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, EnterobacteralesSession 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