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1358. In vitro Activity of Ceftazidime–Avibactam and Comparator Agents Against Pseudomonas aeruginosa Causing Intra-Abdominal, Lower Respiratory, and Urinary Tract Infections Collected in Latin America as Part of the INFORM Global Surveillance Program, 2012–2016

BACKGROUND: The non-β-lactam β-lactamase inhibitor avibactam (AVI) is active against class A, C, and some class D β-lactamases, in combination with ceftazidime (CAZ) has been approved by the FDA and EMA for treatment of intra-abdominal infections (IAI), lower respiratory tract infections (LRTI), and...

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Autores principales: Wise, Mark, Kazmierczak, Krystyna, Stone, Gregory G, 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/PMC6252817/
http://dx.doi.org/10.1093/ofid/ofy210.1189
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author Wise, Mark
Kazmierczak, Krystyna
Stone, Gregory G
Sahm, Dan
author_facet Wise, Mark
Kazmierczak, Krystyna
Stone, Gregory G
Sahm, Dan
author_sort Wise, Mark
collection PubMed
description BACKGROUND: The non-β-lactam β-lactamase inhibitor avibactam (AVI) is active against class A, C, and some class D β-lactamases, in combination with ceftazidime (CAZ) has been approved by the FDA and EMA for treatment of intra-abdominal infections (IAI), lower respiratory tract infections (LRTI), and urinary tract infections (UTI). This study reports on the in vitro activity of (CAZ-AVI) and comparators vs. P. aeruginosa collected from IAIs, LRTIs, and UTIs in Latin America as part of the INFORM surveillance study from 2012 to 2016. METHODS: For INFORM surveillance over 2012–2016 in Latin America, 1,595 nonduplicate P. aeruginosa isolates linked to IAIs, LRTIs, and UTIs were collected from 26 clinical sites in six countries. Susceptibility testing was done using broth microdilution according to CLSI guidelines and using CLSI 2018 breakpoints. CAZ was tested with AVI at a fixed concentration of 4 mg/mL. Meropenem (MEM) nonsusceptible organisms were screened for β-lactamase genes by PCR. RESULTS: Among the full collection of P. aeruginosa, CAZ-AVI showed consistently higher % susceptibilities than all comparators except for colistin (CST) for all infection sources. The addition of AVI to CAZ resulted in an increase in susceptibility ranging from 14.2% (IAI) to 19.5% (UTI). Against the non-metallo-β-lactamase (MBL) harboring subset, CAZ-AVI showed extremely potent activity (MIC(90), 8 mg/mL) for all infection sources. In this subset, the activity of CAZ-AVI approached that of colistin for IAIs (susceptibility of 93.3% vs. 96.4%, respectively). CONCLUSION: CAZ-AVI demonstrated very good in vitro activity against P. aeruginosa isolates, especially those without MBLs. More isolates were susceptible to CAZ-AVI than to MEM for all infection types. DISCLOSURES: M. Wise, Pfizer Inc.: Consultant, Consulting fee. IHMA, Inc.: Employee, Salary. K. Kazmierczak, Pfizer Inc.: Consultant, Consulting fee. IHMA, Inc.: Employee, Salary. G. G. Stone, Pfizer Inc.: Employee, Salary. AstraZeneca: Former Employee and Shareholder, Salary. D. Sahm, Pfizer Inc.: Consultant, Consulting fee. IHMA, Inc.: Employee, Salary.
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spelling pubmed-62528172018-11-28 1358. In vitro Activity of Ceftazidime–Avibactam and Comparator Agents Against Pseudomonas aeruginosa Causing Intra-Abdominal, Lower Respiratory, and Urinary Tract Infections Collected in Latin America as Part of the INFORM Global Surveillance Program, 2012–2016 Wise, Mark Kazmierczak, Krystyna Stone, Gregory G Sahm, Dan Open Forum Infect Dis Abstracts BACKGROUND: The non-β-lactam β-lactamase inhibitor avibactam (AVI) is active against class A, C, and some class D β-lactamases, in combination with ceftazidime (CAZ) has been approved by the FDA and EMA for treatment of intra-abdominal infections (IAI), lower respiratory tract infections (LRTI), and urinary tract infections (UTI). This study reports on the in vitro activity of (CAZ-AVI) and comparators vs. P. aeruginosa collected from IAIs, LRTIs, and UTIs in Latin America as part of the INFORM surveillance study from 2012 to 2016. METHODS: For INFORM surveillance over 2012–2016 in Latin America, 1,595 nonduplicate P. aeruginosa isolates linked to IAIs, LRTIs, and UTIs were collected from 26 clinical sites in six countries. Susceptibility testing was done using broth microdilution according to CLSI guidelines and using CLSI 2018 breakpoints. CAZ was tested with AVI at a fixed concentration of 4 mg/mL. Meropenem (MEM) nonsusceptible organisms were screened for β-lactamase genes by PCR. RESULTS: Among the full collection of P. aeruginosa, CAZ-AVI showed consistently higher % susceptibilities than all comparators except for colistin (CST) for all infection sources. The addition of AVI to CAZ resulted in an increase in susceptibility ranging from 14.2% (IAI) to 19.5% (UTI). Against the non-metallo-β-lactamase (MBL) harboring subset, CAZ-AVI showed extremely potent activity (MIC(90), 8 mg/mL) for all infection sources. In this subset, the activity of CAZ-AVI approached that of colistin for IAIs (susceptibility of 93.3% vs. 96.4%, respectively). CONCLUSION: CAZ-AVI demonstrated very good in vitro activity against P. aeruginosa isolates, especially those without MBLs. More isolates were susceptible to CAZ-AVI than to MEM for all infection types. DISCLOSURES: M. Wise, Pfizer Inc.: Consultant, Consulting fee. IHMA, Inc.: Employee, Salary. K. Kazmierczak, Pfizer Inc.: Consultant, Consulting fee. IHMA, Inc.: Employee, Salary. G. G. Stone, Pfizer Inc.: Employee, Salary. AstraZeneca: Former Employee and Shareholder, Salary. D. Sahm, Pfizer Inc.: Consultant, Consulting fee. IHMA, Inc.: Employee, Salary. Oxford University Press 2018-11-26 /pmc/articles/PMC6252817/ http://dx.doi.org/10.1093/ofid/ofy210.1189 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
Wise, Mark
Kazmierczak, Krystyna
Stone, Gregory G
Sahm, Dan
1358. In vitro Activity of Ceftazidime–Avibactam and Comparator Agents Against Pseudomonas aeruginosa Causing Intra-Abdominal, Lower Respiratory, and Urinary Tract Infections Collected in Latin America as Part of the INFORM Global Surveillance Program, 2012–2016
title 1358. In vitro Activity of Ceftazidime–Avibactam and Comparator Agents Against Pseudomonas aeruginosa Causing Intra-Abdominal, Lower Respiratory, and Urinary Tract Infections Collected in Latin America as Part of the INFORM Global Surveillance Program, 2012–2016
title_full 1358. In vitro Activity of Ceftazidime–Avibactam and Comparator Agents Against Pseudomonas aeruginosa Causing Intra-Abdominal, Lower Respiratory, and Urinary Tract Infections Collected in Latin America as Part of the INFORM Global Surveillance Program, 2012–2016
title_fullStr 1358. In vitro Activity of Ceftazidime–Avibactam and Comparator Agents Against Pseudomonas aeruginosa Causing Intra-Abdominal, Lower Respiratory, and Urinary Tract Infections Collected in Latin America as Part of the INFORM Global Surveillance Program, 2012–2016
title_full_unstemmed 1358. In vitro Activity of Ceftazidime–Avibactam and Comparator Agents Against Pseudomonas aeruginosa Causing Intra-Abdominal, Lower Respiratory, and Urinary Tract Infections Collected in Latin America as Part of the INFORM Global Surveillance Program, 2012–2016
title_short 1358. In vitro Activity of Ceftazidime–Avibactam and Comparator Agents Against Pseudomonas aeruginosa Causing Intra-Abdominal, Lower Respiratory, and Urinary Tract Infections Collected in Latin America as Part of the INFORM Global Surveillance Program, 2012–2016
title_sort 1358. in vitro activity of ceftazidime–avibactam and comparator agents against pseudomonas aeruginosa causing intra-abdominal, lower respiratory, and urinary tract infections collected in latin america as part of the inform global surveillance program, 2012–2016
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252817/
http://dx.doi.org/10.1093/ofid/ofy210.1189
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