Last data update: May 20, 2024. (Total: 46824 publications since 2009)
Records 1-5 (of 5 Records) |
Query Trace: Kuykendall RJ [original query] |
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Microbroth dilution susceptibility testing of Candida species
Kuykendall RJ , Lockhart SR . Methods Mol Biol 2016 1356 173-81 Antifungal susceptibility testing for Candida species is now widely accepted as a methodology to predict the success or failure of antifungal therapy for some antifungal/Candida species combinations. There are many different ways to perform susceptibility testing of antifungal agents, but broth microdilution has become the most popular over the last 10 years. This chapter describes in detail two methods for antifungal susceptibility testing of Candida species using the commercially available microbroth dilution tray (YeastOne((R))) and a commercially available gradient agar diffusion technique (Etest((R))) for isolates that appear resistant. |
Candida lusitaniae MICs to the echinocandins are elevated but FKS-mediated resistance is rare
Lockhart SR , Pham CD , Kuykendall RJ , Bolden CB , Cleveland AA . Diagn Microbiol Infect Dis 2015 84 (1) 52-54 MIC values were generated for caspofungin, micafungin, and anidulafungin against 106 isolates of C. lusitaniae, and these values were compared to established epidemiologic cutoff values. The majority of isolates were wild type both by MIC value as well as by FKS1 hotspot sequencing. Although C. lusitaniae isolates have MIC values to the echinocandins that are elevated compared to other common species, with regard to known mechanisms of resistance to the echinocandins, isolates with MIC values at or below the epidemiological cutoff values of 0.5 and 1mug/mL for micafungin and anidulafungin, respectively, should be considered wild type. |
The role of FKS mutations in C. glabrata: MIC values, echinocandin resistance and multidrug resistance
Pham CD , Iqbal N , Bolden CB , Kuykendall RJ , Harrison LH , Farley MM , Schaffner W , Beldavs ZG , Chiller TM , Park BJ , Cleveland AA , Lockhart SR . Antimicrob Agents Chemother 2014 58 (8) 4690-6 Candida glabrata is the second leading cause of candidemia in US hospitals. Current guidelines suggest that an echinocandin be used as primary therapy for C. glabrata due to the high rate of resistance to fluconazole. Recent case reports indicate that C. glabrata resistance to echinocandins may be increasing. We performed susceptibility testing on 1380 isolates of C. glabrata collected between 2008 and 2013 from four US cities, Atlanta, Baltimore, Knoxville and Portland. Our analysis showed that 3.1%, 3.3%, and 3.6% of the isolates were resistant to anidulafungin, caspofungin and micafungin, respectively. We screened 1032 of these isolates, including all 77 that had either a resistant or intermediate MIC value to one or more echinocandin, for mutations in the hotspot regions of FKS1 and FKS2, the major mechanism of echinocandin resistance. Fifty-one isolates were identified with hotspot mutations, 16 in FKS1 and 35 in FKS2. All but one of the isolates with an FKS mutation were resistant to one or more echinocandin by susceptibility testing. Of the isolates resistant to one or more echinocandin, 36% were also resistant to fluconazole. Echinocandin resistance among US C. glabrata isolates is a concern especially in light of the fact that a third of those isolates may be multidrug resistant. Further monitoring of US C. glabrata isolates for echinocandin resistance is warranted. |
Development of a Luminex-based multiplex assay for detection of mutations conferring resistance to echinocandins in Candida glabrata
Pham CD , Bolden CB , Kuykendall RJ , Lockhart SR . J Clin Microbiol 2013 52 (3) 790-5 Echinocandins are the recommended treatment for invasive candidiasis due to Candida glabrata. Resistance to echinocandins is known to be caused by non-synonymous mutations in the hotspot-1 (HS1) regions of the FKS1 and FKS2 genes which encode a subunit of the beta-1,3-glucan synthase, the target of the echinocandins. Here, we describe the development of a microsphere-based assay using Luminex MagPix technology to identify mutations in the FKS1 and FKS2 HS1 domains which confer in vitro echinocandin resistance in C. glabrata isolates. The assay is rapid and can be performed with high throughput. The assay was validated using 102 isolates that had FKS1-HS1 and FKS2-HS1 domains previously characterized by DNA sequencing. The assay was 100% concordant with DNA sequencing results. The assay was then used for high throughput screening of 1032 C. glabrata surveillance isolates. Sixteen new isolates with mutations were identified, as well as a mutation new to our collection, del659F. This assay provides a rapid and cost-effective way to screen C. glabrata isolates for echinocandin resistance. |
Validation of 24-hour flucytosine MIC determination as compared to the Clinical and Laboratory Standards Institute M27-A3 broth microdilution reference method 48 hour determination
Lockhart SR , Bolden CB , Iqbal N , Kuykendall RJ . J Clin Microbiol 2011 49 (12) 4322-5 Flucytosine and itraconazole are the only antifungal agents that continue to have a Clinical Laboratory and Standards Institute recommendation for MIC breakpoint readings at 48h only. Here we show good essential and categorical agreement between MIC readings for flucytosine made at 48h and those made at 24h for Candida species. |
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