High prevalence of antifungal resistance in <i>Candida</i> spp. from patients with AIDS

Law, Derek; Moore, Caroline B.; Wardle, Helen M.; Ganguli, L. A.; Keaney, M.G.L.; Denning, David W.

doi:10.1093/jac/34.5.659

Cited by 128 publications

(84 citation statements)

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“…Treatment options are limited to the toxic but fungicidal polyene drugs and the fungistatic azole drugs. Prophylactic use of the azole drugs, combined with their fungistatic nature, has resulted in widespread azole resistance (Georgopapadakou & Walsh, 1996 ;Law et al, 1994). A number of mechanisms have been correlated with azole resistance, including mutation and overexpression of the gene encoding the azole target enzyme, ERG11, and overexpression of the genes encoding the efflux pumps MDR1, CDR1 and CDR2 .…”

Section: Introductionmentioning

confidence: 99%

Homozygosity at the Candida albicans MTL locus associated with azole resistance

et al. 2002

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Antifungal drug resistance in the pathogenic fungus Candida albicans is a serious threat to the growing population of immunocompromised patients. This study describes a significant correlation between loss of heterozygosity at the C. albicans mating-type-like (MTL) locus and resistance to azole antifungals. A pool of 96 clinical isolates consisting of 50 azole-resistant or susceptible dose-dependent isolates and 46 azole-susceptible isolates was screened by PCR for the presence of MTLa1 and MTLα1. These genes were used as markers for the MTLa and MTLα loci. Both loci were present in 84 of the isolates. Six isolates failed to amplify MTLa1 and six failed to amplify MTLα1. Further PCR analysis demonstrated that loss of the MTLa1 and MTLα1 genes corresponded to loss of all of the loci-specific genes, resulting in homozygosity at the MTL locus. Southern analysis and single nucleotide polymorphism (SNP) analysis were used to determine that this loss of heterogeneity was due to replacement of one of the MTL loci with a duplicate of the other locus resulting in two homozygous copies of the MTL locus. Of the 12 homozygous isolates, one isolate was sensitive to azole drugs. Statistical analysis of the data demonstrates a strong correlation between homozygosity at the MTL locus and azole resistance (PT0 003). In a set of serial isolates, an increase in azole resistance correlated with the loss of heterozygosity at the MTL locus, lending further strength to the correlation. Gene disruptions of the MTL loci were found to have no effect on azole susceptibility.

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Section: Introductionmentioning

confidence: 99%

Homozygosity at the Candida albicans MTL locus associated with azole resistance

et al. 2002

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“…vary almost as greatly as the organisms themselves. In addition, the widespread use of antifungal agents may have contributed to a shift in species distributions via the emergence of inherently resistant species as significant pathogens (21,22). Thus, informed therapeutic decisions increasingly require correct and rapid identification of an ever-increasing number of potential pathogens.…”

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confidence: 99%

Molecular Identification of Unusual Pathogenic Yeast Isolates by Large Ribosomal Subunit Gene Sequencing: 2 Years of Experience at the United Kingdom Mycology Reference Laboratory

Linton¹,

Borman²,

Cheung

et al. 2007

J Clin Microbiol

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Rapid identification of yeast isolates from clinical samples is particularly important given their innately variable antifungal susceptibility profiles. We present here an analysis of the utility of PCR amplification and sequence analysis of the hypervariable D1/D2 region of the 26S rRNA gene for the identification of yeast species submitted to the United Kingdom Mycology Reference Laboratory over a 2-year period. A total of 3,033 clinical isolates were received from 2004 to 2006 encompassing 50 different yeast species. While more than 90% of the isolates, corresponding to the most common Candida species, could be identified by using the AUXACOLOR2 yeast identification kit, 153 isolates (5%), comprised of 47 species, could not be identified by using this system and were subjected to molecular identification via 26S rRNA gene sequencing. These isolates included some common species that exhibited atypical biochemical and phenotypic profiles and also many rarer yeast species that are infrequently encountered in the clinical setting. All 47 species requiring molecular identification were unambiguously identified on the basis of D1/D2 sequences, and the molecular identities correlated well with the observed biochemical profiles of the various organisms. Together, our data underscore the utility of molecular techniques as a reference adjunct to conventional methods of yeast identification. Further, we show that PCR amplification and sequencing of the D1/D2 region reliably identifies more than 45 species of clinically significant yeasts and can also potentially identify new pathogenic yeast species.

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“…However, the widespread use of fluconazole to treat candidal infections has led to the emergence of resistant Candida strains, and resistance is now a clinical problem (22,51,52). In one study, approximately onethird of late-stage AIDS patients carried drug-resistant C. albicans in their oral cavities (35). Fluconazole-resistant (FLC R ) C. albicans is now seen in both HIV and non-HIV patients who have never been exposed to fluconazole (38).…”

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confidence: 99%