SA Messer

JMI Laboratories, North Liberty, Iowa, United States

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Publications (189)663.85 Total impact

  • No preview · Article · Jun 2015
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    ABSTRACT: The in vitro activities of isavuconazole, micafungin, and 8 comparator antifungal agents were determined for 1613 clinical isolates of fungi (1320 isolates of Candida spp., 155 of Aspergillus spp., 103 of non-Candida yeasts, and 35 non-Aspergillus molds) collected during a global survey conducted in 2013. The vast majority of the isolates of the 21 different species of Candida, with the exception of Candida glabrata (MIC90, 2μg/mL), Candida krusei (MIC90, 1μg/mL), and Candida guilliermondii (MIC90, 8μg/mL), were inhibited by ≤0.25μg/mL of isavuconazole. C. glabrata and C. krusei were largely inhibited by ≤1μg/mL of isavuconazole. Resistance to fluconazole was seen in 0.5% of Candida albicans isolates, 11.1% of C. glabrata isolates, 2.5% of Candida parapsilosis isolates, 4.5% of Candida tropicalis isolates, and 20.0% of C. guilliermondii isolates. Resistance to the echinocandins was restricted to C. glabrata (1.3-2.1%) and C. tropicalis (0.9-1.8%). All agents except for the echinocandins were active against 69 Cryptococcus neoformans isolates, and the triazoles, including isavuconazole, were active against the other yeasts. Both the mold active triazoles as well as the echinocandins were active against 155 Aspergillus spp. isolates belonging to 10 species/species complex. In general, there was low resistance levels to the available systemically active antifungal agents in a large, contemporary (2013), global collection of molecularly characterized yeasts and molds. Resistance to azoles and echinocandins was most prominent among isolates of C. glabrata, C. tropicalis, and C. guilliermondii. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Apr 2015 · Diagnostic microbiology and infectious disease
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    ABSTRACT: The SENTRY Antifungal Surveillance Program monitors global susceptibility rates of newer and established antifungal agents. We report the in vitro activity of seven antifungal agents against 496 contemporary clinical isolates of yeasts and molds. The isolates were obtained from 20 laboratories in the Asia-Western Pacific (APAC) region during 2010 through 2012. Anidulafungin, caspofungin, micafungin, fluconazole, itraconazole, posaconazole and voriconazole were susceptibility tested using CLSI methods and species-specific interpretive criteria. Sequencing of fks hot spots was performed for echinocandin-resistant strains. Isolates included 13 species of Candida (n=460), 5 species of non-Candida yeasts (21), 5 species of Aspergillus (11) and 4 other molds. Echinocandin resistance was uncommon among eight species of Candida and was only detected in three isolates of Candida glabrata, two from Australia harboring mutations in fks1 (F625S) and fks2 (S663P). Resistance to the azoles was much more common and was observed among all species with the exception of Candida dubliniensis. Fluconazole resistance rates observed with C. glabrata (6.8%) was comparable to that seen with Candida parapsilosis (5.7%) and Candida tropicalis (3.6%). Cross resistance among the triazoles was seen with each of these three species. The mold-active azoles and the echinocandins were all active against isolates of Aspergillus fumigatus. Azole resistance was not detected among the isolates of Cryptococcus neoformans. Antifungal resistance is uncommon among isolates of fungi causing invasive fungal infections in the APAC region. As in other regions of the world, emerging resistance to the echinocandins among invasive isolates of C. glabrata bears close monitoring.The Journal of Antibiotics advance online publication, 22 April 2015; doi:10.1038/ja.2015.29.
    No preview · Article · Apr 2015 · The Journal of Antibiotics
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    ABSTRACT: We report the in vitro activity of nine systemically active antifungal agents against 237 contemporary clinical isolates of yeast and moulds obtained from 13 laboratories in China during 2010 through 2012. Susceptibility testing was performed using CLSI methods. Sequencing of fks hot spots was performed for echinocandin non-wild-type (WT) strains. Isolates included 220 from eight species of Candida, 15 from four species of Aspergillus and one isolate each of Rhodotorula mucilaginosa and Trichosporon asahii. Resistance to amphotericin B (0.0%), flucytosine (0.0-1.7%) and the echinocandins (0.0-3.4%) was distinctly uncommon among C. albicans, C. parapsilosis, C. tropicalis, C. glabrata and C. pelliculosa. Three C. albicans isolates showed resistance to echinocandins and one harboured a mutation in HS1 of fks1. Resistance to the azoles was much more common with resistance to fluconazole, voriconazole and posaconazole detected among isolates of C. glabrata and C. tropicalis. Both C. parapsilosis and C. pelliculosa exhibited decreased susceptibility to fluconazole. Amphotericin B, the mould-active azoles and the echinocandins were all quite active against isolates of A. fumigatus and A. flavus. Consistent with previous studies from China, resistance to fluconazole is prominent among Candida spp. isolates in this country. © 2015 Blackwell Verlag GmbH.
    No preview · Article · Feb 2015 · Mycoses
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    ABSTRACT: Four laboratories tested three isolates of Candida species and two isolates of Aspergillus fumigatus using 96-well plates containing combinations of amphotericin B, anidulafungin, caspofungin, micafungin, fluconazole, itraconazole, posaconazole, and voriconazole. The majority of summation fractional inhibitory concentration indices (ΣFICI) based on the Lowe additivity formula, suggested indifferent drug interactions (ΣFICI > 0.5 and ≤ 4.0) and no instance of drug antagonism (ΣFICI > 4.0). The intra- and inter- laboratory agreement rates were superior when MIC100 readings were used as end-points (CI=99%). Copyright © 2014, American Society for Microbiology. All Rights Reserved.
    Full-text · Article · Dec 2014 · Antimicrobial Agents and Chemotherapy
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    ABSTRACT: MGCD290, a Hos2 fungal histone deacetylase inhibitor showed modest activity when tested alone (MIC range, 0.12-4 μg/ml; MIC50/90, 0.5/4 μg/ml) against C. glabrata (n=15; 14 fks mutants; 5 also fluconazole-resistant), C. albicans (8 fks mutants; 2 also fluconazole-resistant), C. tropicalis (4 fks mutants), and C. krusei (3 fks mutants). However, MGCD290 showed synergy or partial synergy for 33.3, 30.1, 36.7 and 80.0% of the isolates when tested with anidulafungin, caspofungin, micafungin and fluconazole, respectively. Favorable interactions were achieved with low concentrations of MGCD290 (0.015 to 0.25 μg/ml) and categorical shifts were observed in 2 of 8 (25.0%) isolates of C. albicans and 2 of 3 (66.7%) isolates of C. krusei. In addition, 4 of the 5 (80.0%) fluconazole- resistant isolates of C. glabrata. MGCD290 exerts a distinctly favorable influence on the MICs of fluconazole and the echinocandins, resulting in conversion from resistance to susceptibility regardless of fks mutations.
    No preview · Article · Nov 2014 · Diagnostic Microbiology and Infectious Disease
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    ABSTRACT: Background: The importance of antifungal surveillance was highlighted by the increasing resistance among certain species and breakthrough infections. We evaluated 1,846 fungal clinical isolates against 9 antifungals using CLSI reference broth microdilution methods (BMD). Additionally, 1,206 isolates were tested using polysorbate-80 (P-80). Methods: 1,846 isolates collected in 2013 (31 countries) were tested by CLSI BMD and interpretive criteria. Echinocandins (EC), amphotericin B (AMB) and fluconazole (FLC) were also tested using 0.002% P-80 supplemented broth. Isolates were identified using MALDI-TOF MS and/or DNA sequencing. Results: EC, AMB and FLC were active against common Candida spp. (Table). EC-resistance ranged from 0.0 to 2.8% (anidulafungin for C. glabrata [CGLA]). 11.9 and 11.6% of the CGLA and C. tropicalis were resistant to FLC, respectively. Two A. fumigatus displayed elevated MIC values for itraconazole (≥4 µg/mL). All C. neoformanshad MIC < epidemiological cutoff values for azoles. P-80 lowered the MIC values for EC for all species, but not for FLC. AMB MIC values were lower and ranges broader (0.03-0.5 µg/mL) when compared with reference BMD (0.5-2 µg/mL). Conclusion: EC and azoles were potent against yeasts and moulds. P-80 use broadened MIC ranges for AMB; however, differences in the growth patterns in RPMI + P-80, requirement for new QC ranges and a possible effect in cell growth reported previously in bacteria might be an impediment to the use of P-80 for antifungal BMD testing. Organism (no. tested [no. tested with P-80]) MIC/MEC50/90 for CLSI BMD (with P-80) Anidulafungin Caspofungin Amphotericin B Fluconazole C. albicans (712 [475]) 0.015/0.06 (≤0.008/≤0.008) 0.03/0.03 (≤0.008/≤0.008) 1/1 (0.06/0.12) 0.12/0.25 (0.25/0.25) C. glabrata (252 [156]) 0.06/0.12 (0.015/0.015) 0.03/0.06 (≤0.008/≤0.008) 1/1 (0.12/0.12) 8/64 (4/32) C. parapsilosis (215 [149]) 2/2 (1/2) 0.25/0.5 (0.06/0.06) 1/1 (0.12/0.25) 1/2 (1/4) C. tropicalis (155 [90]) 0.015/0.03 (≤0.008/≤0.008) 0.03/0.03 (≤0.008/≤0.008) 1/1 (0.06/0.12) 0.5/32 (0.5/1) C. krusei (49 [29]) 0.06/0.06 (0.03/0.03) 0.12/0.25 (0.03/0.03) 1/2 (0.25/0.25) 32/64 (32/64) A. fumigatus (142 [94]) ≤0.008/0.03 (≤0.008/≤0.008) 0.03/0.03 (≤0.008/≤0.008) 2/2 (0.25/0.5) -/-
    No preview · Conference Paper · Oct 2014
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    ABSTRACT: In this study, 1717 fungal clinical isolates causing invasive fungal infections were evaluated against nine antifungal agents using Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution methods. The isolates comprised 1487 Candida spp., 109 Aspergillus spp., 86 non-Candida yeasts (including 52 isolates of Cryptococcus neoformans) and 35 rare moulds obtained during 2012 from 72 hospitals worldwide. Echinocandin resistance among Candida spp. was low, and resistance rates to anidulafungin, caspofungin and micafungin varied from 0.0% to 2.8% among different species. Echinocandin-resistant Candida glabrata were shown to have fks mutations (fks2 HS1 F659Y, F659del, S663F and S663P), and fluconazole resistance was also observed in those strains. One Candida krusei and one Candida dubliniensis had L701 M or S645P fks1 mutations, respectively. Candida tropicalis and C. glabrata had higher fluconazole resistance rates of 6.1% and 6.9%, respectively, compared with other Candida spp. Fluconazole-resistant C. tropicalis were collected in five countries (USA, China, Germany, Belgium and Thailand). Voriconazole was active against all Candida spp., inhibiting 91.2–99.7% of isolates using species-specific breakpoints. All agents except for the echinocandins and posaconazole were active against Cr. neoformans. Triazoles were active against other yeasts [MIC90 (minimum inhibitory concentration encompassing 90% of isolates tested), 2 μg/mL]. The echinocandins and the mould-active triazoles were active against Aspergillus [MIC/MEC90 (minimum effective concentration encompassing 90% of isolates tested) range, 0.015–2 μg/mL], but the activity of these agents was limited against uncommon mould species (MIC/MEC90 range, 4 μg/mL to >16 μg/mL).
    No preview · Article · Oct 2014 · International Journal of Antimicrobial Agents
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    ABSTRACT: The in vitro activity of isavuconazole and nine antifungal comparator agents was assessed using reference broth microdilution methods against 1,421 common and uncommon species of Candida from a 2012 global survey. Isolates were identified using CHROMagar, biochemical methods and sequencing of ITS and/or 28S regions. Candida spp. were classified as either susceptible or resistant and as wild type (WT) or non-WT using CLSI clinical breakpoints or epidemiological cutoff values, respectively, for the antifungal agents. Isolates included 1,421 organisms from 21 different species of Candida. Among Candida spp., resistance to all 10 tested antifungal agents was low (0.0-7.9 %). The vast majority of each species of Candida, with the exception of Candida glabrata, Candida krusei, and Candida guilliermondii (modal MICs of 0.5 µg/ml), were inhibited by ≤0.12 µg/ml of isavuconazole (99.0 %; range 94.3 % [Candida tropicalis] to 100.0 % [Candida lusitaniae and Candida dubliniensis]). C. glabrata, C. krusei, and C. guilliermondii were largely inhibited by ≤1 µg/ml of isavuconazole (89.7, 96.9 and 92.8 %, respectively). Decreased susceptibility to isavuconazole was most prominent with C. glabrata where the modal MIC for isavuconazole was 0.5 µg/ml for those strains that were SDD to fluconazole or WT to voriconazole, and was 4 µg/ml for those that were either resistant or non-WT to fluconazole or voriconazole, respectively. In conclusion, these data document the activity of isavuconazole and generally the low resistance levels to the available antifungal agents in a large, contemporary (2012), global collection of molecularly characterized species of Candida.
    No preview · Article · Jun 2014 · Mycopathologia
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    ABSTRACT: The antifungal broth microdilution (BMD) method of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) was compared with Clinical and Laboratory Standards Institute (CLSI) BMD method M27-A3 for amphotericin B, flucytosine, anidulafungin, caspofungin, micafungin, fluconazole, isavuconazole, itraconazole, posaconazole, and voriconazole susceptibility testing of 357 isolates of Candida. The isolates were selected from global surveillance collections to represent both wildtype (WT) and non-WT MIC results for the azoles (12% of fluconazole and voriconazole results were non-WT) and the echinocandins (6% of anidulafungin and micafungin results were non-WT). The study collection included 114 isolates of C. albicans, 73 of C. glabrata, 76 of C. parapsilosis, 60 of C. tropicalis, and 34 of C. krusei. The overall essential agreement (EA) between EUCAST and CLSI results ranged from 78.9% (posaconazole) to 99.6% (flucytosine). The categorical agreement (CA) between methods and species of Candida was assessed using previously determined CLSI epidemiological cutoff values (ECVs). The overall CA between methods was 95.0% with 2.5% very major (VM) and major (M) discrepancies. The CA was >93% for all antifungal agents with the exception of caspofungin (84.6%), where 10% of the results were categorized as non-WT by the EUCAST method and WT by the CLSI method. Problem areas with low EA or CA include testing of amphotericin B, anidulafungin, and isavuconazole against C. glabrata, itraconazole and posaconazole against most species, and caspofungin against C. parapsilosis, C. tropicalis, and C. krusei. We confirm high level EA and CA (>90%) between the two methods for testing fluconazole, voriconazole, and micafungin against all five species. The results indicate that the EUCAST and CLSI methods produce comparable results for testing the systemically active antifungal agents against the five most common species of Candida; however, there are several areas where additional steps toward harmonization are warranted.
    No preview · Article · Jun 2014 · Diagnostic microbiology and infectious disease
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    ABSTRACT: This study addressed the application of anidulafungin as a surrogate marker to predict the susceptibility of Candida to caspofungin due to unacceptably high interlaboratory variation of caspofungin MIC values. CLSI reference broth microdilution methods and species-specific interpretive criteria were used to test 4,290 strains of Candida (eight species), including 71 strains with documented fks mutations. Caspofungin MIC values were compared with those of anidulafungin to determine the percentage of categorical agreement (CA) and very major (VME), major (ME), and minor error rates, as well as the ability to detect fks mutants. For all 4,290 isolates the CA was 97.1% (0.2% VME and ME, 2.5% minor errors) using anidulafungin as the surrogate. Among the 62 isolates of Candida albicans (4 isolates), C. tropicalis (5 isolates), C. krusei (4 isolates), C. kefyr (2 isolates), and C. glabrata (47 isolates) that were nonsusceptible (NS; either intermediate [I] or resistant [R]) to both caspofungin and anidulafungin, 52 (83.8%) contained a mutation in fks1 or fks2. Eight mutants of C. glabrata, two of C. albicans, and one each of C. tropicalis and C. krusei were classified as susceptible (S) to both antifungal agents. The remaining 7 mutants (2 C. albicans and 5 C. glabrata) were susceptible to one of the agents and either intermediate or resistant to the other. Using the epidemiological cutoff value (ECV) of 0.12 μg/ml for both caspofungin and anidulafungin to differentiate wild-type (WT) from non-WT strains of C. glabrata, 42 of the 55 (76.4%) C. glabrata mutants were non-WT and 8 of the 55 (14.5%) were WT for both agents (90.9% concordance). Anidulafungin can accurately serve as a surrogate marker to predict S and R of Candida to caspofungin.
    Full-text · Article · Oct 2013 · Journal of clinical microbiology
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    ABSTRACT: Among 119 echinocandin non-wild-type (non-WT) Candida glabrata strains from two global surveys, mutations in fks hot spots (HSs) were detected in 28 (from 7 countries and 8 U.S. states): 24 strains (85.7%) had non-WT MICs for micafungin, 22 (78.6%) for anidulafungin, and 25 (89.3%) for caspofungin. The most common FKS substitutions among non-WT strains were at positions F659 (n = 7) and S663 (n = 7). Three isolates displaying WT MIC results had F625Y, L630I, and D632Y substitutions or non-HS mutations. Mutations that have been reported to decrease the echinocandin binding to the 1,3-β-d-glucan synthase were categorized as resistant by applying the new CLSI breakpoint criteria for all three echinocandins.
    No preview · Article · Oct 2013 · Antimicrobial Agents and Chemotherapy
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    ABSTRACT: Isavuconazole is a new broad-spectrum triazole with a favorable pharmacokinetic and safety profile. We report the MIC distributions for isavuconazole and 111 isolates of Candida (42 Candida albicans, 25 Candida glabrata, 22 Candida parapsilosis, 14 Candida tropicalis, and 8 Candida krusei isolates), as determined by Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution (BMD) methods. Also, the relative activities of isavuconazole, itraconazole, fluconazole, posaconazole, voriconazole, and the three echinocandins were assessed against a recent (2011) global collection of 1,358 isolates of Candida spp., 101 of Aspergillus spp., 54 of non-Candida yeasts, and 21 of non-Aspergillus molds using CLSI BMD methods. The overall essential agreement (EA) (±2 log2 dilutions) between the CLSI and EUCAST methods was 99.1% (EA at ±1 log2 dilution, 90.1% [range, 80.0 to 100.0%]). The activities of isavuconazole against the larger collection of Candida spp. and Aspergillus spp. were comparable to those of posaconazole and voriconazole; the MIC90 values for isavuconazole, posaconazole, and voriconazole against Candida spp. were 0.5, 1, and 0.25 μg/ml and against Aspergillus spp. were 2, 1, and 1 μg/ml, respectively. Isavuconazole showed good activities against Cryptococcus neoformans (MIC90, 0.12 μg/ml) and other non-Candida yeasts (MIC90, 1 μg/ml) but was less potent against non-Aspergillus molds (MIC90, >8 μg/ml). Isavuconazole MIC values for three mucormycete isolates were 4, 1, and 2 μg/ml, whereas all three were inhibited by 1 μg/ml posaconazole. Isavuconazole demonstrates broad-spectrum activity against this global collection of opportunistic fungi, and the CLSI and EUCAST methods can be used to test this agent against Candida, with highly comparable results.
    Full-text · Article · Jun 2013 · Journal of clinical microbiology
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    ABSTRACT: The SENTRY Antimicrobial Surveillance Program monitors global susceptibility and resistance rates of newer and established antifungal agents. We report the echinocandin and triazole antifungal susceptibility patterns for 3,418 contemporary clinical isolates of yeasts and molds. The isolates were obtained from 98 laboratories in 34 countries during 2010 and 2011. Yeasts not presumptively identified by CHROMagar, the trehalose test, or growth at 42°C and all molds were sequence identified using internal transcribed spacer (ITS) and 28S (yeasts) or ITS, translation elongation factor (TEF), and 28S (molds) genes. Susceptibility testing was performed against 7 antifungals (anidulafungin, caspofungin, micafungin, fluconazole, itraconazole, posaconazole, and voriconazole) using CLSI methods. Rates of resistance to all agents were determined using the new CLSI clinical breakpoints and epidemiological cutoff value criteria, as appropriate. Sequencing of fks hot spots was performed for echinocandin non-wild-type (WT) strains. Isolates included 3,107 from 21 Candida spp., 146 from 9 Aspergillus spp., 84 from Cryptococcus neoformans, 40 from 23 other mold species, and 41 from 9 other yeast species. Among Candida spp., resistance to the echinocandins was low (0.0 to 1.7%). Candida albicans and Candida glabrata that were resistant to anidulafungin, caspofungin, or micafungin were shown to have fks mutations. Resistance to fluconazole was low among the isolates of C. albicans (0.4%), Candida tropicalis (1.3%), and Candida parapsilosis (2.1%); however, 8.8% of C. glabrata isolates were resistant to fluconazole. Among echinocandin-resistant C. glabrata isolates from 2011, 38% were fluconazole resistant. Voriconazole was active against all Candida spp. except C. glabrata (10.5% non-WT), whereas posaconazole showed decreased activity against C. albicans (4.4%) and Candida krusei (15.2% non-WT). All agents except for the echinocandins were active against C. neoformans, and the triazoles were active against other yeasts (MIC90, 2 μg/ml). The echinocandins and triazoles were active against Aspergillus spp. (MIC90/minimum effective concentration [MEC90] range, 0.015 to 2 μg/ml), but the echinocandins were not active against other molds (MEC90 range, 4 to >16 μg/ml). Overall, echinocandin and triazole resistance rates were low; however, the fluconazole and echinocandin coresistance among C. glabrata strains warrants continued close surveillance.
    Full-text · Article · May 2013 · Journal of clinical microbiology
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    ABSTRACT: Background: Fluconazole (FLC) resistance is common in C. glabrata and echinocandins are often used as first-line therapy. Resistance to echinocandin therapy has been associated with FKS1 and FKS2 gene alterations. Methods: We reviewed records of all patients with C. glabrata bloodstream infection at Duke Hospital over the past decade (2001-2010) and correlated treatment outcome with minimum inhibitory concentration (MIC) results and the presence of FKS gene mutations. For each isolate, MICs to FLC and echinocandins (anidulafungin, caspofungin, and micafungin) and FKS1 and FKS2 gene sequences were determined. Results: Two hundred ninety-three episodes (313 isolates) of C. glabrata bloodstream infection were analyzed. Resistance to echinocandins increased from 4.9% to 12.3% and to FLC from 18% to 30% between 2001 and 2010, respectively. Among the 78 FLC resistant isolates, 14.1% were resistant to 1 or more echinocandin. Twenty-five (7.9%) isolates harbored a FKS mutation. The predictor of a FKS mutant strain was prior echinocandin therapy (stepwise multivariable analysis, odds ratio, 19.647 [95% confidence interval, 7.19-58.1]). Eighty percent (8/10) of patients infected with FKS mutants demonstrating intermediate or resistant MICs to an echinocandin and treated with an echinocandin failed to respond or responded initially but experienced a recurrence. Conclusions: Echinocandin resistance is increasing, including among FLC-resistant isolates. The new Clinical and Laboratory Standards Institute clinical breakpoints differentiate wild-type from C. glabrata strains bearing clinically significant FKS1/FKS2 mutations. These observations underscore the importance of knowing the local epidemiology and resistance patterns for Candida within institutions and susceptibility testing of echinocandins for C. glabrata to guide therapeutic decision making.
    Preview · Article · Mar 2013 · Clinical Infectious Diseases
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    ABSTRACT: MK-3118, a glucan synthase inhibitor derived from enfumafungin, and comparator agents were tested against 71 Aspergillus spp., including itraconazole-resistant strains (MIC, ≥4 μg/ml), using CLSI and EUCAST reference broth microdilution methods. The CLSI 90% minimum effective concentration (MEC90)/MIC90 values (μg/ml) for MK-3118, amphotericin B, and caspofungin, respectively, were as follows: 0.12, 2, and 0.03 for Aspergillus flavus species complex (SC); 0.25, 2, and 0.06 for Aspergillus fumigatus SC; 0.12, 2, and 0.06 for Aspergillus terreus SC; and 0.06, 1, and 0.03 for Aspergillus niger SC. Essential agreement between the values found by CLSI and EUCAST (±2 log2 dilution steps) was 94.3%. MK-3118 was determined to be a potent agent regardless of the in vitro method applied, with excellent activity against contemporary wild-type and itraconazole-resistant strains of Aspergillus spp.
    Full-text · Article · Dec 2012 · Antimicrobial Agents and Chemotherapy
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    ABSTRACT: Objectives: To evaluate the activity of the orally bioavailable enfumafungin derivative MK-3118 and comparator antifungal agents tested against a collection of 113 clinical isolates of Candida spp. using CLSI and EUCAST broth microdilution (BMD) methods. Methods: Candida spp. isolates (n=113) were tested by CLSI and EUCAST methods. The collection contained 29 Candida albicans, 29 Candida glabrata, 21 Candida tropicalis, 15 Candida parapsilosis and 19 Candida krusei, including azole- and echinocandin-resistant isolates. CLSI and EUCAST MIC endpoints of 50% and 100% inhibition were determined using visual reading at 24 and 48 h of incubation and spectrophotometric reading at 24 h of incubation, respectively. Results: MK-3118 CLSI MIC results ranged from 0.06 to 16 mg/L depending on species, duration of incubation and endpoint criteria (EC) used. Comparison of CLSI and EUCAST following 24 h of incubation and either 50% or 100% inhibition revealed an essential agreement (EA; ± 2 doubling dilutions) of 99.1% using the 50% inhibition EC and 93.2% using the 100% inhibition EC. MK-3118 (24 h of incubation and 50% EC) was active against all the species tested and displayed similar potency to caspofungin (using CLSI BMD) against C. albicans (MIC90, 1 and 2 mg/L, respectively), C. tropicalis (1 and 1 mg/L, respectively), C. parapsilosis (0.5 and 0.5 mg/L, respectively) and C. krusei (2 and 1 mg/L, respectively), but was 8-fold more potent than caspofungin against C. glabrata strains (MIC90, 2 and 16 mg/L, respectively). MK-3118 was active against fluconazole-resistant strains as well as caspofungin-resistant strains with documented fks mutations. Conclusions: MK-3118 was documented to have potent in vitro activity against Candida spp. when tested by both CLSI and EUCAST BMD methods, with the highest overall EA (99.1%) obtained when MK-3118 MIC results were read after 24 h of incubation using a partial inhibition EC (50%).
    Full-text · Article · Nov 2012 · Journal of Antimicrobial Chemotherapy
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    ABSTRACT: A commercially prepared dried colorimetric microdilution panel (Sensititre Yeast One, TREK Diagnostic Systems, Cleveland, OH, USA) was compared in 3 different laboratories with the Clinical and Laboratory Standards Institute (CLSI) reference microdilution method by testing 2 quality control strains, 25 reproducibility strains, and 404 isolates of Candida spp. against anidulafungin, caspofungin, and micafungin. Reference CLSI BMD MIC end points and YeastOne colorimetric end points were read after 24 h of incubation. Excellent (100%) essential agreement (within 2 dilutions) between the reference and colorimetric MICs was observed. Categorical agreement (CA) between the 2 methods was assessed using the new species-specific clinical breakpoints (CBPs): susceptible (S), ≤0.25 μg/mL; intermediate (I), 0.5 μg/mL; and resistant (R), ≥1 μg/mL, for C. albicans, C. tropicalis, and C. krusei, and ≤2 μg/mL (S), 4 μg/mL (I), and ≥8 μg/mL (R) for C. parapsilosis and all 3 echinocandins. The new CBPs for anidulafungin and caspofungin and C. glabrata are ≤0.12 μg/mL (S), 0.25 μg/mL (I), and ≥0.5 μg/mL (R), whereas those for micafungin are ≤0.06 μg/mL (S), 0.12 μg/mL (I), and ≥0.25 μg/mL (R). Due to the lack of CBPs for any of the echinocandins and C. lusitaniae, the epidemiological cutoff values (ECVs) were used for this species to categorize the isolates as wild-type (WT; MIC ≤ECV) and non-WT (MIC >ECV), respectively, for anidulafungin (≤2 μg/mL/>2 μg/mL), caspofungin (≤1 μg/mL/>1 μg/mL), and micafungin (≤0.5 μg/mL/>0.5 μg/mL). CA ranged from 93.6% (caspofungin) to 99.6% (micafungin) with less than 1% very major or major errors. The YeastOne colorimetric method remains comparable to the CLSI BMD reference method for testing the susceptibility of Candida spp. to the echinocandins when using the new (lower) CBPs and ECVs. Further study using defined fks mutant strains of Candida is warranted.
    Full-text · Article · Jun 2012 · Diagnostic microbiology and infectious disease
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    ABSTRACT: The increasing diversity of opportunistic fungi causing serious invasive fungal infections (IFI) has been documented. Accurate identification (ID) is important in guiding therapy, determining prognosis for IFIs and in epidemiological surveys. We assessed the utility of PCR-based methods for the ID of yeasts and moulds that either were uncommon, failed conventional ID, or represented unusual biochemical or phenotypic profiles of common species. Among 1,790 viable fungal clinical isolates received during the SENTRY Program in 2010, 322 strains from 40 study sites had ID confirmed by molecular methods. Isolates were previously identified in participant institutions. Yeasts that were not confirmed by morphology on CHROMagar, growth at 45 °C (Candida albicans/dubliniensis), or assimilation of trehalose (C. glabrata) as well as non-Candida yeasts and all moulds were amplified and sequenced using primers amplifying one or more of the following genes: ITS, 28S, β-tubulin (Aspergillus spp.), TEF (Fusarium spp.), IGS (Trichosporon spp.). The isolates selected for molecular ID included 149 isolates of Candida species, 77 of Aspergillus species, 73 non-Candida yeasts, and 23 other moulds (a total of 41 different species). Overall, the ID determined by the submitting site was confirmed for 189 isolates (58.7 %): Aspergillus spp. (64.1 % correct); Candida spp. (60.1 % correct); non-Candida yeasts (58.9 % correct); non-Aspergillus moulds (30.4 % correct). Species with high levels of concordance between conventional and molecular ID included A. fumigatus (95.0 %), C. lusitaniae (100 %), C. dubliniensis (92.3 %), C. kefyr (100 %), and C. neoformans (90.2 %). Only 50.0 % of isolates of C. albicans and 59.1 % of C. glabrata selected due to unusual phenotypic or biochemical features were found to be correctly identified by the submitting site. Molecular methods for the identification of fungal pathogens are an important adjunct to the conventional identification of many less common clinically relevant yeasts and moulds including species of Candida with unusual or erroneous phenotypic or biochemical profiles. Molecular confirmation of fungal identification is essential in epidemiological surveys such as SENTRY.
    Full-text · Article · May 2012 · Mycopathologia
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    ABSTRACT: The echinocandin class of antifungal agents is considered to be the first-line treatment of bloodstream infections (BSI) due to Candida glabrata. Recent reports of BSI due to strains of C. glabrata resistant to both fluconazole and the echinocandins are of concern and prompted us to review the experience of two large surveillance programs, the SENTRY Antimicrobial Surveillance Program for the years 2006 through 2010 and the Centers for Disease Control and Prevention population-based surveillance conducted in 2008 to 2010. The in vitro susceptibilities of 1,669 BSI isolates of C. glabrata to fluconazole, voriconazole, anidulafungin, caspofungin, and micafungin were determined by CLSI broth microdilution methods. Fluconazole MICs of ≥64 μg/ml were considered resistant. Strains for which anidulafungin and caspofungin MICs were ≥0.5 μg/ml and for which micafungin MICs were ≥0.25 μg/ml were considered resistant. A total of 162 isolates (9.7%) were resistant to fluconazole, of which 98.8% were nonsusceptible to voriconazole (MIC > 0.5 μg/ml) and 9.3%, 9.3%, and 8.0% were resistant to anidulafungin, caspofungin, and micafungin, respectively. There were 18 fluconazole-resistant isolates that were resistant to one or more of the echinocandins (11.1% of all fluconazole-resistant isolates), all of which contained an acquired mutation in fks1 or fks2. By comparison, there were no echinocandin-resistant strains detected among 110 fluconazole-resistant isolates of C. glabrata tested in 2001 to 2004. These data document the broad emergence of coresistance over time to both azoles and echinocandins in clinical isolates of C. glabrata.
    Full-text · Article · Jan 2012 · Journal of clinical microbiology

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  • 2007-2015
    • JMI Laboratories
      North Liberty, Iowa, United States
  • 1996-2014
    • University of Iowa
      • Department of Pathology
      Iowa City, Iowa, United States
  • 2011
    • Richmond VA Medical Center
      Richmond, Virginia, United States
    • Case Western Reserve University
      Cleveland, Ohio, United States
  • 2009-2011
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 1998-2008
    • University of Iowa Children's Hospital
      Iowa City, Iowa, United States
    • University of California, San Francisco
      • Division of Infectious Diseases
      San Francisco, California, United States
    • Medical University of South Carolina
      • Department of Pediatrics
      Charleston, South Carolina, United States
  • 2006
    • Tufts University
      Бостон, Georgia, United States
  • 2003
    • Kinki University
      Ōsaka, Ōsaka, Japan