Friday, 17 July 2009

Drug resistance fears over killer fungal disease


Treatments for the most common airborne fungal disease are proving less effective due to increased resistance to the anti-fungal drugs used to combat infections.

Aspergillosis is an incurable disease of the lungs caused by fungal Aspergillus. It is treated using compounds called azoles but researchers at The University of Manchester have found that the fungus has been able to mutate making treatment ineffective.

The research, published in the prestigious US journal Emerging Infectious Diseases, showed that 13 out of 14 affected patients recently treated by the team did not respond to therapy and that numerous mutations were responsible.

Lead researcher Professor David Denning, whose clinic is based at the University Hospital of South Manchester, said that most of the fungus strains, or isolates, were completely resistant to all oral antifungals, leading the doctors to resort to long-term intravenous therapy.

"While the very first azole-resistant isolates were identified in the late 1980s in California, the first UK resistant Aspergillus wasn’t found until 1999 and now we have dozens,” said Professor Denning, who is Director of the National Aspergillosis Centre.

“Antifungal resistance rates have been rising since 2004 and stood at 17% in 2007, a trend that has continued into 2008 and 2009. Patients from all over the UK were found to have resistance, mostly related to long-term treatment of incurable Aspergillus disease."

In 2008, workers in Nijmegen in the Netherlands reported a similar rise in resistance, related to a single resistance mutation, also found in Aspergillus grown from soil. They suggest that extensive azole use in agriculture may be responsible. About one third of all fungicide use in farming is azoles.

Currently, the only class of antifungal that can be used orally for Aspergillus infection and allergy are the azoles, principally itraconazole, voriconazole and posaconazole.

“We also found cross-resistance to voriconazole (65%) and posaconazole (74%) in those isolates we tested that were resistant to itraconazole,” said Professor Denning. “The result depends on the particular mutation conferring resistance.

“Patients can be treated with intravenous amphotericin B or caspofungin, but these are not useful when patients leave hospital, or have allergic aspergillosis."

Report we quote was published in full by Manchester University

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