Lack of efficacy of echinocandins against high metabolic activity biofilms of Candida parapsilosis clinical isolates

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CLINICAL MICROBIOLOGY - SHORT COMMUNICATION

Lack of efficacy of echinocandins against high metabolic activity biofilms of Candida parapsilosis clinical isolates Danilo Yamamoto Thomaz 1 & Marcia de Souza Carvalho Melhem 2 Gil Benard 1 & Gilda Maria Barbaro Del Negro 1

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João Nobrega de Almeida Júnior 1,3

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Received: 30 September 2019 / Accepted: 17 December 2019 # Sociedade Brasileira de Microbiologia 2020

Abstract Candida parapsilosis produces biofilm, which colonizes catheters and other invasive medical devices that are manipulated by health care workers. In previous studies, C. parapsilosis in vitro biofilms have exhibited high resistance rates against conventional antifungals, but susceptibility to both echinocandins and lipid formulations of amphotericin B (lipid complex and liposomal). However, a recent study showed good activity of amphotericin B deoxycholate on the biomass of C. parapsilosis biofilms. Although moderate activity of echinocandins has been demonstrated against low metabolic activity biofilms of C. parapsilosis, few studies have analyzed the action of these drugs on high metabolic activity biofilms. Moreover, high biofilm-forming isolates have been associated with central venous catheter-related fungemia outbreaks and higher mortality rates. Therefore, it is relevant to verify the activity of the main antifungal drugs against high metabolic activity biofilms of C. parapsilosis. Our study aimed to evaluate the in vitro activity of amphotericin B deoxycholate, anidulafungin, caspofungin, and micafungin against high biofilmforming and high metabolic activity clinical isolates of C. parapsilosis. Our results showed good activity of amphotericin B against C. parapsilosis biofilms, but none of the echinocandin drugs was effective. This suggests that amphotericin B deoxycholate may be a better choice than echinocandins for the treatment of biofilm-associated infections by C. parapsilosis, mainly in countries with insufficient health care resources to purchase lipid formulations of amphotericin B. These results warn of the possibility of persistent catheter-related candidemia caused by high biofilm-forming C. parapsilosis strains when treated with echinocandin drugs. Keywords Candida parapsilosis . Biofilm . XTT . Amphotericin B . Echinocandins . Antifungal resistance

Introduction Candida spp. are among the main agents of bloodstream infections worldwide, not only due to implementation of high Responsible Editor: Rosana Puccia. * Gilda Maria Barbaro Del Negro [email protected] 1

Laboratory of Medical Mycology – LIM-53, Clinical Dermatology Division, Hospital das Clínicas and Instituto de Medicina Tropical de São Paulo, Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas Carvalho de Aguiar, 500 - Prédio 2 - Andar térreo, Cerqueira Cesar, São Paulo, SP 05403-000, Brazil

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Federal University of Mato Grosso do Sul, MS, and Mycology Unit, Adolfo Lutz Institute, Secretary of Health, São Paulo, Brazil

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Central Laboratory Division – LIM-03, Hospital das Clínicas, Faculdade de Med