IN VITRO ACTIVITY OF AZTREONAM-AVIBACTAM AGAINST CLINICAL ISOLATES OF ENTEROBACTERALES COLLECTED IN BRAZIL FOR THE ATLAS SURVEILLANCE PROGRAM, 2018–2023

Aztreonam-avibactam (ATM-AVI) was developed for the treatment of infections caused by Enterobacterales, particularly carbapenem-resistant isolates that produce metallo-β-lactamases (MBLs). Aztreonam is stable to hydrolysis by MBLs, while avibactam inhibits class A and C β-lactamases, which may also be co-produced with MBLs that inactivate aztreonam. In this study, the in vitro activity of ATM-AVI was evaluated against clinical isolates of Enterobacterales, both MBL producers and non-producers, collected as part of the global ATLAS surveillance program. A total of 3151 non-duplicate Enterobacterales isolates collected from different infection sites in Brazilian hospitals between 2018 and 2023 were evaluated. Susceptibility testing was performed using broth microdilution. Antimicrobial susceptibility profiles were interpreted according to BrCAST (2025) breakpoints, including the established breakpoint for ATM-AVI of > 4 mg/L. Carbapenemase-encoding genes were investigated by PCR followed by sequencing. The majority of Enterobacterales species evaluated were Klebsiella pneumoniae (36.0%; n = 1137), followed by Escherichia coli (31.6%; n = 998) and Enterobacter sp. (12.6%; n = 399). Overall, ATM-AVI inhibited 100% of isolates (MIC50/90, 0.06/0.25 mg/L), including those producing carbapenemases (588/960 isolates tested [61.2%]). Overall susceptibility to colistin (MIC50/90, 0.25/>8 mg/L), meropenem (MIC50/90, ≤ 0.06/> 16 mg/L), cefepime (MIC50/90, ≤ 0.125/> 32 mg/L), and aztreonam (MIC50/90, 0.25/> 64 mg/L) was 85.7%, 80.6%, 58.4%, and 56.9%, respectively. Among the 960 isolates tested for carbapenemases, 119 (12.4%) were positive for NDM-1 and 492 (51.2%) for KPC. Twenty-five isolates showed coproduction of two carbapenemases, 24 with KPC-2+NDM-1 and one with KPC-2+IMP-1. All 492 KPC-positive isolates were 100% and 94.72% susceptible to ATM-AVI and ceftazidime-avibactam, respectively. ATM-AVI demonstrated excellent in vitro activity, inhibiting 100% of Enterobacterales isolates, both carbapenemase producers and non-producers, including MBLs. Antibiotics that retain activity against MBL-producing bacteria represent an urgent medical need, especially given the rising prevalence of severe infections caused by these difficult-to-treat microorganisms.