Unseen Drivers of Antimicrobial Resistance: The Role of Industrial Agriculture and Climate Change in This Global Health Crisis

Round 1

Reviewer 1 Report

Very complete and in-depth narrative review on this "hot" topic. Previous experiences and findings are well presented and addressed to; as are potential solutions as well. Likely, the final chapter (future directions) could be a bit shortened, as normally constitutes a "dotted points" of five to seven or eight sentences.

Overall, a very informative, and updated review.

Author Response

We thank the reviewer for their time and helpful comments.

Comment 1: Likely, the final chapter (future directions) could be a bit shortened, as normally constitutes a "dotted points" of five to seven or eight sentences.

Response 1: We appreciate the comment and agree that the general format for a future directions section could follow this suggestion. We believe that the comprehensive nature of this review that encompasses many domains requires a more detailed future directions section that describes the multidisciplinary actions needed to combat antimicrobial resistance with an emphasis on the role of education and future research. We broke the future directions section up into paragraphs for readability. We have added 2 diagrammatic figures that illustrate key principles in the future directions section that help break up the text and enhance the narrative.

Reviewer 2 Report

This review addresses the important problem of antibiotic resistance development among bacterial pathogens, which threaten millions of lives worldwide. The paper provides a comprehensive analysis of the origins of AMR and the various factors influencing its widespread distribution. The material presented in the review is interesting and of significant value for researchers working on the AMR problem.

One limitation of the paper is the lack of visual representation of major facts and discoveries. This review is organized as a long, plain text with only one figure and one table, which are rather superficial and not very informative. By incorporating more figures and tables, the paper would become more accessible and engaging for readers. Visual aids would help summarize complex information, highlight key points, and provide a clearer understanding of the relationships between agricultural practices, climate change, and AMR. The authors should consider that their potential readers are busy researchers who would prefer to grasp information from schematics and tables rather than reading 12 pages of plain text.

Additionally, I have a few minor comments.

1) This sentence in lines 387-390 is confusing: “study examining the effect of temperature on AMR found that increases of 10°C associated with increases in AMR in E. coli by 4.2%, K. pneumoniae by 2.2%, and Staphylococcus aureus by 2.7% in the U.S. based on past trends in AMR [86].” It should be specified that the 10°C increase in the MacFadden et al. study refers to spatial variation in temperature across different regions, not a seasonal or annual increase. This distinction is important to avoid confusion, as this paragraph follows a discussion on climate change, and readers might assume the paper is referring to a 10°C increase in average annual temperature, which would be highly unrealistic.  

2) In lines 104-124, the authors lengthily discuss a novel lecture course established at the University of Illinois. While I fully support the idea of considering the role of education in combating AMR, the authors should summarize approaches and courses offered at different universities in the USA or worldwide. A comparison table of these courses would be appropriate here. The current text reads like a commercial advertisement for the course at the University of Illinois, which is not appropriate in a scientific review paper.

3) In lines 225-226 use S. enterica Typhimurium or simply Thyphimurium, as S. Thyphimurium is not a correct taxonomic name.

4) Line 311, check whether references to table 1 should be in small or capital case (e.g. table 1 or Table 1).

5) Line 382 – K. pneumoniae should be in italics.

Author Response

We thank the reviewer for their time and helpful comments. We believe that the suggested changes improve the readability of the article.

Comment 1: One limitation of the paper is the lack of visual representation of major facts and discoveries. This review is organized as a long, plain text with only one figure and one table, which are rather superficial and not very informative. By incorporating more figures and tables, the paper would become more accessible and engaging for readers. Visual aids would help summarize complex information, highlight key points, and provide a clearer understanding of the relationships between agricultural practices, climate change, and AMR. The authors should consider that their potential readers are busy researchers who would prefer to grasp information from schematics and tables rather than reading 12 pages of plain text.

Response 1: We have added 6 schematic figures throughout the text that help illustrate key concepts discussed. These include the following figures:  on page 4 line 250 depicting the influence of industrial agricultural practices on soil microbiota, on page 7 line 419 depicting the effects of antimicrobial use in livestock on AMR, on page 8 line 430 depicting potential transmission of resistant bacteria from agricultural sources to humans through food, on page 10 line 497 depicting the effects of climate change on agricultural productivity and antimicrobial resistance, on page 14 line 638 depicting regenerative agricultural practices, and on page 15 line 703 depicting the different stakeholders and activities needed to address antimicrobial resistance.

Comment 2: This sentence in lines 387-390 is confusing: “study examining the effect of temperature on AMR found that increases of 10°C associated with increases in AMR in E. coli by 4.2%, K. pneumoniae by 2.2%, and Staphylococcus aureus by 2.7% in the U.S. based on past trends in AMR [86].” It should be specified that the 10°C increase in the MacFadden et al. study refers to spatial variation in temperature across different regions, not a seasonal or annual increase. This distinction is important to avoid confusion, as this paragraph follows a discussion on climate change, and readers might assume the paper is referring to a 10°C increase in average annual temperature, which would be highly unrealistic.  

Response 2: We agree and have clarified that the association of antimicrobial resistance is across regional differences in temperature and not increases in temperature within the same region. The mention of the study by MacFadden et al. is now on lines 526-529 and reads "A study examining the effect of geographical variation in temperature on AMR found that a 10°C increase in temperature across regions was associated with increases in AMR in E. coli by 4.2%, K. pneumoniae by 2.2%, and Staphylococcus aureus by 2.7% in the U.S."

Comment 3: In lines 104-124, the authors lengthily discuss a novel lecture course established at the University of Illinois. While I fully support the idea of considering the role of education in combating AMR, the authors should summarize approaches and courses offered at different universities in the USA or worldwide. A comparison table of these courses would be appropriate here. The current text reads like a commercial advertisement for the course at the University of Illinois, which is not appropriate in a scientific review paper.

Response 3: We have pared down the discussion of the Microbiomes Matter elective and now highlight key differences between the course and other existing courses on antimicrobial stewardship, see lines 186-191. We felt that the narrative sufficed to highlight the limitations of existing courses.

Comment 4: In lines 225-226 use S. enterica Typhimurium or simply Thyphimurium, as S. Thyphimurium is not a correct taxonomic name.

Response 4: We mention Salmonella enterica serovar Typhimurium as such earlier in the text in line 299-300. We have changed other mentions to "S. enterica Typhimurium" in lines 302 and 303.

Comment 5: Line 311, check whether references to table 1 should be in small or capital case (e.g. table 1 or Table 1).

Response 5: We have capitalized Table 1 in line 441.

Comment 6: Line 382 – K. pneumoniae should be in italics.

Response 6: We have italicized all mentions of K. pneumoniae in lines 520, 521, 523, and 528.