scholarly journals In vitro activity of rezafungin against common and rare Candida species and Saccharomyces cerevisiae

2019 ◽  
Vol 74 (12) ◽  
pp. 3505-3510 ◽  
Author(s):  
Zoltán Tóth ◽  
Lajos Forgács ◽  
Jeffrey B Locke ◽  
Gábor Kardos ◽  
Fruzsina Nagy ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amphotericin B ◽  
Candida Species ◽  
Sensu Stricto ◽  
Candida Guilliermondii ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Candida Auris ◽  
In Vitro Susceptibility

Abstract Background Rezafungin is a novel echinocandin with excellent activity against common Candida species; however, limited data are available regarding rare Candida species. Methods We determined the in vitro susceptibility of 689 clinical isolates of 5 common and 19 rare Candida species, as well as Saccharomyces cerevisiae. The activity of rezafungin was compared with that of anidulafungin, caspofungin, micafungin, amphotericin B and fluconazole, using CLSI broth microdilution methodology (Fourth Edition: M27). Results Rezafungin MIC90 values were 0.06 mg/L for Candida albicans (n=125), Candida tropicalis (n=51), Candida dubliniensis (n=22), Candida inconspicua (n=41), Candida sojae (n=10), Candida lipolytica (n=10) and Candida pulcherrima (n=10), 0.12 mg/L for Candida glabrata (n=81), Candida krusei (n=53), Candida kefyr (n=52) and Candida fabianii (n=15), 0.25 mg/L for Candida lusitaniae (n=46) and Candida auris (n=19), 0.5 mg/L for Candida metapsilosis (n=15) and S. cerevisiae (n=21), 1 mg/L for Candida orthopsilosis (n=15) and Candida guilliermondii (n=27) and 2 mg/L for Candida parapsilosis sensu stricto (n=59). Caspofungin MIC90 values were 0.25–2 mg/L for all species, while micafungin and anidulafungin MIC90 values were similar to those of rezafungin. Fluconazole resistance was found in C. albicans (5.6%) and C. glabrata (4.9%); rezafungin was effective against these isolates as well. Amphotericin B MIC values did not exceed 2 mg/L. Conclusions Rezafungin showed excellent in vitro activity against both WT and azole-resistant Candida species, as well as against S. cerevisiae. Rezafungin had similar activity to other echinocandins (excluding caspofungin) against common Candida species and, notably, against clinically relevant uncommon Candida species.

scholarly journals In vitro activity of anidulafungin in combination with amphotericin B or voriconazole against biofilms of five Candida species

2016 ◽  
Vol 71 (12) ◽  
pp. 3449-3452 ◽  
Author(s):  
A. Valentín ◽  
E. Cantón ◽  
J. Pemán ◽  
M. E. Fernandez-Rivero ◽  
M. A. Tormo-Mas ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Candida Species ◽  
Vitro Activity ◽  
In Vitro Activity

scholarly journals 733. Ibrexafungerp Demonstrates Potent and Consistent In Vitro Activity Against >400 Global Candida auris Isolates, Including isolates with Elevated MIC’s to Echinocandins

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S417-S417
Author(s):  
Katyna Borroto-Esoda ◽  
David A Angulo ◽  
Nkechi Azie
Keyword(s):  
Vitro Activity ◽  
Multi Drug Resistance ◽  
In Vitro Activity ◽  
Candida Auris ◽  
In Vitro Susceptibility ◽  
Healthcare Facilities ◽  
Highly Active ◽  
Synthase Inhibitor ◽  
Global Threat

Abstract Background Candida auris is an urgent global threat; a pathogen associated with high mortality (up to 60%), multi-drug resistance, the ability to spread from person-to-person and surface-to-person, presenting high risk for outbreaks in healthcare facilities. Echinocandins are the first-line treatment for patients with Candida auris infections given the high degree of resistance to azoles and polyenes. Ibrexafungerp is a novel IV/oral glucan synthase inhibitor (triterpenoid) antifungal with activity against Candida, Aspergillus and Pneumocystis spp, in Phase 3 development. We will present a compilation of >400 Candida auris isolates from four studies, including 32 Candida auris isolates with elevated MIC’s to the echinocandins. Methods In vitro MIC data for ibrexafungerp against Candida auris isolates were compiled from across 4 independent studies with the majority of isolates originating in the US and India. In vitro susceptibility was determined by broth micro-dilution using CLSI (M27-S3) and/or EUCAST methods. Overall, 445 isolates were evaluated including 32 isolates with elevated MIC values to one or more echinocandins. Results The ibrexafungerp MIC90 value against the 445 clinical isolates was 1 μg/mL; the modal and MIC50 values were 0.5 μg/mL each. These results were consistent across the four studies and no differences were observed between MIC results generated using CLSI or EUCAST methods. Similar results were obtained for the 32 isolates with elevated MIC values to one or more of the echinocandins. Among this population, the mode, MIC50 and MIC90 were 0.5, 0.5, and 1 μg/mL, respectively. Only 1/32 of the echinocandin-resistant isolates had reduced sensitivity to ibrexafungerp (defined as > 2-dilutions vs the mode). This isolate was pan-resistant with elevated MICs to all three echinocandins (MICs = 4 μg/mL) as well as fluconazole (MIC >256 μg/mL) and amphotericin B (MIC = 1 μg/mL). Conclusion This data demonstrates that ibrexafungerp possesses potent and consistent in vitro activity against Candida auris and remains highly active against C. auris isolates with high MIC’s to the echinocandins. Disclosures Katyna Borroto-Esoda, PhD, SCYNEXIS, Inc. (Employee, Shareholder) David A. Angulo, MD, SCYNEXIS, Inc. (Employee, Shareholder) Nkechi Azie, MD, SCYNEXIS, Inc. (Employee, Shareholder)

scholarly journals In vitro susceptibility testing of Candida species isolated from blood stream infections to five conventional antifungal drugs

2019 ◽  
pp. 124-129
Author(s):  
Mahdis Hosein Khezri ◽  
Farideh Zaini ◽  
Parivash Kordbache ◽  
Mohammad Ghahri ◽  
Pegah Ardi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Candida Species ◽  
Bloodstream Infections ◽  
Blood Stream ◽  
Candida Guilliermondii ◽  
Antifungal Drugs ◽  
In Vitro Susceptibility ◽  
Dose Dependent

Candida is an opportunistic fungal pathogen which can cause fatal bloodstream infections (BSIs) in immunocompromised and immunodeficient persons. In this study, the susceptibility of 196 Candida species isolated from bloodstream infections (BSI) to 5 antifungal drugs were conducted from October 2014 through October 2017. The antifungal drugs used in this study were including fluconazole, itraconazole, voriconazole, Amphotericin B and Caspofungin. From 196 studied isolates, Candida albicans comprised 63.3% of the isolates, followed by C.parapsilosis (18.9 %), C. glabrata (8.7%), C. tropicalis (6.1%), C.krusei (2%) and C.gillermundii (1%). In this study, all isolates of Candida albicans and Candida non-albicans species were completely resistant to voriconazole and itraconazole. Of the 196 Candida isolates, 80 isolates with MIC of 32-16 μg/ml had a dose dependent susceptibility to fluconazole and 111 isolates showed resistance (MIC=64 μg / ml) and only 5 isolates were sensitive (MIC=8 μg / ml) to fluconazole. In this study, out of 196 isolates, 37 isolates were sensitive to amphotericin (MIC=1 μg/ml) and 159 isolates were resistant to amphotericin B (MIC>1 μg/ml). Caspofungin was effective on 104 isolates (MIC<2 μg/ml) and 92 isolates were non-susceptible (MIC>2 μg / ml) to this drug. Out of 124 isolates of Candida albicans, 3 were susceptible, 61 susceptible dose dependent and 60 were resistant to fluconazole. Only 24 isolates were susceptible to amphotericin B and 100 isolates showed resistance to this antifungal drug. Eighty-eight isolates were sensitive to caspofungin and 36 isolates were insensitive. With respect to susceptibility to fluconazole, among 37 isolates of Candida parapsilosis, one was identified as susceptible, 13 isolates were susceptible dose dependent and 13 were resistant. Of these isolates, five were susceptible and 32 isolates were resistant to amphotericin B and caspofungin. Of 12 isolates of Candida tropicalis, 11 showed resistance and 1 was susceptible dose dependent to fluconazole. Of these isolates, 11 were resistant to amphotericin B and 1 isolate was sensitive. Ultimately, only 2 isolates showed susceptibility to caspofungin. Out of 17 isolates of Candida glabrata, 13 isolates were resistant, and 4 isolates had a dose-dependent sensitivity to fluconazole. Eight isolates were susceptible and 9 isolates were resistant to caspofungin. Seven isolates were susceptible and 10 isolates were resistant to amphotericin B. All four Candida krusei isolates showed resistance to the five drugs used in the study. Of the two Candida guilliermondii isolates, both were resistant to amphotericin B, but 1 was sensitive to fluconazole and 1 was identified to be dose-dependent susceptible. One isolate was resistant to and the other one was susceptible to caspofungin. Our findings shows the prevalence of resistant candida species to conventional treatments and indicate that candidemia caused by Candida resistant species is incrasing. Keywords: Candidiasis; Antifungal drugs; Candidemia; Iran

scholarly journals 1592. Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales and Pseudomonas aeruginosa With Overexpression of AmpC β-Lactamase From Phase 3 Clinical Trials

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S792-S793
Author(s):  
Lynn-Yao Lin ◽  
Dmitri Debabov ◽  
William Chang ◽  
Urania Rappo
Keyword(s):  
Clinical Trials ◽  
Active Agent ◽  
Complicated Urinary Tract Infection ◽  
Carbapenem Resistance ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Control Groups ◽  
In Vitro Susceptibility ◽  
Intra Abdominal Infection

Abstract Background AmpC overproduction is a main mechanism of carbapenem resistance, in the absence of acquired carbapenemases. Ceftazidime-avibactam (CAZ-AVI) has potent in vitro activity against AmpC-producing P. aeruginosa and Enterobacterales that are resistant to carbapenems and other β-lactams. Methods Activity of CAZ-AVI and comparators was evaluated against AmpC-overproducing Enterobacterales (n=77) and P. aeruginosa (n=53) collected from 4 CAZ-AVI clinical trials: RECLAIM (complicated intra-abdominal infection [cIAI]), REPRISE (cIAI/complicated urinary tract infection [cUTI]), RECAPTURE (cUTI) and REPROVE (hospital-acquired pneumonia/ventilator associated pneumonia). In vitro susceptibility of CAZ-AVI and comparators was performed by broth microdilution using ThermoFisher custom panels. CLSI breakpoints were used to determine susceptibility. Quantitative PCR and microarray data were used to characterize presence and expression of AmpC. Clinical response at test of cure was assessed. Results Against 77 AmpC-overproducing Enterobacterales isolates, meropenem-vaborbactam (MVB) (98.7% susceptible [S]), CAZ-AVI (96.1% S), and meropenem (MEM) (96.1% S) had similar in vitro activity (Table), with greater in vitro activity than amikacin (AMK) (84.4% S), gentamicin (61.0% S), and ceftolozane-tazobactam (TZC) (35.1% S). Clinical cures in patients with baseline AmpC-overproducing Enterobacterales were 21/26 (81%) in CAZ-AVI group vs 17/20 (85%) in control groups. Against 53 AmpC-overproducing P. aeruginosa isolates, CAZ-AVI (73.6% S) showed greater in vitro activity than AMK (69.8% S), TZC (58.5% S), and MEM (37.7% S). Clinical cures in patients with baseline AmpC-overproducing P. aeruginosa were 12/14 (86%) in CAZ-AVI group vs 9/12 (75%) in control groups. MIC distributions against the same P aeruginosa isolates were CAZ-AVI (MIC50/90, 4/ &gt;64 µg/mL), MVB (MIC50/90, 8/32 µg/mL), and MEM (MIC50/90, 8/32 µg/mL). Table Conclusion CAZ-AVI was the most active agent against AmpC-overproducing P. aeruginosa with higher proportion of clinical cure than controls. CAZ-AVI was also among the most active agents against AmpC-overproducing Enterobacterales, with &gt;96% isolates susceptible. Disclosures Lynn-Yao Lin, MS, AbbVie (Employee) Dmitri Debabov, PhD, AbbVie (Employee) William Chang, BS, AbbVie (Employee) Urania Rappo, MD, MS, PharmD, Allergan (before its acquisition by AbbVie) (Employee)

scholarly journals In vitro susceptibility of Helicobacter pylori to protolichesterinic acid from the lichen Cetraria islandica.

1997 ◽  
Vol 41 (1) ◽  
pp. 215-217 ◽  
Author(s):  
K Ingolfsdottir ◽  
M A Hjalmarsdottir ◽  
A Sigurdsson ◽  
G A Gudjonsdottir ◽  
A Brynjolfsdottir ◽  
...  
Keyword(s):  
Duodenal Ulcer ◽  
Helicobacter Pylori ◽  
Plant Extracts ◽  
Active Component ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Salt Form ◽  
Traditional Use ◽  
In Vitro Susceptibility

With reference to the traditional use of Cetraria islandica (Iceland moss) for relief of gastric and duodenal ulcer, plant extracts were screened for in vitro activity against Helicobacter pylori. (+)-Protolichesterinic acid, an aliphatic alpha-methylene-gamma-lactone, was identified as an active component. The MIC range of protolichesterinic acid, in free as well as salt form, was 16 to 64 micrograms/ml.

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

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S312-S313 ◽  
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.

Sign in / Sign up

Export Citation Format

Share Document