A comprehensive review of research underscores the widespread distribution of beta-lactamase resistance genes in Enterobacteriaceae across human, animal, and environmental sources in the United States. The study, which analyzed 335 articles published between 1981 and April 2022, provides critical insights into the molecular epidemiology of these resistance genes, which are central to the rise of antimicrobial resistance (AMR).
The review identified 169 distinct beta-lactamase genes, including 22 key genes such as blaCTX-M-15 and blaCMY-2, found in human-associated, animal, and environmental isolates. These genes contribute to resistance against beta-lactam antibiotics, including penicillins and cephalosporins. The study revealed significant variation in the distribution of these resistance genes, with human samples making up the majority of studies (137 out of 335).
blaCTX-M-15 was the most frequently detected gene, present in 10.7% of E coli isolates, with higher prevalence in human samples (13.1%) compared to animal (8.6%) and environmental (.8%) sources. Similarly, blaCMY-2 was detected in 10.6% of E coli isolates, with notable differences across sources: 41.3% in humans, 1.6% in animals, and 16.2% in environmental samples.
Babafela Awosile, DVM, MVSc, PhD, DACVPM (Epidemiology), assistant professor of epidemiology at Texas Tech School of Veterinary Medicine, and one of the investigators in the study, explains that while the research does not aim to definitively establish transmission pathways, it offers important insights into the distribution of beta-lactamase genes across the One Health interface.
"This study does not intend to establish a specific pathway, however, based on the distribution of beta-lactamases across the One Health interface, it was obvious that the human domain of the One Health harbors the majority of the beta-lactamases in the review," Awosile noted. "This is consistent with our findings from a similar work we published last year (titled Beta-lactamase genes in bacteria from food animals, retail meat, and human surveillance programs in the United States from 2002 to 2021). In both studies, we found a lot of beta-lactamases in Enterobacteriales that were not found/reported in animals. This study further raised the question that food animals are reservoirs of AMR to humans. Could there be a possibility of other sources of exposure to humans unrelated to animals? In addition, we do recognize that most human-related beta-lactamases may have originated from clinical cases compared to animal sources that are mostly from apparently healthy states."
The study’s findings underscore the importance of addressing blaCTX-M-15 and blaCMY-2, both of which mediate resistance to third-generation cephalosporins, a critical class of antibiotics. Awosile emphasized the wide-reaching public health implications of these findings, particularly in the context of increasing AMR concerns.
"Both blaCTX-M-15 and blaCMY-2 genes are considered important beta-lactamase genes mediating resistance to cephalosporin antimicrobials, especially the critically important third-generation cephalosporins. While blaCTX-M-15 is more common in the human domain and blaCMY-2 more in the animal domain of One Health, the public health implications across the One Health sources are associated with the development of refractory microbial treatment failure, antimicrobial escalation, increased hospitalization, nosocomial and community disseminations, morbidity and mortality in extreme cases in both human and animal health," he said. "We believe the findings from this study will provide evidence-based information that further supports the current integrated AMR surveillance activities (eg NARMS), antimicrobial stewardship initiatives, and policies across One Health domains in the USA."
The review also found that sequence type (ST) 131, a strain of E coli most commonly associated with blaCTX-M-15, is a particularly concerning strain. Known for its widespread distribution, ST131 presents a substantial public health challenge in community settings and healthcare environments.
What You Need To Know
The study reveals the widespread presence of beta-lactamase genes like blaCTX-M-15 and blaCMY-2 across human, animal, and environmental sources, emphasizing the need for integrated surveillance.
The prevalence of E coli sequence type ST131, associated with blaCTX-M-15, poses a significant public health risk due to its easy transmission in community and healthcare settings.
The variation in detection rates of beta-lactamase genes across different sources highlights the need for targeted surveillance to address antimicrobial resistance more effectively.
"ST131 carrying blaCTXM-15 E coli is known as an epidemic strain of global importance due to its widespread and ease of dissemination," Awosile explained. "The predominance of the strain as observed in this review further elucidates the importance and the extent of the distribution across the One Health domain, although more common in the human domain. This strain poses a greater risk of dissemination not only in the community but also in healthcare settings. This predominance calls for renewed efforts and interventions to minimize the dissemination, especially in the human health sectors. Also, effort needs to be directed towards other non-human sources to prevent transmission to humans."
One of the study's findings was the variation in the detection rates of beta-lactamase genes across different One Health domains. While this may seem like a challenge for AMR monitoring, Awosile sees it as an opportunity for targeted surveillance.
"Variation in the detection rate of beta-lactamase genes across different sources may not necessarily be a challenge but provide an opportunity for target-based surveillance of these beta-lactamase genes especially in a resource-limited situation," he said. "More resources, surveillance, and intervention efforts can be directed toward predominant beta-lactamase-carrying bacteria."
This study underscores the need for integrated AMR surveillance and strategies to address the spread of resistance across the One Health continuum. The findings show the presence of beta-lactamase genes in the US and highlight the role of ongoing research and collaboration across human, animal, and environmental health sectors. Understanding the distribution of resistance genes can help public health officials and researchers guide efforts to protect human and animal health from multidrug-resistant infections.
Reference
Rahman MK, Rodriguez-Mori H, Loneragan G, Awosile B. One Health distribution of beta-lactamases in Enterobacterales in the United States: A systematic review and meta-analysis. Int J Antimicrob Agents. 2024; doi: https://doi.org/10.1016/j.ijantimicag.2024.107422
