scholarly journals Assessment of the In Vitro Antifungal Activity of SCY-078 Against a Collection of C. parapsilosis Clinical Isolates

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S368-S369
Author(s):  
Stephen Barat ◽  
David Angulo ◽  
Katyna Borroto-Esoda ◽  
Mahmoud Ghannoum
Keyword(s):  
Antifungal Activity ◽  
Clinical Isolates ◽  
Wild Type ◽  
The Us ◽  
Type C ◽  
Synthase Inhibitor ◽  
In Vitro Antifungal Activity ◽  
The Eu ◽  
Research Grant

Abstract Background Global rates of candidemia caused by C. parapsilosis are increasing with differences detected between neonates and adult patients (50% vs. 12%, respectively) and across geographic regions (5% vs. 25% in Iceland and Spain, respectively). SCY-078 is a novel, oral and intravenous, triterpenoid glucan synthase inhibitor under development for the treatment of invasive candidiasis. This study evaluated the in vitro antifungal activity of SCY-078 against a collection of clinical C. parapsilosis isolates. Methods Retrospective analysis of data from 7 independent studies evaluating the activity of SCY-078 is presented. Data were available for 206 C. parapsilosis isolates collected between 2008 and 2015 in the US and EU. The collection included 186 wild-type isolates as well as 14 azole-resistant, and 6 echinocandin-resistant isolates. Minimum inhibitory concentrations (MIC) were determined according to the CLSI M27-A3 and EUCAST E.DEF 7.3 guidelines. Comparator compounds varied across studies and included fluconazole, micafungin (MCF), caspofungin (CSP), and anidulafungin (ANI). MIC50 and MIC90 values were defined as the concentrations inhibiting growth of 50% and 90% of isolates, respectively. Echinocandin and azole resistance were determined based on CLSI M27-A4 guidelines. Results The MIC50 values obtained for SCY-078 against the wild-type C. parapsilosis isolates across the 7 studies ranged from 0.25 to 1 μg/mL and the MIC90 values ranged from 0.25 -2 µg/mL. Among the echinocandins, MIC90 values ranged from 0.5 to 2 µg/mL (CSP), 1 to 4 µg/mL (MCF) and 2 to 4 µg/mL (ANI). SCY-078 was active against the 14 azole-resistant isolates (MIC ranging from 0.25 to 2 µg/mL). Similar activity was observed across the 6 echinocandin-resistant isolates with MIC values for SCY-078 ranging from 0.25 to 1 µg/mL. Among the 4 most recent studies in the US and EU (2013–2015) C. parapsilosis isolates represented 14 – 20% of the Candidaisolates; rates were similar in the EU and US. Conclusion SCY-078 demonstrated potent activity against C. parapsilosis clinical isolates. Notably, SCY-078 was effective against all the echinocandin and azole resistant C. parapsilosis isolates tested. Disclosures S. Barat, Scynexis, Inc: Employee, Salary; D. Angulo, Scynexis, Inc.: Employee, Salary; K. Borroto-Esoda, Scynexis Inc.: Consultant, Consulting fee; M. Ghannoum, Scynexis, Inc.: Consultant, Investigator and Scientific Advisor, Consulting fee, Research grant and Research support

scholarly journals Disruption of the ech42 (Endochitinase-Encoding) Gene Affects Biocontrol Activity in Trichoderma harzianum P1

1999 ◽  
Vol 12 (5) ◽  
pp. 419-429 ◽  
Author(s):  
S. L. Woo ◽  
B. Donzelli ◽  
F. Scala ◽  
R. Mach ◽  
G. E. Harman ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Trichoderma Harzianum ◽  
Pythium Ultimum ◽  
Single Copy ◽  
Wild Type ◽  
Gene Encoding ◽  
Culture Filtrates ◽  
In Vitro Antifungal Activity ◽  
Better Than

The biocontrol strain P1 of Trichoderma harzianum was genetically modified by targeted disruption of the single-copy ech42 gene encoding for the secreted 42-kDa endochitinase (CHIT42). Stable mutants in which ech42 was interrupted, and unable to produce CHIT42, were obtained and characterized. These mutants lacked the ech42 transcript, the protein, and endochitinase activity in culture filtrates, and they were unable to clear a medium containing colloidal chitin. Other chitinolytic and glucanolytic enzymes expressed during mycoparasitism were not affected by the disruption of ech42. The disrupted mutant D11 grew and sporulated similarly to the wild type. In vitro antifungal activity of the ech42 disruptant culture filtrates against Botrytis cinerea and Rhizoctonia solani was reduced about 40%, compared with wild type; antifungal activity was fully restored by adding an equivalent amount of CHIT42 as secreted by P1. The mutant exhibited the same biocontrol effect against Pythium ultimum as strain P1, but the antagonism against B. cinerea on bean leaves by the mutant was significantly reduced (33% less biocontrol), compared with strain P1. Conversely, the endochitinase-deficient mutant performed better than the wild type (16% improvement of survival) in biocontrol experiments in soil infested with the soilborne fungus R. solani. These results indicate that the antagonistic interaction between the T. harzianum strain and various fungal hosts is based on different mechanisms.

In vitro antifungal activity of luliconazole against clinical isolates from patients with dermatomycoses

2006 ◽  
Vol 12 (3) ◽  
pp. 163-165 ◽  
Author(s):  
Hiroyasu Koga ◽  
Yuri Tsuji ◽  
Kazuyoshi Inoue ◽  
Kazuo Kanai ◽  
Toshiro Majima ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Clinical Isolates ◽  
In Vitro Antifungal Activity

scholarly journals Broad In Vitro Activity Analysis of Tedizolid Compared with Other Agents against a Global Collection of Gram-Positive Isolates Causing Bloodstream Infections (2014–2016)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S370-S370
Author(s):  
Rodrigo E Mendes ◽  
Dee Shortridge ◽  
Helio S Sader ◽  
Leonard R Duncan ◽  
Robert K Flamm
Keyword(s):  
Bloodstream Infections ◽  
Clinical Isolates ◽  
Gram Positive ◽  
Highly Active ◽  
Pharmacodynamic Profile ◽  
The Us ◽  
Star Program ◽  
Viridans Group Streptococci ◽  
Research Grant

Abstract Background Tedizolid (TZD) is an oxazolidinone derivative with oral and intravenous formulations approved for the treatment of acute bacterial skin and skin structure infections in the US, European countries, and other regions. This study evaluated TZD’s and comparators’ activity against a collection of clinical isolates causing bloodstream infections (BSI). Methods A total of 7,284 gram-positive isolates collected during the Surveillance of Tedizolid Activity and Resistance (STAR) Program for 2014–2016 were included. Bacteria were identified by standard algorithms and MALDI-TOF-MS. Susceptibility (S) testing was performed by CLSI methods, and interpretation used CLSI and EUCAST criteria. Results This Staphylococcus aureus collection contained 33.8% methicillin-resistant isolates. TZD was the most potent agent tested against all S. aureus (MIC50/90, 0.12/0.12 µg/mL; 100.0%S) and the MRSA subset (Table). Other tested agents described in Table also had in vitro MRSA coverage. 15.6% of enterococci were vancomycin-resistant, which were mostly Enterococcus faecium (59.8%). Linezolid (LZD), ampicillin, daptomycin (DAP), and vancomycin (VAN) showed equivalent MIC50 values (1 µg/mL) against E. faecalis, but these MIC50 results were 8-fold higher than TZD (MIC50, 0.12 µg/mL). Although LZD and DAP were highly active (98.9–99.4%S) against E. faecium, TZD MICs were 8- to 16-fold lower that LZD and DAP. Ceftaroline (CPT) showed the lowest MIC values against Streptococcus pneumoniae, whereas TZD and VAN were similarly active. TZD and CPT showed the lowest MIC90 values against viridans group streptococci, while CPT, ceftriaxone, and penicillin had the lowest MIC90 results against β-hemolytic streptococci. Conclusion TZD had potent activities against this global population of gram-positive clinical isolates that caused BSI. This in vitro potency and a favorable pharmacodynamic profile may suggest TZD is a promising candidate for treating BSI caused by gram-positive isolates, especially E. faecium. Disclosures R. E. Mendes, Merck: Research Contractor, Research grant; D. Shortridge, Merck: Research Contractor, Research grant; H. S. Sader, Merck: Research Contractor, Research grant; L. R. Duncan, Merck: Research Contractor, Research grant; R. K. Flamm, Merck: Research Contractor, Research grant

scholarly journals Inhibition of RNA Synthesis as a Therapeutic Strategy against Aspergillus and Fusarium: Demonstration of In Vitro Synergy between Rifabutin and Amphotericin B

1998 ◽  
Vol 42 (3) ◽  
pp. 509-513 ◽  
Author(s):  
Cornelius J. Clancy ◽  
Yue C. Yu ◽  
Alfred Lewin ◽  
M. Hong Nguyen
Keyword(s):  
Antifungal Activity ◽  
Rna Polymerase ◽  
Amphotericin B ◽  
Rna Synthesis ◽  
Therapeutic Strategy ◽  
Clinical Isolates ◽  
Positive Interactions ◽  
Bacterial Rna ◽  
In Vitro Antifungal Activity

ABSTRACT We investigated the in vitro antifungal activity of amphotericin B, alone and in combination with rifabutin, an inhibitor of bacterial RNA polymerase, against 26 clinical isolates of Aspergillus and 25 clinical isolates of Fusarium. Synergy or additivism between these drugs was demonstrated against all isolates tested. Amphotericin B MICs were reduced upon combination with rifabutin from a mean of 0.65 μg/ml to a mean of 0.16 μg/ml againstAspergillus, and from a mean of 0.97 μg/ml to a mean of 0.39 μg/ml against Fusarium (P < 0.000001 for both). Similarly, the MICs of rifabutin were reduced upon combination with amphotericin B from a mean of >32 μg/ml to a mean of 1.1 μg/ml against both fungi (P < 0.000001 for both). These positive interactions were corroborated by a colony count study with two Fusarium isolates, for which treatment with the combination of subinhibitory concentrations of amphotericin B (at concentrations 2- and 4-fold less than the MIC) and rifabutin (at concentrations ranging from 4- to 64-fold less than the MIC) resulted in 3.2-log reductions in colony counts compared to those after treatment with either drug alone. Inhibition of RNA synthesis was shown to be the mechanism of antifungal activity. These results suggest that inhibition of fungal RNA synthesis might be a potential target for antifungal therapy.

In vitro Antifungal Activity of Sertaconazole Compared with Nine Other Drugs against 250 Clinical Isolates of Dermatophytes and Scopulariopsis brevicaulis

Chemotherapy ◽  
2004 ◽  
Vol 50 (6) ◽  
pp. 308-313 ◽  
Author(s):  
A.J. Carrillo-Muñoz ◽  
A. Guglietta ◽  
C. Palacín ◽  
J. Casals ◽  
O. del Valle ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Clinical Isolates ◽  
Scopulariopsis Brevicaulis ◽  
In Vitro Antifungal Activity

scholarly journals In Vitro Antifungal Activity of Novel Triazole Efinaconazole and Five Comparators against Dermatophyte Isolates

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Ali Rezaei-Matehkolaei ◽  
Sadegh Khodavaisy ◽  
Mohamad Mahdi Alshahni ◽  
Takashi Tamura ◽  
Kazuo Satoh ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Trichophyton Rubrum ◽  
Geometric Mean ◽  
Clinical Isolates ◽  
The Novel ◽  
Large Collection ◽  
Content Type ◽  
Trichophyton Interdigitale ◽  
In Vitro Antifungal Activity

ABSTRACT The objective of this study was to assess the in vitro activity of the novel triazole antifungal drug, efinaconazole, and five comparators (luliconazole, lanoconazole, terbinafine, itraconazole, and fluconazole) against a large collection of Trichophyton interdigitale and Trichophyton rubrum clinical isolates. The geometric mean MICs were the lowest for luliconazole (0.0005 μg/ml), followed by lanoconazole (0.002 μg/ml), efinaconazole (0.007 μg/ml), terbinafine (0.011 μg/ml), itraconazole (0.095 μg/ml), and fluconazole (12.77 μg/ml). It appears that efinaconazole, lanoconazole, and luliconazole are promising candidates for the treatment of dermatophytosis due to T. interdigitale and T. rubrum .

Sign in / Sign up

Export Citation Format

Share Document