scholarly journals 719. Susceptibility Testing of Oteseconazole (VT-1161) Against Clinical Isolates from Phase 3 Clinical Studies in Subjects with Recurrent Vulvovaginal Candidiasis

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S459-S459
Author(s):  
Mahmoud Ghannoum ◽  
Thorsten Degenhardt ◽  
Karen Person ◽  
Stephen Brand
Keyword(s):  
Susceptibility Testing ◽  
Acute Infection ◽  
Antifungal Susceptibility ◽  
Reference Method ◽  
Current Treatment ◽  
Vulvovaginal Candidiasis ◽  
Clinical Isolates ◽  
Phase 3 ◽  
Recurrent Vulvovaginal Candidiasis ◽  
Treatment Standard

Abstract Background Oteseconazole (VT-1161) is a novel, investigational oral therapy that is currently under FDA review for the treatment of recurrent vulvovaginal candidiasis (RVVC). Susceptibility testing was performed on all viable clinical isolates collected from three Phase 3 studies to determine the susceptibility of causative pathogens to oteseconazole versus the current treatment standard of care, fluconazole. Methods Vaginal cultures were obtained at screening and at all subsequent study visits throughout the duration of the studies (approx. 48 Weeks) and submitted to a central mycology laboratory for fungal species identification and storage. Susceptibility testing was conducted in accordance with the CLSI Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeast M27-Ed4. Results Candida albicans was identified as the primary causative pathogen in 87% of women with RVVC presenting with an acute infection, followed by C. glabrata (8%). Other non-albicans species including; C. parapsilosis, C. tropicalis, C. krusei, C. dubliniensis, C. kefyr and Saccharomyces cerevisiae were responsible for < 1% of infections. A total of 1910 isolates were collected. The MIC range, MIC50 and MIC90 values against all isolates for oteseconazole were ≤ 0.0005 to > 0.25, 0.002 and 0.06 µg/mL, respectively. In comparison, the MIC range, MIC50 and MIC90 values for fluconazole were, ≤ 0.06 to > 32, 0.25 and 8 µg/mL respectively. The MIC range, MIC50 and MIC90 values against all C.glabrata isolates for oteseconazole were 0.002 to > 0.25, 0.03 and 0.125 µg/mL, respectively. In comparison, the MIC range, MIC50 and MIC90 values for fluconazole were, ≤ 0.06 to 32, 2 and 8 µg/mL respectively. Conclusion Oteseconazole demonstrated very low MIC values against most Candida strains, including fluconazole resistant isolates, aligning with clinical study outcomes. Oteseconazole MICs against C. glabrata strains were approximately 6-fold lower than fluconazole. Disclosures Mahmoud Ghannoum, PhD, Mycovia Pharmaceuticals (Grant/Research Support, Research Grant or Support) Thorsten Degenhardt, Ph.D, Mycovia Pharmaceuticals (Employee, Shareholder) Karen Person, M.S., Mycovia Pharmaceuticals, Inc. (Employee)Mycovia Pharmaceuticals, Inc. (Employee) Stephen Brand, Ph.D, Mycovia Pharmaceuticals (Employee)

Use of spectrophotometric reading for in vitro antifungal susceptibility testing ofAspergillusspp.

1999 ◽  
Vol 45 (10) ◽  
pp. 871-874 ◽  
Author(s):  
Eric Dannaoui ◽  
Florence Persat ◽  
Marie-France Monier ◽  
Elisabeth Borel ◽  
Marie-Antoinette Piens ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Susceptibility Testing ◽  
Clinical Laboratory ◽  
Antifungal Susceptibility ◽  
Reference Method ◽  
Antifungal Susceptibility Testing ◽  
Aspergillus Species ◽  
National Committee ◽  
Broth Microdilution Method

A comparative study of visual and spectrophotometric MIC endpoint determinations for antifungal susceptibility testing of Aspergillus species was performed. A broth microdilution method adapted from the National Committee for Clinical Laboratory Standards (NCCLS) was used for susceptibility testing of 180 clinical isolates of Aspergillus species against amphotericin B and itraconazole. MICs were determined visually and spectrophotometrically at 490 nm after 24, 48, and 72h of incubation, and MIC pairs were compared. The agreement between the two methods was 99% for amphotericin B and ranged from 95 to 98% for itraconazole. It is concluded that spectrophotometric MIC endpoint determination is a valuable alternative to the visual reference method for susceptibility testing of Aspergillus species.Key words: antifungal, susceptibility testing, Aspergillus, spectrophotometric reading.

Value of antifungal susceptibility testing in recurrent vulvovaginal Candidiasis by Non -Albicans Candida

2021 ◽  
Vol 30 (1) ◽  
pp. 161-167
Author(s):  
Ghada A. Mokhtar ◽  
Mohamed Sh. Ramadan ◽  
Shymaa Yahia
Keyword(s):  
Amphotericin B ◽  
Candida Species ◽  
Antifungal Susceptibility ◽  
High Sensitivity ◽  
Common Species ◽  
Vulvovaginal Candidiasis ◽  
Recurrent Vulvovaginal Candidiasis ◽  
Sensitivity Pattern ◽  
Vaginal Swabs ◽  
Vitek 2

Background: Vulvovaginal candidiasis (VVC) is regarded as a prevalent vaginal infection and mainly results from Candida albicans. Nevertheless, there has recently been a prominent shift in candidiasis etiology regarding non-albicans Candida (NAC) species with achieving importance. For women with more than three episodes annually are described as recurrent vulvovaginal candidiasis (RVVC). Objectives: To isolate, speciate, and determine the value of antifungal sensitivity pattern of candida species isolated from patients developed (RVVC). Methodology: High vaginal swabs (HVS) were taken from patients with RVVC and cultured on ordinary mycological media. Any significant candida growth was identified and speciated by VITEK 2 system. Their antifungal sensitivity was done by disc diffusion approach governed by CLSI guidelines. Results: A total of 110 Candida species from 250 high vaginal swabs were isolated. Among all candida species isolated from patients with RVCC, C.albicanis accounts for 44% while NAC accounts for 56% with C.glabrata most common species isolated. Voriconazole, amphotericin B, and nystatin showed high sensitivity rates (92 %, 89%, and 84% respectively) on all candida species (C.albicans and NAC) isolated from patients with RVVC. Conclusion: In RVCC there is increase in NAC (56%) with C.glabrata most common species isolated. Voriconazole, Nystatin, and amphotericin B have the best antifungal activity against all spp.

In vitro activity of olorofim against clinical isolates of Scedosporium species and Lomentospora prolificans using EUCAST and CLSI methodologies

2020 ◽  
Vol 75 (12) ◽  
pp. 3582-3585
Author(s):  
Olga Rivero-Menendez ◽  
Manuel Cuenca-Estrella ◽  
Ana Alastruey-Izquierdo
Keyword(s):  
Amphotericin B ◽  
Susceptibility Testing ◽  
Antifungal Susceptibility ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Scedosporium Apiospermum ◽  
In Vitro Activity ◽  
Scedosporium Dehoogii ◽  
Scedosporium Species

Abstract Objectives To evaluate the in vitro activity of olorofim, a new broad-spectrum antifungal with a novel mechanism of action, against a collection of 123 Spanish clinical isolates belonging to five Scedosporium species and Lomentospora prolificans. Methods The activity of olorofim against Scedosporium apiospermum (n = 30), Scedosporium boydii (n = 30), Scedosporium ellipsoideum (n = 10), Scedosporium aurantiacum (n = 20), Scedosporium dehoogii (n = 3) and Lomentospora prolificans (n = 30) was compared with that of amphotericin B, voriconazole, isavuconazole and micafungin by performing EUCAST and CLSI reference methods for antifungal susceptibility testing. Results Amphotericin B and isavuconazole showed MICs ≥2 mg/L for all the species evaluated and voriconazole was moderately active (GM, MIC50 and MIC90 values ≤2 mg/L) against all of them except L. prolificans. Micafungin was effective against S. apiospermum complex strains, but exhibited elevated MECs for S. dehoogii and S. aurantiacum. Olorofim showed low MICs for all the Scedosporium strains tested (GM values were lower than 0.130 and 0.339 by the EUCAST method and the CLSI method, respectively, for all of the species), including those belonging to the MDR species L. prolificans, for which GM values were 0.115 and 0.225 mg/L by the EUCAST method and the CLSI method, respectively, while the GMs for the rest of the antifungals evaluated were higher than 3.732 mg/L using both methodologies. Conclusions Olorofim displayed promising in vitro activity against the Scedosporium and L. prolificans strains tested, some of which have reduced susceptibility to the antifungals that are currently in use.

scholarly journals In Vitro Interaction between Isavuconazole and Tacrolimus, Cyclosporin A, or Sirolimus against Aspergillus Species

2020 ◽  
Vol 6 (3) ◽  
pp. 103 ◽  
Author(s):  
Patrick Schwarz ◽  
Eric Dannaoui
Keyword(s):  
Cyclosporin A ◽  
Aspergillus Terreus ◽  
Susceptibility Testing ◽  
Inhibitory Concentration ◽  
Antifungal Susceptibility ◽  
Reference Method ◽  
Common Species ◽  
Minimal Inhibitory Concentrations ◽  
In Vitro Interaction

The interaction of isavuconazole with immunosuppressors (tacrolimus, cyclosporin A, or sirolimus) against 30 Aspergillus isolates belonging to the most common species responsible for invasive aspergillosis in humans (Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans, Aspergillus niger, and Aspergillus terreus) was evaluated in vitro by a microdilution checkerboard technique based on the EUCAST reference method for antifungal susceptibility testing. The interpretation of the results was performed based on the fractional inhibitory concentration index. The combination of isavuconazole with tacrolimus, cyclosporin A, or sirolimus, was synergistic for 56, 20, or 10% of the isolates, respectively. Interestingly synergy of the combination of isavuconazole with tacrolimus was also achieved for the majority of azole-resistant isolates of A. fumigatus, and for all A. niger isolates with isavuconazole minimal inhibitory concentrations ≥ 8 µg/mL. Antagonistic interactions were never observed for any combination tested.

scholarly journals Colistin and Isavuconazole Interact Synergistically In Vitro against Aspergillus nidulans and Aspergillus niger

2020 ◽  
Vol 8 (9) ◽  
pp. 1447
Author(s):  
Patrick Schwarz ◽  
Elie Djenontin ◽  
Eric Dannaoui
Keyword(s):  
Aspergillus Niger ◽  
Aspergillus Nidulans ◽  
Susceptibility Testing ◽  
Antifungal Susceptibility ◽  
Reference Method ◽  
Important Species ◽  
Agar Diffusion ◽  
Agar Diffusion Assay ◽  
Diffusion Assay

The in vitro interactions of isavuconazole in combination with colistin were evaluated against 55 clinical Aspergillus species isolates belonging to the five most important species (Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans, Aspergillus niger, and Aspergillus terreus) responsible for human aspergillosis by a microdilution checkerboard technique based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) reference method for antifungal susceptibility testing. Selected isolates (A. nidulans, n = 10; A. niger, n = 15) were additionally evaluated by an agar diffusion assay using isavuconazole gradient concentration strips with or without colistin incorporated Roswell Parc Memorial Institute (RPMI) agar. Interpretation of the checkerboard results was done by the fractional inhibitory concentration index. Using the checkerboard method, combination isavuconazole–colistin was synergistic for 100% of the 15 A. nidulans isolates and for 60% of the 20 A. niger isolates. No interactions were found for any of the other isolates. By agar diffusion assay, minimal inhibitory concentrations (MICs) in combination decreased compared to isavuconazole alone for 92% of the isolates. No interactions were found for any A. nidulans isolates, but synergy was observed for 40% of the A. niger isolates. A poor essential agreement of EUCAST and gradient concentration strip MICs at ± 2 log2 dilutions with 0% was obtained. Antagonistic interactions were never observed regardless of the technique used.

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.

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