Does agricultural use of azole fungicides contribute to resistance in the human pathogen Aspergillus fumigatus?

Azole resistance in human fungal pathogens has increased over the past twenty years, especially in immunocompromised patients. Similarities between medical and agricultural azoles, and extensive azole (14α‐demethylase inhibitor, DMI) use in crop protection, prompted speculation that resistance in patients with aspergillosis originated in the environment. Aspergillus species, and especially Aspergillus fumigatus, are the largest cause of patient deaths from fungi. Azole levels in soils following crop spraying, and differences in sensitivity between medical and agricultural azoles (DMIs), indicate weaker selection in cropping systems than in patients receiving azole therapy. Most fungi have just one CYP51 paralogue (isozyme CYP51B), but in Aspergillus sp. mutations conferring azole resistance are largely confined to a second paralogue, CYP51A. Binding within the active centre is similar for medical and agricultural azoles but differences elsewhere between the two paralogues may ensure selection depends on the DMI used on crops. Two imidazoles, imazalil and prochloraz, have been widely used since the early 1970s, yet unlike triazoles they have not been linked to resistance in patients. Evidence that DMIs are the origin, or increase the frequency, of azole resistance in human fungal pathogens is lacking. Limiting DMI use would have serious impacts on disease control in many crops, and remove key tools in anti‐resistance strategies. © 2017 Society of Chemical Industry     

Therapy of systemic fungal infections: a pharmacologic perspective

An increase in the incidence of severe, invasive, systemic fungal infections has been noted over the last decade in human and veterinary medicine. Reports of drug resistance and therapeutic failure to currently available antifungal agents have also been on the rise. Many factors are likely to be involved in these trends, including immune suppression and the use of broad-spectrum antibiotics. The use of fungistatic drugs, suboptimal doses, compounded drugs, poorly absorbed drug formulations, and inadequate tissue penetrations of antifungals also contribute to the development of acquired resistance. Because of the unique chemical complexities of the antifungal agents, drug/drug and drug/food interactions may also play a significant role in poor therapeutic outcome. This review summarizes the pharmacology and toxicology of the antifungal agents in current use for systemic mycosis and introduces some of the newer antifungal agents that anecdotally show very promising results.     

Sensitivities to DMI fungicides in populations of Podosphaera fusca in south central Spain

BACKGROUND: Cucurbit powdery mildew elicited by Podosphaera fusca (Fr.) U Braun & N Shishkoff limits crop production in Spain. Disease control is largely dependent on fungicides such as sterol demethylation inhibitors (DMIs). Fungicide resistance is an increasing problem in this pathogen. To overcome such risk, it is necessary to design rational control programmes based upon knowledge of field resistance. The aim of this study was to investigate the state of DMI sensitivity of Spanish P. fusca populations and provide tools for improved disease management. RESULTS: Using a leaf‐disc assay, sensitivity to fenarimol, myclobutanil and triadimenol of 50 isolates of P. fusca was analysed to determine discriminatory concentrations between sensitive and resistant isolates. As no clearly different groups of isolates could be identified, discriminatory concentrations were established on the basis of maximum fungicide field application rate, 100 mg L^?1 for the three fungicides tested. Subsequently, a survey of DMI resistance was carried out in different provinces located in the south central area of Spain during the cucurbit growing seasons in 2002, 2003 and 2004. Examination of a collection of 250 isolates revealed that 23% were resistant to fenarimol and 7% to triadimenol, the provinces of Almería, Badajoz and Murcia being the locations with the highest frequencies of resistance. By contrast, no resistance to myclobutanil was found. CONCLUSION: Results show that fenarimol and, to a lesser extent, triadimenol have become less efficient for controlling cucurbit powdery mildew in Spain. These are important observations that should lead to reconsideration of the current disease management programmes. Copyright © 2010 Society of Chemical Industry