Intermittent Short-Term Infusion vs. Continuous Infusion of Piperacillin: Steady State Concentrations in Porcine Cervical Spine Tissue Evaluated by Microdialysis

Round 1

Reviewer 1 Report

The article „Intermittent short-term infusion vs. continuous infusion of the piperacillin: steady state concentration in porcine cervical spine tissue evaluated by microdialysis“ is relatively well written and is suitable to be published in the MDPI Antibiotics Journal. It is of clinical relevance, and the only weakness is that the authors used different total piperacillin doses for short-term and continuous infusion. This fact is already mentioned in the discussion, but I think there should be some explanation for this difference. Different amounts of piperacillin will influence the pharmacokinetic parameters. It is also a pity that no samples were taken in the first 360 minutes of the experiment. My opinion is that this information, especially for STI, would also be valuable for the readers.

I also have some other minor comments that the authors should consider to comment or improve before the article is accepted.

1.       In the introduction part, I would expect some comments about the selection of the sampling place (intervertebral disc, vertebral cancellous bone).

2.       Chapter 2.1 (Relative recovery) seems weird to me. Relative recovery of what? Piperacillin? I am also confused about the references here. Does it mean that the recovery values are comparable to already published results? The chapter should be rewritten.

3.       The table 1 and 2 should be reformated to fit only one page. Bellow the table 1 and 2, I recommend adding an explanation for the abbreviations and statistical analysis method used to calculate the p values (including how the data are presented). P-values that indicate statistically significant differences between the CI and STI groups shout be marked by the asterisk.

4.       Figure 1 A and B are of different sizes. Please unify the size. The description should include the information about how the data are presented (mean +- SD?). Is it correct that some error bars are missing in Figure 1B (plasma)?

5.       Why is the baseline sample not presented in Figure 1?

6.       In the discussion or introduction, the authors should discuss the selection of the MIC targets (4, 8, and 16 ug/ml). Mentioning the selection of MIC targets only in the Materials and Methods part in chapter 4.2 seems insufficient.   

7.       Line 170 – please include information about how was piperacillin administered in the study with critically ill patients.

8.       Line 201 – include the information if the STI administration of piperacillin was according to the recommendation of the manufacturer (dose amount and dose intervals)

9.       Line 224 – I am confused about equations 1 and 2. When you insert the result from equation 1 (in percentage) into equation 2, you will not get the right results. I think multiplication by 100 should be removed to avoid confusion. E.g. in the article by Hansen et al. 2018 (DOI:10.1111/bcp.13468), equation 1 doesn't calculate the results in percentage. Could you please correct or comment on this?

10.   Line 291, 294 and 295 – are the units (mL) correct? I would expect uL units.

 

11.   Have you checked that the Tazobactam does not interfere with the Piperacillin and Benzylpenicillin concentration measurement during the UHPLC-UV analysis? Retention times for Tazobactam, Benzylpenicillin and Piperacillin should be included in chapter 4.6. 

Author Response

Thank you for taking your time to revise our manuscript, this we are very greatful for. 

Author Response File: Author Response.pdf

Reviewer 2 Report

Hi,

Please see my comments in the attached Word document. 

Thanks, 

Li

Comments for author File: Comments.pdf

Author Response

Thank you for taking your time to revise our manuscript and your interest, this we are very greatful for. 

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

The revised version looks much better. All my questions have been well addressed. I agree to accept this manuscript in its present form.

Author Response

Thank you for taking your time to review our manuscript, this is much appreciated. 

Author Response File: Author Response.docx