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711. Exebacase (Lysin CF-301) Activity Against Staphylococcus aureus (S. aureus) Isolates From Bacteremic Patients Enrolled in a Phase 2 Study (CF-301-102)

BACKGROUND: Exebacase (CF-301) is a novel, recombinantly-produced, bacteriophage-derived lysin (cell wall hydrolase) which is the first lysin to report Phase 2 (Ph2) results which demonstrated 42.8% higher clinical responder rates with a single dose of exebacase used in addition to standard of care...

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Autores principales: Anastasiou, Diane, Cassino, Cara, Schuch, Raymond
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811034/
http://dx.doi.org/10.1093/ofid/ofz360.779
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author Anastasiou, Diane
Cassino, Cara
Schuch, Raymond
author_facet Anastasiou, Diane
Cassino, Cara
Schuch, Raymond
author_sort Anastasiou, Diane
collection PubMed
description BACKGROUND: Exebacase (CF-301) is a novel, recombinantly-produced, bacteriophage-derived lysin (cell wall hydrolase) which is the first lysin to report Phase 2 (Ph2) results which demonstrated 42.8% higher clinical responder rates with a single dose of exebacase used in addition to standard of care antibiotics (SOC) vs. SOC alone for the treatment of methicillin-resistant S. aureus (MRSA) bacteremia including endocarditis. We examined exebacase activity by broth microdilution (BMD) against baseline methicillin-sensitive S. aureus (MSSA) and MRSA isolates from each of the 116 participants in the recently complete exebacase”first in-patient’ Ph2 study (NCT03163446). METHODS: Patients with complicated bacteremia or endocarditis caused by S. aureus were enrolled into Study CF-301-102 at study centers in the United States, EU, Latin America, Israel, and Russia from 2017 and 2018. Baseline isolates from blood cultures were collected prior to administration of exebacase. Exebacase MICs against 117 isolates of MSSA (n = 74) and MRSA (n = 43) were determined at a central laboratory using a modified BMD approved by the CLSI for exebacase AST. RESULTS: The exebacase MICs of baseline patient isolates from the Ph2 study ranged from 0.125 – 2 µg/mL and the MIC(50/90) values for all MSSA and MRSA isolates were 0.5/1 µg/mL. Exebacase MICs reported in a recent surveillance study were similar, with MIC(50/90) values of 0.5/1 µg/mL. Of the 6 total subjects with EXE MICs of 2, 3 were clinical responders, 2 were indeterminate (not available for assessment), and 1 was a clinical nonresponder at Day 14. CONCLUSION: Exebacase was highly active against all baseline S. aureus isolates from blood cultures obtained from bacteremic patients enrolled in the Ph2 study. Based on data from previously presented exposure target attainment animal studies, PK/PD modeling and preliminary nonclinical breakpoint assessments, we expected that strains with MIC values of ≤2 µg/mL will have been susceptible to the Ph2 clinical exebacase dose determined based on target attainment studies under study in Ph2. DISCLOSURES: All authors: No reported disclosures.
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spelling pubmed-68110342019-10-28 711. Exebacase (Lysin CF-301) Activity Against Staphylococcus aureus (S. aureus) Isolates From Bacteremic Patients Enrolled in a Phase 2 Study (CF-301-102) Anastasiou, Diane Cassino, Cara Schuch, Raymond Open Forum Infect Dis Abstracts BACKGROUND: Exebacase (CF-301) is a novel, recombinantly-produced, bacteriophage-derived lysin (cell wall hydrolase) which is the first lysin to report Phase 2 (Ph2) results which demonstrated 42.8% higher clinical responder rates with a single dose of exebacase used in addition to standard of care antibiotics (SOC) vs. SOC alone for the treatment of methicillin-resistant S. aureus (MRSA) bacteremia including endocarditis. We examined exebacase activity by broth microdilution (BMD) against baseline methicillin-sensitive S. aureus (MSSA) and MRSA isolates from each of the 116 participants in the recently complete exebacase”first in-patient’ Ph2 study (NCT03163446). METHODS: Patients with complicated bacteremia or endocarditis caused by S. aureus were enrolled into Study CF-301-102 at study centers in the United States, EU, Latin America, Israel, and Russia from 2017 and 2018. Baseline isolates from blood cultures were collected prior to administration of exebacase. Exebacase MICs against 117 isolates of MSSA (n = 74) and MRSA (n = 43) were determined at a central laboratory using a modified BMD approved by the CLSI for exebacase AST. RESULTS: The exebacase MICs of baseline patient isolates from the Ph2 study ranged from 0.125 – 2 µg/mL and the MIC(50/90) values for all MSSA and MRSA isolates were 0.5/1 µg/mL. Exebacase MICs reported in a recent surveillance study were similar, with MIC(50/90) values of 0.5/1 µg/mL. Of the 6 total subjects with EXE MICs of 2, 3 were clinical responders, 2 were indeterminate (not available for assessment), and 1 was a clinical nonresponder at Day 14. CONCLUSION: Exebacase was highly active against all baseline S. aureus isolates from blood cultures obtained from bacteremic patients enrolled in the Ph2 study. Based on data from previously presented exposure target attainment animal studies, PK/PD modeling and preliminary nonclinical breakpoint assessments, we expected that strains with MIC values of ≤2 µg/mL will have been susceptible to the Ph2 clinical exebacase dose determined based on target attainment studies under study in Ph2. DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2019-10-23 /pmc/articles/PMC6811034/ http://dx.doi.org/10.1093/ofid/ofz360.779 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Anastasiou, Diane
Cassino, Cara
Schuch, Raymond
711. Exebacase (Lysin CF-301) Activity Against Staphylococcus aureus (S. aureus) Isolates From Bacteremic Patients Enrolled in a Phase 2 Study (CF-301-102)
title 711. Exebacase (Lysin CF-301) Activity Against Staphylococcus aureus (S. aureus) Isolates From Bacteremic Patients Enrolled in a Phase 2 Study (CF-301-102)
title_full 711. Exebacase (Lysin CF-301) Activity Against Staphylococcus aureus (S. aureus) Isolates From Bacteremic Patients Enrolled in a Phase 2 Study (CF-301-102)
title_fullStr 711. Exebacase (Lysin CF-301) Activity Against Staphylococcus aureus (S. aureus) Isolates From Bacteremic Patients Enrolled in a Phase 2 Study (CF-301-102)
title_full_unstemmed 711. Exebacase (Lysin CF-301) Activity Against Staphylococcus aureus (S. aureus) Isolates From Bacteremic Patients Enrolled in a Phase 2 Study (CF-301-102)
title_short 711. Exebacase (Lysin CF-301) Activity Against Staphylococcus aureus (S. aureus) Isolates From Bacteremic Patients Enrolled in a Phase 2 Study (CF-301-102)
title_sort 711. exebacase (lysin cf-301) activity against staphylococcus aureus (s. aureus) isolates from bacteremic patients enrolled in a phase 2 study (cf-301-102)
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811034/
http://dx.doi.org/10.1093/ofid/ofz360.779
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