In vitro activity of eravacycline against common ribotypes of Clostridioides difficile

Abstract Background Eravacycline is a novel synthetic fluorocycline antibacterial approved for complicated intra-abdominal infections. Objectives The purpose of this study was to assess the in vitro activities of eravacycline and comparator antibiotics against contemporary clinical isolates of Clostridioides difficile representing common ribotypes, including isolates with decreased susceptibility to metronidazole and vancomycin. Methods Clinical C. difficile strains from six common or emerging ribotypes were used to test the in vitro activities of eravacycline and comparator antibiotics (fidaxomicin, vancomycin and metronidazole) by broth microdilution. In addition, MBC experiments, time–kill kinetic studies and WGS experiments were performed. Results A total of 234 isolates were tested, including ribotypes RT001 (n = 37), RT002 (n = 41), RT014-020 (n = 39), RT027 (n = 42), RT106 (n = 38) and RT255 (n = 37). MIC50/90 values were lowest for eravacycline (≤0.0078/0.016 mg/L), followed by fidaxomicin (0.016/0.063 mg/L), metronidazole (0.25/1.0 mg/L) and vancomycin (2.0/4.0 mg/L). MBCs were lower for eravacycline compared with vancomycin for all ribotypes tested. Both vancomycin and eravacycline demonstrated bactericidal killing, including for epidemic RT027. The presence of the tetM or tetW resistance genes did not affect the MIC of eravacycline. Conclusions This study demonstrated potent in vitro activity of eravacycline against a large collection of clinical C. difficile strains that was not affected by ribotype, susceptibility to vancomycin or the presence of certain tet resistance genes. Further development of eravacycline as an antibiotic to be used in patients with Clostridioides difficile infection is warranted.

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.756 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S312-S313 ◽

Cited By ~ 2

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.

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In vitro activity of the novel antibacterial agent ibezapolstat (ACX-362E) against Clostridioides difficile

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa134 ◽

2020 ◽

Author(s):

Beverly Murray ◽

Cindy Wolfe ◽

Andrea Marra ◽

Chris Pillar ◽

Dean Shinabarger

Keyword(s):

Therapeutic Potential ◽

Oral Treatment ◽

Clinical Development ◽

Vitro Activity ◽

The Novel ◽

In Vitro Activity ◽

Clostridioides Difficile ◽

Clostridioides Difficile Infection ◽

Time Kill

Abstract Background Ibezapolstat (ACX-362E) is the first DNA polymerase IIIC inhibitor undergoing clinical development for the oral treatment of Clostridioides difficile infection (CDI). Methods In this study, the in vitro activity of ibezapolstat was evaluated against a panel of 104 isolates of C. difficile, including those with characterized ribotypes (e.g. 027 and 078) and those producing toxin A or B and was shown to have similar activity to those of comparators against these strains. Results The overall MIC50/90 (mg/L) for ibezapolstat against evaluated C. difficile was 2/4, compared with 0.5/4 for metronidazole, 1/4 for vancomycin and 0.5/2 for fidaxomicin. In addition, the bactericidal activity of ibezapolstat was evaluated against actively growing C. difficile by determining the MBC against three C. difficile isolates. Time–kill kinetic assays were additionally performed against the three C. difficile isolates, with metronidazole and vancomycin as comparators. Conclusions The killing of C. difficile by ibezapolstat was observed to occur at concentrations similar to its MIC, as demonstrated by MBC:MIC ratios and reflected in time–kill kinetic assays. This activity highlights the therapeutic potential of ibezapolstat for the treatment of CDI.

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Comparison of in vitro activity of quinolone antibiotics and vancomycin against gentamicin- and methicillin-resistant Staphylococcus aureus by time-kill kinetic studies.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.30.6.823 ◽

1986 ◽

Vol 30 (6) ◽

pp. 823-827 ◽

Cited By ~ 31

Author(s):

J K Foster ◽

J R Lentino ◽

R Strodtman ◽

C DiVincenzo

Keyword(s):

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Kinetic Studies ◽

Vitro Activity ◽

In Vitro Activity ◽

Methicillin Resistant ◽

Quinolone Antibiotics ◽

Time Kill

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1360. Antimicrobial Activity of Cefepime in Combination with VNRX-5133 Against a Global Collection of Enterobacteriaceae Including Resistant Phenotypes

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.1191 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S416-S417 ◽

Cited By ~ 3

Author(s):

Meredith Hackel ◽

Dan Sahm

Keyword(s):

Vitro Activity ◽

In Vitro Activity ◽

First Line ◽

First Line Therapy ◽

Carbapenem Resistant ◽

Line Therapy ◽

Resistant Strains ◽

Further Development ◽

Dose Dependent

Abstract Background VNRX-5133 is a novel cyclic boronate-based broad-spectrum β-lactamase inhibitor with potent and selective direct inhibitory activity against both serine- and metallo-β-lactamases (Ambler Classes A, B, C, and D). In this analysis, we evaluated the activity of cefepime (FEP) in combination with VNRX-5133 and comparators against 1,120 recent Enterobacteriaceae clinical isolates, including carbapenem-resistant strains. Methods MICs of FEP with VNRX-5133 fixed at 4 µg/mL (FEP/VNRX-5133) were determined following CLSI M07-A10 guidelines against 1,120 Enterobacteriaceae from community and hospital infections collected globally in 2012–2013. Resistant phenotypes were based on 2017 CLSI breakpoints. As FEP/VNRX-5133 breakpoints have not yet been established, the FEP 2 g q8h susceptible dose-dependent (SDD) breakpoint of ≤8 µg/mL was considered for comparative purposes. Results FEP/VNRX-5133 showed potent in vitro activity against drug-resistant subsets of Enterobacteriaceae, with MIC90 values ranging from 1 µg/mL against ceftazidime-, levofloxacin-, or piperacillin–tazobactam-nonsusceptible isolates, to 8 µg/mL against meropenem-nonsusceptible isolates. FEP/VNRX-5133 inhibited >93% of all resistant subsets at ≤8 µg/mL. Conclusion Cefepime in combination with VNRX-5133 demonstrated potent in vitro activity against Enterobacteriaceae, including cephalosporin-, fluoroquinolone- and carbapenem-resistant (CRE) isolates. Because this drug combination exhibited substantial potential for the treatment of infections caused by isolates often resistant to first-line therapy, further development is warranted. Disclosures M. Hackel, IHMA, Inc.: Employee, Salary. VenatoRx: Consultant, Consulting fee. D. Sahm, IHMA, Inc.: Employee, Salary. VenatoRx: Consultant, Consulting fee.

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In Vitro Activity of Pentamidine Alone and in Combination with Antibiotics against Multidrug-Resistant Clinical Pseudomonas aeruginosa Strains

Antibiotics ◽

10.3390/antibiotics9120885 ◽

2020 ◽

Vol 9 (12) ◽

pp. 885

Author(s):

Soraya Herrera-Espejo ◽

Tania Cebrero-Cangueiro ◽

Gema Labrador-Herrera ◽

Jerónimo Pachón ◽

María Eugenia Pachón-Ibáñez ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Public Health Problem ◽

Multidrug Resistant ◽

Vitro Activity ◽

Synergistic Activity ◽

In Vitro Activity ◽

Hospital Acquired Infections ◽

Time Kill ◽

Hospital Acquired

Multidrug-resistant (MDR) Pseudomonas aeruginosa is a public health problem causing both community and hospital-acquired infections, and thus the development of new therapies for these infections is critical. The objective of this study was to analyze in vitro the activity of pentamidine as adjuvant in combinations to antibiotics against seven clinical P. aeruginosa strains. The Minimum Inhibitory Concentration (MIC) was determined following standard protocols, and the results were interpreted according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints; however, the gentamicin activity was interpreted according to the Clinical and Laboratory Standards Institute (CLSI) recommendations. The bactericidal in vitro activity was studied at 1×MIC concentrations by time–kill curves, and also performed in three selected strains at 1/2×MIC of pentamidine. All studies were performed in triplicate. The pentamidine MIC range was 400–1600 μg/mL. Four of the strains were MDR, and the other three were resistant to two antibiotic families. The combinations of pentamidine at 1×MIC showed synergistic activity against all the tested strains, except for pentamidine plus colistin. Pentamidine plus imipenem and meropenem were the combinations that showed synergistic activity against the most strains. At 1/2×MIC, pentamidine plus antibiotics were synergistic with all three analyzed strains. In summary, pentamidine in combination with antibiotics showed in vitro synergy against multidrug-resistant P. aeruginosa clinical strains, which suggests its possible use as adjuvant to antibiotics for the therapy of infections from MDR P. aeruginosa.

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Comparison of in vitro Activity of Two New Triazoles, Voriconazole and SCH-56592, and Fluconazole Against Candida albicans by Time-Kill Methodology

Journal of Infectious Disease Pharmacotherapy ◽

10.1300/j100v04n03_03 ◽

1999 ◽

Vol 4 (3) ◽

pp. 21-34 ◽

Cited By ~ 1

Author(s):

David Burgess

Keyword(s):

Candida Albicans ◽

Vitro Activity ◽

In Vitro Activity ◽

Time Kill

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In Vitro 24-Hour Time-Kill Studies of Vancomycin and Linezolid in Combination versus Methicillin-Resistant Staphylococcus aureus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00237-09 ◽

2009 ◽

Vol 53 (10) ◽

pp. 4495-4497 ◽

Cited By ~ 35

Author(s):

Shveta Rani Singh ◽

Alfred E. Bacon ◽

David C. Young ◽

Kimberly A. Couch

Keyword(s):

Staphylococcus Aureus ◽

Conventional Therapy ◽

Methicillin Resistant Staphylococcus Aureus ◽

Antagonistic Activity ◽

Vitro Activity ◽

Synergistic Activity ◽

In Vitro Activity ◽

Methicillin Resistant ◽

Time Kill

ABSTRACT Many clinicians are trying unique strategies, including vancomycin and linezolid in combination, for treatment of patients who do not respond to conventional therapy against methicillin (meticillin)-resistant Staphylococcus aureus. In our study, which illustrated in vitro activity only, no synergistic activity was seen when the two agents were combined. Conversely, antagonistic activity occurred in three of five strains when linezolid was added to vancomycin. Our results indicate that vancomycin and linezolid in combination should be avoided.

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