Multiple colony antifungal susceptibility testing detects polyresistance in clinical Candida cultures: a European Confederation of Medical Mycology excellence centers study

Knoll, Miriam A.; Lackner, Nina; Ulmer, Hanno; Samardzic, Eldina; Steinmann, Joerg; Krause, Robert; Verhasselt, Hedda Luise; Rath, Peter‐Michael; Fuchs, Frieder; Köehler, Philipp; Denis, Blandine; Hamane, Samia; Alanio, Alexandre; Lass‐Flörl, Cornelia

doi:10.1016/j.cmi.2022.04.014

Cited by 12 publications

(7 citation statements)

References 25 publications

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“…In another study, WGSs of strains from 3 independent C. albicans colonies from oral cultures of healthy volunteers clearly demonstrated that each strain was unique, mostly due to SNPs and short-range LOH 29 . In a multi-center study, 5.6% and 8.1% of positive Candida cultures from blood and any clinical site, respectively, had antifungal polyresistance, defined as heterogenous susceptibility testing results among 5 independent colonies 30 . Such mixed populations were detected in 15.3% of C. glabrata -positive clinical samples, a frequency in keeping with our description of unrecognized azole-resistant strains in 2 of 10 patients.…”

Section: Discussionmentioning

confidence: 99%

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Genotypic diversity and unrecognized antifungal resistance among populations of Candida glabrata from positive blood cultures

Badrane,

Cheng,

Dupont

et al. 2023

Nat Commun

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The longstanding model is that most bloodstream infections (BSIs) are caused by a single organism. We perform whole genome sequencing of five-to-ten strains from blood culture (BC) bottles in each of ten patients with Candida glabrata BSI. We demonstrate that BCs contain mixed populations of clonal but genetically diverse strains. Genetically distinct strains from two patients exhibit phenotypes that are potentially important during BSIs, including differences in susceptibility to antifungal agents and phagocytosis. In both patients, the clinical microbiology lab recovered a fluconazole-susceptible index strain, but we identify mixed fluconazole-susceptible and –resistant populations. Diversity in drug susceptibility is likely clinically relevant, as fluconazole-resistant strains were subsequently recovered by the clinical laboratory during persistent or relapsing infections. In one patient, unrecognized respiration-deficient small colony variants are fluconazole-resistant and significantly attenuated for virulence during murine candidiasis. Our data suggest a population-based model of C. glabrata genotypic and phenotypic diversity during BSIs.

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Section: Discussionmentioning

confidence: 99%

“…Such mixed populations were detected in 15.3% of C. glabrata -positive clinical samples, a frequency in keeping with our description of unrecognized azole-resistant strains in 2 of 10 patients. Contemporaneous strains in the multicenter study did not differ by multilocus sequence type, but WGS was not performed 30 .…”

Section: Discussionmentioning

confidence: 99%

Genotypic diversity and unrecognized antifungal resistance among populations of Candida glabrata from positive blood cultures

Badrane,

Cheng,

Dupont

et al. 2023

Nat Commun

View full text Add to dashboard Cite

show abstract

“…In another study, WGS of strains from 3 independent C. albicans colonies from oral cultures of healthy volunteers clearly demonstrated that each strain was unique, mostly due to SNPs and short-range LOH 29 . Finally, in a multi-center study, 5.6% and 8.1% of positive Candida cultures from blood and any clinical sites, respectively, had antifungal polyresistance, defined as heterogenous susceptibility testing results among 5 independent colonies 30 . Such mixed populations were detected in 15.3% of C. glabratapositive clinical samples, a frequency in keeping with our description of unrecognized azole-resistant strains in 2 of 10 patients.…”

Section: Discussionmentioning

confidence: 99%

Genotypic diversity and unrecognized antifungal resistance among populations of Candida glabrata from positive blood cultures

Badrane

Cheng

Dupont

et al. 2023

Preprint

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The longstanding paradigm is that most bloodstream infections (BSIs) are caused by a single organism. We performed whole genome sequencing of five-to-ten strains from blood culture (BC) bottles in each of ten patients with Candida glabrata BSI. We demonstrated that BCs contained mixed populations of clonal but genetically diverse strains. Genetically distinct strains from two patients exhibited phenotypes that were potentially important during BSIs, including differences in susceptibility to antifungal agents and phagocytosis. In both patients, the clinical microbiology lab recovered a fluconazole-susceptible index strain, but we identified mixed fluconazole-susceptible and –resistant populations. Diversity in drug susceptibility was likely clinically relevant, as fluconazole-resistant strains were subsequently recovered by the clinical laboratory during persistent or relapsing infections. In one patient, unrecognized respiration-deficient small colony variants were fluconazole-resistant and significantly attenuated for virulence during murine candidiasis. Our data suggest a new population-based paradigm of C. glabrata genotypic and phenotypic diversity during BSIs.

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“…In more detail, heteroresistance refers to isogenic populations with small subpopulations of resistant cells ( 17 ), while polyresistance refers to the phenotypical variability in clinical AFST, including the presence of two distinct strains. In a recent study, we found that upon separate testing of single colonies, heterogeneous MICs from same-species clinical Candida cultures occurred in 8% of clinical samples ( 19 ). MLST and RAPD did not reveal a uniform genetic correlate in the strains studied but rather suggested a phenotypical expression of genomic variability.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple colony testing refers to the separate AFST of usually five distinct colonies from a Candida culture ( 19 , 23 ) and was performed here by an anidulafungin disk diffusion assay ( 24 , 25 ). Empty 6 mm sterile paper disks were impregnated with 20 μL containing 2 μg anidulafungin, 1% dimethyl sulfoxide (DMSO), and 0.1% polysorbate 80 (Tween 80) and were then left to dry at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of Inoculum Preparation for Etest and EUCAST Broth Dilution to Detect Anidulafungin Polyresistance in Candida glabrata

Knoll

Samardzic

Posch

et al. 2022

Antimicrob Agents Chemother

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The influence of inoculum preparation in EUCAST broth dilution and Etest to detect the coexistence of resistant and susceptible Candida subpopulations (defined as polyresistance [PR]) was evaluated. Cocultures of two echinocandin-resistant and susceptible clinical C. glabrata strains were used to simulate the occurrence of mixed populations in clinical samples, and antifungal susceptibility testing was performed with standard and modified approaches of inoculum preparation.

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Multiple colony antifungal susceptibility testing detects polyresistance in clinical Candida cultures: a European Confederation of Medical Mycology excellence centers study

Cited by 12 publications

References 25 publications

Genotypic diversity and unrecognized antifungal resistance among populations of Candida glabrata from positive blood cultures

Genotypic diversity and unrecognized antifungal resistance among populations of Candida glabrata from positive blood cultures

Genotypic diversity and unrecognized antifungal resistance among populations of Candida glabrata from positive blood cultures

Evaluation of Inoculum Preparation for Etest and EUCAST Broth Dilution to Detect Anidulafungin Polyresistance in Candida glabrata

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