DOI: 10.1128/spectrum.00762-26 ISSN: 2165-0497
In vitro
susceptibility testing of aztreonam-avibactam against predominantly NDM-producing
Enterobacterales
in Peru
Coralith Garcia, Yelinda Reyes, Lizeth Astocondor, Liliana Caytuiro, Maribel Riveros, Catherine Amaro, Stephanie Andrade, Luis Hernández, Roxana Sandoval, Giancarlo Peréz-Lazo, Carolina Cucho, Manuel Melo, Ivan Sabogal, Liz Lino, Edwin Cuaresma, Araceli Olivares, Arnaldo Lachira, Kattya Michilot, Juan Ramos, Roberto Diaz, Alexander Briones, Segundo Burgos, Diego Cuicapuza, Pablo Tsukayama, Fiorella Krapp ABSTRACT
Metallo-β-lactamase-producing
Enterobacterales
are distributed worldwide, but some Latin American countries show a higher prevalence. Aztreonam-avibactam (ATM-AVI) may be an option for treating these infections. To evaluate
in vitro
susceptibility to aztreonam (ATM) alone and ATM-AVI in carbapenem-non-susceptible
Enterobacterales
isolates, based on the type of carbapenemase production, we prospectively collected carbapenem-non-susceptible
Enterobacterales
isolates from Peruvian hospitals during 2023–2024. Identification and susceptibility testing were performed by commercial panels and disk diffusion. Carbapenemases were detected by immunochromatography. ATM and ATM-AVI MICs were determined using broth microdilution panels with avibactam fixed at 4 µg/mL. The non-susceptible isolates to ATM-AVI and those with double production of carbapenemases underwent whole-genome sequencing. A total of 438
Enterobacterales
isolates were analyzed; carbapenemase production was detected in 422 (96.3%) and NDM was the most frequent (61.9%). Coproduction of NDM + KPC in
K. pneumoniae
and NDM + OXA-48-like in
Escherichia coli
was observed. Overall, 99.3% were susceptible to ATM-AVI; MIC
50
and MIC
90
were 0.12 and 2 µg/mL, respectively. Overall,
K. pneumoniae
isolates had lower MIC
50
and MIC
90
values to ATM-AVI (0.12 and 0.5 µg/mL) compared to
E. coli
(0.5 and 4 µg/mL). Three
E. coli
isolates were resistant to ATM-AVI (MIC ≥ 8 µg/mL), they belonged to ST410, ST167, and ST10 and harbored a YRIN insertion in PBP3 along with CYM-type, PER-type, and CTX-M-type beta-lactamase genes. ATM-AVI demonstrated potent activity against carbapenem-non-susceptible
Enterobacterales
, including those producing NDM, which is the carbapenemase most frequently detected in Peruvian hospitals.
IMPORTANCE
Enterobacterales
isolates cause common illnesses in humans. Carbapenems are the antibiotics used to treat several of these infections, and increasingly, isolates resistant to these antibiotics are found. The most important mechanism of resistance to carbapenem among
Enterobacterales
is the production of enzymes called carbapenemases. Our results allowed us to recognize that NDM is the most frequent type of carbapenemase detected. Most of the antimicrobials available do not cover the
E
nterobacterales carrying NDM carbapenemase. In this scenario, we found that the new combination of drugs, aztreonam-avibactam, has high
in vitro
efficacy against most of the carbapenem-resistant isolates and against those isolates carrying NDM carbapenemase.