Trends in coagulase-negative staphylococci (CoNS), England, 2010–2021
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Objective. To review the epidemiology of coagulase-negative staphylococci (CoNS) in England over the recent 12 year period.
Methods. Laboratory-confirmed CoNS reported from sterile sites in patients in England to the UK Health Security Agency (UKHSA) between 2010 and 2021 were extracted from the national laboratory database and analysed.
Results. Overall, 668 857 episodes of CoNS were reported. Unspeciated CoNS accounted for 56 % (374 228) of episodes, followed by Staphylococcus epidermidis (26 %; 174 050), S. hominis (6.5 %; 43 501) and S. capitis (3.9 %; 25 773). Unspeciated CoNS increased by 8.2 % (95 % CI, 7.1–9.3) annually between 2010 and 2016, then decreased annually by 6.4 % (95 % CI: −4.8 to −7.9) until 2021. Speciated CoNS increased by 47.6 % (95 % CI, 44.5–50.9) annually between 2010 and 2016 and increased annually by 8.9 % (95 % CI: 5.1 to 12.8) until 2021. Antimicrobial susceptibility profiles differed by species.
Conclusions. Reports of CoNS from normally sterile body sites in patients in England increased between 2010 and 2016 and remained stable between 2017 and 2021. There has been a striking improvement in species-level identification of CoNS in recent years. Monitoring trends in CoNS epidemiology is crucial for development of observational and clinical intervention studies on individual species.
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Thank you for addressing the reviewers comments. This paper has now been accepted for publication in Access Microbiology.
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The work presented is clear and the arguments well formed. This is a study that would be of interest to the field and community. The reviewers have highlighted minor concerns with the work presented. Please ensure that you address their comments.
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Comments to Author
[Thank you for the opportunity to review « Trends in coagulase negative staphylococci (CoNS), England 2010-2021. This manuscript described the epidemiology of Coagulase negative staphylococci in England from normally sterile sites over a long period of 12 years. This is a very interesting article, which provides an overview of both the different species and the antibiotic resistance of CoNS. It makes an important contribution to inform a better epidemiological and clinical understanding of different species of CoNS 1- Methodological rigour, reproducibility and availability of underlying data The methodology is rigorous and all underlying data are available in the supplementary data. 2- Presentation of results The results are well presented. They show both the evolution of different species and the …
Comments to Author
[Thank you for the opportunity to review « Trends in coagulase negative staphylococci (CoNS), England 2010-2021. This manuscript described the epidemiology of Coagulase negative staphylococci in England from normally sterile sites over a long period of 12 years. This is a very interesting article, which provides an overview of both the different species and the antibiotic resistance of CoNS. It makes an important contribution to inform a better epidemiological and clinical understanding of different species of CoNS 1- Methodological rigour, reproducibility and availability of underlying data The methodology is rigorous and all underlying data are available in the supplementary data. 2- Presentation of results The results are well presented. They show both the evolution of different species and the evolution of antibiotic resistance in all CoNS and within different species. In the part of the results, it would have been interesting to see if there were differences in the distribution of species according to the clinical site. 3- How the style and organization of the paper communicates and represents key findings The manuscript is well written, scientifically sound and is easy to read. 4- Literature analysis or discussion In figure 5 S. lugdunensis presents lower percentages of resistance to antibiotics than the other species (S. epidermidis or S. haemolyticus). Do you have any hypotheses to explain these results? 5- Some suggestions and minor edits are outlined below - Data summary : explain the abbreviation SGSS - Line 101 explain the abbreviation UKHSA - Line 115 explain the abbreviation AMR - Line 226 figure S1 is redundant with figure 4 - Replace Gentamycin by "Gentamicin" in figure S4 table S12, S11, S13, S14, S15 et S16
Please rate the manuscript for methodological rigour
Very good
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
Paranthaman et al. provide an extensive analysis on trends of CoNS and highlight their strong heterogeneity in both occurrence and AMR. Given its tremendous data set and consequent significance, this study is of clinical importance to interpret CoNS trends in Western Europe. COMMENTS L52 "Due to the risk of deductive disclosure, the authors are unable to share the raw data." This is very understandable, though I would've like to see at least some raw data regarding the incidence of different species and their antibiograms. Bacteria are not prone to GPDR like humans are - researchers can take advantages from that when sharing data :) L64 "with over 45 different species recognised to date [1, 2]" Perhaps also include the latest CoNS paper from Becker: PMID 32056452. L93 I would like some …
Comments to Author
Paranthaman et al. provide an extensive analysis on trends of CoNS and highlight their strong heterogeneity in both occurrence and AMR. Given its tremendous data set and consequent significance, this study is of clinical importance to interpret CoNS trends in Western Europe. COMMENTS L52 "Due to the risk of deductive disclosure, the authors are unable to share the raw data." This is very understandable, though I would've like to see at least some raw data regarding the incidence of different species and their antibiograms. Bacteria are not prone to GPDR like humans are - researchers can take advantages from that when sharing data :) L64 "with over 45 different species recognised to date [1, 2]" Perhaps also include the latest CoNS paper from Becker: PMID 32056452. L93 I would like some introduction to the UKHSA. It is first mentioned in the Methods, without even explaining the abbreviation. For non-English readers, please introduce the UKSHA briefly in the introduction. L86 "In England, diagnostic laboratories are required by law to report all..." Yes, this is an amazingly strong point! I would certainly bring this (more) up in the discussion - researchers from other countries are envious, as I prove myself. Having an integral view on these clinical relevant isolates (despite any compliance) it a great asset. L107 "intermediate" So EUCAST is not applied in English labs? Otherwise, the term has been "susceptible, increased exposure" for 'I' since 2019. L132 "Statistical analysis" This section is very thorough, which I much appreciate. It also suggests that author KP (if I understand well from the Author Contributions section) is strong on statistics. Still, I'm missing the most important part about AMR data analysis: how was corrected for duplicate isolates? Especially since they are from blood, imagine a patient having been tested 5 times in a week because of bacteraemia (which is not uncommon); if the outcome is S. haemolyticus 5 times that is erythromcyin resistant, it would overestimate erythromcyin resistance in your analysis. I really would like to know how only the first isolates per patient per species were included for AMR data analysis and incidence analysis. It is also unclear if antibiograms were left as-is, or if raw antiobitic results were re-evaluated according to a certain guideline. Different labs might use different guidelines, so there might be incorporation bias here, which is now unseen. L193 "unspeciated CoNS accounted for 56%" Yes, this is a typical MALDI-TOF MS effect, which is greatly shown in figure 1. I see that this confirm what is more broadly seen in Europe, where most labs implemented MALDI-TOF between 2011 and 2015, and inceasingly used it. Also like the ggplot2 visualisations, they look awesome. Table 2 I'm a bit amazed that no S. pettenkoferi was observed at all, especially given your huge number of cases - was this expected? This is a technical bias, or are S. pettenkoferi numbers known to be low in England? Strange. S. sciuri is still mentioned, although it was renamed to Mammaliicoccus sciuri (Madhaiyan et al). I would state this in the table caption and leave it from the rest of the analysis. It's seemingly no Staphylococcus at all... L216 "S. schleiferi" Yes, so this is a bit hard; this species could have contained the subspecies S. schleiferi coagulans, and this subspecies has been reclassified to the coagulase-positive (!) S. coagulans. I assume it was unknown to you which of your S. schleiferi isolates were of this subspecies, but this should be noted in the manuscript somewhere. L240 "Trends in susceptibility to nine antibiotics" I feels this section is very short and doesn't really give proper attribution to the amazing data you have. Also, reading this results section, this manuscript seems to have similarities with a recently published CoNS paper by Berends et al (PMID 36144403), although it's nowhere mentioned to compare results with. That's very strange - I would compare results with the recent study in the discussion, especially regarding antibiotic susceptibility. L267 "To better understand the reasons for improved species-level identification" Why are you going into new results here? This is the discussion section, and I would consider your lab techniques analysis part of the results. You could also add a nice plot of it. Now L267 to L274 feels very out-of-place, and also lacks discussion about the 'why' and the differences in time. L275 "Infants under 12 months of age" As a microbiologist, I would be much interested in the dispersion of S. capitis, as more and more of its virulent strains/clones are increasingly spreading across Europe. Is there anything known about this in your data? That would be highly clinically relevant to add. L283 "As expected, we noted high levels of antimicrobial resistance among CoNS." Sure, but your observations do not compare well with the paper I previously mentioned. You show strong heterogenous trends within species for pretty much all antibiotics, while they (in the very same study period, same methodology and same region in Western Europe) show this only for S. haemoloticus and not for e.g. S. capitis at all (see figure https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9506452/figure/microorganisms-10-01801-f003/). I would like to understand this and would like some hypotheses about the differences. How should we (as sidestanding microbiologists) interpret this? L306 "Nevertheless, this comprehensive review of CoNS" I don't think this should be called a review. I think it's a retrospective cross-sectional study, and calling it comprehensive with this limited amount of words is perhaps a bit misplaced. OTHERWISE: I greatly enjoyed reading your work and I'm especially fond of how the tables and figures in the (quite extensive!) supplementary materials were shared. My two key points are: - Methodology of de-duplicating isolates - Comparison with similar studies These at least should be addressed in a future version.
Please rate the manuscript for methodological rigour
Good
Please rate the quality of the presentation and structure of the manuscript
Very 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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