scholarly journals In vitro activity of D0870 compared with those of other azoles against fluconazole-resistant Candida spp.

1995 ◽  
Vol 39 (4) ◽  
pp. 868-871 ◽  
Author(s):  
H M Wardle ◽  
D Law ◽  
C B Moore ◽  
C Mason ◽  
D W Denning
Keyword(s):  
Optical Density ◽  
Resistance Mechanisms ◽  
Vitro Activity ◽  
Cross Resistance ◽  
Significant Shift ◽  
Significant Activity ◽  
In Vitro Activity ◽  
Candida Spp ◽  
Fluconazole Resistant

We compared the in vitro activity of a new triazole, D0870, with those of fluconazole, itraconazole, and ketoconazole against 41 clinical isolates of fluconazole-resistant Candida belonging to nine different species. The 50% inhibitory concentrations (IC50s) were determined by a microdilution method with morpholinopropanesulfonic acid (MOPS)-buffered RPMI medium and an inoculum of approximately 10(4) yeasts per ml. After incubation for 48 h at 37 degrees C the optical density at 550 nm was measured. The IC50 was the lowest drug concentration which reduced the optical density at 550 nm by > or = 50% compared with that for a drug-free control. D0870 had significant activity against many of the isolates. Its activity was comparable to that of ketoconazole, slightly superior to that of itraconazole, and markedly superior to that of fluconazole against Candida albicans. Against Candida glabrata, Candida krusei, and Candida inconspicua, it had activity similar to those of itraconazole and ketoconazole but had activity superior to that of fluconazole. D0870 IC50s for some isolates were increased. This may be due to cross-resistance mechanisms because the IC50s of both itraconazole and ketoconazole for these isolates were often high. When IC50s and IC80s were compared there was a marked organism and drug variation. With C. glabrata much higher endpoints for itraconazole were observed when an IC80 endpoint was used. For C. albicans there was also a significant shift upward in endpoints for itraconazole and ketoconazole. Values were changed little when IC50 and IC80 endpoints of D0870 were compared. For 35 of 41 isolates tested the D0870 IC50 was less than the 2.5-mg/liter breakpoint threshold proposed previously. Therefore, D0870 may be a useful agent for the therapy of infections caused by fluconazole-resistant Candida spp.

scholarly journals Activity of SCH 56592 compared with those of fluconazole and itraconazole against Candida spp.

1997 ◽  
Vol 41 (10) ◽  
pp. 2310-2311 ◽  
Author(s):  
D Law ◽  
C B Moore ◽  
D W Denning
Keyword(s):  
Vitro Activity ◽  
In Vitro Activity ◽  
Candida Spp ◽  
Fluconazole Resistant

The in vitro activity of Schering 56592, a new azole drug, was compared with those of fluconazole and itraconazole against 103 isolates of Candida comprising 10 different species. Schering 56592 was more active than itraconazole and fluconazole, and it was active against many fluconazole-resistant isolates.

scholarly journals In Vitro Activity of Carbosilane Cationic Dendritic Molecules on Prevention and Treatment of Candida Albicans Biofilms

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 918
Author(s):  
Irene Heredero-Bermejo ◽  
Natalia Gómez-Casanova ◽  
Sara Quintana ◽  
Juan Soliveri ◽  
Francisco Javier de la Mata ◽  
...  
Keyword(s):  
Cell Viability ◽  
Biofilm Formation ◽  
Fungal Pathogens ◽  
Resistance Mechanisms ◽  
Antifungal Drugs ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Candida Spp ◽  
Screening Process

Candida spp. are one of the most common fungal pathogens. Biofilms formed by Candidaalbicans offer resistance mechanisms against most antifungal agents. Therefore, development of new molecules effective against these microorganisms, alone or in combination with antifungal drugs, is extremely necessary. In the present work, we carried out a screening process of different cationic carbosilane dendritic molecules against C. albicans. In vitro activity against biofilm formation and biofilms was tested in both Colección Española de Cultivos Tipo (CECT) 1002 and clinical C. albicans strains. Cytotoxicity was studied in human cell lines, and biofilm alterations were observed by scanning electron microscopy (SEM). Antifungal activity of the carbosilane dendritic molecules was assessed by monitoring cell viability using both established and novel cell viability assays. One out of 14 dendritic molecules tested, named BDSQ024, showed the highest activity with a minimum biofilm inhibitory concentration (MBIC) for biofilm formation and a minimum biofilm damaging concentration (MBDC) for existing biofilm of 16–32 and 16 mg/L, respectively. Synergy with amphotericin (AmB) and caspofungin (CSF) at non-cytotoxic concentrations was found. Therefore, dendritic compounds are exciting new antifungals effective at preventing Candida biofilm formation and represent a potential novel therapeutic agent for treatment of C. albicans infection in combination with existing clinical antifungals.

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

scholarly journals 1375. In vitro Activity of Cefiderocol and Comparator Agents against Gram-Negative Isolates from Cancer Patients

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S421-S422 ◽  
Author(s):  
Kenneth V I Rolston ◽  
Bahgat Gerges ◽  
Issam Raad ◽  
Samuel L Aitken ◽  
Ruth Reitzel ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Active Agent ◽  
Vitro Activity ◽  
Significant Activity ◽  
In Vitro Activity ◽  
Research Support ◽  
Gram Negative ◽  
E Coli ◽  
Research Grant

Abstract Background Gram-negative bacilli (GNB) are now the predominant cause of bacterial infection in cancer patients (CP). Many GNB are problematic because they have become resistant to commonly used antibiotics. Cefiderocol (CFDC), a novel siderophore cephalosporin, is active against a wide spectrum of GNB. We evaluated its in vitro activity and that of eleven comparator agents against GNB isolated from CP. Methods A total of 341 recent GNB blood isolates from CP were tested using CLSI approved methods for MIC determination by broth microdilution. Comparator agents were amikacin (A), aztreonam (AZ), ceftazidime (CZ), ceftazidime/avibactam (CAV), cefepime (CEF), ciprofloxacin (CIP), colistin (CL), meropenem (MR), ceftolozane/tazobactam (C/T), tigecycline (TG), and trimethoprim/sulfamethoxazole (T/S). Results CFDC MIC90s as mg/L were: S. maltophilia [50 isolates] 0.25, E. coli (ESBL−) [50 isolates] 0.5, E. coli (ESBL+) [51 isolates] 2.0, K. pneumoniae (ESBL− and +) [60 isolates] 0.5; K. pneumoniae (CRE) [22 isolates] 2.0; P. aeruginosa (MDR) [32 isolates] 1.0; E. cloacae [27 isolates] 4.0; Achromobacter spp. [15 isolates] 0.12. CFDC inhibited P. agglomerans, Burkholderia spp., Sphingomonas spp., Ochrobactrum spp. at ≤1 mg/L [23 total isolates] and Elizabethkingia spp. and R. radiobacter at ≤8 mg/L [11 total isolates]. Among comparator agents, only T/S had consistent activity against S. maltophilia. For E. coli (ESBL− and +) MR, TG, CAV, CL were most active. For K. pneumoniae (ESBL–and +) MR, CAV were most active. For K. pneumoniae (CRE) and P. aeruginosa (MDR), none of the comparators had significant activity. For E. cloacae, MR, A, CAV, TG were most active. Among the uncommon organisms, MR and TG had the greatest activity. Conclusion Although susceptibility breakpoints have yet to be determined, CFDC has significant activity (≤4 mg/L) against most problematic Gram-negative organisms causing infections in CP based on available pharmacokinetic/pharmacodynamic data. In particular, its activity against S. maltophilia was superior to the comparators. Also, it was the most active agent against P. aeruginosa (MDR) and K. pneumoniae (CRE). Based on our results, CFDC warrants clinical evaluation for the treatment of blood stream infections caused by GNB in CP. Disclosures K. V. I. Rolston, Merck: Investigator, Research grant; JMI Laboratories: Investigator, Research grant; Shionogi (Japan): Investigator, Research grant. B. Gerges, Shionogi: Collaborator, Research support. S. L. Aitken, Shionogi: Scientific Advisor, Consulting fee; Merck: Scientific Advisor, Consulting fee; Medicines Co: Scientific Advisor, Consulting fee; Achaogen: Scientific Advisor, Consulting fee; Zavante: Scientific Advisor, Consulting fee; R. Prince, Shionogi: Investigator, Research support. Merck: Investigator, Research support.

In-vitro activity of voriconazole (UK-109,496), LY303366 and other antifungal agents against oral Candida spp. isolates from HIV-infected patients

1999 ◽  
Vol 44 (5) ◽  
pp. 697-700 ◽  
Author(s):  
M. Chávez ◽  
S. Bernal ◽  
A. Valverde ◽  
M. J. Gutierrez ◽  
G. Quindós ◽  
...  
Keyword(s):  
Antifungal Agents ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Candida Spp ◽  
Oral Candida

scholarly journals In vitro activity of the novel echinocandin CD101 at pH 7 and 4 against Candida spp. isolates from patients with vulvovaginal candidiasis

2017 ◽  
Vol 72 (5) ◽  
pp. 1355-1358 ◽  
Author(s):  
Dina A. Boikov ◽  
Jeffrey B. Locke ◽  
Kenneth D. James ◽  
Ken Bartizal ◽  
Jack D. Sobel
Keyword(s):  
Vulvovaginal Candidiasis ◽  
Vitro Activity ◽  
The Novel ◽  
In Vitro Activity ◽  
Candida Spp

scholarly journals 681. In vitro Activity of the β-Lactamase Inhibitor QPX7728 in Combination with Several β-Lactams Against Acinetobacter baumannii (AB) and Pseudomonas aeruginosa (PSA)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S310-S311 ◽  
Author(s):  
Olga Lomovskaya ◽  
Jill Lindley ◽  
Debora Rubio-Aparicio ◽  
Kirk J Nelson ◽  
Mariana Castanheira
Keyword(s):  
Resistance Mechanisms ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Microdilution Method ◽  
Carbapenem Resistant ◽  
Broth Microdilution Method ◽  
Data Representative ◽  
Lactamase Inhibitor

Abstract Background QPX7728 (QPX) is a novel broad-spectrum boron-containing inhibitor of serine- and metallo-β-lactamases (MBLs). We evaluated the in vitro activity of QPX combined with several β-lactams against carbapenem-resistant AB (CRAB) and PSA clinical isolates with varying β-lactam resistance mechanisms. Methods A total of 503 CRAB (meropenem [MEM] MIC ≥8 µg/mL) and 762 PSA clinical isolates were tested by the reference broth microdilution method against β-lactams alone and combined with QPX (4 µg/mL and 8 µg/mL). PSA isolates were selected to represent the normal distribution of MEM, ceftazidime–avibactam (CAZ-AVI), and ceftolozane-tazobactam (TOL-TAZ) resistance according to 2017 surveillance data (representative panel). Additionally, 262 PSA isolates that were either nonsusceptible (NS) to MEM (MIC, ≥4 µg/mL) or to TOL-TAZ (MIC, ≥8 µg/mL), or resistant (R) to CAZ-AVI (MIC, ≥16 µg/mL) (challenge panel) were also tested. Within this 262 strain challenge set, 56 strains carried MBLs and the majority also had nonfunctional OprD. Results Against CRAB, QPX at 4 and 8 µg/mL increased the potency of all β-lactams tested. MEM-QPX was the most potent combination (table) displaying MIC50/MIC90 at 1/8 and 0.5/4 µg/mL with QPX at fixed 4 and 8 µg/mL, respectively. Susceptibility (S) to MEM was restored in >95% of strains. Against the 500 PSA from the representative panel, S for all QPX combinations was >90%. For the challenge panel, TOL-QPX and piperacillin (PIP)-QPX were the most potent combinations, restoring S in 76–77% of strains. TOL-QPX and MEM-QPX or cefepime (FEP)-QPX restored the MIC values to S rates when applying the CLSI breakpoint for the compound alone (comparison purposes only) in ~90% and ~75% of non-MBL-producing strains, respectively, vs. 60–70% for TOL-TAZ and CAZ-AVI. PIP-QPX reduce the MIC values to S values for PIP-TAZ in ~60% of MBL-producing strains vs. 20–30% and 3–7% for other QPX combinations and non-QPX tested combinations, respectively. Conclusion Combinations of QPX with various β-lactam antibiotics displayed potent activity against CRAB and resistant PSA isolates and warrant further investigation. Disclosures All authors: No reported disclosures.

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