Descriptive analysis of targeted carbapenemase genes and antibiotic susceptibility profiles among carbapenem-resistant Acinetobacter baumannii tested in the Antimicrobial Resistance Laboratory Network—United States, 2017–2020

Abstract

Acinetobacter baumannii is a Gram-negative bacillus that can cause severe and difficult-to-treat healthcare-associated infections. A. baumannii can harbor mobile genetic elements carrying genes that produce carbapenemase enzymes, further limiting therapeutic options for infections. In the United States, the Antimicrobial Resistance Laboratory Network (AR Lab Network) conducts sentinel surveillance of carbapenem-resistant Acinetobacter baumannii (CRAB). Participating clinical laboratories sent CRAB isolates to the AR Lab Network for characterization, including antimicrobial susceptibility testing and molecular detection of class A ( Klebsiella pneumoniae carbapenemase), class B (Active-on-Imipenem, New Delhi metallo-β-lactamase, and Verona integron-encoded metallo-β-lactamase), and class D (Oxacillinase, bla OXA-23-like , bla OXA-24/40-like , bla OXA-48-like , and bla OXA-58-like ) carbapenemase genes. During 2017‒2020, 6,026 CRAB isolates from 45 states were tested for targeted carbapenemase genes; 1% (64 of 5,481) of CRAB tested for targeted class A and class B genes were positive, but 83% (3,351 of 4,041) of CRAB tested for targeted class D genes were positive. The number of CRAB isolates carrying a class A or B gene increased from 2 of 312 (<1%) tested in 2017 to 26 of 1,708 (2%) tested in 2020. Eighty-three percent (2,355 of 2,846) of CRAB with at least one of the targeted carbapenemase genes and 54% (271 of 500) of CRAB without were categorized as extensively drug resistant; 95% (42 of 44) of isolates carrying more than one targeted gene had difficult-to-treat susceptibility profiles. CRAB isolates carrying targeted carbapenemase genes present an emerging public health threat in the United States, and their rapid detection is crucial to improving patient safety. IMPORTANCE The Centers for Disease Control and Prevention has classified CRAB as an urgent public health threat. In this paper, we used a collection of >6,000 contemporary clinical isolates to evaluate the phenotypic and genotypic properties of CRAB detected in the United States. We describe the frequency of specific carbapenemase genes detected, antimicrobial susceptibility profiles, and the distribution of CRAB isolates categorized as multidrug resistant, extensively drug-resistant, or difficult to treat. We further discuss the proportion of isolates showing susceptibility to Food and Drug Administration-approved agents. Of note, 84% of CRAB tested harbored at least one class A, B, or D carbapenemase genes targeted for detection and 83% of these carbapenemase gene-positive CRAB were categorized as extensively drug resistant. Fifty-four percent of CRAB isolates without any of these carbapenemase genes detected were still extensively drug-resistant, indicating that infections caused by CRAB are highly resistant and pose a significant risk to patient safety regardless of the presence of one of these carbapenemase genes.

Epidemiological, phylogenetic, and resistance heterogeneity amongAcinetobacter baumanniiin a major US Deep South healthcare center

“…The value of surveilling local population structures remains to be determined, as the contribution of Ab phylogeny to pathogenesis and clinical outcomes is unclear. However, consistent with prior findings 28 , we observed that CR Ab lineages can harbor unique antimicrobial resistance features that may influence local medical practices. For example, OXA-23 has historically been the most prevalent carbapenamase among CR Ab and, thus, is a target of current and emergent rapid molecular detection tools in clinical labs 29 .…”

“…However, we identified U.S. isolates belonging to CC2, CC108, and CC499 that display carbapenem resistance via other resistance determinants (i.e., OXA-24 or the FtsI A515V polymorphism), and the mechanism of carbapenem resistance among CC406 isolates remains to be identified 13,22 (Figure S4). During the preparation of this manuscript, Sabour, et al reported that carbapenemase gene content among CRAb differed by region, and these genes did not appear to always confer the same degree of resistance 28 . Though Sabour et al did not evaluate whether degree of carbapenem resistance was dependent on lineage, lineage-associated differences were observed previously 13 and in our study (i.e., OXA-23-associated IPM resistance was greater among CC2 isolates compared to CC250 isolates, Figure S2).…”