Group A streptococcus isolated in Guyana with reduced susceptibility to β-lactam antibiotics
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Introduction. Streptococcus pyogenes [group A streptococci (GAS)] is the causative agent of pharyngitis and various other syndromes involving cellulitis, streptococcal toxic shock syndrome (STSS), and necrotising fasciitis. Although the prevalence of GAS infections globally remains high, necessitating the widespread use of β-lactam antibiotics, GAS have remained largely susceptible to these agents. However, there have been several reports of GAS with reduced susceptibility harbouring mutations in genes for penicillin-binding proteins (PBPs). The objectives of this study were to examine the in vitro β-lactam susceptibility patterns of group A streptococci, determine the prevalence of drug resistance, and ascertain whether such resistance could be attributed to mutations in specific PBP genes.
Methods. In this study, we sought to use Sanger sequencing to identify mutations in PBP genes of Streptococcus pyogenes isolated from patients that required inpatient and outpatient care that could confer reduced PBP affinity for penicillin and/or cephalosporin antibiotics. All isolates were screened for susceptibility to penicillin, amoxicillin, and cefazolin using E-test strips.
Results. While there were no documented cases of reduced susceptibility to penicillin or amoxicillin, 13 isolates had reduced susceptibility to cefazolin. Examination of pbp1a by Sanger sequencing revealed several isolates with single amino acid substitutions, which could potentially reduce the affinity of PBP 1A for cefazolin and possibly other first-generation cephalosporins.
Conclusion. Penicillin and penicillin-derived antibiotics remain effective treatment options for GAS infections, but active surveillance is needed to monitor for changes to susceptibility patterns against these and other antibiotics and understand the genetic mechanisms contributing to them.
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This is a study that would be of interest to the field and community.
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The work presented is clear and the arguments well formed. This study would be a valuable contribution to the existing literature. This is a study that would be of interest to the field and community. Please see comments from peer-reviewers below and address their concerns and suggestions. We look forward to receiving your revised submission.
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Comments to Author
Although some modifications were made, the study provides relevant information on cases of group A streptococci, in Guiana that did not exhibit susceptibility to a first-generation cephalosporin and characterizes the probable mutation associated with this resistance. General questions -Please justify the statement that the 13 isolates are not susceptible to cefazolin. Wouldn't it be more accurate to say that present reduced susceptibility? -For cefazolin there are no established NCCLS break points for Streptococcus pyogenes the authors used the penicillin breakpoints to interpret the cefazolin MICs. Other studies use NCCLS breakpoints established for Streptococcus pneumoniae or Staphylococcus aureus (Ref 11) or the results obtained were compared with control strain MIC values. Please justify your …
Comments to Author
Although some modifications were made, the study provides relevant information on cases of group A streptococci, in Guiana that did not exhibit susceptibility to a first-generation cephalosporin and characterizes the probable mutation associated with this resistance. General questions -Please justify the statement that the 13 isolates are not susceptible to cefazolin. Wouldn't it be more accurate to say that present reduced susceptibility? -For cefazolin there are no established NCCLS break points for Streptococcus pyogenes the authors used the penicillin breakpoints to interpret the cefazolin MICs. Other studies use NCCLS breakpoints established for Streptococcus pneumoniae or Staphylococcus aureus (Ref 11) or the results obtained were compared with control strain MIC values. Please justify your approach - It would be interesting to try to re-sequence the pbp2X gene. Abstract Line 26: It would be interesting to include a paragraph about antibiotic resistance in the abstract. Line 29: The S pyogenes isolates evaluated in this study do not only come from hospitalized patients, but also from patients treated on an outpatient basis. - It would be important to place a sentence in the abstract with the objective of this study. Introduction Lines 46 e 47: these data refer specifically to invasive pyogenes (ref 2). Line 50: It would be interesting to also cite other articles. Lines 51-58: It would be interesting to place references immediately after each statement. Lines 69, 70: "using genetic sequencing to characterize such resistance" is not an objective, but a methodology employed, I suggest that this sentence be modified focusing on the study question. Discussion Line 204: It would be interesting to further discuss the mutation in the PBPs 1A gene, found in this study, and its relationship with resistance to B lactams.
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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Comments to Author
The paper structure and reasoning for the study solid. Presentation, organization, and literature analysis were good. There are a few items that should either be done to strengthen the paper or at least be addressed by the authors. 1) Should include the BLAST alignment for the sample isolates against PBP1a for whichever S. pyogenes clone you used . 2) What primers were used for the Sanger Sequencing? 3) Why did the authors not pick isolates and grow more of them to keep as stocks and use to try sending off to genewiz again for pbp2x sequencing? 4) Why not try 16S alignment with their samples to confirm the phylogeny on the samples that made it through your S. Pyogenes decision tree identification?
Please rate the manuscript for methodological rigour
Satisfactory
Plea…
Comments to Author
The paper structure and reasoning for the study solid. Presentation, organization, and literature analysis were good. There are a few items that should either be done to strengthen the paper or at least be addressed by the authors. 1) Should include the BLAST alignment for the sample isolates against PBP1a for whichever S. pyogenes clone you used . 2) What primers were used for the Sanger Sequencing? 3) Why did the authors not pick isolates and grow more of them to keep as stocks and use to try sending off to genewiz again for pbp2x sequencing? 4) Why not try 16S alignment with their samples to confirm the phylogeny on the samples that made it through your S. Pyogenes decision tree identification?
Please rate the manuscript for methodological rigour
Satisfactory
Please rate the quality of the presentation and structure of the manuscript
Satisfactory
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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