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Abstract
References
Discussion Forum (0)
Avibactam is a serine-β-lactamase inhibitor in development with aztreonam for treatment of infections caused by drug-resistant Enterobacterales, especially carbapenem-resistant isolates co-producing serine- and metallo-β-lactamases, which are often resistant to agents from multiple drug classes. This study evaluated the in vitro activity of aztreonam-avibactam and comparators against Enterobacterales collected globally as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program from 2016 to 2019.
Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standards – Eleventh Edition. CLSI document M07-Ed11. 2018. CLSI, Wayne, PA. European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters, version 11.0, 2021. Lob SH, Kazmierczak KM, Badal RE, Hackel MA, Bouchillon SK, Biedenbach DJ, Sahm, DF. 2015. Trends in susceptibility of Escherichia coli from intra-abdominal infections to ertapenem and comparators in the United States according to data from the SMART program, 2009 to 2013. Antimicrob Agents Chemother 59:3606-3610.
Abstract number: 1593

Session Type: 1-hour Mini Oral Flash

Session Title: 1-hour Mini Oral Flash

Authors(s): K. Kazmierczak (1), F. Arhin (2), G. Stone (3), D. Sahm (1)

Authors Affiliations(s): (1) IHMA, United States, (2) Pfizer, Inc, Canada, (3) Pfizer, Inc, United States

Background:

Avibactam is a serine-β-lactamase inhibitor in development with aztreonam for treatment of infections caused by drug-resistant Enterobacterales, especially carbapenem-resistant isolates co-producing serine- and metallo-β-lactamases, which are often resistant to agents from multiple drug classes. This study evaluated the in vitro activity of aztreonam-avibactam and comparators against Enterobacterales collected globally as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program from 2016 to 2019.

Methods:

60,546 non-duplicate clinical isolates of specified bacterial species were collected in 233 medical centres located in 52 countries in Europe, Asia/Pacific (excluding China and India), Middle East/Africa, and Latin America. Susceptibility testing was performed by CLSI broth microdilution and interpreted using EUCAST 2020 breakpoints. Aztreonam-avibactam was tested at a fixed concentration of 4 mg/L avibactam. Isolates with a multidrug resistant (MDR) phenotype were defined as resistant by EUCAST guidelines to ≥3 of 7 sentinel agents (amikacin, aztreonam, cefepime, colistin, levofloxacin, meropenem, and piperacillin-tazobactam).

Results:

18.5% (n=11,214) of Enterobacterales collected globally displayed an MDR phenotype, including 33.1%, 18.7%, and 17.1% of collected Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae isolates, respectively. Aztreonam-avibactam tested with MIC90 values of 0.12 mg/L against all Enterobacterales, 0.5 mg/L against the overall set of MDR isolates, and 0.12-2 mg/L against MDR isolates of the examined species (Table). The tested comparators showed percentages of susceptibility ≤85% against the overall collection of MDR isolates, but species-specific differences were observed. Percentages of susceptibility to last-line agents were 86-99% among MDR E. coli, 76.6% (n=2650) of which were resistant to only three sentinel agents, predominantly the combination of aztreonam, cefepime and levofloxacin. Susceptibilities to comparators were ≤89% among MDR isolates of E. cloacae and K. pneumoniae, of which 51.0% and 68.1%, respectively, were resistant to ≥4 sentinel agents. A total of 99.8% (11,196 of 11,214) of MDR Enterobacterales were inhibited by ≤8 mg/L of aztreonam-avibactam, including 99.6%, 99.8% and >99.9% of E. coli, E. cloacae and K. pneumoniae isolates, respectively, with an MDR phenotype.

Conclusions:

Based on MIC90 values, aztreonam-avibactam demonstrated potent in vitro activity against multidrug resistant Enterobacterales collected globally. Aztreonam-avibactam could be an effective therapy for difficult-to-treat infections caused by drug-resistant Enterobacterales.

Keyword(s): Aztreonam-avibactam, Multi-drug Resistant, Enterobacterales

Abstract number: 1593

Session Type: 1-hour Mini Oral Flash

Session Title: 1-hour Mini Oral Flash

Authors(s): K. Kazmierczak (1), F. Arhin (2), G. Stone (3), D. Sahm (1)

Authors Affiliations(s): (1) IHMA, United States, (2) Pfizer, Inc, Canada, (3) Pfizer, Inc, United States

Background:

Avibactam is a serine-β-lactamase inhibitor in development with aztreonam for treatment of infections caused by drug-resistant Enterobacterales, especially carbapenem-resistant isolates co-producing serine- and metallo-β-lactamases, which are often resistant to agents from multiple drug classes. This study evaluated the in vitro activity of aztreonam-avibactam and comparators against Enterobacterales collected globally as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program from 2016 to 2019.

Methods:

60,546 non-duplicate clinical isolates of specified bacterial species were collected in 233 medical centres located in 52 countries in Europe, Asia/Pacific (excluding China and India), Middle East/Africa, and Latin America. Susceptibility testing was performed by CLSI broth microdilution and interpreted using EUCAST 2020 breakpoints. Aztreonam-avibactam was tested at a fixed concentration of 4 mg/L avibactam. Isolates with a multidrug resistant (MDR) phenotype were defined as resistant by EUCAST guidelines to ≥3 of 7 sentinel agents (amikacin, aztreonam, cefepime, colistin, levofloxacin, meropenem, and piperacillin-tazobactam).

Results:

18.5% (n=11,214) of Enterobacterales collected globally displayed an MDR phenotype, including 33.1%, 18.7%, and 17.1% of collected Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae isolates, respectively. Aztreonam-avibactam tested with MIC90 values of 0.12 mg/L against all Enterobacterales, 0.5 mg/L against the overall set of MDR isolates, and 0.12-2 mg/L against MDR isolates of the examined species (Table). The tested comparators showed percentages of susceptibility ≤85% against the overall collection of MDR isolates, but species-specific differences were observed. Percentages of susceptibility to last-line agents were 86-99% among MDR E. coli, 76.6% (n=2650) of which were resistant to only three sentinel agents, predominantly the combination of aztreonam, cefepime and levofloxacin. Susceptibilities to comparators were ≤89% among MDR isolates of E. cloacae and K. pneumoniae, of which 51.0% and 68.1%, respectively, were resistant to ≥4 sentinel agents. A total of 99.8% (11,196 of 11,214) of MDR Enterobacterales were inhibited by ≤8 mg/L of aztreonam-avibactam, including 99.6%, 99.8% and >99.9% of E. coli, E. cloacae and K. pneumoniae isolates, respectively, with an MDR phenotype.

Conclusions:

Based on MIC90 values, aztreonam-avibactam demonstrated potent in vitro activity against multidrug resistant Enterobacterales collected globally. Aztreonam-avibactam could be an effective therapy for difficult-to-treat infections caused by drug-resistant Enterobacterales.

Keyword(s): Aztreonam-avibactam, Multi-drug Resistant, Enterobacterales

In Vitro activity of aztreonam/avibactam and comparator agents against multidrug-resistant Enterobacterales collected globally as part of the ATLAS Surveillance Program, 2016-2019
Krystyna Kazmierczak
Krystyna Kazmierczak
Author(s): Francis Arhin,  
Francis Arhin
Affiliations:
Pfizer, Inc.
Gregory Stone,  
Gregory Stone
Affiliations:
Pfizer, Inc.
Daniel Sahm
Daniel Sahm
Affiliations:
IHMA
ESCMID eAcademy. Kazmierczak K. 07/09/2021; 332700; 1593; Disclosure(s): This study was sponsored by Pfizer and funded in whole or in part with Federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority, under OT number HHSO100201500029C. IHMA received financial support from Pfizer in connection with the study and the development of this poster. KK and DS are employees of IHMA. FA and GS are employees of Pfizer.
Abstract
References
Discussion Forum (0)
Avibactam is a serine-β-lactamase inhibitor in development with aztreonam for treatment of infections caused by drug-resistant Enterobacterales, especially carbapenem-resistant isolates co-producing serine- and metallo-β-lactamases, which are often resistant to agents from multiple drug classes. This study evaluated the in vitro activity of aztreonam-avibactam and comparators against Enterobacterales collected globally as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program from 2016 to 2019.
Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standards – Eleventh Edition. CLSI document M07-Ed11. 2018. CLSI, Wayne, PA. European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters, version 11.0, 2021. Lob SH, Kazmierczak KM, Badal RE, Hackel MA, Bouchillon SK, Biedenbach DJ, Sahm, DF. 2015. Trends in susceptibility of Escherichia coli from intra-abdominal infections to ertapenem and comparators in the United States according to data from the SMART program, 2009 to 2013. Antimicrob Agents Chemother 59:3606-3610.
Abstract number: 1593

Session Type: 1-hour Mini Oral Flash

Session Title: 1-hour Mini Oral Flash

Authors(s): K. Kazmierczak (1), F. Arhin (2), G. Stone (3), D. Sahm (1)

Authors Affiliations(s): (1) IHMA, United States, (2) Pfizer, Inc, Canada, (3) Pfizer, Inc, United States

Background:

Avibactam is a serine-β-lactamase inhibitor in development with aztreonam for treatment of infections caused by drug-resistant Enterobacterales, especially carbapenem-resistant isolates co-producing serine- and metallo-β-lactamases, which are often resistant to agents from multiple drug classes. This study evaluated the in vitro activity of aztreonam-avibactam and comparators against Enterobacterales collected globally as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program from 2016 to 2019.

Methods:

60,546 non-duplicate clinical isolates of specified bacterial species were collected in 233 medical centres located in 52 countries in Europe, Asia/Pacific (excluding China and India), Middle East/Africa, and Latin America. Susceptibility testing was performed by CLSI broth microdilution and interpreted using EUCAST 2020 breakpoints. Aztreonam-avibactam was tested at a fixed concentration of 4 mg/L avibactam. Isolates with a multidrug resistant (MDR) phenotype were defined as resistant by EUCAST guidelines to ≥3 of 7 sentinel agents (amikacin, aztreonam, cefepime, colistin, levofloxacin, meropenem, and piperacillin-tazobactam).

Results:

18.5% (n=11,214) of Enterobacterales collected globally displayed an MDR phenotype, including 33.1%, 18.7%, and 17.1% of collected Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae isolates, respectively. Aztreonam-avibactam tested with MIC90 values of 0.12 mg/L against all Enterobacterales, 0.5 mg/L against the overall set of MDR isolates, and 0.12-2 mg/L against MDR isolates of the examined species (Table). The tested comparators showed percentages of susceptibility ≤85% against the overall collection of MDR isolates, but species-specific differences were observed. Percentages of susceptibility to last-line agents were 86-99% among MDR E. coli, 76.6% (n=2650) of which were resistant to only three sentinel agents, predominantly the combination of aztreonam, cefepime and levofloxacin. Susceptibilities to comparators were ≤89% among MDR isolates of E. cloacae and K. pneumoniae, of which 51.0% and 68.1%, respectively, were resistant to ≥4 sentinel agents. A total of 99.8% (11,196 of 11,214) of MDR Enterobacterales were inhibited by ≤8 mg/L of aztreonam-avibactam, including 99.6%, 99.8% and >99.9% of E. coli, E. cloacae and K. pneumoniae isolates, respectively, with an MDR phenotype.

Conclusions:

Based on MIC90 values, aztreonam-avibactam demonstrated potent in vitro activity against multidrug resistant Enterobacterales collected globally. Aztreonam-avibactam could be an effective therapy for difficult-to-treat infections caused by drug-resistant Enterobacterales.

Keyword(s): Aztreonam-avibactam, Multi-drug Resistant, Enterobacterales

Abstract number: 1593

Session Type: 1-hour Mini Oral Flash

Session Title: 1-hour Mini Oral Flash

Authors(s): K. Kazmierczak (1), F. Arhin (2), G. Stone (3), D. Sahm (1)

Authors Affiliations(s): (1) IHMA, United States, (2) Pfizer, Inc, Canada, (3) Pfizer, Inc, United States

Background:

Avibactam is a serine-β-lactamase inhibitor in development with aztreonam for treatment of infections caused by drug-resistant Enterobacterales, especially carbapenem-resistant isolates co-producing serine- and metallo-β-lactamases, which are often resistant to agents from multiple drug classes. This study evaluated the in vitro activity of aztreonam-avibactam and comparators against Enterobacterales collected globally as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program from 2016 to 2019.

Methods:

60,546 non-duplicate clinical isolates of specified bacterial species were collected in 233 medical centres located in 52 countries in Europe, Asia/Pacific (excluding China and India), Middle East/Africa, and Latin America. Susceptibility testing was performed by CLSI broth microdilution and interpreted using EUCAST 2020 breakpoints. Aztreonam-avibactam was tested at a fixed concentration of 4 mg/L avibactam. Isolates with a multidrug resistant (MDR) phenotype were defined as resistant by EUCAST guidelines to ≥3 of 7 sentinel agents (amikacin, aztreonam, cefepime, colistin, levofloxacin, meropenem, and piperacillin-tazobactam).

Results:

18.5% (n=11,214) of Enterobacterales collected globally displayed an MDR phenotype, including 33.1%, 18.7%, and 17.1% of collected Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae isolates, respectively. Aztreonam-avibactam tested with MIC90 values of 0.12 mg/L against all Enterobacterales, 0.5 mg/L against the overall set of MDR isolates, and 0.12-2 mg/L against MDR isolates of the examined species (Table). The tested comparators showed percentages of susceptibility ≤85% against the overall collection of MDR isolates, but species-specific differences were observed. Percentages of susceptibility to last-line agents were 86-99% among MDR E. coli, 76.6% (n=2650) of which were resistant to only three sentinel agents, predominantly the combination of aztreonam, cefepime and levofloxacin. Susceptibilities to comparators were ≤89% among MDR isolates of E. cloacae and K. pneumoniae, of which 51.0% and 68.1%, respectively, were resistant to ≥4 sentinel agents. A total of 99.8% (11,196 of 11,214) of MDR Enterobacterales were inhibited by ≤8 mg/L of aztreonam-avibactam, including 99.6%, 99.8% and >99.9% of E. coli, E. cloacae and K. pneumoniae isolates, respectively, with an MDR phenotype.

Conclusions:

Based on MIC90 values, aztreonam-avibactam demonstrated potent in vitro activity against multidrug resistant Enterobacterales collected globally. Aztreonam-avibactam could be an effective therapy for difficult-to-treat infections caused by drug-resistant Enterobacterales.

Keyword(s): Aztreonam-avibactam, Multi-drug Resistant, Enterobacterales

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