scholarly journals Manogepix, the Active Moiety of the Investigational Agent Fosmanogepix, Demonstrates In vitro Activity against Members of the Fusarium oxysporum and Fusarium solani Species Complexes

2021 ◽  
Author(s):  
Hamid Badali ◽  
Hoja P. Patterson ◽  
Carmita J. Sanders ◽  
Barbara Mermella ◽  
Connie F.C. Gibas ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Fusarium Oxysporum ◽  
Amphotericin B ◽  
Fusarium Solani ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Investigational Agent ◽  
Active Moiety ◽  
Species Complexes

We evaluated the in vitro activity of manogepix against Fusarium oxysporum and Fusarium solani species complexes (FOSC and FSSC, respectively) isolates per CLSI M38 broth microdilution methods. Manogepix demonstrated activity against both FOSC (MEC range ≤0.015-0.03; MIC 50% growth inhibition range ≤0.015-0.125) and FSSC (≤0.015 μg/mL; ≤0.015-0.25 μg/mL). Amphotericin B was also active (MIC range 0.25-4 μg/mL), while the triazoles (1->16 μg/mL) and micafungin (MEC ≥8 μg/mL) had limited activity.

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 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 In vitro activity of a new echinocandin, LY303366, compared with those of amphotericin B and fluconazole against clinical yeast isolates.

1997 ◽  
Vol 41 (5) ◽  
pp. 1156-1157 ◽  
Author(s):  
O Uzun ◽  
S Kocagöz ◽  
Y Cetinkaya ◽  
S Arikan ◽  
S Unal
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method

The in vitro activity of LY303366, a new echinocandin derivative, was evaluated with 191 yeast isolates by a broth microdilution method. The MICs at which 50% of the isolates were inhibited were 0.125 microg/ml for Candida albicans and C. tropicalis, 0.25 microg/ml for C. krusei, C. kefyr, and C. glabrata, and 2.0 microg/ml for C. parapsilosis.

scholarly journals In Vitro Activities of Posaconazole, Fluconazole, Itraconazole, Voriconazole, and Amphotericin B against a Large Collection of Clinically Important Molds and Yeasts

2006 ◽  
Vol 50 (6) ◽  
pp. 2009-2015 ◽  
Author(s):  
F. Sabatelli ◽  
R. Patel ◽  
P. A. Mann ◽  
C. A. Mendrick ◽  
C. C. Norris ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Fungal Pathogens ◽  
The Other ◽  
The Novel ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Large Collection ◽  
Time Intervals ◽  
Yeasts And Molds

ABSTRACT The in vitro activity of the novel triazole antifungal agent posaconazole (Noxafil; SCH 56592) was assessed in 45 laboratories against approximately 19,000 clinically important strains of yeasts and molds. The activity of posaconazole was compared with those of itraconazole, fluconazole, voriconazole, and amphotericin B against subsets of the isolates. Strains were tested utilizing Clinical and Laboratory Standards Institute broth microdilution methods using RPMI 1640 medium (except for amphotericin B, which was frequently tested in antibiotic medium 3). MICs were determined at the recommended endpoints and time intervals. Against all fungi in the database (22,850 MICs), the MIC50 and MIC90 values for posaconazole were 0.063 μg/ml and 1 μg/ml, respectively. MIC90 values against all yeasts (18,351 MICs) and molds (4,499 MICs) were both 1 μg/ml. In comparative studies against subsets of the isolates, posaconazole was more active than, or within 1 dilution of, the comparator drugs itraconazole, fluconazole, voriconazole, and amphotericin B against approximately 7,000 isolates of Candida and Cryptococcus spp. Against all molds (1,702 MICs, including 1,423 MICs for Aspergillus isolates), posaconazole was more active than or equal to the comparator drugs in almost every category. Posaconazole was active against isolates of Candida and Aspergillus spp. that exhibit resistance to fluconazole, voriconazole, and amphotericin B and was much more active than the other triazoles against zygomycetes. Posaconazole exhibited potent antifungal activity against a wide variety of clinically important fungal pathogens and was frequently more active than other azoles and amphotericin B.

scholarly journals Microdilution Susceptibility Testing of Amphotericin B, Itraconazole, and Voriconazole against Clinical Isolates of Aspergillus and FusariumSpecies

1999 ◽  
Vol 37 (12) ◽  
pp. 3946-3951 ◽  
Author(s):  
Sevtap Arikan ◽  
Mario Lozano-Chiu ◽  
Victor Paetznick ◽  
Sunaina Nangia ◽  
John H. Rex
Keyword(s):  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Fusarium Solani ◽  
Susceptibility Testing ◽  
Clinical Laboratory ◽  
Narrow Range ◽  
National Committee ◽  
In Vitro Activity ◽  
Microdilution Method

We compared the activities of amphotericin B, itraconazole, and voriconazole against clinical Aspergillus(n = 82) and Fusarium (n= 22) isolates by a microdilution method adopted from the National Committee for Clinical Laboratory Standards (NCCLS-M27A). RPMI 1640 (RPMI), RPMI 1640 supplemented to 2% glucose (RPMI-2), and antibiotic medium 3 supplemented to 2% glucose (AM3) were used as test media. MICs were determined after 24, 48, and 72 h. A narrow range of amphotericin B MICs was observed for Aspergillus isolates, with minor variations among species. MICs for Fusariumisolates were higher than those for Aspergillus isolates. MICs of itraconazole were prominently high for two previously defined itraconazole-resistant Aspergillus fumigatus isolates andFusarium solani. Voriconazole showed good in vitro activity against itraconazole-resistant isolates, but the MICs of voriconazole for F. solani were high. RPMI was the most efficient medium for detection of itraconazole-resistant isolates, followed by RPMI-2. While the significance remains unclear, AM3 lowered the MICs, particularly those of amphotericin B.

scholarly journals In Vitro Interactions of Micafungin with Amphotericin B against Clinical Isolates of Candida spp.

2008 ◽  
Vol 52 (4) ◽  
pp. 1529-1532 ◽  
Author(s):  
Carolina Serena ◽  
Marçal Mariné ◽  
Guillermo Quindós ◽  
Alfonso J. Carrillo ◽  
J. F. Cano ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Amphotericin B ◽  
Drug Concentration ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Candida Spp ◽  
Synergistic Interactions ◽  
Time Kill ◽  
In Vitro Interactions

ABSTRACT The in vitro activity of amphotericin B in combination with micafungin was evaluated against 115 isolates representing seven species of Candida. Overall, the percentages of synergistic interactions were 50% and 20% when the MIC-2 (lowest drug concentration to cause a prominent reduction in growth) and MIC-0 (lowest drug concentration to cause 100% growth inhibition) end point criteria, respectively, were used. Antagonism was not observed. Some of the interactions were confirmed by time-kill assays.

scholarly journals Extraction and Fractionation Effects on Antiplasmodial Activity and Phytochemical Composition of Palicourea hoffmannseggiana

2021 ◽  
Vol 8 (01) ◽  
pp. e34-e42
Author(s):  
Leticia Hiromi Ohashi ◽  
Douglas Costa Gontijo ◽  
Maria Fernanda Alves do Nascimento ◽  
Luciano Ferreira Margalho ◽  
Geraldo Célio Brandão ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Scale Up ◽  
Indole Alkaloid ◽  
Ethanol Extract ◽  
Parasite Growth ◽  
In Vitro Activity ◽  
Acid Base ◽  
Leaf Extracts ◽  
Leaf Powder

AbstractThe present study on Palicourea hoffmannseggiana, which was collected at Marapanim, state of Pará, Brazil, comprises the preparation of different stem and leaf extracts and fractions. Ethanol, hydroethanol, and water extracts were prepared by several methods and evaluated for in vitro activity against resistant Plasmodium falciparum (W2 strain), disclosing a low parasite growth inhibition effect (< 50%). Dereplication by UPLC-DAD-ESI−MS of the leaf ethanol extract showed the presence of two known alkaloids, lyalosidic and strictosidinic acids, along with a sinapoyl ester of lyalosidic acid, with m/z 719.33 [M+H]+, which is possibly a new monoterpene indole alkaloid representative. Sequential liquid-liquid acid-base alkaloid separations from the leaf ethanol extract as well as directly from leaf powder afforded fractions of increased parasite growth inhibition, reaching up to 92.5±0.7%. The most bioactive fractions were shown to contain the β-carboline alkaloids harmane and 4-methyl-β-carboline, along with N-methyl-tryptamine and N-acetyl-tryptamine, while monoterpene indole alkaloids were detected in inactive fractions of these processes. The present results demonstrate that these preliminary fractionation methods can lead to significantly active fractions supporting an adequate scale-up to carrying out the isolation of anti-plasmodial compounds.

scholarly journals In Vitro Activity of Ibrexafungerp, a Novel Glucan Synthase Inhibitor against Candida glabrata Isolates with FKS Mutations

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Natalie S. Nunnally ◽  
Kizee A. Etienne ◽  
David Angulo ◽  
Shawn R. Lockhart ◽  
Elizabeth L. Berkow
Keyword(s):  
Candida Glabrata ◽  
Vitro Activity ◽  
Good Activity ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Glucan Synthase ◽  
Content Type ◽  
Synthase Inhibitor

ABSTRACT Ibrexafungerp is a first-in-class glucan synthase inhibitor. In vitro activity was determined for 89 Candida glabrata isolates with molecularly identified FKS1 or FKS2 mutations conferring resistance to the echinocandins. All isolates were resistant to at least one echinocandin (i.e., anidulafungin, caspofungin, or micafungin) by broth microdilution. Results for ibrexafungerp were compared with those for each echinocandin. Ibrexafungerp had good activity against all echinocandin-resistant C. glabrata isolates.

scholarly journals In Vitro Activities of Daptomycin against 2,789 Clinical Isolates from 11 North American Medical Centers

2001 ◽  
Vol 45 (6) ◽  
pp. 1919-1922 ◽  
Author(s):  
Arthur L. Barry ◽  
Peter C. Fuchs ◽  
Steven D. Brown
Keyword(s):  
Clinical Isolates ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
In Vitro Susceptibility ◽  
Medical Centers ◽  
Mueller Hinton ◽  
Calcium Cations ◽  
Important Exception ◽  
Mueller Hinton Broth

ABSTRACT The in vitro activity of daptomycin is affected by the concentration of calcium cations in the test medium. Mueller-Hinton broth is currently adjusted to contain 10 to 12.5 mg of magnesium per liter and 20 to 25 mg of calcium per liter, but for testing of daptomycin, greater concentrations of calcium (50 mg/liter) are recommended to better resemble the normal concentration of ionized calcium in human serum. Two levels of calcium were used for broth microdilution tests of 2,789 recent clinical isolates of gram-positive bacterial pathogens. MICs of daptomycin were two- to fourfold lower when the broth contained additional calcium. For most species, however, the percentages of strains that were inhibited by 2.0 μg of daptomycin per ml were essentially identical with the two broth media. Enterococci were the important exception; i.e., 92% were inhibited when tested in calcium-supplemented broth but only 35% were inhibited by 2.0 μg/ml without the additional calcium. This type of information should be considered when selecting criteria for defining in vitro susceptibility to daptomycin.

Murepavadin antimicrobial activity against and resistance development in cystic fibrosis Pseudomonas aeruginosa isolates

2020 ◽  
Author(s):  
María Díez-Aguilar ◽  
Marta Hernández-García ◽  
María-Isabel Morosini ◽  
Ad Fluit ◽  
Michael M Tunney ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Spontaneous Mutation ◽  
Lung Surfactant ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Agar Dilution

Abstract Background Murepavadin, a novel peptidomimetic antibiotic, is being developed as an inhalation therapy for treatment of Pseudomonas aeruginosa respiratory infection in people with cystic fibrosis (CF). It blocks the activity of the LptD protein in P. aeruginosa causing outer membrane alterations. Objectives To determine the in vitro activity of murepavadin against CF P. aeruginosa isolates and to investigate potential mechanisms of resistance. Methods MIC values were determined by both broth microdilution and agar dilution and results compared. The effect of artificial sputum and lung surfactant on in vitro activity was also measured. Spontaneous mutation frequency was estimated. Bactericidal activity was investigated using time–kill assays. Resistant mutants were studied by WGS. Results The murepavadin MIC50 was 0.125 versus 4 mg/L and the MIC90 was 2 versus 32 mg/L by broth microdilution and agar dilution, respectively. Essential agreement was &gt;90% when determining in vitro activity with artificial sputum or lung surfactant. It was bactericidal at a concentration of 32 mg/L against 95.4% of the strains within 1–5 h. Murepavadin MICs were 2–9 two-fold dilutions higher for the mutant derivatives (0.5 to &gt;16 mg/L) than for the parental strains. Second-step mutants were obtained for the PAO mutS reference strain with an 8×MIC increase. WGS showed mutations in genes involved in LPS biosynthesis (lpxL1, lpxL2, bamA2, lptD, lpxT and msbA). Conclusions Murepavadin characteristics, such as its specific activity against P. aeruginosa, its unique mechanism of action and its strong antimicrobial activity, encourage the further clinical evaluation of this drug.

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