Hashimoto response 1
At first, we apologized that we found mistake in the Abstract. We chaged
phrases from “… apheresis independently predicted postoperative MRSA.” to
“… aphresis independently predicted postoperative MRSA acquisition.” Please
check the Abstract.
We have replied to all comments by 3 reviewers in a point-by-point manner.
Dr. Santoro-Lopes pointed out 14 problems.
Major compulsory revisions
1. Dr. Santoro-Lopes pointed out that the expression of “a case-control study”
was not correct in the Title.
---In addition to the Dr. Santoro-Lopes’s comment, Dr. Kalbfleisch also
recommended to eliminate “a case control study” from the Title. We changed
the title from “…a case control study” to “…a retrospective cohort study”.
Please check it.
2. Dr. Santoro-Lopes recommended to clarify which variable was associated
with the acquisition of MRSA, “perioperative aperesis” or “perioperative
dialysis and/or apheresis”?
---We were sorry that it was confusing to understand which variable was
associated with the acquisition of MRSA. We standardized the phareses to
“dialysis and/or apheresis” through the manuscript. Please check the
followings: Abstract section, Risk factors for the appearance of MRSA after
LDLT subsection of Results section, second paragraph of Discussion section
and Table 3.
3. Dr. Santoro-Lopes recommended to change phrases from "prevalence" to
"incidence" in the Abstract and in the Conclusion.
---We changed phrases accordingly. Please check the Abstract and the
Conclusion.
4. Dr. Santoro-Lopes recommended to clarify how the patients were screened
in the preoperative phage.
--- Screened specimens consisted of swabs of the anterior nares, pharynx,
sputum, urine, and stool, perioperatively. In addition, swabs of wound or
skin lesions, bile, and discharge from the abdominal cavity were collected
postoperatively. We changed the first paragraph of Definition of MRSA
colonization subsection of Methods section. Please check it.
Hashimoto response 2
5. Dr. Santoro-Lopes recommended to clarify the diagnostic work-up for
patients with suspected infection.
--- A catheter or blood sample was also submitted when infection was suspected
as the followings: fever (> 38° C), chills, or hypotension. We changed phrases
accordingly in the first paragraph of Definition of MRSA colonization
subsection of Methods section. Please check it.
6. Dr. Santoro-Lopes recommended to explain what method was used to determine
the minimum inhibitory concentration of oxacillin.
---We used the microdilution method to determine the minimum inhibitory
concentration of oxacillin. We changed phrases accordingly in the third
paragraph of Definition of MRSA colonization subsection of Methods section.
Please check it.
7. Dr. Santoro-Lopes asked how frequent the patients were treated with
antibiotics after the perioperative antimicrobial prophylaxis was stopped.
He also recommended to analyze the possible association between MRSA
acquisition and the postoperative frequency of use of antimicrobial drugs
that were prescribed to treat infectious complications.
--- According to the reiviewer's recommendation, we added the following
comments in Acquisition of MRSA after LDLT subsection of Results section:
"After the perioperative prophylactic antimicrobials were stopped,
additional therapeutic antimicrobials were administered for infectious
episodes in 91 of 123 (74%) patients without MRSA acquisition and 33 of 35
(94%) with MRSA acquisition, respectively. The median duration of the these
additional therapeutic antimicrobials were 10 (range, 0-74) and 21 (range,
0-21) days in patients without MRSA acquisition and with MRSA acquisition,
respectively." Please check it.
The reviewer also recommended to analyze the possible association
between MRSA acquisition and the postoperative frequency of use of
antimicrobials. However, it was difficult to analyze whether the postoperative
frequency of use of antimicrobials increased a risk of MRSA acquisition in
the present study. The median period of time between LDLT and detection of
MRSA was postoperative day 18, and 17 of 35 (49%) patients acquired with
MRSA within 2 weeks after the operation. Although additional antimicrobials
were administered more frequently in patients with MRSA acquisition than
without MRSA acquisition during the study period, it remained unclear whether
it was a cause or an effect of MRSA acquisition. We added the comments in
the fifth paragraph of Discussion section. Please check it.
Hashimoto response 3
8. Dr. Santoro-Lopes pointed out that it was difficult understand the
description that “of 35 patients with MRSA positive cultures, 7 subsequently
developed MRSA infection”, because 4 patients who developed MRSA infection
did not have a previous positive result of a surveillance culture.
--- We were sorry that it was confusing to understand. We changed phrases
from “Of the 35 patients with MRSA-positive cultures, 7(20%) subsequently…”
to “Of the 31 patients with MRSA-positive cultures, 7(23%) subsequently…”
in the first paragraph of Discussion section. Please check it.
Minor Essential Revisions
9. Dr. Santoro-Lopes pointed out that the abbreviation DDLT was not explained
in the first paragraph of Background section.
---We changed phrases from “DDLT” to “deceased donor liver transplantation
(DDLT)” in the first paragraph of Background section. Please check it.
10. Dr. Santoro-Lopes recommendded to change phrases from “etiology of MRSA”
to “factors associated with the acquisition of MRSA” in the third and the
fourth paragraph of Background section.
---We changed phrases accordingly. Please check the third and the fourth
paragraph of Background section.
11. Dr. Santoro-Lopes recommended to change phrases from “cefotaxim” to
“cefotaxime” in Perioperative management subsection of Methods section.
---We changed phrases accordingly. Please check Perioperative management
subsection of Methods section.
12. Dr. Santoro-Lopes pointed out that it was not necessary to repeat the
results of OR and 95% confidence intervals that were shown in Table 3.
---We deleted the results of OR and 95% confidence intervals in Risk factors
for the appearance of MRSA after LDLT subsection in Results section. Please
check it.
13. Dr. Santoro-Lopes pointed out that Reference 9 was mistakenly quoted.
---We were sorry to make a mistake. We quoted Reference 7 on behalf of Reference
9 in the first paragraph of Discussion section. Please check it.
Discretionary Revisions
14. Dr. Santoro-Lopes recommended to replace expression “colonization and/or
infection with methicillin-resistant Staphylococcus aureus” with
“acquisition of MRSA” in the Title and in other parts of the text. He also
Hashimoto response 4
recommended to replace the expression “appearance of MRSA” with “acquisition
of MRSA” in the abstract and other parts of the text.
---We changed phrases from “colonization and/or infection with
methicillin-resistant Staphylococcus aureus” to “acquisition of MRSA” in
the text and other parts of the text. Please check the following parts:Title,
Abstract, the second paragraph of Discussion section, Table 2, Table 3, and
Figure.
We changed phrases from “appearance of MRSA” to “acquisition of MRSA”
in the abstract and other parts of the text. Please check the following
parts:Abstract, subtitle of the first subsection of Results section,
Acquisition of MRSA after LDLT subsection of Results section, subtitle of
the second subsection of Results section, Risk factors for the acquisition
of MRSA after LDLT subsection of Results section, and the fifth paragraph
of Discussion section.
In addition, we changed phrases from “colonization” to “acquisition”
in the fourth paragraph of Discussion section. Please check it.
Hashimoto response 5
Dr. Spelman pointed out 11 problems.
Essential revisions and questions that need to be answered
1. Dr. Spelman pointed out that the abbreviation “LDLT” was used without
being defined in the Abstract and in the first paragraph of the Methods section.
---We already defined the abbreviation “LDLT” as living donor liver
transplantation in the Abstract and in the third paragraph of Background
section. Please check it.
2. Dr. Spelman recommended to include whether the transplant donor underwent
screening.
--- According to ther reviewer’s recommendation, we added that “Donors were
not routinely screened for Staphylococcus aureus perioperatively.” in Donor
selection subsection of Methods section. Please check it.
3. Dr. Spelman recommended to include the length of hospital stay for the
patients.
--- According to the reviewer’s recommendation, we added the description
about the length of hospital stay in Acquisition of MRSA after LDLT subsection
of Results section. Please check it.
4. Dr. Spelman recommend to describe about the compliance with the screening
protocol including the number of swabs for each patient.
-- According to the reviewer's recommendation, we added that "The median
number of screening samples for each patient and the compliances with
surveillance culture for nares, pharynx, sputum, urine, and stool were 9
(range, 1-25), 9 (range, 0-25), 5 (range, 0-25), 9 (range, 1-24), and 6 (range,
0-22) samples, and 82%, 82%, 50%, 80%, and 60%, respectively" in Acquisition
of MRSA subsection of Results section. Please check it.
As for other samples than nares, pharynx, sputum, urine and stool,
it was difficult to check the compliances by the medical record, because
some medical records lacked a daily description about the presence of
intraabdominal drain or biliary stent tube.
5. Dr. Spelman recommended to include a reference for the definition of MRSA.
-- We added a new reference in the third paragraph of Definition of MRSA
colonization subsection of Methods section. We changed the number of other
references accordingly in the text. Please check it.
Hashimoto response 6
6. Dr. Spelman asked whether the product for hand hygiene were used by
non-medical staff in contact with patients.
-- Non-medical staffs in contact with patients also used the product for
handhygiene. We changed phrases from “… handhygiene of patients, and medical
staffs.” to “… handhygiene of patients, medical, and non-medical staffs in
contact with patients.” in Management of precaution for transmission of MRSA
subsection of Methods section. Please check it.
7. Dr. Spelman pointed out that there were a large number of variables included
in the analysis (N=35). He suggested the possibility that one in twenty may
appear ‘significant’ just by chance.
--According to the reviewer’s indication, we added that “A large number of
variables (N=35) were included in the analysis in the present study, and
it might be better to take into consideration of the possibility that
statistical significance appeared by chance.” in the second paragraph of
Discussion section. Please check it.
8. Dr. Spelman pointed out that “duct to duct biliary reconstruction” was
not significant factors by the univariate analysis.
--We apologized that we made a mistake. We deleted phrases “duct to duct
biliary reconstruction (P=0.09)” from Risk factors for the acquisition of
MRSA after LDLT subsection of Results section. Please check it.
9. Dr. Spelman recommended to include in the heading for Table 2 that it
was a univariate analysis. He also recommended to make the headings of the
second and the third columns in Table 2 clearer.
--According to the reviewer’s recommendation, we added the phrases “by the
univariate analysis” in the heading for the Table 2. Please check it.
We also changed phrases from “Colonization and/or infection of MRSA”
to “Acquisition of MRSA” in the headings of the second and third columns
of Table 2. Please check it.
10. Dr. Spelman asked whether the antimicrobials included in the Table 2
were pre-transplant antimicrobials or they also included the perioperative
and post-transplant antimicrobials.
--The antimicrobials included in the Table 2 were only pre-transplant
antimicrobials. We changed phrases from “Use of antimicrobials” to
“Preoperative use of antimicrobials” in Table 2. Please check it.
11. Dr. Spelman recommended to clarify whether “a history of hospital stay”
in Table 2 referred to a hospital stay within a specific time period.
Hashimoto response 7
--According to reviewer’s recommendation, we changed phrases from “History
of hospital stay” to “History of hospital stay (the past 6 months)” in Table
2. Please check it.
Hashimoto response 8
Dr. Kalbfleisch pointed out 8 problems.
Major Compulsory Revisions.
1. Dr. Kalbfleisch recommended to define DDLT in the first paragraph of
Background section..
-- We changed phrases from “DDLT” to “deceased donor liver transplantation
(DDLT)” in the first paragraph of Background section. Please check it.
2. Dr. Kalbfleisch recommended to give the prevalence value of MRSA acquisition
in the Conclusion of Abstract.
-- We added phrases “(35 of 153 patients)” in the Conclusion of Abstract.
Please check it.
Minor Essential Revisions
3. Dr. Kalbfleisch pointed out that percentages should accompany frequency
counts in Table 2.
-- We changed Table 2 accordingly. Please check it.
Discretionary Revisions.
4. Dr. Kalbfleisch recommended to eliminate “a case-control study” from the
Title.
---In addition to Dr. Kalbfleisch the’s comment, Dr. Santoro-Lopes also
recommended to chage phrases from “…-case control study” from the Title.
We changed the title from “…a case control study” to “…a retrospective cohort
study”. Please check it.
5. Dr. Kalbfleisch recommended to change phrases from “… 7 risk factors with
a p value of less than 0.25…” to “… 7 risk factors with a univariate p value
of less than 0.25…” in Risk factors for the Acquisition of MRSA after LDLT
subsection of Results section.
---We changed phrases from “… 7 risk factors with a p value of less than
0.25…” to “… 7 risk factors with a univariate p value of less than 0.25…”
in Risk factors for the Acquisition of MRSA after LDLT subsection of Results
section. Please check it.
6. Dr. Kalbfleisch pointed out that it was not appropriate to use phrases
“independent” for risk factors of MRSA acquisition identified in the
manuscript, because there was no statistical analysis to support this claim.
He also recommended to separate the data into 2 sets by age (<60, 60 and
Hashimoto response 9
older) and to see if perioperative apheresis relates to MRSA acquisition
in each set.
---We deleted phrases “independent”, which was used for risk factors
identified by the multivariate analysis. Accordingly, we added phrases “by
multivariate analysis” in some parts of the manuscript. Please check the
following parts: Methods part of Abstract, Results part of Abstract, Risk
factors for the acquisition of MRSA after LDLT subsection in Results section,
and the second paragraph of Discussion section.
As for the latter recommendation, we added the following comments in
the second paragraph of Discussion section: “When the patients with MRSA
acquisition were separated into 2 sets by age (<60, =>60) in the present
study, the older group had a greater experience of perioperative dialysis
and/or apheresis than the younger group (60% vs 40%). Therefore, perioperative
and/or apheresis might be more closely correlated with MRSA acquisition.”
Please check it.
.
7. Dr. Kalbfleisch recommended to give a “p-level” for comparing group median
levels in Table 2.
---According to the reviewer’s recommendation, we added p value for comparing
group median levels in Table 2. Please check it.
We also added the description that “Wilcoxon rank sum test was used to compare
the quantitative variables” in Statistical analysis subsection of Methods
section. Please check it.
8. Dr. Kalbfleisch pointed out that the results of Table 3 could be added
as a new column in Table 3, although it would be confusing to some readers.
---We consider it would be confusing to some readers to combine Table 2 with
Table 3, and we want to keep Table 2 and Table 3 unchanged. Please check
it.