activity of aztreonam/avibactam and comparators against Enterobacterales isolates from patients with hospital-acquired pneumonia, ventilator-associated pneumonia, and complicated intra-abdominal infections (ATLAS, 2021–2022)
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
Abstract Background Hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP) and complicated intra-abdominal infections (cIAIs) caused by carbapenem-resistant Enterobacterales (CRE) are associated with high mortality. Metallo-β-lactamase (MBL)-producing strains represent therapeutic challenge compromising β-lactams and limiting treatment options. Aztreonam/avibactam is a novel combination designed to overcome MBL-mediated resistance. s1 Objectives To evaluateactivity of aztreonam/avibactam and comparators against Enterobacterales from patients with HAP, VAP or cIAI collected globally (Africa/Middle East, Asia-Pacific, Europe and Latin America) during 2021–22 ATLAS surveillance program focusing on MBL-positive strains. s2 Methods 14 564 Enterobacterales isolates were tested by broth microdilution per CLSI guidelines. CRE isolates underwent molecular characterization and MBL-positive isolates underwent additional molecular and susceptibility analysis, including cefiderocol. MBL-positiveisolates were screened for PBP3 mutations by whole-genome sequencing. MICs were interpreted using EUCAST breakpoints as appropriate. s3 Results Aztreonam/avibactam was 99.5% susceptible (MIC ≤4 mg/L) for all Enterobacterales (MIC0.25 mg/L) and maintained high susceptibility against MDR (98.9%), ESBL (99.0%) and CRE (96.4%). Among 577 MBL-positive isolates (88% NDM), aztreonam/avibactam was 95.1% susceptible, compared with cefiderocol (50.3%), colistin (73.8%) and tigecycline (95.0
Abstract
Abstract Background Hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP) and complicated intra-abdominal infections (cIAIs) caused by carbapenem-resistant Enterobacterales (CRE) are associated with high mortality. Metallo-β-lactamase (MBL)-producing strains represent therapeutic challenge compromising β-lactams and limiting treatment options. Aztreonam/avibactam is a novel combination designed to overcome MBL-mediated resistance. s1 Objectives To evaluateactivity of aztreonam/avibactam and comparators against Enterobacterales from patients with HAP, VAP or cIAI collected globally (Africa/Middle East, Asia-Pacific, Europe and Latin America) during 2021–22 ATLAS surveillance program focusing on MBL-positive strains. s2 Methods 14 564 Enterobacterales isolates were tested by broth microdilution per CLSI guidelines. CRE isolates underwent molecular characterization and MBL-positive isolates underwent additional molecular and susceptibility analysis, including cefiderocol. MBL-positiveisolates were screened for PBP3 mutations by whole-genome sequencing. MICs were interpreted using EUCAST breakpoints as appropriate. s3 Results Aztreonam/avibactam was 99.5% susceptible (MIC ≤4 mg/L) for all Enterobacterales (MIC0.25 mg/L) and maintained high susceptibility against MDR (98.9%), ESBL (99.0%) and CRE (96.4%). Among 577 MBL-positive isolates (88% NDM), aztreonam/avibactam was 95.1% susceptible, compared with cefiderocol (50.3%), colistin (73.8%) and tigecycline (95.0%). Activity was consistent across regions and carbapenemase genotypes, including co-producers of multiple β-lactamases. However,isolates harbouring PBP3 insertions (YRIK/YRIN) and plasmid-mediated AmpC β-lactamases (= 35) were 31.4% susceptible (MIC ≤4 mg/L). s4 Conclusions Aztreonam/avibactam demonstrated potent and consistentactivity against Enterobacterales causing serious hospital infections, including MBL-producing CRE. These findings underscore aztreonam/avibactam’s therapeutic potential and the need for rapid diagnostics and global surveillance to guide regional stewardship and treatment strategies for MDR infections. s5