Implementing a Standard Operating Procedure Is Associated with Improved Vancomycin Target Attainment in Bone and Joint Infections: A Pre-Post Study
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsMajor Comments
The manuscript is good. However, some limitations need to be acknowledged:
- The work is a quality approach, or a “laboratory stewardship” project to achieve the targeted vancomycin through levels. It should be explicitly named as such. The work is not “antibiotic stewardship”. The authors do not report the changes in DDD of the vancomycin administered, or adverse events of a rapid infusion such as allergy, DRESS syndrome (for example doi: 10.1159/000142729), Red Man syndrome, etc., which would be required to be labelled as “antibiotic stewardship”. Please acknowledge that. Your study is a “laboratory stewardship” project.
- The authors investigate the same pre-defined “optimal” dosing of vancomycin use for all sorts of orthopaedic infections suggesting that a rapid attainment of the targeted levels are a necessity. Clinically, this is not the case. Especially in chronic infections with low virulence pathogens, such as epidermidis in diabetic foot osteomyelitis (which, moreover, has been partially amputated or operated), there is no need to achieve serum through levels rapidly (let alone by using intravenous antibiotics such as vancomycin). For example, why should we rapidly achieve the through levels for a chronic infection that is already in place since several months?
- Please acknowledge that your rapid attainment of the trough levels does not lead to a better clinical outcome in terms of remission or revision. If this should be the case (what I doubt), please provide the corresponding data. The rapidity of level attainment might alter the length of hospital stay, but not the outcomes of therapy, with maybe a possible exception for septic patients in the ICU.
- The attainment of predefined levels is not the only pharmacologic parameter of interest, which should be acknowledged. For example, the underlying MIC of the strains to vancomycin (for example doi: 10.1007/s10096-012-1705-8) can play a bigger role than the time delay to obtain “correct” through levels.
- The Discussion is too long and can be easily shortened by the half. Especially, the entire chapter regarding dalbavancin and daptomycin (page 5) is beyond the scope of the article. If the authors insist to name alternative (and more costly) agents, they can mention them in 1 or 2 sentences.
- The Conclusion (page 6) is too long and could be resumed in three or four sentences.
Minor comments
- References 11 and 14 are the same (double).
- Reference 15 has no journal name.
- Reference 5 lacks the authors’ names.
- Reference 8 has no point “.” after the journal name antibiotics.
- I miss the author affiliations on the front page (on purpose?)
- In their SOP, the dose adjustments of vancomycin rely entirely on the GFR, but not weight (Table 1).
- I presume that the Fisher-test (page 2, line 159) corresponds to the “Fisher-exact" test, which represents the more official statistics name.
- Proportionally, the empiric vancomycin use substantially increased in the postintervention period (Table 2). How come? Did the authors shift to more vancomycin therapies?
- The results in the Discussion on page 5, last chapter, are repetitions and redundant.
Author Response
Please see the attachment!
Author Response File:
Author Response.pdf
Reviewer 2 Report
Comments and Suggestions for AuthorsThe manuscript presents a relevant and well-structured pre-post study assessing the effect of implementing a standard operating procedure (SOP) on vancomycin dosing precision in orthopedic patients. The topic is clinically important, addressing real-world pharmacological optimization and antimicrobial stewardship. The study is well-written, methodologically sound, and supported by strong statistical analyses. However, a few aspects require revision to enhance the manuscript’s quality.
- The paper effectively highlights the importance of SOPs in optimizing vancomycin therapy, yet the novel contribution compared with prior institutional studies (especially reference 9, by the same authors) should be more clearly differentiated.
- The pre-post design is appropriate for a pragmatic study; however, potential temporal confounders (such as staff turnover, improved laboratory turnaround, or concurrent antimicrobial stewardship initiatives) should be discussed. Please add a paragraph to the Limitations section explaining how these factors could influence target attainment independent of SOP implementation.
- Figures 1–3 effectively illustrate trends, but their resolution and labeling could be improved for publication.
- The manuscript is overall polished. Minor stylistic edits:
- Replace “meaningfully improved pharmacologic precision” with “significantly enhanced pharmacologic precision.”
- Avoid redundancy (e.g., repeating “protocol-first approach” several times).
- Ensure consistent use of abbreviations (e.g., use “TDM” after first mention).
Author Response
Please see the attachment.
Author Response File:
Author Response.pdf
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsThe reviewers incorporated most of my reamrks into the revised version.
I have no objection for the publication of this revised manuscript.
Reviewer 2 Report
Comments and Suggestions for AuthorsThe current version is appropriate for publication.

