scholarly journals Effect of pH onIn VitroSusceptibility of Candida glabrata and Candida albicans to 11 Antifungal Agents and Implications for Clinical Use

2012 ◽  
Vol 56 (3) ◽  
pp. 1403-1406 ◽  
Author(s):  
Claire S. Danby ◽  
Dina Boikov ◽  
Rina Rautemaa-Richardson ◽  
Jack D. Sobel
Keyword(s):  
Amphotericin B ◽  
Candida Glabrata ◽  
Antifungal Agents ◽  
Susceptibility Testing ◽  
Low Ph ◽  
Clinical Use ◽  
Effect Of Ph ◽  
Content Type ◽  
Clinical Observations

ABSTRACTThe treatment of vulvovaginal candidiasis (VVC) due toCandida glabratais challenging, with limited therapeutic options. Unexplained disappointing clinical efficacy has been reported with systemic and topical azole antifungal agents in spite ofin vitrosusceptibility. Given that the vaginal pH of patients with VVC is unchanged at 4 to 4.5, we studied the effect of pH on thein vitroactivity of 11 antifungal agents against 40C. glabrataisolates and compared activity against 15 fluconazole-sensitive and 10 reduced-fluconazole-susceptibilityC. albicansstrains.In vitrosusceptibility to flucytosine, fluconazole, voriconazole, posaconazole, itraconazole, ketoconazole, clotrimazole, miconazole, ciclopirox olamine, amphotericin B, and caspofungin was determined using the CLSI method for yeast susceptibility testing. Test media were buffered to pHs of 7, 6, 5, and 4. Under conditions of reduced pH,C. glabrataisolates remained susceptible to caspofungin and flucytosine; however, there was a dramatic increase in the MIC90for amphotericin B and every azole drug tested. Although susceptible to other azole drugs tested at pH 7,C. albicansstrains with reduced fluconazole susceptibility also demonstrated reduced susceptibility to amphotericin B and all azoles at pH 4. In contrast, fluconazole-sensitiveC. albicansisolates remained susceptible at low pH to azoles, in keeping with clinical observations. In selecting agents for treatment of recurrentC. glabratavaginitis, clinicians should recognize the limitations ofin vitrosusceptibility testing utilizing pH 7.0.

scholarly journals In VitroActivity of ASP2397 against Aspergillus Isolates with or without Acquired Azole Resistance Mechanisms

2015 ◽  
Vol 60 (1) ◽  
pp. 532-536 ◽  
Author(s):  
Maiken Cavling Arendrup ◽  
Rasmus Hare Jensen ◽  
Manuel Cuenca-Estrella
Keyword(s):  
Amphotericin B ◽  
Target Gene ◽  
Antifungal Agents ◽  
Susceptibility Testing ◽  
Resistance Mechanisms ◽  
Azole Resistance ◽  
Wild Type ◽  
Resistance Mutations ◽  
Content Type

ABSTRACTASP2397 is a new compound with a novel and as-yet-unknown target different from that of licensed antifungal agents. It has activity againstAspergillusandCandida glabrata. We compared itsin vitroactivity against wild-type and azole-resistantA. fumigatusandA. terreusisolates with that of amphotericin B, itraconazole, posaconazole, and voriconazole. Thirty-four isolates, including 4 wild-typeA. fumigatusisolates, 24A. fumigatusisolates with alterations in CYP51A TR/L98H (5 isolates), M220 (9 isolates), G54 (9 isolates), and HapE (1 isolate), andA. terreusisolates (2 wild-type isolates and 1 isolate with an M217I CYP51A alteration), were analyzed. EUCAST E.Def 9.2 and CLSI M38-A2 MIC susceptibility testing was performed. ASP2397 MIC50values (in milligrams per liter, with MIC ranges in parentheses) determined by EUCAST and CLSI were 0.5 (0.25 to 1) and 0.25 (0.06 to 0.25) againstA. fumigatusCYP51A wild-type isolates and were similarly 0.5 (0.125 to >4) and 0.125 (0.06 to >4) against azole-resistantA. fumigatusisolates, respectively. These values were comparable to those for amphotericin B, which were 0.25 (0.125 to 0.5) and 0.25 (0.125 to 0.25) against wild-type isolates and 0.25 (0.125 to 1) and 0.25 (0.125 to 1) against isolates with azole resistance mechanisms, respectively. In contrast, MICs for the azole compounds were elevated and highest for itraconazole: >4 (1 to >4) and 4 (0.5 to >4) against isolates with azole resistance mechanisms compared to 0.125 (0.125 to 0.25) and 0.125 (0.06 to 0.25) against wild-type isolates, respectively. ASP2397 was active againstA. terreusCYP51A wild-type isolates (MIC 0.5 to 1), whereas MICs of both azole and ASP2397 were elevated for the mutant isolate. ASP2397 displayedin vitroactivity againstA. fumigatusandA. terreusisolates which was independent of the presence or absence of azole target gene resistance mutations inA. fumigatus. The findings are promising at a time when azole-resistantA. fumigatusis emerging globally.

scholarly journals In VitroActivity of a Novel Broad-Spectrum Antifungal, E1210, Tested against Aspergillus spp. Determined by CLSI and EUCAST Broth Microdilution Methods

2011 ◽  
Vol 55 (11) ◽  
pp. 5155-5158 ◽  
Author(s):  
Michael A. Pfaller ◽  
Frederick Duncanson ◽  
Shawn A. Messer ◽  
Gary J. Moet ◽  
Ronald N. Jones ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Broad Spectrum ◽  
Antifungal Agents ◽  
Susceptibility Testing ◽  
Hyphal Growth ◽  
Wild Type ◽  
Minimum Effective Concentration ◽  
Content Type ◽  
Excellent Activity

ABSTRACTE1210 is a first-in-class broad-spectrum antifungal that suppresses hyphal growth by inhibiting fungal glycophosphatidylinositol (GPI) biosynthesis. In the present study, we extend these findings by examining the activity of E1210 and comparator antifungal agents againstAspergillusspp. by using the methods of the Clinical and Laboratory Standards Institute (CLSI) and the European Committee for Antimicrobial Susceptibility Testing (EUCAST) to test wild-type (WT) as well as amphotericin B (AMB)-resistant (-R) and azole-R strains (as determined by CLSI methods). Seventy-eight clinical isolates ofAspergilluswere tested including 20 isolates ofAspergillus flavusspecies complex (SC), 22 ofA. fumigatusSC, 13 ofA. nigerSC, and 23 ofA. terreusSC. The collection included 15 AMB-R (MIC, ≥2 μg/ml) isolates ofA. terreusSC and 10 itraconazole-R (MIC, ≥4 μg/ml) isolates ofA. fumigatusSC (7 isolates),A. nigerSC (2 isolates), andA. terreusSC (1 isolate). Comparator antifungal agents included anidulafungin, caspofungin, amphotericin B, itraconazole, posaconzole, and voriconazole. Both CLSI and EUCAST methods were highly concordant for E1210 and all comparators. The essential agreement (EA; ±2 log2dilution steps) was 100% for all comparisons with the exception of posaconazole versusA. terreusSC (EA = 91.3%). The minimum effective concentration (MEC)/MIC90values (μg/ml) for E1210, anidulafungin, caspofungin, itraconazole, posaconazole, and voriconazole, respectively, were as follows for each species: forA. flavusSC, 0.03, ≤0.008, 0.12, 1, 1, and 1; forA. fumigatusSC, 0.06, 0.015, 0.12, >8, 1, and 4; forA. nigerSC, 0.015, 0.03, 0.12, 4, 1, and 2; and forA. terreusSC, 0.06, 0.015, 0.12, 1, 0.5, and 1. E1210 was very active against AMB-R strains ofA. terreusSC (MEC range, 0.015 to 0.06 μg/ml) and itraconazole-R strains ofA. fumigatusSC (MEC range, 0.03 to 0.12 μg/ml),A. nigerSC (MEC, 0.008 μg/ml), andA. terreusSC (MEC, 0.015 μg/ml). In conclusion, E1210 was a very potent and broad-spectrum antifungal agent regardless ofin vitromethod applied, with excellent activity against AMB-R and itraconazole-R strains ofAspergillusspp.

scholarly journals Antifungal Activity of SCY-078 and Standard Antifungal Agents against 178 Clinical Isolates of Resistant and Susceptible Candida Species

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Wiley A. Schell ◽  
A. M. Jones ◽  
Katyna Borroto-Esoda ◽  
Barbara D. Alexander
Keyword(s):  
Candida Glabrata ◽  
Antifungal Agents ◽  
Candida Parapsilosis ◽  
Candida Krusei ◽  
Wild Type ◽  
Content Type ◽  
Clinical Resistance ◽  
Excellent Activity ◽  
Candida Lusitaniae

ABSTRACT SCY-078 in vitro activity was determined for 178 isolates of resistant or susceptible Candida albicans, Candida dubliniensis, Candida glabrata, Candida krusei, Candida lusitaniae, and Candida parapsilosis, including 44 Candida isolates with known genotypic (FKS1 or FKS2 mutations), phenotypic, or clinical resistance to echinocandins. Results were compared to those for anidulafungin, caspofungin, micafungin, fluconazole, and voriconazole. SCY-078 was shown to have excellent activity against both wild-type isolates and echinocandin- and azole-resistant isolates of Candida species.

scholarly journals In Vitro Activity of Chlorhexidine Compared with Seven Antifungal Agents against 98 Fusarium Isolates Recovered from Fungal Keratitis Patients

2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Claudy Oliveira dos Santos ◽  
Eva Kolwijck ◽  
Henrich A. van der Lee ◽  
Marlou C. Tehupeiory-Kooreman ◽  
Abdullah M. S. Al-Hatmi ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Antifungal Agents ◽  
Culture Collection ◽  
Fungal Keratitis ◽  
Molecular Techniques ◽  
Temperate Climate ◽  
Eye Drops ◽  
Fungal Culture ◽  
Content Type

ABSTRACT Fungal keratitis is a common but severe eye infection in tropical and subtropical areas of the world. In regions with a temperate climate, the frequency of infection is rising in patients with contact lenses and following trauma. Early and adequate therapy is important to prevent disease progression and loss of vision. The management of Fusarium keratitis is complex, and the optimal treatment is not well defined. We investigated the in vitro activity of chlorhexidine and seven antifungal agents against a well-characterized collection of Fusarium isolates recovered from patients with Fusarium keratitis. The fungus culture collection of the Center of Expertise in Mycology Radboudumc/CWZ was searched for Fusarium isolates that were cultured from cornea scrapings, ocular biopsy specimens, eye swabs, and contact lens fluid containers from patients with suspected keratitis. The Fusarium isolates that were cultured from patients with confirmed keratitis were all identified using conventional and molecular techniques. Antifungal susceptibility testing was performed according to the EUCAST broth microdilution reference method. The antifungal agents tested included amphotericin B, voriconazole, posaconazole, miconazole, natamycin, 5-fluorocytosine, and caspofungin. In addition, the activity of chlorhexidine was determined. The fungal culture collection contained 98 Fusarium isolates of confirmed fungal keratitis cases from 83 Dutch patients and 15 Tanzanian patients. The isolates were collected between 2007 and 2017. Fusarium oxysporum (n = 24, 24.5%) was the most frequently isolated species followed by Fusarium solani sensu stricto (n = 18, 18.4%) and Fusarium petroliphilum (n = 11, 11.2%). Amphotericin B showed the most favorable in vitro inhibition of Fusarium species followed by natamycin, voriconazole, and chlorhexidine, while 5-fluorocytosine, posaconazole, miconazole, and caspofungin showed no relevant inhibiting effect. However, chlorhexidine showed fungicidal activity against 90% of F. oxysporum strains and 100% of the F. solani strains. Our study supports the clinical efficacy of chlorhexidine and therefore warrants its further clinical evaluation for primary therapy of fungal keratitis, particularly in low and middle income countries where fungal keratitis is much more frequent and, currently, antifungal eye drops are often unavailable.

scholarly journals A Revised Species Concept for OpportunisticMucorSpecies Reveals Species-Specific Antifungal Susceptibility Profiles

2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Lysett Wagner ◽  
Sybren de Hoog ◽  
Ana Alastruey-Izquierdo ◽  
Kerstin Voigt ◽  
Oliver Kurzai ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Susceptibility Testing ◽  
Species Concept ◽  
Antifungal Susceptibility ◽  
Content Type ◽  
Mucor Indicus ◽  
Species Specific ◽  
Susceptibility Profiles ◽  
High Mics

ABSTRACTRecently, the species concept of opportunisticMucor circinelloidesand its relatives has been revised, resulting in the recognition of its classical formae as independent species and the description of new species. In this study, we used isolates of all clinically relevantMucorspecies and performed susceptibility testing using the EUCAST reference method to identify potential species-specific susceptibility patterns.In vitrosusceptibility profiles of 101 mucoralean strains belonging to the genusMucor(72), the closely related speciesCokeromyces recurvatus(3),Rhizopus(12),Lichtheimia(10), andRhizomucor(4) to six antifungals (amphotericin B, natamycin, terbinafine, isavuconazole, itraconazole, and posaconazole) were determined. The most active drug for all Mucorales was amphotericin B. Antifungal susceptibility profiles of pathogenicMucorspecies were specific for isavuconazole, itraconazole, and posaconazole. The species formerly united inM. circinelloidesshowed clear differences in their antifungal susceptibilities.Cokeromyces recurvatus,Mucor ardhlaengiktus,Mucor lusitanicus(M. circinelloidesf.lusitanicus), andMucor ramosissimusexhibited high MICs to all azoles tested.Mucor indicuspresented high MICs for isavuconazole and posaconazole, andMucor amphibiorumandMucor irregularisshowed high MICs for isavuconazole. MIC values ofMucorspp. for posaconazole, isavuconazole, and itraconazole were high compared to those forRhizopusand the Lichtheimiaceae (LichtheimiaandRhizomucor). Molecular identification combined within vitrosusceptibility testing is recommended forMucorspecies, especially if azoles are applied in treatment.

scholarly journals Comparison of the Sensititre YeastOne and CLSI M38-A2 Microdilution Methods in Determining the Activity of Amphotericin B, Itraconazole, Voriconazole, and Posaconazole against Aspergillus Species

2018 ◽  
Vol 56 (10) ◽  
Author(s):  
Hsuan-Chen Wang ◽  
Ming-I Hsieh ◽  
Pui-Ching Choi ◽  
Chi-Jung Wu
Keyword(s):  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Susceptibility Testing ◽  
Geometric Mean ◽  
Antifungal Susceptibility ◽  
Reference Method ◽  
Aspergillus Species ◽  
Broth Microdilution ◽  
Content Type

ABSTRACT This study compared the YeastOne and reference CLSI M38-A2 broth microdilution methods for antifungal susceptibility testing of Aspergillus species. The MICs of antifungal agents were determined for 100 Aspergillus isolates, including 54 Aspergillus fumigatus (24 TR34/L98H isolates), 23 A. flavus, 13 A. terreus, and 10 A. niger isolates. The overall agreement (within 2 2-fold dilutions) between the two methods was 100%, 95%, 92%, and 90% for voriconazole, posaconazole, itraconazole, and amphotericin B, respectively. The voriconazole geometric mean (GM) MICs were nearly identical for all isolates using both methods, whereas the itraconazole and posaconazole GM MICs obtained using the YeastOne method were approximately 1 dilution lower than those obtained using the reference method. In contrast, the amphotericin B GM MIC obtained using the YeastOne method was 3.3-fold higher than that observed using the reference method. For the 24 A. fumigatus TR34/L98H isolates assayed, the categorical agreement (classified according to the CLSI epidemiological cutoff values) was 100%, 87.5%, and 83.3% for itraconazole, voriconazole, and posaconazole, respectively. For four A. niger isolates, the itraconazole MICs were >8 μg/ml using the M38-A2 method due to trailing growth, whereas the corresponding itraconazole MICs obtained using the YeastOne method were all ≤0.25 μg/ml without trailing growth. These data suggest that the YeastOne method can be used as an alternative for azole susceptibility testing of Aspergillus species and for detecting the A. fumigatus TR34/L98H isolates but that this method fails to detect A. niger isolates exhibiting trailing growth with itraconazole. Additionally, for isolates with azole MICs that approach or that are at susceptibility breakpoints or with high amphotericin B MICs detected using the YeastOne method, further MIC confirmation using the reference CLSI method is needed.

scholarly journals Genetic Diversity and In Vitro Antifungal Susceptibility of 200 Clinical and Environmental Aspergillus flavus Isolates

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Mojtaba Taghizadeh-Armaki ◽  
Mohammad Taghi Hedayati ◽  
Saham Ansari ◽  
Saeed Mahdavi Omran ◽  
Sasan Saber ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Aspergillus Flavus ◽  
Susceptibility Testing ◽  
Antifungal Susceptibility ◽  
Content Type ◽  
Microdilution Method ◽  
Microsatellite Genotype ◽  
Broth Microdilution Method ◽  
In Vitro Antifungal Susceptibility

ABSTRACT Aspergillus flavus has been frequently reported as the leading cause of invasive aspergillosis in certain tropical and subtropical countries. Two hundred A. flavus strains originating from clinical and environmental sources and collected between 2008 and 2015 were phylogenetically identified at the species level by analyzing partial β-tubulin and calmodulin genes. In vitro antifungal susceptibility testing was performed against antifungals using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution method. In addition, genotyping was performed using a short-tandem-repeat (STR) assay of a panel of six microsatellite markers (A. flavus 2A, 2B, 2C, 3A, 3B, and 3C), in order to determine the genetic variation and the potential relationship between clinical and environmental isolates. The geometric means of the minimum inhibitory concentrations/minimum effective concentrations (MICs/MECs) of the antifungals across all isolates were (in increasing order): posaconazole, 0.13 mg/liter; anidulafungin, 0.16 mg/liter; itraconazole, 0.29 mg/liter; caspofungin, 0.42 mg/liter; voriconazole, 0.64 mg/liter; isavuconazole, 1.10 mg/liter; amphotericin B, 3.35 mg/liter; and flucytosine, 62.97 mg/liter. All of the clinical isolates were genetically different. However, an identical microsatellite genotype was found between a clinical isolate and two environmental strains. In conclusion, posaconazole and anidulafungin showed the greatest in vitro activity among systemic azoles and echinocandins, respectively. However, the majority of the A. flavus isolates showed reduced susceptibility to amphotericin B. Antifungal susceptibility of A. flavus was not linked with the clinical or environmental source of isolation. Microsatellite genotyping may suggest an association between clinical and environmental strains, although this requires further investigation.

scholarly journals In VitroAntifungal Susceptibility of Clinically Relevant Species Belonging to Aspergillus SectionFlavi

2013 ◽  
Vol 57 (4) ◽  
pp. 1944-1947 ◽  
Author(s):  
Sarah S. Gonçalves ◽  
Alberto M. Stchigel ◽  
Josep Cano ◽  
Josep Guarro ◽  
Arnaldo L. Colombo
Keyword(s):  
Amphotericin B ◽  
Antifungal Agents ◽  
Antifungal Susceptibility ◽  
Reference Method ◽  
Content Type

ABSTRACTThein vitroantifungal susceptibility of 77 isolates belonging to different clinically relevant species ofAspergillussectionFlavi, including those of different phylogenetic clades ofA. flavus, was tested for nine antifungal agents using a microdilution reference method (CLSI, M38-A2). Terbinafine and the echinocandins demonstrated lower MICs/MECs for all species evaluated, followed by posaconazole. Amphotericin B showed MICs ≥ 2 μg/ml for 38 (49.4%) of the 77 isolates tested.

scholarly journals In vitro susceptibility to antifungal agents of clinical and environmental Cryptococcus neoformans isolated in Southern of Brazil

2001 ◽  
Vol 43 (5) ◽  
pp. 267-270 ◽  
Author(s):  
Sydney Hartz ALVES ◽  
Loiva T. OLIVEIRA ◽  
Jane M. COSTA ◽  
Irina LUBECK ◽  
Agnes Kiesling CASALI ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Susceptibility Testing ◽  
Clinical Isolates ◽  
Environmental Isolates ◽  
Aids Patients ◽  
In Vitro Susceptibility ◽  
Minimal Inhibitory Concentrations

The purpose of the present study was to compare the susceptibility to four antifungal agents of 69 Cryptococcus neoformans strains isolated from AIDS patients with that of 13 C. neoformans strains isolated from the environment. Based on the NCCLS M27-A methodology the Minimal Inhibitory Concentrations (MICs) obtained for amphotericin B, itraconazole and ketoconazole were very similar for clinical and environmental isolates. Clinical isolates were less susceptible to fluconazole than environmental isolates. The significance of these findings and aspects concerning the importance, role and difficulties of C. neoformans susceptibility testing are also discussed.

scholarly journals Comparison of MIC Test Strip and Sensititre YeastOne with the CLSI and EUCAST Broth Microdilution Reference Methods for In Vitro Antifungal Susceptibility Testing of Cryptococcus neoformans

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Fatima Zohra Delma ◽  
Abdullah M. S. Al-Hatmi ◽  
Jochem B. Buil ◽  
Hein van der Lee ◽  
Marlou Tehupeiory-Kooreman ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Susceptibility Testing ◽  
Antifungal Susceptibility ◽  
Test Strip ◽  
Error Rates ◽  
Broth Microdilution ◽  
Content Type ◽  
In Vitro Antifungal Susceptibility

ABSTRACT We compared MIC test strip (MTS) and Sensititre YeastOne (SYO) methods with EUCAST and CLSI methods for amphotericin B, 5-fluocytosine, fluconazole, voriconazole, and isavuconazole against 106 Cryptococcus neoformans isolates. The overall essential agreement between the EUCAST and CLSI methods was >72% and >94% at ±1 and ±2 dilutions, respectively. The essential agreements between SYO and EUCAST/CLSI for amphotericin B, 5-flucytosine, fluconazole, and voriconazole were >89/>93% and between MTS and EUCAST/CLSI were >57/>75%. Very major error rates were low for amphotericin B and fluconazole (<3%) and a bit higher for the other drugs (<8%).

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