Optimizing Antimicrobial Drug Dosing in Critically Ill Patients

Round 1

Reviewer 1 Report

I have no comments. Accept the manuscript in the present form

Author Response

REVIEWER 1

I have no comments. Accept the manuscript in the present form

Response: The authors thank the reviewer for the positive comments.

Reviewer 2 Report

Coelho et al. reported a comprehensive review about the challenges and the tools to optimize the antimicrobial dosing to maximize exposure and effectiveness in critically sepsis and septic shock patients. The authors discussed the pharmacokinetics and pharmacodynamics of selected drugs and their dosing, being focused on the possible strategies to improve, and optimize therapeutic efficacy together with reduced toxicity in critically ill patients.

The review is very well-designed and presented. The authors have covered most of the recent studies together with clear explanation of the different strategies that could be followed to optimize individual dosing to maximize exposure and effectiveness of drugs in critically ill patients. I have really enjoyed reading this article. I would definitely recommend the publication of this review after addressing the following minor concerns;

• the authors should check for grammatical errors, minor English editing is needed.
• the authors should include supporting figs, especially for points 2-5. These figs would be of beneficial to clarify their discussion.
• why the author selected antibiotic and/or antimicrobial? what the fact of such selection? please clarify in text.
• it would be of beneficial if authors shortly covers different methods of TDM
• the authors should extend their introduction, it's poorly cover the topic

Author Response

REVIEWER 2

Coelho et al. reported a comprehensive review about the challenges and the tools to optimize the antimicrobial dosing to maximize exposure and effectiveness in critically sepsis and septic shock patients. The authors discussed the pharmacokinetics and pharmacodynamics of selected drugs and their dosing, being focused on the possible strategies to improve, and optimize therapeutic efficacy together with reduced toxicity in critically ill patients.

The review is very well-designed and presented. The authors have covered most of the recent studies together with clear explanation of the different strategies that could be followed to optimize individual dosing to maximize exposure and effectiveness of drugs in critically ill patients. I have really enjoyed reading this article. I would definitely recommend the publication of this review after addressing the following minor concerns;

Response: The authors thank the reviewer for the positive comments and agree with the suggestions made to improve the manuscript. Point by point responses have been provided and the manuscript´s text has been adjusted accordingly.

• the authors should check for grammatical errors, minor English editing is needed.

Response: We thank you for the point made. The manuscript has been reviewed by a native English-speaking peer and the recommended grammatical improvements have been made.

• the authors should include supporting figs, especially for points 2-5. These figs would be of beneficial to clarify their discussion.

Response: The authors thank the reviewer for this relevant suggestion. An additional supporting figure focusing on relevant PK aspects of frequently prescribed antimicrobials has been added to the manuscript.

• why the author selected antibiotic and/or antimicrobial? what the fact of such selection? please clarify in text.

Response: This is indeed an aspect that should be clarified. The authors thought it pertinent to review the most frequently prescribed classes of antimicrobials in the critical care setting. This has been clarified in the manuscript’s text (introduction).

• it would be of beneficial if authors shortly covers different methods of TDM

Response: The authors agree that this information greatly benefits the manuscript. Different methods of TDM have been summarized and added to the manuscript’s text (section 5 – strategies to optimize dosing, paragraph 6 inserted).

• the authors should extend their introduction, it's poorly cover the topic

Response: The authors thank the reviewer for this suggestion and agree that it will benefit the manuscript. The introduction has been extended accordingly.