Characterization of carbapenem-resistant Enterobacterales and
Pseudomonas aeruginosa
carrying multiple carbapenemase genes—Antimicrobial Resistance Laboratory Network, 2018–2022
Authors: Sabour Sarah , Harrington Kristin R. V. , Martinson Ellen , Bhatnagar Amelia S. , Huang Jennifer Y. , Duffy Dustin , Bantle Katie , Lutgring Joseph D. , Karlsson Maria , Brown Allison C. 
Published: November 2024

ABSTRACT

Carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant
Pseudomonas aeruginosa
(CRPA) are significant public health threats, particularly when harboring carbapenemases. Literature describing the frequencies and phenotypic and genotypic characteristics of isolates harboring multiple carbapenemase genes is limited. Using data collected from the Antimicrobial Resistance Laboratory Network (AR Lab Network) in 2018–2022, we describe CRE and CRPA isolates that harbor multiple acquired carbapenemase genes. Clinical laboratories submitted CRE and CRPA isolates to AR Lab Network public health laboratories for additional characterization that included antimicrobial susceptibility testing and detection of five targeted carbapenemase genes. Isolates were classified as non-carbapenemase producing (non-CP) when negative for carbapenemase production and all targeted carbapenemase genes, or positive for a single-CP (SCP) or multiple-carbapenemase (MCP) targeted gene. Among 79,799 CREs tested, 27,599 (35%) were SCP and 611 (1%) were MCP. MCP-CRE most often carried
bla
KPC
/
bla
NDM
(
n
= 285, 47%). Both SCP-CRE and MCP-CRE were most commonly
Klebsiella
spp.
Enterobacter
spp. and
Escherichia coli
isolates harboring MCP were detected at slightly higher frequencies (18% and 15%;
n
= 109 and
n
= 88, respectively) than
Enterobacter
spp. and
Escherichia coli
isolates harboring SCP (13% and 13%;
n
= 3,653 and 3,471, respectively). The number of MCP-CRE detected increased from 54 of 5,105 (1%) in 2018 to 223 of 6,994 (3%) in 2022. Among 54,490 CRPA tested, 2% (
n
= 1,249) were SCP and 31 were MCP. MCP-CRPA most often carried
bla
VIM
/
bla
IMP
(
n
= 13, 42%). A higher proportion of MCP-CRE (97%,
n
= 330) isolates were categorized as resistant to meropenem, compared to SCP-CRE (79%;
n
= 11,227) and non-CP (13%;
n
= 2,683). Although MCP organisms represent a small proportion of total CP detected in the AR Lab Network, there is a need for continued monitoring and additional research.

IMPORTANCE
Carbapenemase-producing organisms are of significant clinical and public health concerns, and rapid detection and containment of such threats are vital to preventing their spread. In this article, we used a collection of over 130,000 contemporary isolates to evaluate frequencies and phenotypic and genotypic properties of CRE and CRPA isolates harboring multiple carbapenemase genes across the United States, from 2018 to 2022. Of note, 95% and 100% of CRE and CRPA isolates co-harbored at least one metallo-β-lactamase gene, respectively, indicating a high proportion of isolates originating from patients with difficult-to-treat infections. Both clinical and public health professionals across the nation can use these data and key findings to better understand the molecular landscape of these isolates. Timely detection and control of these organisms are essential to combating the spread of antibiotic resistance and ensuring the availability of effective treatment options for patients.