scholarly journals In Vitro Activity of Ibrexafungerp against a Collection of Clinical Isolates of Aspergillus, Including Cryptic Species and Cyp51A Mutants, Using EUCAST and CLSI Methodologies

2021 ◽  
Vol 7 (3) ◽  
pp. 232
Author(s):  
Olga Rivero-Menendez ◽  
Juan Carlos Soto-Debran ◽  
Manuel Cuenca-Estrella ◽  
Ana Alastruey-Izquierdo
Keyword(s):  
Cryptic Species ◽  
Antifungal Susceptibility ◽  
Sensu Stricto ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Moderate Activity ◽  
In Vitro Activity ◽  
Synthesis Inhibitor ◽  
Complex Species

Ibrexafungerp is a new orally-available 1,3-β-D-glucan synthesis inhibitor in clinical development. Its in vitro activity and that of amphotericin B, voriconazole, and micafungin were evaluated against a collection of 168 clinical isolates of Aspergillus spp., including azole–susceptible and azole–resistant (Cyp51A mutants) Aspergillus fumigatus sensu stricto (s.s.) and cryptic species of Aspergillus belonging to six species complexes showing different patterns of antifungal resistance, using EUCAST and CLSI antifungal susceptibility testing reference methods. Ibrexafungerp displayed low geometric means of minimal effective concentrations (MECs) against A. fumigatus s.s. strains, both azole susceptible (0.040 mg/L by EUCAST and CLSI versus 1.231 mg/L and 0.660 mg/L for voriconazole, respectively) and azole resistant (0.092 mg/L and 0.056 mg/L, EUCAST and CLSI, while those for voriconazole were 2.144 mg/L and 2.000 mg/L). Ibrexafungerp was active against most of the cryptic species of Aspergillus tested, yielding MEC values only comparable to those of micafungin. Nevertheless, this new compound exhibited a moderate activity against A. ustus complex species, MECs ≥ 0.5 mg/L against Aspergillus insuetus and Aspergillus keveii strains, and was inactive against the Aspergillus alliaceus isolates tested (MEC90s ≥ 16 mg/L). All in all, ibrexafungerp shows encouraging in vitro results against cryptic species of Aspergillus and azole–susceptible and azole resistant strains of A. fumigatus, some of which are difficult to treat using the available therapeutic options.

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 1282. Manogepix, the Active Moiety of the Investigational Agent Fosmanogepix, Demonstrates In vitro Activity Against Members of the Fusarium oxysporum and Fusarium solani Species Complexes

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S656-S656
Author(s):  
Hamid Badali ◽  
Hoja Patterson ◽  
Carmita Sanders ◽  
Barbara Mermella ◽  
Connie Gibas ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Antifungal Susceptibility ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Research Support ◽  
Inhibition Of Growth ◽  
Active Moiety ◽  
Species Complexes

Abstract Background Invasive fusariosis is associated with marked morbidity and mortality in immunocompromised hosts, and treatment options are limited. Common etiologic agents include members of the F. oxysporum and F. solani species complexes (FOSC and FSSC, respectively). Manogepix (MGX), the active moiety of fosmanogepix, is a novel GWT1 inhibitor with broad antifungal activity. Fosmanogepix has previously shown in vivo efficacy in an immunocompromised murine model of invasive fusariosis. Our objective was to evaluate the in vitro activity of MGX against FOSC and FSSC isolates. Methods Clinical isolates of FOSC (n=49) and FSSC (19) were identified by combined phenotypic characteristics and DNA sequence analysis of the translation elongation factor 1-alpha (TEF1α) and RNA polymerase II second largest subunit (RPB2). Antifungal susceptibility testing was performed by CLSI M38 broth microdilution. Minimum effective concentrations (MEC) and minimum inhibitory concentrations (MIC) were read after 48 hours of incubation at 50% and 100% inhibition of growth for MGX, and MIC values were read for amphotericin B, posaconazole, isavuconazole, and voriconazole at 100% inhibition of growth. Results MGX demonstrated potent in vitro activity against both FOSC and FSSC isolates. Against the 49 FOSC isolates, the MGX MECs ranged from <0.015-0.03 mg/mL, and MICs at the 50% inhibition of growth endpoint ranged from <0.015-0.12 mg/mL (Table). MIC values were higher when read at 100% inhibition of growth. Similar results were observed against FSSC isolates (MEC and MIC ranges <0.015 and <0.015-0.25 mg/mL, respectively). MGX MEC and MIC 50% inhibition values were in close agreement for both FOSC and FSSC isolates. Of the other antifungals tested, amphotericin B demonstrated in vitro good activity (MIC ranges 1-4 and 0.25-4 mg/mL against FOSC and FSSC, respectively). In contrast, the azoles demonstrated reduced susceptibility (MIC range 1- >16 mg/mL). MIC/MEC values (mcg/mL) for manogepix and other antifungals against FOSC and FSSC isolates Conclusion MGX demonstrated in vitro activity against FOSC and FSSC clinical isolates. Both changes in fungal morphology (MEC) and reductions in growth (MIC 50% inhibition) were observed. Clinical studies are ongoing to determine the efficacy of fosmanogepix in patients with invasive fungal infections. Disclosures Ashraf S. Ibrahim, PhD, Astellas Pharma (Research Grant or Support) Karen J. Shaw, PhD, Amplyx (Consultant)Forge Therapeutics (Consultant) Nathan P. Wiederhold, PharmD, Astellas (Grant/Research Support)BioMerieux (Grant/Research Support)Cepheid (Grant/Research Support)Covance (Grant/Research Support)F2G (Grant/Research Support)Gilead (Speaker’s Bureau)Mayne Pharma (Advisor or Review Panel member)Sfunga (Grant/Research Support)

scholarly journals 1280. In-Vitro Activity of Cefiderocol, Imipenem/Relebactam, & Ceftazidime/Avibactam in Ceftolozane/Tazobactam Resistant Strains of Multidrug Resistant Pseudomonas aeruginosa

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S655-S655
Author(s):  
Daniel Navas ◽  
Angela Charles ◽  
Amy Carr ◽  
Jose Alexander
Keyword(s):  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Resistance Testing ◽  
Clinical Samples ◽  
In Vitro Activity ◽  
Carbapenemase Gene ◽  
Resistant Strains

Abstract Background The activity of imipenem/relebactam (I/R), ceftazidime/avibactam (CZA) and cefiderocol (FDC) were evaluated against clinical isolates of multidrug resistant (MDR) strains of P. aeruginosa which was resistant to ceftolozane/tazobactam (C/T). The recent increase of MDR P. aeruginosa strains isolated from clinical samples has prompted research and development of new antimicrobials that can withstand its multiple resistance mechanisms. C/T is an effective option for treatment of MDR P. aeruginosa in our facility with only 10% of resistance in MDR strains, but the emergence of resistance may occur due to the presence of a carbapenemase gene or an ampC mutation. Methods Antimicrobial susceptibility testing for C/T Etest® (bioMérieux, Inc.) were performed on all MDR strains initially screened by the VITEK2® (bioMérieux, Inc.). 10% (n=20) of all MDR isolates were resistant to C/T by the CLSI 2019 breakpoints. These resistant isolates were tested for presence of a carbapenemase gene using the GeneXpert CARBA-R (Cepheid®) PCR and against CZA Etest® (bioMérieux, Inc.) I/R gradient strips (Liofilchem®) and FDC broth microdilution (Thermo Scientific™ Sensititre™). Results A total of 20 clinical isolates of MDR P. aeruginosa resistant to C/T were tested following standardized CLSI protocols and techniques. All 20 isolates were screened for the presence of a carbapenemase gene (blaVIM, blaNDM, blaKPC, blaOXA-48, blaIMP). A blaVIM gene was detected in 6 (30%) out of 20 isolates. FDC demonstrated the greatest activity with 85% (n=17) of susceptible isolates (CLSI MIC <4µg/dL). CZA (CLSI MIC <8µg/dL) and I/R (FDA MIC <2µg/dL) showed 15% (n=3) and 10% (n=2) of susceptible isolates respectively. FDC was active against all 6 blaVIM isolates, where all 6 strains were resistant to CZA and I/R as expected. 3 isolates tested non-susceptible against FDC; additional characterization was not performed at this time. Conclusion Based on these results, FDC demonstrated the greatest in-vitro activity against C/T resistant strains of MDR P. aeruginosa. FDC also demonstrated activity against all 6 MDR P. aeruginosa carrying blaVIM gene. FDC is a strong option to consider on MDR P. aeruginosa strains based on a resistance testing algorithm and a cost/effective protocol. Disclosures All Authors: No reported disclosures

In vitro activity of olorofim against clinical isolates of the Fusarium oxysporum and Fusarium solani species complexes

Mycoses ◽  
2021 ◽  
Author(s):  
Hamid Badali ◽  
Connie Cañete‐Gibas ◽  
Hoja Patterson ◽  
Carmita Sanders ◽  
Barbara Mermella ◽  
...  
Keyword(s):  
Fusarium Oxysporum ◽  
Fusarium Solani ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Species Complexes

scholarly journals In Vitro Activity of Posaconazole against Clinical Isolates of Dermatophytes

2001 ◽  
Vol 39 (11) ◽  
pp. 4208-4209 ◽  
Author(s):  
F. Barchiesi ◽  
D. Arzeni ◽  
V. Camiletti ◽  
O. Simonetti ◽  
A. Cellini ◽  
...  
Keyword(s):  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity
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