Aztreonam/avibactam activity against clinical isolates of Enterobacterales collected in Europe, Asia and Latin America in 2019

Abstract

Abstract Background Aztreonam is a monobactam stable to hydrolysis by metallo-β-lactamases (MBLs) and avibactam is a non-β-lactam β-lactamase inhibitor that effectively inhibits serine carbapenemases (CPs). Aztreonam/avibactam is under clinical development for treatment of serious infections caused by Gram-negative bacteria, including MBL-producers. Objectives To evaluate the in vitro activity of aztreonam/avibactam against clinical Enterobacterales isolates. Methods 8787 Enterobacterales were collected consecutively from 64 medical centres located in Western Europe (W-EU; n = 4616; 26 centres in 10 nations), Eastern Europe (E-EU; n = 1554; 11 centres in 9 nations), the Asia-Pacific region (APAC; n = 1456; 17 centres in 9 nations), and Latin America (LATAM; n = 1161; 10 centres in 6 nations). Susceptibility tests were performed by reference broth microdilution methods and interpreted according to EUCAST criteria. Results 99.9% of isolates were inhibited at aztreonam/avibactam MIC of ≤8 mg/L (MIC50/90, ≤0.03/0.12 mg/L), including 99.7% of carbapenem-resistant (CRE; n = 396; MIC50/90, 0.25/0.5 mg/L) and 99.7% of multidrug-resistant isolates (n = 1706; MIC50/90, 0.06/0.5 mg/L). CRE rates were 1.2%, 12.9%, 5.2%, and 5.8% in W-EU, E-EU, APAC, and LATAM, respectively (4.5% overall). A CP was identified in 90.2% of CRE isolates. The most common CPs were variants of KPC (35.9% of CRE), NDM (29.0%), and OXA-48 (26.8%). The highest aztreonam/avibactam MIC value among MBL-producers (n = 110; MIC50/90, 0.12/0.5 mg/L) was 2 mg/L. Susceptibility rates for ceftriaxone, meropenem, levofloxacin, and amikacin were highest in W-EU (80.9%, 99.0%, 80.7% and 97.9%, respectively) and lowest in E-EU (52.0%, 88.9%, 54.1%, and 84.2%, respectively). Conclusions Our results support clinical development of aztreonam/avibactam to treat infections caused by Enterobacterales, including MBL-producers.