Clinical impact and public health challenges of a PVL-MRSA bacteraemia outbreak amongst people who inject drugs in South Yorkshire, UK
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Background. Panton–Valentine leukocidin (PVL) Staphylococcus aureus (SA) is an emergent public health concern. PVL toxin has been mostly associated with methicillin-sensitive S. aureus (MSSA)-related skin and soft tissue infections occurring in high-risk groups such as people who inject drugs (PWID). The emergence of PVL methicillin-resistant S. aureus (MRSA) infection is causing severe and life-threatening disease in PWID.
Clinical cases. We present an outbreak of eight PVL-MRSA bacteraemia cases at a UK teaching hospital between 2018 and 2022. An additional four patients developed bacteraemia with PVL-negative MRSA of the same multilocus sequence type (MLST). All patients were PWID and aged 33–51 years old. Four patients developed MRSA bacterial endocarditis. Three patients died. These cases represent the initial cases detected at Doncaster and Bassetlaw Teaching Hospitals of what is an ongoing and developing outbreak.
Management. An outbreak investigation has been undertaken in association with the UK Health Security Agency. Epidemiological factors have been explored, including via direct contact at a local sheltered accommodation and the possibility of a contaminated drug supply. Whole-genome sequencing confirmed that all isolates were closely related and of the same MLST (sequence type 5). A community substance misuse group disseminated health education on the prevention of PVL-MRSA. Preventing infection in PWID presents a major challenge due to the impact of addiction on engagement with services and the significant barriers faced by our patients in observing infection prevention measures.
Conclusion. PVL-MRSA is of major public health concern and outbreak investigation and mapping out local epidemiological patterns plays a vital role in preventing further spread throughout the community. Additionally, this work enables targeted and early treatment in patients in high-risk categories for disease. These cases of PVL-MRSA infection in PWID highlights the transmissibility, pathogenic potential and severe clinical disease spectrum within this population. Further work is required to tackle transmission and infection from this pathogenic strain.
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The work presented is clear and the arguments well formed.
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The work presented is clear and the arguments well formed. However I invite you to address the referees comments, especially in the context of adding more details to the methods. Furthermore, as highlighted by the referees, please address whether a Ethics statement/approval is needed for the sequencing performed on patients isolates.
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Comments to Author
In this manuscript by Beaumont et al., the authors describe the initial cases in an ongoing outbreak of PVL-MRSA bacteraemia infections in people who inject drugs (PWID). They conducted a retrospective analysis of patient case notes and electronic medical records. Additionally, whole genome sequencing was performed on each isolate, confirming genetic relatedness and comparison to the national reference WGS archive found additional related cases outside of South Yorkshire. Finally, the authors discuss the clinical management of these cases and the challenges of containing an outbreak of PVL-MRSA infections in PWIDs. The authors provide a good background of PVL-MRSA, with supported references. In addition, the discussion of challenges in treating PVL-MRSA and containing this outbreak in PWIDs is …
Comments to Author
In this manuscript by Beaumont et al., the authors describe the initial cases in an ongoing outbreak of PVL-MRSA bacteraemia infections in people who inject drugs (PWID). They conducted a retrospective analysis of patient case notes and electronic medical records. Additionally, whole genome sequencing was performed on each isolate, confirming genetic relatedness and comparison to the national reference WGS archive found additional related cases outside of South Yorkshire. Finally, the authors discuss the clinical management of these cases and the challenges of containing an outbreak of PVL-MRSA infections in PWIDs. The authors provide a good background of PVL-MRSA, with supported references. In addition, the discussion of challenges in treating PVL-MRSA and containing this outbreak in PWIDs is excellent. The manuscript could be improved by providing more detail on the methodology used for WGS and by providing more information on patient characteristics and the clinical treatment of each patient in the result section. Overall, the authors provide a well written and interesting manuscript. Specific comments: 1. Methodological rigour, reproducibility and availability of underlying data Line 111 - More detail is needed for this methodology section. Specifically, how was genomic DNA extracted and genome sequencing conducted, how was PVL testing conducted and what was the SNP threshold used for determining genetic relatedness? 2. Presentation of results Line 124 - Could the authors provide more detail on whether the patients had any comorbidities? Line 125 - In addition, could the authors state whether any of the patients had recent healthcare contact (e.g.
Please rate the manuscript for methodological rigour
Satisfactory
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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Comments to Author
The manuscript provides data on S. aureus PVL prevalence in clinical isolates from intravenous drug users and patient outcomes. Data are clearly communicated. The title could be re-worded to sound more scientific. For example replace/ re-word "people who inject drugs" to "intravenous drug users" in the title. WGS data is available on ENA, but requires additional description in methods section. Lines 112-113 what are the SNP thresholds, and software/databases used for the analysis? Data summary/tables are clear, but could be presented better, in a more comprehensive breakdown. For examples authors could include a breakdown of each PVL+/- vs gender ratio of each class also. Literature analysis needs work. Introduction needs improvement in terms of referencing the literature for statements. Example: …
Comments to Author
The manuscript provides data on S. aureus PVL prevalence in clinical isolates from intravenous drug users and patient outcomes. Data are clearly communicated. The title could be re-worded to sound more scientific. For example replace/ re-word "people who inject drugs" to "intravenous drug users" in the title. WGS data is available on ENA, but requires additional description in methods section. Lines 112-113 what are the SNP thresholds, and software/databases used for the analysis? Data summary/tables are clear, but could be presented better, in a more comprehensive breakdown. For examples authors could include a breakdown of each PVL+/- vs gender ratio of each class also. Literature analysis needs work. Introduction needs improvement in terms of referencing the literature for statements. Example: Line 77 "There is much debate around its role as a virulence factor." Remove this statement or use a reference to support this. Several statements in the Introduction is not referenced. Other comments: - All over manuscript, please replace "Bacteraemias" with "bacteraemia cases", or "bacteraemia". -Staphylococcus aureus and Staphylococcal pneumonia all over MS needs to be italicised. Ethics statement: Is there ethics approval associated with the WGS analysis of patient isolates?
Please rate the manuscript for methodological rigour
Good
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Partially support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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