In Vitro Susceptibility of Sporothrix schenckii to Six Antifungal Agents Determined Using Three Different Methods

ABSTRACT The in vitro susceptibility of Sporothrix schenckii to antifungal drugs has been determined with three different methods. Nineteen Peruvian clinical isolates of S. schenckii were tested against amphotericin B (AB), flucytosine (FC), fluconazole (FZ), itraconazole (IZ), voriconazole (VZ), and ketoconazole (KZ). Modified NCCLS M38-A, Sensititre YeastOne (SYO), and ATB Fungus 2 (ATBF2) methods were used to determine the MICs. ATCC isolates of Candida parapsilosis, Candida krusei, and Aspergillus flavus were used for quality control. Sporothrix inocula were prepared with the mycelial form growing on potato dextrose agar at 28 ± 2°C. MICs of AB, FC, FZ, and IZ were determined with all three methods, VZ with M38-A and SYO, and KZ with only SYO. The three methods showed high MICs of FZ and FC (MIC90 of 0.5 μg/ml), being homogeneously lower than those of IZ and KZ. The M38-A method showed a variable MIC range of VZ (4.0 to 16 μg/ml); the geometric mean (GM) was 9.3 μg/ml. The MIC range of AB was wide (0.06 to 16 μg/ml), but the GM was 1.2 μg/ml, suggesting that the MIC is strain dependent. Agreement (two log2 dilutions) between commercial techniques and the modified M38-A method was very high with FZ, IZ, and FC. In AB and VZ, the agreement was lower, being related to the antifungal concentrations of each method. The highest activity against S. schenckii was found with IZ and KZ. Lack of activity was observed with FZ, VZ, and FC. When AB is indicated for sporotrichosis, the susceptibility of the strain must be analyzed. Commercial quantitative antifungal methods have a limited usefulness in S. schenckii.

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MICs and minimum fungicidal concentrations of amphotericin B, itraconazole, posaconazole and terbinafine in Sporothrix schenckii

Journal of Medical Microbiology ◽

10.1099/jmm.0.007609-0 ◽

2009 ◽

Vol 58 (12) ◽

pp. 1607-1610 ◽

Cited By ~ 32

Author(s):

Carolina Pereira Silveira ◽

Josep M. Torres-Rodríguez ◽

Eidi Alvarado-Ramírez ◽

Francisca Murciano-Gonzalo ◽

Maribel Dolande ◽

...

Keyword(s):

Amphotericin B ◽

Latin American ◽

Geometric Mean ◽

Sporothrix Schenckii ◽

Mycelial Form ◽

Appropriate Treatment ◽

Inappropriate Treatment ◽

Immunosuppressed Patients ◽

Identification Of Species

The in vitro susceptibility of 62 isolates of Sporothrix schenckii in its mycelial form, from Latin-American countries (Peru, Venezuela, Brazil and Uruguay) and Spain, to amphotericin B (AB), itraconazole (IZ), posaconazole (PZ) and terbinafine (TB) was determined by measuring the MICs and minimum fungicidal concentrations (MFCs) using a standardized Clinical and Laboratory Standards Institute method. In general, TB was the most active drug, with the lowest geometric mean (GM) MIC and MFC values amongst isolates from the five countries tested. IZ and PZ showed almost the same activity against all strains tested, except for isolates from Uruguay where IZ gave the highest GM MIC (10.68 mg l−1). AB showed the widest MIC range (0.03–16.0 mg l−1); however, this drug was less active against 79 % of isolates (MICs above 1 mg l−1). MFCs were 5 to 20 times higher than the MICs, but the lowest GM MFC and range values were found for TB. IZ and PZ gave the highest GM MFC. MFC may be a better predictor of therapeutic response than MIC, especially in immunosuppressed patients, making the use of IZ and PZ an inappropriate treatment. There were some differences in susceptibility according to the geographical source of the isolates, with the MIC being lower for TB in Venezuelan strains (P=0.066) and the MFC higher for PZ in Peruvian strains (P=0.02). Thus, geographical origin may be important for appropriate treatment, and may relate to the identification of species of the S. schenckii complex.

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In Vitro Susceptibility of Talaromyces Marneffei In Malaysia: Comparison of Yeast and Mycelial Phases

10.21203/rs.3.rs-1158654/v1 ◽

2021 ◽

Author(s):

Xue Ting Tan ◽

Nurliyana binti Mohd Shuhairi ◽

Stephanie Jane Ginsapu ◽

Surianti Binti Shukor ◽

Fairuz Binti Amran

Keyword(s):

Amphotericin B ◽

Geometric Mean ◽

Antifungal Susceptibility ◽

Etiologic Agent ◽

Mycelial Form ◽

In Vitro Susceptibility ◽

Terbinafine Hydrochloride ◽

Acquired Immunodeficiency ◽

Immunodeficiency Syndrome

Abstract Talaromyces marneffei is an etiologic agent of talaromycosis. It can cause serious complications and death in immunocompromised patients, particularly in acquired immunodeficiency syndrome (AIDS) patients. This infectious disease is endemic in Southeast Asia including Malaysia. To date, published reports on the antifungal susceptibility profile of T. marneffei is very limited. The objective of this study is to determine the minimum inhibitory concentration (MIC) of T. marneffei in yeast and mycelial phases in Malaysia. In the year 2020, 27 clinical strains of T. marneffei were received from various hospitals in Malaysia. The identification was carried out using microscopic, macroscopic and molecular methods. Following that, the susceptibility of each isolate in both yeast and mycelial form to thirteen common antifungals was performed according to the broth microdilution in Clinical & Laboratory Standards Institute (CLSI) M38 method. The antifungals tested were anidulafungin, micafungin sodium, caspofungin diacetate, 5-fluorocytosine, amphotericin B and terbinafine hydrochloride, posaconazole, voriconazole, itraconazole, ketoconazole, ravuconazole, clotrimazole and isavuconazole. The geometric mean of all antifungals other than anidulafungin, micafungin sodium, caspofungin diacetate and 5-fluorocytosine against T. marneffei mould (mycelial) were >2 μg/ml. However, the geometric mean of all antifungals against T. marneffei yeast was <2 μg/ml. Our in vitro data suggests promising activities of amphotericin B, terbinafine hydrochloride, posaconazole, voriconazole, itraconazole, ketoconazole, ravuconazole, clotrimazole and isavuconazole against yeast and mould phases of T. marneffei.

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In vitro susceptibility of isolates ofSporothrix schenckiito amphotericin B, itraconazole, and terbinafine: comparison of yeast and mycelial forms

Canadian Journal of Microbiology ◽

10.1139/w06-040 ◽

2006 ◽

Vol 52 (9) ◽

pp. 843-847 ◽

Cited By ~ 20

Author(s):

Lidiane Meire Kohler ◽

Betânia Maria Soares ◽

Daniel de Assis Santos ◽

Maria Elisabete Da Silva Barros ◽

Júnia Soares Hamdan

Keyword(s):

Amphotericin B ◽

Clinical Laboratory ◽

Sporothrix Schenckii ◽

Clinical Findings ◽

In Vitro Tests ◽

Mycelial Form ◽

In Vitro Susceptibility ◽

Significant Difference ◽

Different Levels

Forty-three clinical isolates of Sporothrix schenckii derived from humans and animals were evaluated in vitro for their susceptibility to amphotericin B, itraconazole, and terbinafine. MICs were determined by the method of micro dilution in liquid media, using protocols M27-A2 for the yeast form and M38-A for the mycelial form, both standardized by the Clinical Laboratory Standards Institute. In general, higher MICs were found for the mycelial form (intervals of up to two dilutions). In the case of amphotericin B, a significant difference in activity was observed, with higher values (p < 0.05) found for the mycelial form. MICs for itraconazole and terbinafine were similar for both yeast and mycelial forms but slightly higher for mycelia. Although data presented here indicate different levels of susceptibility when both growth forms were compared, indicating an intrinsic difference between them, it is still difficult to draw a consensus as to which form correlates better with clinical findings. More studies are necessary to determine the criteria for in vitro tests that will lead to efficient therapeutic choices.Key words: Sporothrix schenckii, susceptibility testing, antifungal drug.

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Fluconazole MIC and the Fluconazole Dose/MIC Ratio Correlate with Therapeutic Response among Patients with Candidemia

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.8.3171-3177.2005 ◽

2005 ◽

Vol 49 (8) ◽

pp. 3171-3177 ◽

Cited By ~ 120

Author(s):

Cornelius J. Clancy ◽

Victor L. Yu ◽

Arthur J. Morris ◽

David R. Snydman ◽

M. Hong Nguyen

Keyword(s):

Therapeutic Response ◽

Geometric Mean ◽

Therapeutic Failure ◽

Response To Therapy ◽

Success Rates ◽

Therapeutic Success ◽

Data Set ◽

In Vitro Susceptibility ◽

Dose Dependent

ABSTRACT We tested 32 Candida isolates recovered in the early 1990s from the bloodstreams of patients with candidemia for in vitro susceptibility to fluconazole and determined if MIC and/or the daily dose of fluconazole/MIC ratio correlated with the response to therapy. This is a unique data set since 87.5% (28/32) of patients were treated with fluconazole doses now considered to be inadequate (≤200 mg), which contributed to high therapeutic failure rates (53% [17/32]). The geometric mean MIC and dose/MIC ratio for isolates associated with therapeutic failure (11.55 μg/ml and 14.3, respectively) differed significantly from values associated with therapeutic success (0.95 μg/ml and 219.36 [P = 0.0009 and 0.0004, respectively]). The therapeutic success rates among patients infected with susceptible (MIC ≤ 8 μg/ml), susceptible-dose dependent (S-DD) (MIC = 16 or 32 μg/ml), and resistant (MIC ≥ 64 μg/ml) isolates were 67% (14/21), 20% (1/5), and 0% (0/6), respectively. A dose/MIC ratio >50 was associated with a success rate of 74% (14/19), compared to 8% (1/13) for a dose/MIC ratio ≤50 (P = 0.0003). Our data suggest that both fluconazole MIC and dose/MIC ratio correlate with the therapeutic response to fluconazole among patients with candidemia. In clinical practice, dose/MIC ratio might prove easier to interpret than breakpoint MICs, since it quantitates the effects of increasing fluconazole doses that are alluded to in the S-DD designation.

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Comparison of NCCLS and 3-(4,5-Dimethyl-2-Thiazyl)-2,5-Diphenyl-2H-Tetrazolium Bromide (MTT) Methods of In Vitro Susceptibility Testing of Filamentous Fungi and Development of a New Simplified Method

Journal of Clinical Microbiology ◽

10.1128/jcm.38.8.2949-2954.2000 ◽

2000 ◽

Vol 38 (8) ◽

pp. 2949-2954 ◽

Cited By ~ 147

Author(s):

Joseph Meletiadis ◽

Jacques F. G. M. Meis ◽

Johan W. Mouton ◽

J. Peter Donnelly ◽

Paul E. Verweij

Keyword(s):

Filamentous Fungi ◽

Clinical Laboratory ◽

Colorimetric Method ◽

Antifungal Drugs ◽

National Committee ◽

In Vitro Susceptibility ◽

Initial Inoculum ◽

Tetrazolium Bromide ◽

Mtt Method

The susceptibility of 30 clinical isolates belonging to six different species of filamentous fungi (Aspergillus fumigatus, Aspergillus flavus, Scedosporium prolificans, Scedosporium apiospermum, Fusarium solani, and Fusarium oxysporum) was tested against six antifungal drugs (miconazole, voriconazole, itraconazole, UR9825, terbinafine, and amphotericin B) with the microdilution method recommended by the National Committee for Clinical Laboratory Standards (NCCLS) (M38-P). The MICs were compared with the MICs obtained by a colorimetric method measuring the reduction of the dye 3-(4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) to formazan by viable fungi. The levels of agreement between the two methods were 96 and 92% for MIC-0 (clear wells) and MIC-1 (75% growth reduction), respectively. The levels of agreement were always higher for Aspergillus spp. (97% ± 2.5%), followed byScedosporium spp. (87% ± 10.3%) and Fusariumspp. (78% ± 7.8%). The NCCLS method was more reproducible than the MTT method: 98 versus 95% for MIC-0 and 97 versus 90% for MIC-1. However, the percentage of hyphal growth as determined visually by the NCCLS method showed several discrepancies when they were compared with the percentages of MTT reduction. A new simplified assay that incorporates the dye MTT with the initial inoculum and in which the fungi are incubated with the dye for 48 h or more was developed, showing comparable levels of agreement and reproducibility with the other two methods. Furthermore, the new assay was easier to perform and more sensitive than the MTT method.

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688. In Vitro Activity of Eravacycline, a New Tetracycline Analog, and Comparators Against the Six Most Commonly Isolated Ribotypes of Clostridioides difficile

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.756 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S312-S313 ◽

Cited By ~ 2

Author(s):

Eugenie Basseres ◽

Julie Miranda ◽

Anne J Gonzales-Luna ◽

Travis J Carlson ◽

Tasnuva Rashid ◽

...

Keyword(s):

Geometric Mean ◽

Vitro Activity ◽

In Vitro Activity ◽

Large Collection ◽

In Vitro Susceptibility ◽

Clostridioides Difficile ◽

Clostridioides Difficile Infection ◽

Abdominal Infections ◽

Insight Into

Abstract Background Eravacycline is a novel, tetracycline class antibacterial indicated for the treatment of complicated intra-abdominal infections in adults. In clinical trials, patients given eravacycline had a low likelihood of developing Clostridioides difficile infection (CDI). We hypothesized this was likely due, in part, to the in vitro susceptibility of eravacycline to C. difficile. The purpose of this study was to test the in vitro susceptibility of eravacycline vs. comparators on contemporary clinical isolates representing common ribotypes, including isolates with decreased susceptibility to metronidazole and vancomycin. Methods Two hundred and thirty-four isolates from our biobank were selected from the six most common ribotypes (F001, F002, F014-020, F027, F106, and F255). Minimum inhibitory concentrations (MIC) at 24 hours were measured according to CLSI guidelines for eravacycline, vancomycin, metronidazole and fidaxomicin. MICs results were tabulated and are presented as the geometric mean by ribotype. Results Geometric MIC results are shown in Table 1. Eravacycline was the most potent antimicrobial tested followed by fidaxomicin, metronidazole, and vancomycin. Results were consistent amongst all ribotypes, including isolates with reduced susceptibility to vancomycin and metronidazole. Conclusion Eravacycline displayed potent in vitro activity against a large collection of clinical C. difficile isolates. These data provide insight into why patients given eravacycline had a low likelihood of developing CDI and support further research to better understand the use of eravacycline to prevent or potentially treat patients with CDI. Disclosures All authors: No reported disclosures.

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