Targeted Combination Antibiotic Therapy Induces Remission in Treatment-Naïve Crohn’s Disease: A Case Series
M.T. Collins
Round 1
Reviewer 1 Report
This report is novel and a major contribution to the field of paratuberculosis as a zoonotic pathogen. The following minor edits are intended to strengthen the work, listed by line number.
12 The statement begins: “Single centre case….” is not a complete sentence.
40 Change “a” to “the” as in “MAP is the causative organism”.
41 “Johne’s disease” is not fully in quotation marks and the “d” is normally not capitalized. Also, remove the uncertainty in this sentence such that it reads: “It belongs to the Mycobacterium avium Complex (MAC), one of many non-tuberculous mycobacteria (NTM) which are distinct from mycobacteria in the Mycobacterium tuberculosis Complex (MTBC).”
42 The word “complex” should not be italicized.
43 This sentence, beginning “It is currently thought … “ is poorly written and can be deleted.
45 Missing reference.
47 The sentence beginning “It is unclear….” makes no sense and should be re-written. I do think that the lack of validated diagnostic tests for MAP in humans should be mentioned in the introduction of this manuscript, but this sentence fails to do this in a meaningful way.
50 Suggested revision: “…targeting MAP, i.e. anti-mycobacterial therapy (AMAT), have been…”
55 Suggested revision: “This is an important distinction, mycobacteria in the MAC are notoriously difficult to treat. Even for more susceptible mycobacteria like those in the MTBC, cure rates of only 81% are the norm (World Health Organization Data 2017).”
63 Do not capitalize the words rifamycin or macrolide or clofazimine.
66 Change to read: “NTMs require….” (delete the “s” in require). The word “data” is plural and thus the sentence should read “data are…”.
68 Change “longest reproductive rate” to “slowest growth rate of all NTMs.”
115 Anemia is mentioned here, and hemoglobin measurements are described in the methods section (see line 88) but no such results are in Table 1. Likewise, ESR is mentioned in the methods (line 88) but no data are found in Table 1. Likewise, ferritin levels are mentioned on line 116 but no results are found in Table 1. So, either fix table 1 or describe the results in the text.
124 The acronym “LFTs” is not defined.
148 Suggested revision: “In summary, AMAT therapy alone induced, and later re-induced, remission of CD.”
149 The acronym “RCTs” is not defined.
159 Hyphenate “treatment-naïve” as you did elsewhere.
165 Suggested revision: “Once accurate diagnostic testing is for MAP infections of humans is available, especially if it can include antimicrobial sensitivity testing of MAP isolates, this theory can be confirmed and treatment regimens better optimized.”
170 The meaning of the sentence beginning “Once a few….” Is unclear and should be re-written.
179 Do not capitalize clofazamine.
180 Suggested revision: “Given the severe impact of CD on patients and their families,…..”
All references should all be reviewed for accuracy.
Examples of possible errors, by ref number:
10&11 Is LIVER supposed to be in all caps?
13 Parallel is misspelled
20-36 Bacterial names are not italicized as they should be.
22 A portion of the article title seems missing.
25 Insert space between “a” and Mycobacterium (which should also be italicized)
30 The end of the article title seems in error (why pdf ???)
Author Response
Thank you to the reviewer for his time and comments. They have all been addressed:
12 The statement begins: “Single centre case….” is not a complete sentence. Amended
40 Change “a” to “the” as in “MAP is the causative organism”. Amended
41 “Johne’s disease” is not fully in quotation marks and the “d” is normally not capitalized. Also, remove the uncertainty in this sentence such that it reads: “It belongs to the Mycobacterium avium Complex (MAC), one of many non-tuberculous mycobacteria (NTM) which are distinct from mycobacteria in the Mycobacterium tuberculosis Complex (MTBC).” Amended
42 The word “complex” should not be italicized. Amended
43 This sentence, beginning “It is currently thought … “ is poorly written and can be deleted. Amended
45 Missing reference. included
47 The sentence beginning “It is unclear….” makes no sense and should be re-written. I do think that the lack of validated diagnostic tests for MAP in humans should be mentioned in the introduction of this manuscript, but this sentence fails to do this in a meaningful way. Amended
50 Suggested revision: “…targeting MAP, i.e. anti-mycobacterial therapy (AMAT), have been…” Amended
55 Suggested revision: “This is an important distinction, mycobacteria in the MAC are notoriously difficult to treat. Even for more susceptible mycobacteria like those in the MTBC, cure rates of only 81% are the norm (World Health Organization Data 2017).” Amended
63 Do not capitalize the words rifamycin or macrolide or clofazimine. Amended
66 Change to read: “NTMs require….” (delete the “s” in require). The word “data” is plural and thus the sentence should read “data are…”. Amended
68 Change “longest reproductive rate” to “slowest growth rate of all NTMs.” Amended
115 Anemia is mentioned here, and hemoglobin measurements are described in the methods section (see line 88) but no such results are in Table 1. Likewise, ESR is mentioned in the methods (line 88) but no data are found in Table 1. Likewise, ferritin levels are mentioned on line 116 but no results are found in Table 1. So, either fix table 1 or describe the results in the text. Amended
124 The acronym “LFTs” is not defined. Amended
148 Suggested revision: “In summary, AMAT therapy alone induced, and later re-induced, remission of CD.” Amended
149 The acronym “RCTs” is not defined. Amended
159 Hyphenate “treatment-naïve” as you did elsewhere. Amended
165 Suggested revision: “Once accurate diagnostic testing is for MAP infections of humans is available, especially if it can include antimicrobial sensitivity testing of MAP isolates, this theory can be confirmed and treatment regimens better optimized.” Amended
170 The meaning of the sentence beginning “Once a few….” Is unclear and should be re-written. Amended
179 Do not capitalize clofazamine. Amended
180 Suggested revision: “Given the severe impact of CD on patients and their families,…..” Amended
All references should all be reviewed for accuracy.
10&11 Is LIVER supposed to be in all caps? Amended
13 Parallel is misspelled Amended
20-36 Bacterial names are not italicized as they should be. Amended
22 A portion of the article title seems missing. Amended
25 Insert space between “a” and Mycobacterium (which should also be italicized) Amended
30 The end of the article title seems in error (why pdf ???) Amended
Reviewer 2 Report
Authors present a high-quality experimental manuscript that describes targeted combination antibiotic therapy that induces remission in treatment-naïve Crohn’s Disease. Authors report for the first time the outcomes of patients with CD treated with first-line anti-mycobacterial antibiotic therapy (AMAT). The manuscript is well-written and a pleasure to read. Authors observed that for 8 patients the median Crohn’s Disease Activity Index (CDAI) score decreased significantly from 289 prior to treatment to 62 at the 12 month follow up. Based on the results, authors conclude that: - Improvement in clinical symptoms and inflammatory markers was achieved in all eight patients receiving AMAT as sole therapy by 6 weeks. - AMAT as first-line therapy can demonstrate a rapid improvement of Crohn’s Disease. - Clinical remission (CDAIAuthor Response
Thank you to the Reviewer's comments and feedback. We have addressed the English and reviewed and updated the results section.
Sincerely,
