Activity Profile In Vitro of Micafungin against Spanish Clinical Isolates of Common and Emerging Species of Yeasts and Molds

Cuenca‐Estrella, Manuel; Gómez-López, Alicia; Mellado, Emilia; Monzón, Araceli; Buitrago, María J.; Rodríguez-Tudela, Juan Luis

doi:10.1128/aac.01543-08

Cited by 47 publications

(29 citation statements)

References 23 publications

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“…Muñoz et al identified prior use of antifungal agents (mainly fluconazole) as the only factor that independently predicted the presence of a C. krusei BSI (17). It is worth noting that not all strains of C. glabrata are necessarily resistant to fluconazole and that other species can exhibit fluconazole resistance (2,8). This may explain, at least in part, the different conclusions obtained in our study in comparison with those obtained by previously described approaches.…”

Section: Discussioncontrasting

confidence: 56%

Risk Factors for Fluconazole-Resistant Candidemia

Garnacho-Montero

Díaz-Martín

García-Cabrera

et al. 2010

Antimicrob Agents Chemother

102

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Bloodstream infections (BSIs) due to Candida species are a serious complication in hospitalized patients. Candidemia is associated with a high mortality rate and has obvious effects on resource use (11). Over the past few decades, the incidence of candidemia has increased markedly (2, 3). Moreover, the increment of candidemia caused by Candida species other than Candida albicans is a common finding in recent series (3, 12). These species include C. glabrata and C. krusei, which tend to be more resistant to fluconazole and therefore present a particular challenge for clinical management.Diverse studies highlight the importance of early and appropriate empirical therapy in invasive Candida infection (14, 21). Fluconazole is currently considered the initial therapy for most adult patients with candidemia (20). As the selection of empirical therapy is driven in large part by the likely epidemiology, there is a need to identify patients at risk of candidemia caused by species resistant to fluconazole in order to begin with adequate empirical antifungal therapy.In order to provide guidance to clinicians to initiate empirical treatment for candidemia, prior studies have addressed risk factors for candidemia caused by non-albicans Candida spp.(1, 9, 10, 23) or by potentially fluconazole-resistant organisms (Candida glabrata and Candida krusei) (16, 23, 28) but have not taken into consideration in vitro resistance to fluconazole. In these studies, prior fluconazole exposure was an independent risk factor for candidemia caused by non-albicans Candida species (1) or by potentially fluconazole-resistant species (23), whereas other studies did not find this association (16,28). Therefore, to the best of our knowledge, the risk factors for microbiologically proven fluconazole-resistant Candida spp. BSIs have not been comprehensively studied. We conducted the prospective single-center study described here to identify the variables associated with the diagnosis of fluconazole-resistant candidemia. Our working hypothesis was that fluconazole administration is an independent risk factor only in the emergence of BSIs caused by fluconazole-resistant Candida. MATERIALS AND METHODSHospital. The prospective study described here was carried out in the Virgen del Rocío University Hospital, a large urban hospital with teaching accreditation, from January 2004 to June 2009. The hospital has a solid organ (liver, heart, kidney) transplantation program and an active bone marrow transplantation

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Section: Discussioncontrasting

confidence: 56%

Risk Factors for Fluconazole-Resistant Candidemia

Garnacho-Montero

Díaz-Martín

García-Cabrera

et al. 2010

Antimicrob Agents Chemother

102

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“…The echinocandins are the newest class of antifungal agents, and recent studies have found favorable results for the use of echinocandins such as micafungin, caspofungin, or aminocandin for the treatment of invasive aspergillosis (145,283,616,617). Indeed, most Aspergillus species tested, with the exception of A. flavus and certain A. nidulans isolates, are susceptible to micafungin (128). The echinocandins act in a fungistatic manner against A. fumigatus, and recently, resistance to the echinocandins has been identified for numerous Aspergillus species.…”

Section: Aspergillus Fumigatus Drug Resistance: the Echinocandinsmentioning

confidence: 99%

Regulatory Circuitry Governing Fungal Development, Drug Resistance, and Disease

Shapiro

Robbins

Cowen

2011

Microbiol Mol Biol Rev

492

547

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SUMMARY Pathogenic fungi have become a leading cause of human mortality due to the increasing frequency of fungal infections in immunocompromised populations and the limited armamentarium of clinically useful antifungal drugs. Candida albicans , Cryptococcus neoformans , and Aspergillus fumigatus are the leading causes of opportunistic fungal infections. In these diverse pathogenic fungi, complex signal transduction cascades are critical for sensing environmental changes and mediating appropriate cellular responses. For C. albicans , several environmental cues regulate a morphogenetic switch from yeast to filamentous growth, a reversible transition important for virulence. Many of the signaling cascades regulating morphogenesis are also required for cells to adapt and survive the cellular stresses imposed by antifungal drugs. Many of these signaling networks are conserved in C. neoformans and A. fumigatus , which undergo distinct morphogenetic programs during specific phases of their life cycles. Furthermore, the key mechanisms of fungal drug resistance, including alterations of the drug target, overexpression of drug efflux transporters, and alteration of cellular stress responses, are conserved between these species. This review focuses on the circuitry regulating fungal morphogenesis and drug resistance and the impact of these pathways on virulence. Although the three human-pathogenic fungi highlighted in this review are those most frequently encountered in the clinic, they represent a minute fraction of fungal diversity. Exploration of the conservation and divergence of core signal transduction pathways across C. albicans , C. neoformans , and A. fumigatus provides a foundation for the study of a broader diversity of pathogenic fungi and a platform for the development of new therapeutic strategies for fungal disease.

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“…is not uniform. Several studies have reported that the species of Candida most frequently involved in human infections, Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata, and Candida krusei, usually exhibit low MICs of voriconazole, although the voriconazole MICs for strains with resistance to fluconazole are proportionally higher than are those for fluconazole-susceptible isolates (3)(4)(5)13).…”

mentioning

confidence: 99%

Frequency of Voriconazole Resistance In Vitro among Spanish Clinical Isolates of Candida spp. According to Breakpoints Established by the Antifungal Subcommittee of the European Committee on Antimicrobial Susceptibility Testing

Cuenca‐Estrella

Gómez-López

Cuesta

et al. 2011

Antimicrob Agents Chemother

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A total of 4,226 Spanish clinical isolates of Candida spp. were analyzed to assess resistance to voriconazole according to breakpoints established by the European Committee for Antimicrobial Susceptibility Testing (where susceptibility [S] to voriconazole corresponds to a MIC of <0.12 mg/liter). Resistance was uncommon among Candida albicans (5%), C. parapsilosis (1.2%), and C. tropicalis (11%) isolates. Voriconazole MICs of >0.12 mg/liter were more frequent among Candida glabrata and C. krusei isolates. A significant percentage of voriconazole-resistant strains came from oropharyngeal infections and exhibited high MICs of other azoles.The Subcommittee on Antifungal Susceptibility of the European Committee for Antimicrobial Susceptibility Testing (AFST-EUCAST) has determined breakpoints for voriconazole for Candida species. The clinical breakpoints have been set for intravenous and oral doses (18). The in vitro activity of this azole agent against Candida spp. is not uniform. Several studies have reported that the species of Candida most frequently involved in human infections, Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata, and Candida krusei, usually exhibit low MICs of voriconazole, although the voriconazole MICs for strains with resistance to fluconazole are proportionally higher than are those for fluconazole-susceptible isolates (3-5, 13).The EUCAST has developed a standard procedure to set interpretative breakpoints for antimicrobial susceptibility testing (AST). The clinical breakpoints define the organism as susceptible (S), intermediate (I), and resistant (R) to antifungal drugs. The susceptibility and resistance categories are related to high likelihoods of clinical success and clinical failure, respectively. The EUCAST has also defined epidemiological cutoff values (ECOFF values, or ECVs) which are based on the wild-type distributions of MICs for microorganisms. These ECOFF values can help to determine breakpoints when there is limited statistical support for correlation of clinical response with MICs (7,8,12).Wild-type microorganisms are defined by the absence of acquired and mutational mechanisms of resistance to the antifungal. With the distribution of the wild type and its highest MIC having been determined, organisms with acquired or mutational resistance mechanisms can be identified readily as organisms with reduced susceptibility compared with the highest MIC for the wild type. These organisms are called the non-wild-type population. The EUCAST has defined the MIC encompassing the wild-type population as the ECOFF value. The MICs of voriconazole for defining wild-type Candida spp. are Յ0.125 mg/liter for C. albicans, C. tropicalis, and C. parapsilosis and Յ1 mg/liter for C. glabrata and C. krusei (6,15).A clinical response of 76% was achieved for infections due to C. albicans, C. tropicalis, and C. parapsilosis when the MICs were lower than or equal to 0.12 mg/liter (9, 10, 14). Wild-type populations of those species were therefore considered to be susceptible to ...

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Activity Profile In Vitro of Micafungin against Spanish Clinical Isolates of Common and Emerging Species of Yeasts and Molds

Cited by 47 publications

References 23 publications

Risk Factors for Fluconazole-Resistant Candidemia

Risk Factors for Fluconazole-Resistant Candidemia

Regulatory Circuitry Governing Fungal Development, Drug Resistance, and Disease

Frequency of Voriconazole Resistance In Vitro among Spanish Clinical Isolates of Candida spp. According to Breakpoints Established by the Antifungal Subcommittee of the European Committee on Antimicrobial Susceptibility Testing

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