For Debate: May the Use of the Polyene Macrolide Natamycin as a Food Additive Foster Emergence of Polyene-Resistance in Candida Species?

Natamycin is approved almost worldwide as a food additive for surface treatment of cheese and sausages. Its use is considered to be safe as Natamycin is extremely sensitive to ultraviolet light and an acidic pH, so that products exposed to light in the retail industry and food stores are likely free from Natamycin. However, the use of an acid-, heat- and light stable Natamycin formulation in yoghurt has recently been authorized in the USA as well as in Australia and New Zealand. Furthermore, yoghurt is stored in sealed cups in refrigerated shelves, so it will not be exposed to light and thus not be inactivated during storage. Consequently, the resident flora will be exposed to Natamycin and it may exert a resistance selective pressure on faecal Candida spp. hypothetically selecting strains being resistant to Amphothericin B. In this review literature has been evaluated addressing the questions if Natamycin may foster emergence of polyene-resistance. This concern is supported by the facts that first, polyene-resistance could be elicited in vitro and in vivo . Second, as Azoles being used in agriculture and hospitals as well as polyenes share some common resistance mechanisms a polyene-resistance reservoir does exist in environmental and clinical fungal isolates. Third, Natamycin may amplify Amphothericin B resistance as fourth, resistance can in principal be spread amongst fungi by horizontal gene transfer. To preserve clinical efficacy of Amphothericin B for treatment of serious, life threatening infections, the use of Natamycin as a food-preservative should be limited to an absolute minimum.