Rising Clindamycin Resistance in Group A Streptococcus in an Irish Healthcare Institution
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Abstract
Group A streptococcus (GAS) can cause serious invasive disease in humans with a high mortality rate. An increase in GAS infections was reported in Ireland in 2022, and this increase has been sustained in 2023 and is paralleled by similar trends in Europe. Rising antimicrobial resistance is a global problem and presents significant challenges to clinicians treating GAS infection. There was a reported increase in clindamycin resistance in GAS isolates in Ireland in 2022. We examined antimicrobial susceptibility patterns of GAS isolates in our institution in 2022. Although all GAS isolates included in our study were susceptible to penicillin, we noted a high clindamycin resistance rate of 28% in our invasive GAS isolates. We also noted high tetracycline and erythromycin resistance, 43% and 30%, respectively. Our results could have implications for empiric antimicrobial prescribing guidelines for skin and soft tissue infections, which often include clindamycin as it inhibits the production of many virulence factors associated with GAS. In addition, macrolides are often the first line recommended antibiotic for patients with anaphylaxis to penicillin. This study emphasises the importance of continuous surveillance and antimicrobial susceptibility testing of invasive and non-invasive isolates in order to monitor trends in increasing antimicrobial resistance.
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I am pleased to tell you that your article has now been accepted for publication in Access Microbiology. The work presented is clear and the arguments well formed. The manuscript is well written and contributes to the literature. Thank you for addressing all reviewers comments satisfactorily and in a timely manner.
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Thank you for submitting your revised manuscript for publication in Access Microbiology and for addressing the reviewer's comments. However, further amendments are still needed and I will be pleased to consider a revised manuscript along with a document including a point by point response to the reviewers comments. Your revised manuscript may be returned to one or more of the original reviewers, along with your itemised response to the reviewers’ comments.
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Comments to Author
The authors describe an interesting situation in a specific Irish hospital because the rates of clindamycin and erythromycin resistance are very high comparing with the national data from Ireland in 2022. The authors have modified the manuscript according to the reviewers' suggestions. But some modifications are still necessary to reach enough quality for publication. MAJOR COMMENTS Lines 129-135: this paragraph should be redone keeping in mind which genes/mechanisms are responsible for tetracycline, erythromycin and clindamycin resistance; and if these genes can be co-vehicularized in the same mobile genetic element. Please, omit descriptions of tetracycline-clindamycin co-resistance because it has little meaning, describe tetra-erythro and erythro-clinda co-resistance, and that none clindamycin-R and …
Comments to Author
The authors describe an interesting situation in a specific Irish hospital because the rates of clindamycin and erythromycin resistance are very high comparing with the national data from Ireland in 2022. The authors have modified the manuscript according to the reviewers' suggestions. But some modifications are still necessary to reach enough quality for publication. MAJOR COMMENTS Lines 129-135: this paragraph should be redone keeping in mind which genes/mechanisms are responsible for tetracycline, erythromycin and clindamycin resistance; and if these genes can be co-vehicularized in the same mobile genetic element. Please, omit descriptions of tetracycline-clindamycin co-resistance because it has little meaning, describe tetra-erythro and erythro-clinda co-resistance, and that none clindamycin-R and erythromycin-S isolate was found. Lines 134-135: "30 isolates were fully resistant", correct this mistake. Lines 153-162: An important limitation of the study is that only invasive isolates have been emm-typed. For this reason, we cannot know the origin of so high resistance rates. The most frequent emm1, emm12 and emm28 serotypes in Ireland in 2022 are mainly susceptible to antimicrobials. What about the hypothesis of a local outbreak of emm9, emm27 or another resistant serotype? Or a multiclonal explanation? We do not have enough microbiological information to answer this questions. Please, add these ideas to the manuscript because the clue of the study is here. This links with paragraph 196-206 where the authors conclude the importance of surveillance. If an increase in resistance rates is detected, additional typing of non-invasive isolates would be justified. Line 184: Tetracycline susceptibility testing is basic in terms of microbiological surveillance, but tetracyclines are not used to treat iGAS infections. Please, modify it. MINOR COMMENTS Lines 137-142: Add here results related with emm types (9, 27 and 87): number of isolates and antimicrobial resistance for each emm type. And remove duplicate data from discussion. Lines 153-162: emm9 and particularly emm27 are uncommon emm types; therefore, it is not easy to find studies with a representative number of isolates for each. But emm87 is very common in template countries and is not associated with any type of resistance. Reference 14 includes only one emm87 isolate which is not representative; please select another reference. See Villalón et al (https://doi.org/10.1007/s10096-021-04279-2 ) as an example. The authors can choose another study with representative data for emm87.
Please rate the manuscript for methodological rigour
Good
Please rate the quality of the presentation and structure of the manuscript
Satisfactory
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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Thank you for submitting your manuscript for publication in Access Microbiology. It has been examined by expert reviewers who have concluded that the work is of potential interest to the readership of Access Microbiology. However, based on the comments received, it is clear that a major revision of this manuscript will be required before a decision can be made on its publication. I will be pleased to consider a revised manuscript along with a document including a point by point response to each of the reviewers comments. Your revised manuscript may be returned to one or more of the original reviewers, along with your itemised response to the reviewers’ comments. Access Microbiology operates an Open Data policy and therefore, the susceptibility results for all isolates must be made publicly available. Please deposit all supporting data …
Thank you for submitting your manuscript for publication in Access Microbiology. It has been examined by expert reviewers who have concluded that the work is of potential interest to the readership of Access Microbiology. However, based on the comments received, it is clear that a major revision of this manuscript will be required before a decision can be made on its publication. I will be pleased to consider a revised manuscript along with a document including a point by point response to each of the reviewers comments. Your revised manuscript may be returned to one or more of the original reviewers, along with your itemised response to the reviewers’ comments. Access Microbiology operates an Open Data policy and therefore, the susceptibility results for all isolates must be made publicly available. Please deposit all supporting data in a recommended repository and is made publicly available. Please contact us at acmi@microbiologysociety.org if you have any questions. I look forward to receiving a revised manuscript.
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Comments to Author
The authors describe an interesting situation in Ireland because the rates of clindamycin and erythromycin resistance are very high if we compare the data from other European countries in 2022. The 2022-2023 iGAS outbreak was mainly caused by emm1 and emm12 serotypes susceptible to macrolides and clindamycin. Major comments The strains were typed in a Reference Laboratory but the serotypes are not informed in the manuscript. Antimicrobial resistance in GAS is concentrated in specific clones. It is necessary to know which serotypes are responsible of the high rates of resistance in MMUH and compare with national Irish data and other countries. emm typing is mandatory in GAS surveillance. The authors should compile these data and redo the article according the new information. Methods: Describe …
Comments to Author
The authors describe an interesting situation in Ireland because the rates of clindamycin and erythromycin resistance are very high if we compare the data from other European countries in 2022. The 2022-2023 iGAS outbreak was mainly caused by emm1 and emm12 serotypes susceptible to macrolides and clindamycin. Major comments The strains were typed in a Reference Laboratory but the serotypes are not informed in the manuscript. Antimicrobial resistance in GAS is concentrated in specific clones. It is necessary to know which serotypes are responsible of the high rates of resistance in MMUH and compare with national Irish data and other countries. emm typing is mandatory in GAS surveillance. The authors should compile these data and redo the article according the new information. Methods: Describe identification, ATB and emm typing methods. Results: Please, explain if clindamycin-resistance rates include strains with susceptible MICs but inducible MLSB phenotype. What about tetracycline and erythromycin co-resistance? Do show the clindamycin-resistant serotypes this kind of co-resistance? References: Some references should be updated. And new article references should be added. Minor comments Line 48. GAS is a facultative anaerobic microorganism. Please, correct it. Line 68. n = 64. Is it ok? Line 70. It seems there is a mistake (2021?-2019) repeated along the manuscript. Line 87. HPSC? Please, explain. Reference definition of invasive GAS case. Line 91. Which statistical variables were analyzed? Figure 1. For an easier understanding: Percentages of clindamycin resistance should be indicated in A, B and C. Fluid = sterile fluid? Swabs: Please, specify sample type. It is so nonspecific... HVS: Are representative of invasive infections?
Please rate the manuscript for methodological rigour
Satisfactory
Please rate the quality of the presentation and structure of the manuscript
Poor
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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Comments to Author
In the abstract, page 2, line 35 and 36: the authors stated "Our results could have implications for empiric antimicrobial prescribing guidelines for skin and soft tissue infections, that which often include clindamycin as an antitoxin agent" what did you mean by antitoxin agent in this situation? In the method section: - What is the method used for antimicrobial susceptibility testing? And what are the antibiotics tested and according to what reference do you interpret your results as sensitive or resistant? - Page 3, line 87 and 88: "The HPSC definition (2021) of invasive GAS was used to determine if the isolates were from invasive GAS", you need to add this reference. In the results section: - The authors should clearly state the sites from which samples were taken and the number of each type of …
Comments to Author
In the abstract, page 2, line 35 and 36: the authors stated "Our results could have implications for empiric antimicrobial prescribing guidelines for skin and soft tissue infections, that which often include clindamycin as an antitoxin agent" what did you mean by antitoxin agent in this situation? In the method section: - What is the method used for antimicrobial susceptibility testing? And what are the antibiotics tested and according to what reference do you interpret your results as sensitive or resistant? - Page 3, line 87 and 88: "The HPSC definition (2021) of invasive GAS was used to determine if the isolates were from invasive GAS", you need to add this reference. In the results section: - The authors should clearly state the sites from which samples were taken and the number of each type of sample. - You mentioned that you collected 121 samples; however in the paragraph from line 110 to 116 the total number of samples are 129 samples. - Page 3, line 107: what did you mean by "from GP samples"? It should be written in full and the abbreviation to be put between brackets. - Line 110 and 111, "The majority of samples (81.8%, n=99) were labelled as swabs" you should mention the site of sample. In the discussion, page 4, line 136 and 137: Linezolid, a synthetic oxazolidinone, also exerts antitoxin effects against GAS and can be considered an alternative to clindamycin. What did you mean by antitoxin effect in this situation?
Please rate the manuscript for methodological rigour
Poor
Please rate the quality of the presentation and structure of the manuscript
Poor
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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