PREreview del Antibiotic-resistance plasmid amplified among MRSA cases in an urban jail and its connected communities

Summary:

This paper looks at the role of urban jails in amplifying antibiotic-resistant MRSA plasmids and their spread to surrounding communities. Jails have been recognized as transmission hotspots for MRSA due to the close contact conditions and connections to socioeconomically disadvantaged neighborhoods with elevated infection rates. 

Using genomic epidemiology, researchers analyzed 308 MRSA isolates from Cook County Jail (2015-2018) and 774 isolates from the connected Cook County Health system. They employed a genome-wide association study to identify genetic variants associated with transmission linkage, or isolates within 20 single nucleotide variants of each other. Researchers identified a plasmid carrying the ermC gene responsible for erythromycin and clindamycin resistance to be positively associated with transmission in both jail and community settings. The plasmid was present in 52% of jail-acquired infections versus 14% of intake colonizations, suggesting amplification within the facility. Topical clindamycin use was associated with ermC carriage in both populations but occurred more frequently in jail populations. Community members with recent jail exposure were more likely to harbor ermC-positive strains, as were those genomically linked to recently incarcerated individuals. 

The paper’s findings point to antibiotic use in correctional settings as a mode for amplifying resistance in the broader community. Its findings suggest a need for intervention at the carceral level. 

Strengths:

This paper’s key strengths lie in its utilization of strong genomic epidemiology methods to evaluate MRSA transmission dynamics between an urban jail and connected communities. Using a genome-wide association study provided critical insights into valuable insights into MRSA transmission dynamics between an urban jail and connected communities. 

Major Revisions:

Given that the data taken from the jail predated the community data by 1-4 years, the authors overstate the causality of their findings. The title uses "amplified," which implies a causal mechanism that cannot be established from the observational data, particularly given the temporal misalignment between datasets. The paper does not adequately consider alternative explanations, such as shared risk factors or community networks that could explain the association between jail exposure and ermC without invoking direct transmission. This issue can be fixed by using more neutral language such as “associated with” rather than “amplified”. The authors should enhance their discussion section by including discussion of alternative explanations for observed associations, such as shared risk factors, healthcare networks,or parallel selective pressures. They should qualify all conclusions about jail-to-community transmission with appropriate caveats about temporal and methodological constraints.

Another key issue lies in the usage of a 20 SNV threshold, which becomes problematic across this 1-4 year temporal gap as evolutionary distance accumulates over time, potentially leading to systematic underestimation of jail-community connections. The authors should acknowledge this as a study limitation, adding an analysis comparing ermC prevalence trends in Cook County Health  data before and after 2015 to assess whether changes coincide with potential jail effects.

The authors should look into addressing critical limitations in distinguishing between autonomous plasmids and chromosomally integrated sequences. The current approach does not distinguish between autonomous plasmids, chromosomal integrations of ermC cassettes, prophage-carried resistance genes, or transposon-mediated insertions which are key to understanding horizontal gene transfer mechanisms and transmission dynamics. Authors should add an analysis of plasmid-specific genes beyond ermC to confirm plasmid architecture, examining read-pair mapping patterns to identify integration junctions versus circular molecules. They should modify the methods to explicitly acknowledge this limitation and qualify interpretations about horizontal transfer potential based on detection method constraints.

Minor Revisions: 

Authors should better acknowledge the systematic differences that extend beyond incarceration status. The populations differ fundamentally in demographics, health status, healthcare access patterns, and clinical characteristics, making direct comparisons potentially misleading without appropriate adjustment. Authors should include this as a major limitation, including demographic and clinical characteristic comparisons between populations in supplementary tables. 

Conclusion: 

Overall, this paper provides a valuable contribution to the field, providing important insights into the role that carceral settings play in MRSA plasmid amplification. With some edits to the analysis and discussion to better account for a few inherent study flaws, I would strongly recommend this paper for publication.

Competing interests

The author declares that they have no competing interests.

Use of Artificial Intelligence (AI)

The author declares that they used generative AI to come up with new ideas for their review.