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1355. Global Activity of Imipenem–Relebactam and Comparators Against Clinical Gram-Negative Pathogens – SMART 2017

BACKGROUND: Relebactam (REL), formerly MK-7655, is a β-lactamase inhibitor of class A and C β-lactamases that is in development in combination with imipenem (IMI). In this study, we evaluated the activity of IMI/REL against recent clinical isolates of Gram-negative bacilli (GNB) collected globally a...

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Autores principales: Lob, Sibylle, Kazmierczak, Krystyna, Hoban, Daryl, Hackel, Meredith, Young, Katherine, Motyl, Mary, Sahm, Dan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252988/
http://dx.doi.org/10.1093/ofid/ofy210.1186
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author Lob, Sibylle
Kazmierczak, Krystyna
Hoban, Daryl
Hackel, Meredith
Young, Katherine
Motyl, Mary
Sahm, Dan
author_facet Lob, Sibylle
Kazmierczak, Krystyna
Hoban, Daryl
Hackel, Meredith
Young, Katherine
Motyl, Mary
Sahm, Dan
author_sort Lob, Sibylle
collection PubMed
description BACKGROUND: Relebactam (REL), formerly MK-7655, is a β-lactamase inhibitor of class A and C β-lactamases that is in development in combination with imipenem (IMI). In this study, we evaluated the activity of IMI/REL against recent clinical isolates of Gram-negative bacilli (GNB) collected globally as part of the SMART surveillance program. METHODS: In 2017, 188 hospitals in 54 countries each collected up to 100 consecutive Gram-negative aerobic or facultatively anaerobic pathogens from lower respiratory tract infections, 75 from intra-abdominal infections, and 75 from urinary tract infections. MICs were determined for 41,319 GNB, including 30,864 Enterobacteriaceae and 6,933 P. aeruginosa isolates, using CLSI broth microdilution and interpreted with CLSI breakpoints; for comparison purposes, IMI susceptible breakpoints were applied to IMI/REL. RESULTS: Susceptibilities to IMI/REL and comparators of the 10 most commonly found Enterobacteriaceae species and P. aeruginosa are shown below. [Image: see text] IMI/REL showed activity >90% against seven of the top 10 Enterobacteriaceae species, typically ~5 to 35 percentage points higher than the β-lactam comparators, and it was active against 89% of P. aeruginosa, ~15 to 25 percentage points higher than the β-lactam comparators. Only amikacin and colistin showed similar or higher activity for most species, with colistin showing little activity against Proteeae and Serratia. CONCLUSION: IMI/REL could provide an important treatment option against infections with Gram-negative pathogens, especially since amikacin and colistin are associated with significant morbidity, including nephrotoxicity and ototoxicity, and amikacin is typically used in combination with another antibiotic. DISCLOSURES: S. Lob, IHMA, Inc.: Employee, Salary. Merck: Consultant, Consulting fee. K. Kazmierczak, Merck: Consultant, Consulting fee. IHMA, Inc.: Employee, Salary. D. Hoban, IHMA, Inc.: Employee, Salary. Merck: Consultant, Consulting fee. M. Hackel, IHMA, Inc.: Employee, Salary. Merck: Consultant, Consulting fee. K. Young, Merck: Employee and Shareholder, Dividends and Salary. M. Motyl, Merck: Employee and Shareholder, Dividends and Salary. D. Sahm, IHMA, Inc.: Employee, Salary. Merck: Consultant, Consulting fee.
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spelling pubmed-62529882018-11-28 1355. Global Activity of Imipenem–Relebactam and Comparators Against Clinical Gram-Negative Pathogens – SMART 2017 Lob, Sibylle Kazmierczak, Krystyna Hoban, Daryl Hackel, Meredith Young, Katherine Motyl, Mary Sahm, Dan Open Forum Infect Dis Abstracts BACKGROUND: Relebactam (REL), formerly MK-7655, is a β-lactamase inhibitor of class A and C β-lactamases that is in development in combination with imipenem (IMI). In this study, we evaluated the activity of IMI/REL against recent clinical isolates of Gram-negative bacilli (GNB) collected globally as part of the SMART surveillance program. METHODS: In 2017, 188 hospitals in 54 countries each collected up to 100 consecutive Gram-negative aerobic or facultatively anaerobic pathogens from lower respiratory tract infections, 75 from intra-abdominal infections, and 75 from urinary tract infections. MICs were determined for 41,319 GNB, including 30,864 Enterobacteriaceae and 6,933 P. aeruginosa isolates, using CLSI broth microdilution and interpreted with CLSI breakpoints; for comparison purposes, IMI susceptible breakpoints were applied to IMI/REL. RESULTS: Susceptibilities to IMI/REL and comparators of the 10 most commonly found Enterobacteriaceae species and P. aeruginosa are shown below. [Image: see text] IMI/REL showed activity >90% against seven of the top 10 Enterobacteriaceae species, typically ~5 to 35 percentage points higher than the β-lactam comparators, and it was active against 89% of P. aeruginosa, ~15 to 25 percentage points higher than the β-lactam comparators. Only amikacin and colistin showed similar or higher activity for most species, with colistin showing little activity against Proteeae and Serratia. CONCLUSION: IMI/REL could provide an important treatment option against infections with Gram-negative pathogens, especially since amikacin and colistin are associated with significant morbidity, including nephrotoxicity and ototoxicity, and amikacin is typically used in combination with another antibiotic. DISCLOSURES: S. Lob, IHMA, Inc.: Employee, Salary. Merck: Consultant, Consulting fee. K. Kazmierczak, Merck: Consultant, Consulting fee. IHMA, Inc.: Employee, Salary. D. Hoban, IHMA, Inc.: Employee, Salary. Merck: Consultant, Consulting fee. M. Hackel, IHMA, Inc.: Employee, Salary. Merck: Consultant, Consulting fee. K. Young, Merck: Employee and Shareholder, Dividends and Salary. M. Motyl, Merck: Employee and Shareholder, Dividends and Salary. D. Sahm, IHMA, Inc.: Employee, Salary. Merck: Consultant, Consulting fee. Oxford University Press 2018-11-26 /pmc/articles/PMC6252988/ http://dx.doi.org/10.1093/ofid/ofy210.1186 Text en © The Author(s) 2018. 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
Lob, Sibylle
Kazmierczak, Krystyna
Hoban, Daryl
Hackel, Meredith
Young, Katherine
Motyl, Mary
Sahm, Dan
1355. Global Activity of Imipenem–Relebactam and Comparators Against Clinical Gram-Negative Pathogens – SMART 2017
title 1355. Global Activity of Imipenem–Relebactam and Comparators Against Clinical Gram-Negative Pathogens – SMART 2017
title_full 1355. Global Activity of Imipenem–Relebactam and Comparators Against Clinical Gram-Negative Pathogens – SMART 2017
title_fullStr 1355. Global Activity of Imipenem–Relebactam and Comparators Against Clinical Gram-Negative Pathogens – SMART 2017
title_full_unstemmed 1355. Global Activity of Imipenem–Relebactam and Comparators Against Clinical Gram-Negative Pathogens – SMART 2017
title_short 1355. Global Activity of Imipenem–Relebactam and Comparators Against Clinical Gram-Negative Pathogens – SMART 2017
title_sort 1355. global activity of imipenem–relebactam and comparators against clinical gram-negative pathogens – smart 2017
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252988/
http://dx.doi.org/10.1093/ofid/ofy210.1186
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