Reviewer's report 
 Steroid-Refractory Ulcerative Colitis Treated with Corticosteroids, Metronidazole and Title: 
Vancomycin: a Case Report 
 2  25 September 2004 Version: Date: 
 Steven Siarakas Reviewer: 
Reviewer's report: 
General 
This is an interesting report of a rare rheumatological complication following Clostridium difficile infection. This complication is more common following other enteric infections such as with Campylobacter or Yersinia. The treatment combination administered to treat this patient’s infectious 
chronic diarrhoeal illness is also unique by combing antibiotics that are usually administered 
singularly, including an anti-inflammatory agent and extending treatment for 3 months. The report continues to claim a 4.5-year “remission” before the return of symptoms was treated with a 2-month approach that was considered to resolve the initial episode. 
I believe this a well written and logically set out report that should be accepted for publication after 
the following remarks are considered by the editorial board and commented on by the authors. ------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) There are a couple of points the authors may wish to consider discussing in this report. 
1. There is a case report from Cohen et al discussing the mutation of a toxin A+ B- C. difficile variant 
isolated from a patient that has relapsing episodes of C difficile induced diarrhoea. Cohen’s case 
report parallels this case report and may help explain the negative cytotoxicity assay (toxin B test). “Cohen SH, Tang YJ, Hansen B, Silva J Jr. Isolation of a toxin B-deficient mutant strain of 
Clostridium difficile in a case of recurrent C.difficile-associated diarrhea. Clin Infect Dis. 1998 
Feb;26(2):410-2” 
2. The word “remission” infers to me that there is a stay of effect by the infective organism and that 
the relapse is caused by the same strain. Without genetic typing of the strains in the two episodes it 
is not clear whether the spore of the original infecting organism re-germinated or is there a new infecting variant strain. The later possibility is not evident in the report and should be discussed as a plausible event. 
3. Was spore culture undertaken in the “remission” period? This would help establish if there was 
spore colonization or genuine organism eradication. 
4. Was resistance testing performed on the C. difficile isolates? This might also explain therapy 
failure of the antibiotics used singularly. There are NCCLS guidelines advocating the testing of 
anaerobic bacteria especially in patients failing therapy. “ NCCLS M11-A5, Methods for Antimicrobial
Susceptibility testing of anaerobic bacteria; 5th edition, page 2” 
5. Advocating 2-3 months of metronidazole and vancomycin therapy was successful for treating this 
patient and I have personal experience of the improvement of diarrhoeal diseases with long term vancomycin use. However the flip side to long term antibiotic use is the global problem of antibiotic 
resistance. Antibiotic resistance to C. difficile is increasingly being reported in the literature and there 
is controversial discussion that vancomycin therapy may be contributing to the increased prevalence 
of vancomycin resistant enterococci. I think that this report should touch on the growing problem of 
antibiotic resistance, advocate responsible targeted treatment and express the value of antibiotic 
susceptibility testing on isolates from relapsing C. difficile infections to guide therapy. “Hecht DW.Prevalence of antibiotic resistance in anaerobic bacteria: worrisome developments. Clin Infect Dis. 2004 Jul 1;39(1):92-7; Poduval RD, Kamath RP, Corpuz M, Norkus EP, Pitchumoni CS. 
Clostridium difficile and vancomycin-resistant enterococcus: the new nosocomial alliance. Am J 
Gastroenterol. 2000 Dec;95(12):3513-5; Pelaez T, Alcala L, Alonso R, Rodriguez-Creixems M, Garcia-Lechuz JM, Bouza E. Reassessment of Clostridium difficile susceptibility to metronidazole and vancomycin. Antimicrob Agents Chemother. 2002 Jun;46(6):1647-50.” 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Accept after minor essential revisions What next?: 
 An article of importance in its field Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
'None'
Reviewer's report 
 Steroid-Refractory Ulcerative Colitis Treated with Corticosteroids, Metronidazole and Title: 
Vancomycin: a Case Report 
 2  25 September 2004 Version: Date: 
 Steven Siarakas Reviewer: 
Reviewer's report: 
General 
This is an interesting report of a rare rheumatological complication following Clostridium difficile infection. This complication is more common following other enteric infections such as with Campylobacter or Yersinia. The treatment combination administered to treat this patient’s infectious 
chronic diarrhoeal illness is also unique by combing antibiotics that are usually administered 
singularly, including an anti-inflammatory agent and extending treatment for 3 months. The report continues to claim a 4.5-year “remission” before the return of symptoms was treated with a 2-month approach that was considered to resolve the initial episode. 
I believe this a well written and logically set out report that should be accepted for publication after 
the following remarks are considered by the editorial board and commented on by the authors. ------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) There are a couple of points the authors may wish to consider discussing in this report. 
1. There is a case report from Cohen et al discussing the mutation of a toxin A+ B- C. difficile variant 
isolated from a patient that has relapsing episodes of C difficile induced diarrhoea. Cohen’s case 
report parallels this case report and may help explain the negative cytotoxicity assay (toxin B test). “Cohen SH, Tang YJ, Hansen B, Silva J Jr. Isolation of a toxin B-deficient mutant strain of 
Clostridium difficile in a case of recurrent C.difficile-associated diarrhea. Clin Infect Dis. 1998 
Feb;26(2):410-2” 
2. The word “remission” infers to me that there is a stay of effect by the infective organism and that 
the relapse is caused by the same strain. Without genetic typing of the strains in the two episodes it 
is not clear whether the spore of the original infecting organism re-germinated or is there a new infecting variant strain. The later possibility is not evident in the report and should be discussed as a plausible event. 
3. Was spore culture undertaken in the “remission” period? This would help establish if there was 
spore colonization or genuine organism eradication. 
4. Was resistance testing performed on the C. difficile isolates? This might also explain therapy 
failure of the antibiotics used singularly. There are NCCLS guidelines advocating the testing of 
anaerobic bacteria especially in patients failing therapy. “ NCCLS M11-A5, Methods for Antimicrobial
Susceptibility testing of anaerobic bacteria; 5th edition, page 2” 
5. Advocating 2-3 months of metronidazole and vancomycin therapy was successful for treating this 
patient and I have personal experience of the improvement of diarrhoeal diseases with long term vancomycin use. However the flip side to long term antibiotic use is the global problem of antibiotic 
resistance. Antibiotic resistance to C. difficile is increasingly being reported in the literature and there 
is controversial discussion that vancomycin therapy may be contributing to the increased prevalence 
of vancomycin resistant enterococci. I think that this report should touch on the growing problem of 
antibiotic resistance, advocate responsible targeted treatment and express the value of antibiotic 
susceptibility testing on isolates from relapsing C. difficile infections to guide therapy. “Hecht DW.Prevalence of antibiotic resistance in anaerobic bacteria: worrisome developments. Clin Infect Dis. 2004 Jul 1;39(1):92-7; Poduval RD, Kamath RP, Corpuz M, Norkus EP, Pitchumoni CS. 
Clostridium difficile and vancomycin-resistant enterococcus: the new nosocomial alliance. Am J 
Gastroenterol. 2000 Dec;95(12):3513-5; Pelaez T, Alcala L, Alonso R, Rodriguez-Creixems M, Garcia-Lechuz JM, Bouza E. Reassessment of Clostridium difficile susceptibility to metronidazole and vancomycin. Antimicrob Agents Chemother. 2002 Jun;46(6):1647-50.” 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Accept after minor essential revisions What next?: 
 An article of importance in its field Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
'None'
Please review this paper.
user
Reviewer's report 
 Steroid-Refractory Ulcerative Colitis Treated with Corticosteroids, Metronidazole and Title: 
Vancomycin: a Case Report 
 2  25 September 2004 Version: Date: 
 Steven Siarakas Reviewer: 
Reviewer's report: 
General 
This is an interesting report of a rare rheumatological complication following Clostridium difficile infection. This complication is more common following other enteric infections such as with Campylobacter or Yersinia. The treatment combination administered to treat this patient’s infectious 
chronic diarrhoeal illness is also unique by combing antibiotics that are usually administered 
singularly, including an anti-inflammatory agent and extending treatment for 3 months. The report continues to claim a 4.5-year “remission” before the return of symptoms was treated with a 2-month approach that was considered to resolve the initial episode. 
I believe this a well written and logically set out report that should be accepted for publication after 
the following remarks are considered by the editorial board and commented on by the authors. ------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) There are a couple of points the authors may wish to consider discussing in this report. 
1. There is a case report from Cohen et al discussing the mutation of a toxin A+ B- C. difficile variant 
isolated from a patient that has relapsing episodes of C difficile induced diarrhoea. Cohen’s case 
report parallels this case report and may help explain the negative cytotoxicity assay (toxin B test). “Cohen SH, Tang YJ, Hansen B, Silva J Jr. Isolation of a toxin B-deficient mutant strain of 
Clostridium difficile in a case of recurrent C.difficile-associated diarrhea. Clin Infect Dis. 1998 
Feb;26(2):410-2” 
2. The word “remission” infers to me that there is a stay of effect by the infective organism and that 
the relapse is caused by the same strain. Without genetic typing of the strains in the two episodes it 
is not clear whether the spore of the original infecting organism re-germinated or is there a new infecting variant strain. The later possibility is not evident in the report and should be discussed as a plausible event. 
3. Was spore culture undertaken in the “remission” period? This would help establish if there was 
spore colonization or genuine organism eradication. 
4. Was resistance testing performed on the C. difficile isolates? This might also explain therapy 
failure of the antibiotics used singularly. There are NCCLS guidelines advocating the testing of 
anaerobic bacteria especially in patients failing therapy. “ NCCLS M11-A5, Methods for Antimicrobial
Susceptibility testing of anaerobic bacteria; 5th edition, page 2” 
5. Advocating 2-3 months of metronidazole and vancomycin therapy was successful for treating this 
patient and I have personal experience of the improvement of diarrhoeal diseases with long term vancomycin use. However the flip side to long term antibiotic use is the global problem of antibiotic 
resistance. Antibiotic resistance to C. difficile is increasingly being reported in the literature and there 
is controversial discussion that vancomycin therapy may be contributing to the increased prevalence 
of vancomycin resistant enterococci. I think that this report should touch on the growing problem of 
antibiotic resistance, advocate responsible targeted treatment and express the value of antibiotic 
susceptibility testing on isolates from relapsing C. difficile infections to guide therapy. “Hecht DW.Prevalence of antibiotic resistance in anaerobic bacteria: worrisome developments. Clin Infect Dis. 2004 Jul 1;39(1):92-7; Poduval RD, Kamath RP, Corpuz M, Norkus EP, Pitchumoni CS. 
Clostridium difficile and vancomycin-resistant enterococcus: the new nosocomial alliance. Am J 
Gastroenterol. 2000 Dec;95(12):3513-5; Pelaez T, Alcala L, Alonso R, Rodriguez-Creixems M, Garcia-Lechuz JM, Bouza E. Reassessment of Clostridium difficile susceptibility to metronidazole and vancomycin. Antimicrob Agents Chemother. 2002 Jun;46(6):1647-50.” 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Accept after minor essential revisions What next?: 
 An article of importance in its field Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
'None'
assistant