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Successful treatment of chronic mucocutaneous candidiasis caused by azole-resistant Candida albicans with posaconazole.

ABSTRACT: Refractory or recurrent infections of skin, nails, and the mucous membranes are clinical signs of chronic mucocutaneous candidiasis, frequently associated with immunological defects. Here we describe a 39-years-old female patient, with familial CMC, that presented with an extensive infection caused by an azole-resistant Candida albicans isolate, successfully treated with posaconazole.

SUBMITTER: Firinu D

PROVIDER: S-EPMC3003968 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Successful treatment of chronic mucocutaneous candidiasis caused by azole-resistant Candida albicans with posaconazole.

Firinu Davide D Massidda Orietta O Lorrai Maria Maddalena MM Serusi Loredana L Peralta Monica M Barca Maria Pina MP Serra Paolo P Manconi Paolo Emilio PE

Clinical & developmental immunology 20101201

Refractory or recurrent infections of skin, nails, and the mucous membranes are clinical signs of chronic mucocutaneous candidiasis, frequently associated with immunological defects. Here we describe a 39-years-old female patient, with familial CMC, that presented with an extensive infection caused by an azole-resistant Candida albicans isolate, successfully treated with posaconazole. ...[more]

PMID: 21197459

Similar Datasets

Persistence of Clonal Azole-Resistant Isolates of Candida albicans from a Patient with Chronic Mucocutaneous Candidiasis in Colombia.

Project description:Purpose:The present article describes retrospectively a case of a patient with chronic mucocutaneous candidiasis (CMC) who presented recurrent Candida albicans infection since he was 6 months old. We obtained 16 isolates recovered during a 4-year period. Our purpose was to determinate the susceptibility, genotyping, and the pathogenicity profile in all the isolates. Methods:Sixteen C. albicans were isolated from a 25-year-old male with several recurrent fungal infections admitted to Hospital. The isolates were recovered during 4 years from a different anatomical origin. We typified them by multilocus sequence typing, also we evaluated susceptibility to fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole, caspofungin, and amphotericin B by microdilution method and we also test the pathogenic capacity in the Galleria mellonella model. Results:Genotyping of all clinical isolates showed the persistence of the same diploid sequence type (DST). Isolates changed their susceptibility profile over time, but there were no significant statistical differences in pathogenicity. Conclusion:Herein, a persistent clonal isolates of C. albicans (DST 918) in a patient with CMC, showed changes in its susceptibility profile after several antifungal treatments acquiring gradual resistance to the azole drugs, which did not affect their pathogenicity.

| S-EPMC7045761 | biostudies-literature

Clonal Strain Persistence of Candida albicans Isolates from Chronic Mucocutaneous Candidiasis Patients.

Project description:Chronic mucocutaneous candidiasis (CMC) is a primary immunodeficiency disorder characterised by susceptibility to chronic Candida and fungal dermatophyte infections of the skin, nails and mucous membranes. Molecular epidemiology studies of CMC infection are limited in number and scope and it is not clear whether single or multiple strains inducing CMC persist stably or are exchanged and replaced. We subjected 42 C. albicans individual single colony isolates from 6 unrelated CMC patients to multilocus sequence typing (MLST). Multiple colonies were typed from swabs taken from multiple body sites across multiple time points over a 17-month period. Among isolates from each individual patient, our data show clonal and persistent diploid sequence types (DSTs) that were stable over time, identical between multiple infection sites and exhibit azole resistant phenotypes. No shared origin or common source of infection was identified among isolates from these patients. Additionally, we performed C. albicans MLST SNP genotype frequency analysis to identify signatures of past loss of heterozygosity (LOH) events among persistent and azole resistant isolates retrieved from patients with autoimmune disorders including CMC.

| S-EPMC4743940 | biostudies-literature

Transcriptional response of an azole-resistant Candida parapsilosis isolate [posaconazole].

2011-04-18 | GSE27407 | GEO

Two patients with chronic mucocutaneous candidiasis caused by TRAF3IP2 deficiency.

Project description:BackgroundTRAF3 interacting protein 2 (TRAF3IP2) (Act1) is an adapter protein that interacts with IL-17R via its similar expression to fibroblast growth factor genes and IL-17R domain and coordinates 2 separate proinflammatory pathways following IL-17 cytokine stimulation.ObjectiveWe sought to elucidate the immunologic consequences of TRAF3IP2 homozygous mutations to improve treatments for immunodeficiency patients with chronic mucocutaneous candidiasis.MethodsWe describe 2 patients presenting with chronic mucocutaneous candidiasis who harbor biallelic nonsense mutations in TRAF3IP2. The cellular and molecular features of this genetic defect were assessed using in vitro cytokine assays and protein analysis.ResultsWe show that the homozygous mutation causes complete loss of protein expression. We also show that the absence of TRAF3IP2 was associated with a defective response to combined IL-2/IL-25 (IL-17E) stimulation.ConclusionsFailure to initiate normal signaling downstream of IL-17R engagement likely contributes to the patients' recurrent fungal infections. These findings add to our molecular understanding of genetic defects affecting this critical pathway of antifungal immunity.

| S-EPMC8273085 | biostudies-literature

VT-1161 protects mice against oropharyngeal candidiasis caused by fluconazole-susceptible and -resistant Candida albicans.

Project description:BackgroundCandida albicans, the most common human fungal pathogen, causes chronic mucosal infections in patients with inborn errors of IL-17 immunity that rely heavily on chronic, often lifelong, azole antifungal agents for treatment. However, a rise in azole resistance has predicated a need for developing new antifungal drugs.ObjectivesTo test the in vitro and in vivo efficacy of VT-1161 and VT-1129 in the treatment of oropharyngeal candidiasis with azole-susceptible or -resistant C. albicans strains.MethodsMICs of VT-1161, VT-1129 and nine licensed antifungal drugs were determined for 31 Candida clinical isolates. The drug concentrations in mouse serum and tongues were measured following oral administration. IL-17-signalling-deficient Act1-/- mice were infected with fluconazole-susceptible or fluconazole-resistant C. albicans strains, and the amount of mucosal fungal burden was determined after fluconazole or VT-1161 treatment.ResultsFourteen isolates (45%) were not fluconazole susceptible (MIC ?4?mg/L). VT-1161 and VT-1129 showed significant in vitro activity against the majority of the 31 mucosal clinical isolates (MIC50 0.03 and 0.06?mg/L, respectively), including Candida glabrata (MIC50, 0.125 and 0.25?mg/L, respectively). After oral doses, VT-1161 and VT-1129 concentrations in mouse serum and tongues were well above their MIC50 values. VT-1161 was highly effective as treatment of both fluconazole-susceptible and -resistant oropharyngeal candidiasis in Act1-/- mice.ConclusionsVT-1129 and VT-1161 exhibit significant in vitro activity against Candida strains, including fluconazole-resistant C. albicans and C. glabrata. VT-1161 administration in mice results in significant mucosal drug accumulation and eradicates infection caused by fluconazole-susceptible and -resistant Candida strains.

| S-EPMC5890729 | biostudies-literature

Transcriptional response of an azole-resistant Candida parapsilosis isolate [posaconazole].

Project description:Azole resistance was induced in vitro by growth of a susceptible C. parapsilosis isolate in the presence of posaconazole. Whole genome microarrays were used to compare the transcriptional response of the posaconazole-resistant and susceptible isolates. Transcriptional profile of an in vitro derived posaconazole-resistant isolate of C. parapsilosis (BC014PSC) compared to the susceptible isolate (BC014S). Cell were grown in YPD medium in normoxia at 35 degrees. Each strain was labelled with Cy3 or Cy5. Overall, 3 independent biological replicates were compared; 1 dye swap was performed to normalize dye effects.

2011-04-18 | E-GEOD-27407 | biostudies-arrayexpress

An Azole-Tolerant Endosomal Trafficking Mutant of Candida albicans Is Susceptible to Azole Treatment in a Mouse Model of Vaginal Candidiasis.

Project description:We recently reported that a Candida albicans endosomal trafficking mutant continues to grow after treatment with the azole antifungals. Herein, we report that the vps21?/? mutant does not have a survival advantage over wild-type isolates after fluconazole treatment in a mouse model of vaginal candidiasis. Furthermore, loss of VPS21 does not synergize with established mechanisms of azole resistance, such as overexpression of efflux pumps or of Erg11p, the target enzyme of the azoles. In summary, although loss of VPS21 function enhances C. albicans survival after azole treatment in vitro, it does not seem to affect azole susceptibility in vivo.

| S-EPMC5444139 | biostudies-literature

Identification and characterization of four azole-resistant erg3 mutants of Candida albicans.

Project description:Sterol analysis identified four Candida albicans erg3 mutants in which ergosta 7,22-dienol, indicative of perturbations in sterol ?(5,6)-desaturase (Erg3p) activity, comprised >5% of the total sterol fraction. The erg3 mutants (CA12, CA488, CA490, and CA1008) were all resistant to fluconazole, voriconazole, itraconazole, ketoconazole, and clotrimazole under standard CLSI assay conditions (MIC values, ?256, 16, 16, 8, and 1 ?g ml?¹, respectively). Importantly, CA12 and CA1008 retained an azole-resistant phenotype even when assayed in the presence of FK506, a multidrug efflux inhibitor. Conversely, CA488, CA490, and three comparator isolates (CA6, CA14, and CA177, in which ergosterol comprised >80% of the total sterol fraction and ergosta 7,22-dienol was undetectable) all displayed azole-sensitive phenotypes under efflux-inhibited assay conditions. Owing to their ergosterol content, CA6, CA14, and CA177 were highly sensitive to amphotericin B (MIC values, <0.25 ?g ml?¹); CA1008, in which ergosterol comprised <2% of the total sterol fraction, was less sensitive (MIC, 1 ?g ml?¹). CA1008 harbored multiple amino acid substitutions in Erg3p but only a single conserved polymorphism (E266D) in sterol 14?-demethylase (Erg11p). CA12 harbored one substitution (W332R) in Erg3p and no residue changes in Erg11p. CA488 and CA490 were found to harbor multiple residue changes in both Erg3p and Erg11p. The results suggest that missense mutations in ERG3 might arise in C. albicans more frequently than currently supposed and that the clinical significance of erg3 mutants, including those in which additional mechanisms also contribute to resistance, should not be discounted.

| S-EPMC2976150 | biostudies-literature

Correlation between azole susceptibilities, genotypes, and ERG11 mutations in Candida albicans isolates associated with vulvovaginal candidiasis in China.

Project description:The relationship between susceptibilities to fluconazole and itraconazole and microsatellite CAI genotypes were examined from a total of 154 Candida albicans isolates (97 isolates causing vulvovaginitis in Chinese women and 6 vaginal isolates and 51 oral cavity isolates from asymptomatic carriers). The two dominant genotypes, CAI 30-45 (45 isolates) and CAI 32-46 (33 isolates), associated with vulvovaginitis showed significantly different azole susceptibility patterns with strong statistical support. CAI 32-46 isolates were usually less susceptible to both fluconazole and itraconazole than CAI 30-45 isolates and than the oral isolates with other diversified CAI genotypes. Remarkably different mutation patterns in the azole target gene ERG11 were correspondingly observed among C. albicans isolates representing different genotypes and sources. Isolates with the same or similar CAI genotypes usually possessed identical or phylogenetically closely related ERG11 sequences. Loss of heterozygosity in ERG11 was observed in all the CAI 32-46 isolates but not in the CAI 30-45 isolates and most of the oral isolates sequenced. Compared with the ERG11 sequence of strain SC5314 (X13296), two homozygous missense mutations (G487T and T916C) leading to two amino acid changes (A114S and Y257H) in Erg11p were found in CAI 32-46 isolates. The correlation between azole susceptibility and C. albicans genotype may be of potential therapeutic significance.

| S-EPMC2916359 | biostudies-literature

Formation of azole-resistant Candida albicans by mutation of sterol 14-demethylase P450.

Project description:The sterol 14-demethylase P450 (CYP51) of a fluconazole-resistant isolate of Candida albicans, DUMC136, showed reduced susceptibility to this azole but with little change in its catalytic activity. Twelve nucleotide substitutions, resulting in four amino acid changes, were identified in the DUMC136 CYP51 gene in comparison with a reported CYP51 sequence from a wild-type, fluconazole-susceptible C. albicans strain. Seven of these substitutions, including all of those causing amino acid changes, were located within a region covering one of the putative substrate recognition sites of the enzyme (SRS-1). Polymorphisms within this region were observed in several C. albicans isolates, and some were found to be CYP51 heterozygotes. Among the amino acid changes occurring in this region, only an alteration of Y132 was common among these fluconazole-resistant isolates, which suggests the importance of this residue to the fluconazole resistance of the target enzyme. DUMC136 and another fluconazole-resistant isolate were homozygotes with respect to CYP51, although the typical wild-type, fluconazole-susceptible C. albicans was a CYP51 heterozygote. These findings suggest that part of the fluconazole-resistant phenotype of C. albicans DUMC136 was acquired through a mutation-prone area of CYP51, an area which might promote the formation of fluconazole-resistant CYP51, along with a mechanism(s) which allows the formation of a homozygote of this altered CYP51 in this diploid pathogenic yeast.

| S-EPMC89127 | biostudies-literature

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