Antimicrobial susceptibility and distribution trends among inducible AmpC-producing Enterobacterales at a regional health authority in British Columbia: a 5-year retrospective review

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1. 

   Version published to 10.1099/acmi.0.001122.v2 on Access Microbiology

   Feb 19, 2026
2. 

   Access Microbiology

   Dec 12, 2025

   The reviewers were positive about your manuscript and suggest some areas for improvement. Please respond to all points raised, and pay particular attention to the issues relating to consistency throughout the manuscript. I look forward to receiving a revision. Please let me know us know if you need additional time.

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3. 

   Access Microbiology

   Dec 1, 2025

   Comments to Author

   The authors conducted a retrospective study of a large number of bacterial isolates, comparing species specific antibiotic susceptibilities based on risk of AmpC induction. The topic is of clinical interest and still debated in the antimicrobial field, thus more data to inform practice and future studies is welcome. The manuscript is clear but the methodologies significantly reduce the impact of the findings, precluding the authors from making the conclusions they've made. General comments 1. Please include full organism names in the tables and always clarify abbreviations in the tables. Abstract 2. Introduction: Recommend clarifying the purpose of this study. What is significant about characterizing the existing susceptibility trends? The difficulty in determining inducible AmpC production is that …

   Comments to Author

   The authors conducted a retrospective study of a large number of bacterial isolates, comparing species specific antibiotic susceptibilities based on risk of AmpC induction. The topic is of clinical interest and still debated in the antimicrobial field, thus more data to inform practice and future studies is welcome. The manuscript is clear but the methodologies significantly reduce the impact of the findings, precluding the authors from making the conclusions they've made. General comments 1. Please include full organism names in the tables and always clarify abbreviations in the tables. Abstract 2. Introduction: Recommend clarifying the purpose of this study. What is significant about characterizing the existing susceptibility trends? The difficulty in determining inducible AmpC production is that the antibiotic susceptibilities are misleading and one cannot rely on them to determine if AmpC may be induced. A method to determine their presence (though not definitive) is exposure to the antibiotic that leads to induction and then repeating cultures (and determining genetic relatedness) to see if resistance developed. A one-time susceptibility result is not informative. Moderate risk AmpC inducers could be ceftriaxone susceptible but this does not tell us whether individual susceptible isolates have inducible AmpC. 3. Methods: "MIC data for AmpC isolates…" How did the authors know these were AmpC isolates? Would clarify these were Enterobacterales. 4. Results: Please write out the organism name fully when it first appears. 5. Conclusion: Recommend rewriting the conclusion to include the impact these findings have. It is not immediately clear to the reader how these results should be correlated with outcomes or to establish MIC thresholds given that presence of inducible AmpC in this population is not known. Background 6. Lines 51-54: These lines exemplify the concern with the methodologies in this manuscript listed in comment 2. The authors do not explain whether the susceptibilities obtained in this manuscript are after exposure of the organism to inducing antibiotics or before (in order to provide some evidence that inducible AmpC production may be at play). Just knowing the susceptibility results in the moderate risk AmpC inducers does not inform care since the clinician does not know if there is inducible AmpC production and there is no CLSI approved method to detect it. Thus the IDSA guidelines suggest against ceftriaxone or pip/tazo use in most cases for the moderate risk AmpC inducing organisms (as the authors have written). 7. Line 55: Hafnia is listed as a moderate risk AmpC inducer here but later in the manuscript it is a low risk one. Please clarify. 8. Lines 67-68: These lines are misleading. The caution is due to concern that cefepime MICs in the SDD range could harbor ESBLs. So if an ESBL is known then cefepime should not be used (it's not caution using cefepime with co-production of ESBLs; it should not be used in their presence). 9. Lines 76-77: Please clarify what AmpC organisms are. The citations listed for these are not RCTs. One is a narrative review and the other a metanalysis. 10. Line 80: The authors do not explain how they know these are AmpC producers which is the premise of this paper. MICs in the moderate risk ampC induction group are misleading without knowing if inducible AmpC are present. Results 11. Line 120: Including ceftriaxone and pip/tazo (in cases other than source control has been obtained and/or patients are improving) is misleading since regardless of MIC, these are not recommended antibiotics for patients infected with moderate risk AmpC producers. Please clarify how the authors believe these susceptibilities are helpful. 12. Line 123: It would be helpful to include how much of the population had cefepime MICs in the SDD range separately since there is controversy in the field whether cefepime should be used in these situations. Discussion 13. Lines 148-150: Trends over time were not discussed in the results. Please include these data in the results if discussing them in the discussion. 14. Lines 155-159: The significance of this statement should be clarified. If the 3rd gen cephalosporin is resistant and cefepime is susceptible then presumably AmpC production is ramped up or an ESBL may even be present (less likely). The authors do not distinguish these possibilities. Also, just having susceptibility to cefepime does not mean it should be used clinically in these situations. If the 3rd gen cephalosporin is susceptible then we do not know any information about whether inducible AmpC production is possible. 15. Lines 161-164: The authors should discuss this more deeply. The way this paragraph regarding Hafnia is worded, it implies that Hafnia is higher risk of AmpC induction but that cannot be elucidated with MIC data alone. If Hafnia is more resistant it may just mean that AmpC production is there, but expressed constitutively (so not as concerning since clinicians won't use the ceftriaxone and pip/tazo since it's resistant anyway). The more concerning finding would be if inducible AmpC production is found with exposure to certain beta-lactams since a susceptible result can lead to starting therapy that may fail after AmpC induction begins. The authors did not confirm such a process in Hafnia. 16. Line 166-167: Please include the name of this cephalosporinase 17. Limitations paragraph: The authors should include that they did not confirm AmpC production in their isolates. Also the vast majority of isolates were from the urine (and no information on how bacteriuria vs infection was elucidated). 18. Line 185: The authors imply that cefepime susceptibilities are not routinely reported for AmpC producing organisms. The reviewer is not aware of this as cefepime is now routinely considered a first line agent for AmpC producing organisms (unless there are regional differences that the authors are alluding to). Please clarify this recommendation. Conclusion 19. Line 194: Please state how authors confirmed that the Enterobacterales were AmpC producing. Tables 20. Please include a total number column in Table 1 to get a better sense of the overall numbers 21. Please include years in the tables, not just month and date 22. Consider dividing the organisms into MRAC and LRAC subheadings as the grouping will help with organization

   Please rate the manuscript for methodological rigour

   Poor

   Please rate the quality of the presentation and structure of the manuscript

   Very 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

   Read the original source
4. 

   Access Microbiology

   Oct 2, 2025

   Comments to Author

   I read with interest the paper by Ka-Fung Lo et al. They investigated the antibiotic susceptibility profiles of a collection of Enterobacterales species carrying chromosomal AmpC-type beta-lactamases, identified over a 5-year period in a Canadian region. The work is certainly of interest, given the ongoing therapeutic debate in the literature, which the authors have also clearly presented in their study. However, I have some considerations to bring to the authors' attention, which I hope may help improve the quality of the work. 1) Title: The title should include a reference to the fact that these are inducible chromosomal AmpC; 2) Methods: The authors included data regarding Proteus vulgaris in the results, but did not mention it in the methods. The presence of Proteus vulgaris is, however, …

   Comments to Author

   I read with interest the paper by Ka-Fung Lo et al. They investigated the antibiotic susceptibility profiles of a collection of Enterobacterales species carrying chromosomal AmpC-type beta-lactamases, identified over a 5-year period in a Canadian region. The work is certainly of interest, given the ongoing therapeutic debate in the literature, which the authors have also clearly presented in their study. However, I have some considerations to bring to the authors' attention, which I hope may help improve the quality of the work. 1) Title: The title should include a reference to the fact that these are inducible chromosomal AmpC; 2) Methods: The authors included data regarding Proteus vulgaris in the results, but did not mention it in the methods. The presence of Proteus vulgaris is, however, questionable. It is up to the authors to ensure methodological consistency in their work. 3) Discussion: The authors did not take into account the results of the largest study on ESCPM species conducted in Europe and recently published (see PMID 38367844). It is up to the authors to decide whether to discuss their results in relation to the aforementioned paper. In general, in the discussion, the authors seem more concerned with the limitations of their study than with discussing their own results. I recommend that the authors thoroughly revise this chapter. 4) Tables: From a graphical point of view, the three tables are not very appealing. Perhaps the authors could try creating a bar chart for Table 2. Table 3 would benefit from indicating the resistance breakpoint as well as from a color scale based on the frequency of the results.

   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?

   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

   Read the original source
5. 

   Version published to 10.1099/acmi.0.001122.v1 on Access Microbiology

   Sep 30, 2025