposed to Cryptococcus neoformans. It is ubiquitous in the environment, associated with trees, bird guano and soil. Infection is thought to occur from the inhalation of spores," Day said.

People can be infected for years without knowing it, according to Day. But, if someone who's infected has weakened immunity, the infection can then start to wreak havoc. Common ways people become immune-suppressed are through an HIV infection, taking immune-suppressing medications for organ transplantation, or taking immune-system altering medications for chronic inflammatory diseases, Day explained.

The current study included 299 people with cryptococcal meningitis who were randomly assigned to one of three treatment regimens: amphotericin B alone for four weeks; amphotericin B plus flucytosine for two weeks; or amphotericin B plus fluconazole for two weeks. People in the second and third groups were also given eight weeks of follow-up therapy with fluconazole.

The investigators found that combination therapy with amphotericin B and flucytosine resulted in a 40 percent lower risk of death compared to amphotericin therapy alone. Combination therapy with fluconazole didn't appear to affect survival rates, according to the study.

The combination therapy with flucytosine also resulted in lower levels of Cryptococcus in the spinal fluid, according to the study.

Side effects were similar in all three treatment regimens. Possible side effects are anemia, low levels of potassium, low white blood cell counts and additional infections, the study authors noted.

"This study is the first ever to demonstrate that a combination of antifungal drugs can significantly reduce the risk of death from this disease," Day pointed out.

The reason for the success of this particular combination is that it quickly kills Cryptococcus, according to the author of an accompanying editorial, Dr. John Perfect, of Duke University Medical Center in Durham, N.C. "In cryptococcal meningitis, the principle is set: the rapid killing of yeasts at the site of infection translates into a better outcome," he wrote.

"Long-term success in the treatment of cryptococcal meningitis depends on how well we kill yeasts with the initial treatment regimen," Perfect added.

The study, which was funded by the Wellcome Trust and the British Infection Society, is published in the April 4 issue of the New England Journal of Medicine.

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