Date Published: 5 May 2011
Researchers concerned by drug-resistant strains of Aspergillus fungi
Some strains of Aspergillus fungi, a deadly fungal infection that can affect humans, seem to be developing resistance to current drug treatments at an alarming rate according to scientists involved in a recent study.
Researchers from Manchester University (England, UK) working with colleagues in Newar, USA, have developed a new test that can diagnose Aspergillus infection more effectively than in the past and can also recognise the signs of antifungal resistance to azoles ? the class of drugs used to treat patients with aspergillosis.
The new test uses direct molecular detection rather than culturing the fungus in a Petri dish. Scientists have found that 55% of aspergillosis patients had "telltale signs" known as 'markers' that indicated they had developed resistance to azoles. Analysis of the research results may be compared with resistance rates of 28% carried out by the team only two years ago, but using traditional culturing methods. This study also revealed azole-resistance markers in three-quarters of the small number of aspergillosis patients (eight) whom had never been treated with an azole, suggesting widespread dissemination of resistance.
" Aspergillus significantly worsens asthma symptoms and causes life-threatening infections in those with long-term lung infections or damaged immune systems, such as chemotherapy and transplant patients or people with HIV," said Prof David Denning, of Manchester University.
" Using an ultrasensitive, real-time test for Aspergillus, similar to the method used to diagnose HIV, MRSA and influenza, we have directly detected azole resistance in people with aspergillosis, without first culturing the fungus in a dish. The presence of Aspergillus was detected in many more samples than using traditional culture methods, and 55% were found to contain azole-resistance markers.
This is an extraordinarily high rate of resistance, possibly related to fungicide use in agriculture ? more than a third of 'pesticides' used by UK farmers are azoles ? and long treatment courses in patients, so the findings have major implications for the sustainability of azoles for human antifungal therapy."
According to Manchester University the azoles itraconazole (Johnson & Johnson), voriconazole (Pfizer) and posaconazole (Merck) have annual sales of more than $1bn annually. Conventional diagnosis of aspergillosis is limited by poor culture yield so the true frequency of azole resistance has been unclear.
In this most recent study, the researchers analyzed phlegm from patients with allergic and chronic lung disease caused by Aspergillus and found that almost twice the proportion of individuals tested had resistance markers in their sample compared to a Petri dish (or culture) study carried out by the same team in 2008/9.
Professor Denning added:
" Not only is molecular testing much more sensitive than conventional culture for diagnosis, but it enables testing for resistance, which until now has been impossible if cultures are negative. Given the rising frequency of resistance in Aspergillus in northern Europe, China and the United States, this study provides key data for doctors to shift antifungal therapy in the face of resistance."
References to Papers:
* Denning DW, Park S, Lass-Florl C, Fraczek MG, Kirwan M, Gore R, Smith J, Bueid A, Bowyer P, Perlin DS. High frequency triazole resistance found in non-culturable Aspergillus fumigatus from lungs of patients with chronic fungal disease. Clin Infect Dis 2011;52:1123-9.
* Bueid A, Howard SJ, Moore CB, Richardson MD, Harrison E, Bowyer P, Denning DW. Azole antifungal resistance in Aspergillus fumigatus - 2008 and 2009. J Antimicrob Chemother 2010;65:2116-8.
University, England (UK)