# P-1337. Trends in the co-carriage of multiple carbapenemases among clinical Enterobacterales isolates and the in vitro activity of aztreonam-avibactam, ATLAS 2019-2023

## TL;DR

This study examines the increasing trend of bacteria carrying multiple antibiotic resistance genes and finds that a drug combination remains effective against them.

## Contribution

The study reports a significant rise in co-carriage of multiple carbapenemase genes and confirms aztreonam-avibactam's efficacy against these multidrug-resistant isolates.

## Key findings

- The proportion of isolates carrying two carbapenemase genes increased from 10% in 2019 to 21% in 2023.
- Aztreonam-avibactam showed high in vitro activity (97.7-100% susceptibility) against isolates with single or multiple carbapenemase genes.
- The most common dual carbapenemase genotype was blaNDM+blaOXA-48-like, accounting for 84% of multiple-carbapenemase isolates.

## Abstract

Aztreonam-avibactam (ATM-AVI) is a β-lactam/β-lactamase inhibitor combination to treat infections caused by Gram-negative organisms, particularly those carrying metallo-β-lactamases (MBLs) and other β-lactamases. Aztreonam is stable to hydrolysis by MBLs and avibactam inhibits Class A, C, and some Class D enzymes. We examined ATM-AVI activity against Enterobacterales isolates producing one or more carbapenemase and the frequency of co-production of carbapenemases among isolates collected as a part of the ATLAS global surveillance program (2019-2023).

88,196 isolates from 226 medical centers in 56 countries (excluding mainland China, Canada, and the USA) were collected and tested for susceptibility using the broth microdilution method according to CLSI guidelines. Analysis was performed with CLSI 2024 breakpoints. Isolates testing with meropenem MIC values >1 µg/mL or Escherichia coli, Klebsiella pneumoniae, K. oxytoca, or Proteus mirabilis isolates testing with ceftazidime and/or aztreonam MIC values >2 µg/mL were screened for β-lactamase genes by PCR, which were sequenced when identified.

One or more carbapenemase gene was identified in 7312 isolates. In 2019, 10% of carbapenemase-positive isolates carried two carbapenemase genes, which increased to 21% by 2023 (Figure 1). Among isolates carrying two carbapenemase genes, the blaNDM+blaOXA-48-like genotype accounted for 84%, while blaNDM+blaKPC (7%), blaVIM+blaKPC (5%) and blaNDM+blaGES (2%) were the other most common genotypes (Figure 2). ATM-AVI was active in vitro against (genotype, percent susceptible): Single-carbapenemase positive, 97.7%; multiple-carbapenemase-positive, 98.1%; blaNDM+blaOXA-48-like, 98.0%; blaNDM+blaKPC, 98.8%; blaVIM+blaKPC, 98.1%, and blaNDM+blaGES, 100% (Table 1).

Enterobacterales isolates that produce multiple carbapenemases are on the rise. While the NDM+OXA-48-like combination is still dominant, a plethora of combinations has been observed. While these organisms present complex resistance patterns, ATM-AVI demonstrated potent in vitro activity against them.

Katherine Perez, PhD, Pfizer: Stocks/Bonds (Public Company)