Epidemiology of Echinocandin Resistance in Candida

Grossman, Nina T.; Chiller, Tom; Lockhart, Shawn R.

doi:10.1007/s12281-014-0209-7

Cited by 22 publications

(16 citation statements)

References 44 publications

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“…Echinocandin resistance associated with crossresistance of azoles was reported in C. glabrata (36). The current results are in concordance with the data for a low rate of echinocandin resistance in C. albicans (22,37,38). Shokohi et al (39) detected two (4.6%) caspofungin resistant strains among 44 isolates.…”

Section: Discussionsupporting

confidence: 90%

Antifungal Susceptibility of Candida albicans Isolates at a Tertiary Care Hospital in Bulgaria

Hitkova

Georgieva

Hristova

et al. 2019

Jundishapur J Microbiol

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Background: The precise identification of yeasts and their antifungal sensitivity is a key factor in the choice of a suitable drug for treatment and prevention of fungal infections. Objectives: The aim of the present study was to determine in vitro susceptibility of clinical Candida albicans isolates to nine antifungal agents. Methods: A total of 61 C. albicans isolates were tested. Antifungal susceptibility was evaluated by determination of minimum inhibitory concentrations (MIC). Results: Fifty C. albicans isolates were susceptible to nine antifungal agents. The remaining 11 yeasts were resistant to one or more antifungals. All C. albicans were susceptible to amphotericin B with MICs 0.25 to 1 µg/mL and exhibited sensitivity to 5-fluorocytosine with MIC90 of 0.125 µg/mL. The MIC50 and MIC90 of fluconazole were 0.5 and 32 µg/mL, whereas the MIC50 and MIC90 of voriconazole were considerably lower-0.0078 and 2 µg/mL. The isolates showed susceptibility to echinocandins with MIC90 of micafungin, anidulafungin and caspofungin of 0.015, 0.031, and 0.125 µg/mL, respectively. Of particular interest was detection of seven C. albicans isolates, which expressed a high-level resistance to all azoles and one of them was also resistant to echinocandins. Conclusions: In conclusion, detection of resistance in C. albicans, which is a species typically susceptible to antifungals, is of great importance for clinical practice.

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Section: Discussionsupporting

confidence: 90%

Antifungal Susceptibility of Candida albicans Isolates at a Tertiary Care Hospital in Bulgaria

Hitkova

Georgieva

Hristova

et al. 2019

Jundishapur J Microbiol

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“…While MDR is not a common phenotype among fungal pathogens, it was reported earlier in C. glabrata, with simultaneous acquisition of resistance to echinocandins and to azoles and separate acquisition of resistance to 5-FC (37). In the United States, a significant proportion (30% to 40%) of echinocandin-resistant isolates are also resistant to azoles (38,39). While a recent study (40) suggested an association between MDR and the use of echinocandins and azoles, another investigation (41) described MDR to echinocandins, azoles, and amphotericin B in C. glabrata isolates recovered from a neutropenic patient with prolonged fever.…”

Section: Discussionmentioning

confidence: 88%

Acquired Multidrug Antifungal Resistance in Candida lusitaniae during Therapy

Asner¹,

Giulieri²,

Diezi³

et al. 2015

Antimicrob Agents Chemother

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Candida lusitaniae is usually susceptible to echinocandins. Beta-1,3-glucan synthase encoded by FKS genes is the target of echinocandins. A few missense mutations in the C. lusitaniae FKS1 hot spot 1 (HS1) have been reported. We report here the rapid emergence of antifungal resistance in C. lusitaniae isolated during therapy with amphotericin B (AMB), caspofungin (CAS), and azoles for treatment of persistent candidemia in an immunocompromised child with severe enterocolitis and visceral adenoviral disease. As documented from restriction fragment length polymorphism (RFLP) and random amplified polymorphic DNA (RAPD) analysis, the five C. lusitaniae isolates examined were related to each other. From antifungal susceptibility and molecular analyses, 5 different profiles (P) were obtained. These profiles included the following: profile 1 (P1) (CAS MIC . While S638Y and -P are within HS1, S631Y is in close proximity to this domain but was confirmed to confer candin resistance using a site-directed mutagenesis approach. FLC resistance could be linked with overexpression of major facilitator gene 7 (MFS7) in C. lusitaniae P2 and P4 and was associated with resistance to 5-flurocytosine. This clinical report describes resistance of C. lusitaniae to all common antifungals. While candins or azole resistance followed monotherapy, multidrug antifungal resistance emerged during combined therapy.[ Candida lusitaniae, an opportunistic haploid yeast, remains a rare cause of candidemia. While C. lusitaniae can develop amphotericin B (AMB) resistance (1, 2), it is considered generally susceptible to all systemic antifungal agents (3). Echinocandins are used as first-line therapy for candidemia due to C. lusitaniae. The target of echinocandins is ␤-1,3-glucan synthase and is encoded by FKS genes (4). Three echinocandins, anidulafungin (ANI), caspofungin (CAS), and micafungin (MICA), have been available and widely used for about a decade. As a result, emerging resistance to echinocandins has been reported in several species, including C. albicans, C. dubliniensis, C. kefyr, C. glabrata, C. krusei, C. tropicalis, and C. lusitaniae (5-12). Missense mutations in FKS genes (FKS1 and FKS2) that are situated in different regions (host spot 1 [HS1] and HS2) are responsible for the increase of drug MICs compared to the MICs seen with wild-type isolates. These MIC increases were shown to cause treatment failures in animal experiments similarly to those seen in clinical cases, thus suggesting the emergence of clinical resistance (13). In C. lusitaniae, a single missense mutation in C. lusitaniae FKS1 HS1 at position 645 (S645F) was reported in clinical isolates and resulted in increased MICs of several echinocandins. While recent data documented cross-resistance between echinocandins and azoles in C. glabrata (14), no cross-resistance has yet been reported in C. lusitaniae. The present paper reports the unusual emergence of clinical isolates of C. lusitaniae with documented cross-resistance to candins and azoles following exposure to various ...

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“…A new class of drugs, the echinocandins, has been shown to have fungicidal effects in all Candida species ( Nett and Andes, 2016 ). The echinocandins include caspofungin, micafungin, and anidulafungin ( Grossman et al, 2014 ; Koehler et al, 2014 ; Paramythiotou et al, 2014 ). Echinocandins inhibit (1,3) β- D -glucan synthase, thereby preventing glucan synthesis, which is present in the cell membrane of fungi ( Figure 1 ).…”

Section: Traditional Agents and Mechanisms Of Actionmentioning

confidence: 99%

“…This class of drugs has certain advantages attributable to its effects on the fungal cell wall, including a lower risk of side effects since animal cells do not have this structure. Further, echinocandins can be used in cases of azole-antifungal resistance ( Spampinato and Leonardi, 2013 ; Grossman et al, 2014 ; Maubon et al, 2014 ; Paramythiotou et al, 2014 ).…”

Section: Traditional Agents and Mechanisms Of Actionmentioning

confidence: 99%

Candida Infections and Therapeutic Strategies: Mechanisms of Action for Traditional and Alternative Agents

et al. 2018

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The Candida genus comprises opportunistic fungi that can become pathogenic when the immune system of the host fails. Candida albicans is the most important and prevalent species. Polyenes, fluoropyrimidines, echinocandins, and azoles are used as commercial antifungal agents to treat candidiasis. However, the presence of intrinsic and developed resistance against azole antifungals has been extensively documented among several Candida species. The advent of original and re-emergence of classical fungal diseases have occurred as a consequence of the development of the antifungal resistance phenomenon. In this way, the development of new satisfactory therapy for fungal diseases persists as a major challenge of present-day medicine. The design of original drugs from traditional medicines provides new promises in the modern clinic. The urgent need includes the development of alternative drugs that are more efficient and tolerant than those traditional already in use. The identification of new substances with potential antifungal effect at low concentrations or in combination is also a possibility. The present review briefly examines the infections caused by Candida species and focuses on the mechanisms of action associated with the traditional agents used to treat those infections, as well as the current understanding of the molecular basis of resistance development in these fungal species. In addition, this review describes some of the promising alternative molecules and/or substances that could be used as anticandidal agents, their mechanisms of action, and their use in combination with traditional drugs.

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Epidemiology of Echinocandin Resistance in Candida

Cited by 22 publications

References 44 publications

Antifungal Susceptibility of Candida albicans Isolates at a Tertiary Care Hospital in Bulgaria

Antifungal Susceptibility of Candida albicans Isolates at a Tertiary Care Hospital in Bulgaria

Acquired Multidrug Antifungal Resistance in Candida lusitaniae during Therapy

Candida Infections and Therapeutic Strategies: Mechanisms of Action for Traditional and Alternative Agents

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