In Vitro Activities of 5-Fluorocytosine against 8,803 Clinical Isolates of
            <i>Candida</i>
            spp.: Global Assessment of Primary Resistance Using National Committee for Clinical Laboratory Standards Susceptibility Testing Methods

Pfaller, Michael A.; Messer, S. A.; Boyken, L.; Huynh, Holly K.; Hollis, Richard J.; Diekema, Daniel J.

doi:10.1128/aac.46.11.3518-3521.2002

Cited by 116 publications

(66 citation statements)

References 44 publications

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“…C. albicans was 10% and C. tropicalis was 33.3% resistant to Itraconazole which is comparable to other study which shows resistance of C. albicans ranging from 0-10% and C. tropicalis from 0-21.1%. 16,24,31 These findings suggest emergence of Itraconazole resistance C.tropicalis.…”

Section: Discussionmentioning

confidence: 78%

“…The result shows that the candida isolates were less resistance than other study which describe 0-3% resistance in C. albicans and 7-30% resistance in C.tropicalis. [31][32][33][34] CONCLUSION: Fungal infections and resistance to antifungal agents have been identified as an important problem. Extreme of ages, ICU stay, antimicrobial therapy, indwelling devices have been observed as important predisposing factors.…”

Section: Discussionmentioning

confidence: 99%

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Characterization and Antifungal Susceptibility Pattern of Candida SPP . Isolated From Clinical Specimens

Pradhan¹,

Singh²,

P³

et al. 2015

jemds

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BACKGROUND:With the changing health scenario fungal infections have increased significantly, contributing to morbidity, mortality and health care cost. Candida is major human fungal pathogens that cause both superficial and deep tissue infections. With emergence of nonalbicans Candida species, availability of advanced identification methods and antifungal resistance, the spectrum of candidiasis has changed. OBJECTIVE: The aim of our study was to identify the distribution of Candida species among clinical isolates, risk factors associated with candidiasis and their sensitivity pattern for common antifungal drugs. MATERIALS AND METHODS: One hundred thirty nine different clinical isolates of Candida were collected from indoor patients of a tertiary care centre of Gujarat from May 2009 to June 2010. Identification of Candida species and antifungal susceptibility testing was performed with miniAPI (Analytical Prophylactic Index) (Biomerieux, France) which is an automatic identification and susceptibility testing instrument. RESULTS: We found that the non-albicans Candida were more prevalent than Candida albicans. Candida tropicalis (48.9%) was the most common Candida spp. and also more resistant than that of C.albicans. C.albicans showed resistance against fluconazole (3.5%) and itraconazole (8.8%) whereas C.tropicalis were resistant to amphotericin B (10.3%), fluconazole (20.7%), itraconazole (32.3%), and voriconazole (23.5%) and flucytosine (5.8%). Overall resistance rates of Candida for amphotericin B, fluconazole, itraconazole, and voriconazole and flucytosine were 6.4%, 15.2%, 22.3%, 12.9%, 5% respectively. CONCLUSION: To achieve better clinical results species-level identification of Candida spp. and their antifungal sensitivity testing should be performed.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Characterization and Antifungal Susceptibility Pattern of Candida SPP . Isolated From Clinical Specimens

Pradhan¹,

Singh²,

P³

et al. 2015

jemds

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“…The proportion of 35% of C. tropicalis isolates resistant to 5FC is unusual (3). Other studies report between 0 (12) and 15% (13) with intermediate values (14)(15)(16), and all the isolates stored as C. tropicalis in the CBS collection since 1912 exhibited 5FC MIC <0.5 μg/mL.…”

Section: Discussionmentioning

confidence: 98%

Clonal Population of Flucytosine-ResistantCandida tropicalisfrom Blood Cultures, Paris, France

Desnos‐Ollivier

Bretagne²,

Bernède³

et al. 2008

Emerg. Infect. Dis.

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Candida tropicalis is a diploid ascomycetes yeast responsible for 4%-24% of candidemia. Resistance to fl ucytosine is rarely described for this species but was observed for 45 (35%) of 130 C. tropicalis isolates recovered from blood cultures in the Paris area in a 4-year survey. The aims of this study were to test the hypothesis that the fl ucytosine-resistant isolates could represent a subgroup and to determine the relationship between epidemiologic and genomic data. Epidemiologic data and gene sequences were analyzed, and molecular typing was performed. Our results suggest that a clone of fl ucytosine-resistant isolates, associated with malignancies and a lower mortality than that for other C. tropicalis isolates, is widespread in the Paris area. We propose the analysis of 2 polymorphic microsatellite markers coupled with URA3 sequencing to track the clone. C andida tropicalis is a diploid ascomycetes yeast commonly found on the skin and in digestive tracts of healthy human hosts worldwide (1). Infections caused by C. tropicalis are reported in 4%-24% of patients with candidemia, depending on the country of study, underlying risk factors, and period of study (2). Primary resistance to fl ucytosine (5FC) occurs in <5% of all Candida species except for C. krusei, in which it is detected in up to 28% of isolates (3). It was thus unexpected to observe 35% resistance to 5FC among C. tropicalis isolates recovered from blood cultures in the active surveillance program on yeast-related fungemia implemented by the French National Reference Center for Mycoses and Antifungals (NRCMA) in the Paris area. The YEASTS program is designed to analyze the epidemiologic trends of yeast fungemia by collecting isolates and epidemiologic and clinical data. The second objective is to study the clinical isolates in terms of species, antifungal susceptibility profi les, and genetic diversity to look for associations between subtypes of isolates and epidemiologic/clinical parameters. To test the hypothesis that the 5FC resistant ( R 5FC) isolates could represent a different species or a subgroup, the R 5FC and susceptible ( S 5FC)

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“…Recent large scale studies, however, have revealed primary resistance of C. albicans to be in the range of 3.0 to 6.5% (2,14). It has recently been shown that intrinsic resistance to 5FC is associated with only one of the major clades of C. albicans (18).…”

Section: Discussionmentioning

confidence: 99%

Clade-Specific Flucytosine Resistance Is Due to a Single Nucleotide Change in the FUR1 Gene of Candida albicans

Dodgson¹,

Dodgson

Pujol³

et al. 2004

Antimicrob Agents Chemother

121

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Population studies have indicated that natural resistance to flucytosine (5FC) in Candida albicans is limited to one of the five major clades, clade I. In addition, while 73% of clade I isolates are less susceptible to 5FC (MIC > 0.5 g/ml), only 2% of non-clade I isolates are less susceptible. In order to determine the genetic basis for this clade-specific resistance, we sequenced two genes involved in the metabolism of 5FC that had previously been linked to resistance (cytosine deaminase and uracil phosphoribosyltransferase), in 48 isolates representative of all clades. Our results demonstrate that a single nucleotide change from cytosine to thymine at position 301 in the uracil phosphoribosyltransferase gene (FUR1) of C. albicans is responsible for 5FC resistance. The mutant allele was found only in group I isolates. The 5FC MICs for strains without copies of the mutant allele were almost exclusively <0.25 g/ml, those for strains with one copy of the mutant allele were >0.5 g/ml, and those for strains with two copies of the mutant allele were >16 g/ml. Thus, the two alleles were codominant. The presence of this allele is responsible for clade I-specific resistance to 5FC within the C. albicans population and thus by inference is likely to be the major underlying 5FC resistance mechanism in C. albicans. This represents the first description of the genetic mutation responsible for 5FC resistance.Analyses of the population structure of Candida albicans have revealed five major clades (I, II, III, SA, and E), each exhibiting a degree of geographical specificity (1,19,20,24). Recently, it was demonstrated that natural isolates that had been identified as resistant to flucytosine (5FC) were all members of clade I (18). Furthermore, it was demonstrated that 72% of clade I isolates exhibited reduced susceptibility to 5FC (5FC MIC Ն 0.5 g/ml) compared to 2% of non-clade I isolates (18). The fact that clades maintain their integrity side by side in the same geographical locale, combined with the observation that the majority of clade I isolates are less susceptible to 5FC, indicates that while recombination may occur within a clade, it may be a rare event between different clades (18,24), an interpretation consistent with earlier studies indicating that the population structure of C. albicans is primarily clonal (4,17).Although it has been demonstrated that natural resistance to 5FC is confined to isolates in clade I, the genetic basis of 5FC resistance has not been identified. 5FC enters a cell through the action of cytosine permease (15). Inside the cell, 5FC is converted to 5-fluorouracil (5FU) by cytosine deaminase, encoded by the gene FCY1 (7, 16). 5FU is then converted to 5-fluorouridine monophosphate by uracil phosphoribosyltransferase (UPRTase), encoded by the gene FUR1 (7, 16). 5-Fluorouridine monophosphate is then converted to 5-fluorouridine triphosphate, which, when incorporated into RNA in place of UTP, disrupts protein synthesis (7, 16). In addition, 5FU, when converted to 5-fluorodeoxyuridine monophosphat...

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In Vitro Activities of 5-Fluorocytosine against 8,803 Clinical Isolates of Candida spp.: Global Assessment of Primary Resistance Using National Committee for Clinical Laboratory Standards Susceptibility Testing Methods

Cited by 116 publications

References 44 publications

Characterization and Antifungal Susceptibility Pattern of Candida SPP . Isolated From Clinical Specimens

Characterization and Antifungal Susceptibility Pattern of Candida SPP . Isolated From Clinical Specimens

Clonal Population of Flucytosine-ResistantCandida tropicalisfrom Blood Cultures, Paris, France

Clade-Specific Flucytosine Resistance Is Due to a Single Nucleotide Change in the FUR1 Gene of Candida albicans

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