Title: In vitro susceptibility of clinical Clostridioides difficile isolates in Israel to metronidazole,
vancomycin, fidaxomicin, ridinilazole and ibezapolstat
Version: 3 Date: 24 Feb 2025
Reviewer's report:
Overall comments
The authors present a study that evaluated the in vitro effectiveness of two new antibiotics,
ridinilazole (RDZ) and ibezpolstat (IBZ), against 313 clinical isolates of C. difficile in Israel.
Results showed very low resistance to currently used antibiotics and activity of both RDZ and
IBZ across various strain types.
The manuscript would benefit from English proofreading; there are many missing articles and
some typos.
Although authors performed whole genome sequencing, only sequence type was determined
from this valuable data. The authors should at least investigate mechanisms of resistance
in isolates showing resistance to currently used antimicrobials (see the source for molecular
determinants already published PMID: 38598696)
Specific comments
Title: the title should reflect also susceptibility testing to currently used antimicrobials
line 26: different sequence types
Line 31: fidaxomicin resistance is not mentioned!
line 38: this was not investigated in this study, so it cannot be the study's conclusion.
line 65: "lower concentration needed for treatment" There is no such comparative study.
line 65: CDI recurrence rate
lines 72-73: typos
line 84: "insuperiority" should be " nonsuperiority"?
Line 136: delete technique
line 140: discuss this media use, which cannot detect hem-dependent metronidazole resistance
(PMID: 37438331)
Line 144: ECOFFs?
No control strains were used for AST?
Line 165: submit your data to the PubMLST database and the curator will assign a new ST
number.
Discussion:
a large part of the discussion is dedicated to ST distribution and prevalence, but this was not
the aim of the study. This section should be shortened using a reference to review summarising
epidemiology in the region (PMID: 35240336).
lines 256-258: none of this was investigated in your isolates why iis it discussed?
line 300: ECOFF
Line 353: Helsinki?
Title: In vitro susceptibility of clinical Clostridioides difficile isolates in Israel to metronidazole,
vancomycin, fidaxomicin, ridinilazole and ibezapolstat
Version: 3 Date: 24 Feb 2025
Reviewer's report:
Overall comments
The authors present a study that evaluated the in vitro effectiveness of two new antibiotics,
ridinilazole (RDZ) and ibezpolstat (IBZ), against 313 clinical isolates of C. difficile in Israel.
Results showed very low resistance to currently used antibiotics and activity of both RDZ and
IBZ across various strain types.
The manuscript would benefit from English proofreading; there are many missing articles and
some typos.
Although authors performed whole genome sequencing, only sequence type was determined
from this valuable data. The authors should at least investigate mechanisms of resistance
in isolates showing resistance to currently used antimicrobials (see the source for molecular
determinants already published PMID: 38598696)
Specific comments
Title: the title should reflect also susceptibility testing to currently used antimicrobials
line 26: different sequence types
Line 31: fidaxomicin resistance is not mentioned!
line 38: this was not investigated in this study, so it cannot be the study's conclusion.
line 65: "lower concentration needed for treatment" There is no such comparative study.
line 65: CDI recurrence rate
lines 72-73: typos
line 84: "insuperiority" should be " nonsuperiority"?
Line 136: delete technique
line 140: discuss this media use, which cannot detect hem-dependent metronidazole resistance
(PMID: 37438331)
Line 144: ECOFFs?
No control strains were used for AST?
Line 165: submit your data to the PubMLST database and the curator will assign a new ST
number.
Discussion:
a large part of the discussion is dedicated to ST distribution and prevalence, but this was not
the aim of the study. This section should be shortened using a reference to review summarising
epidemiology in the region (PMID: 35240336).
lines 256-258: none of this was investigated in your isolates why iis it discussed?
line 300: ECOFF
Line 353: Helsinki?
Please review this paper.
user
Title: In vitro susceptibility of clinical Clostridioides difficile isolates in Israel to metronidazole,
vancomycin, fidaxomicin, ridinilazole and ibezapolstat
Version: 3 Date: 24 Feb 2025
Reviewer's report:
Overall comments
The authors present a study that evaluated the in vitro effectiveness of two new antibiotics,
ridinilazole (RDZ) and ibezpolstat (IBZ), against 313 clinical isolates of C. difficile in Israel.
Results showed very low resistance to currently used antibiotics and activity of both RDZ and
IBZ across various strain types.
The manuscript would benefit from English proofreading; there are many missing articles and
some typos.
Although authors performed whole genome sequencing, only sequence type was determined
from this valuable data. The authors should at least investigate mechanisms of resistance
in isolates showing resistance to currently used antimicrobials (see the source for molecular
determinants already published PMID: 38598696)
Specific comments
Title: the title should reflect also susceptibility testing to currently used antimicrobials
line 26: different sequence types
Line 31: fidaxomicin resistance is not mentioned!
line 38: this was not investigated in this study, so it cannot be the study's conclusion.
line 65: "lower concentration needed for treatment" There is no such comparative study.
line 65: CDI recurrence rate
lines 72-73: typos
line 84: "insuperiority" should be " nonsuperiority"?
Line 136: delete technique
line 140: discuss this media use, which cannot detect hem-dependent metronidazole resistance
(PMID: 37438331)
Line 144: ECOFFs?
No control strains were used for AST?
Line 165: submit your data to the PubMLST database and the curator will assign a new ST
number.
Discussion:
a large part of the discussion is dedicated to ST distribution and prevalence, but this was not
the aim of the study. This section should be shortened using a reference to review summarising
epidemiology in the region (PMID: 35240336).
lines 256-258: none of this was investigated in your isolates why iis it discussed?
line 300: ECOFF
Line 353: Helsinki?
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