Haemophilus influenzae blood-stream infection and third-generation cephalosporin susceptibility testing: a comparative case study using EUCAST and CLSI guidelines
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Introduction. In this comparative case study, we discuss clinically relevant discrepancies of antimicrobial susceptibility testing (AST) interpretation for ceftriaxone against a non-typable, beta-lactamase negative, ampicillin-resistant (BLNAR) Haemophilus influenzae isolated from a blood culture.
Case report. A 74-year-old man presented with a 3 day illness characterized by shortness of breath and dry cough, and was noted to be febrile and hypoxic on admission. A blood culture bottle flagged positive with Gram-negative coccobacilli, later identified as Haemophilus influenzae with the patient commenced on ceftriaxone. The isolate was beta-lactamase negative and antibiotic susceptibility testing (AST) using disc diffusion revealed the isolate resistant to ceftriaxone and ampicillin by EUCAST methodology, with the patient subsequently changed to amoxicillin/clavulanate. Further AST using the CLSI methodology in parallel demonstrated discrepant results between the two susceptibility methods. The patient recovered without complications.
Conclusion. This discrepancy could lead to inconsistent reporting of susceptibilities between laboratories, and consequently antibiotic prescribing, especially for invasive isolates. As more laboratories adopt EUCAST methodologies for AST interpretation in Australia and globally, it is important for clinicians to consider the clinical implications of these methodological discrepancies.
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Thank you very much for submitting this revised manuscript to Access Microbiology including all changes suggested. This manuscript is now accepted for publication. Congratulations!
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Thank you very much for submitting your revised manuscript to Access Microbiology and for your efforts in applying the reviewers’ suggestions and comments to your manuscript. This has undoubtedly improved its quality. However, I would like to make some additional suggestions that should be considered in the interest of the reader’s understanding of this case report: • There is an interesting discussion in the response to the reviewers’ comments about the EUCAST/CLSI discrepancies based on the results of Nurnberg et al. (2021). I think including this in the report’s introduction or discussion section (where considered more appropriate) would help to further clarify the point of the study. • Please include when possible the version and release dates of the EUCAST and CLSI guidelines used as reference in this study, not only in the …
Thank you very much for submitting your revised manuscript to Access Microbiology and for your efforts in applying the reviewers’ suggestions and comments to your manuscript. This has undoubtedly improved its quality. However, I would like to make some additional suggestions that should be considered in the interest of the reader’s understanding of this case report: • There is an interesting discussion in the response to the reviewers’ comments about the EUCAST/CLSI discrepancies based on the results of Nurnberg et al. (2021). I think including this in the report’s introduction or discussion section (where considered more appropriate) would help to further clarify the point of the study. • Please include when possible the version and release dates of the EUCAST and CLSI guidelines used as reference in this study, not only in the reference list, but in the main text. • L97, L112: there are references to amino acid substitutions as mutations. It is true that amino acid changes are produced by mutations in the DNA sequence, but both concepts are not interchangeable. As mutations happen at the DNA sequence level, it would be ftsI mutations those causing amino acid substitutions in PBP3. Please correct these sentences accordingly.
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In this manuscript, Merlino et al. present a case report about the course of treatment of a non-typable H. influenzae infection and discuss the discrepancies emerged during the antibiotic resistance tests performed with this isolate. The case is explained with clarity and the manuscript is easy to follow. However, several concerns have emerged after the review process. Please, address the reviewers’ suggestions and comments thoroughly, especially those concerning: • Improvement of the analysis of the literature in the Discussion section. • Clarify the observation of the guidelines provided by the EUCAST and the CLSI, addressing the point made by reviewer 2 that the isolate could be reported as “susceptible” based on the guidelines of both EUCAST and CLSI. • Elaborate and discuss how strategies to address the discrepancies …
In this manuscript, Merlino et al. present a case report about the course of treatment of a non-typable H. influenzae infection and discuss the discrepancies emerged during the antibiotic resistance tests performed with this isolate. The case is explained with clarity and the manuscript is easy to follow. However, several concerns have emerged after the review process. Please, address the reviewers’ suggestions and comments thoroughly, especially those concerning: • Improvement of the analysis of the literature in the Discussion section. • Clarify the observation of the guidelines provided by the EUCAST and the CLSI, addressing the point made by reviewer 2 that the isolate could be reported as “susceptible” based on the guidelines of both EUCAST and CLSI. • Elaborate and discuss how strategies to address the discrepancies presented, if after the revisions this were still appropriate. Please, provide a revised manuscript containing all suggestions and a point-by-point response to the reviewers’ comments within 1 month.
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Comments to Author
The EUCAST guidelines state that "The benzylpenicillin 1 unit disk diffusion screening test shall be used to exclude beta-lactam resistance mechanisms. When the screen is negative (zone diameter ≥12 mm) all cephalosporins for which clinical breakpoints are available, including those with "Note", can be reported susceptible without further testing, except for cefuroxime oral, which if reported, should be reported "susceptible, increased exposure" (I)." Although the benzylpenicillin disks were not used the isolate was found to be BLNAR and therefore I would assume that the isolate could be reported as susceptible not resistant and therefore the two sets of guidelines agree?
Please rate the quality of the presentation and structure of the manuscript
Satisfactory
To what …
Comments to Author
The EUCAST guidelines state that "The benzylpenicillin 1 unit disk diffusion screening test shall be used to exclude beta-lactam resistance mechanisms. When the screen is negative (zone diameter ≥12 mm) all cephalosporins for which clinical breakpoints are available, including those with "Note", can be reported susceptible without further testing, except for cefuroxime oral, which if reported, should be reported "susceptible, increased exposure" (I)." Although the benzylpenicillin disks were not used the isolate was found to be BLNAR and therefore I would assume that the isolate could be reported as susceptible not resistant and therefore the two sets of guidelines agree?
Please rate the quality of the presentation and structure of the manuscript
Satisfactory
To what extent are the conclusions supported by the data?
Not at all
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
1. Description of the case(s): Good. 2. Presentation of results: NA. 3. How the style and organization of the paper communicates and represents key findings: Good. 4. Literature analysis or discussion: very weak. 5. Any other relevant comments: The authors had addressed a problem in the interpretation of breakpoints between EUCAST and CLSI but the case they reported and the discussion they described don't help to solve the problem; as this is a case report that involved only one isolate with only phenotypic antimicrobial results that are not compared with any genotypic correlation.
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Not at all
Do you have any …
Comments to Author
1. Description of the case(s): Good. 2. Presentation of results: NA. 3. How the style and organization of the paper communicates and represents key findings: Good. 4. Literature analysis or discussion: very weak. 5. Any other relevant comments: The authors had addressed a problem in the interpretation of breakpoints between EUCAST and CLSI but the case they reported and the discussion they described don't help to solve the problem; as this is a case report that involved only one isolate with only phenotypic antimicrobial results that are not compared with any genotypic correlation.
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Not at all
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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