“A Difficile-cult Case” – Clostridioides difficile prosthetic joint infection; case report, microbiology, and review of the literature.
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Extra-colonic infections caused by Clostridioides difficile (C. difficile) are exceptionally rare, with prosthetic joint infections (PJI) comprising only a small fraction of reported cases. Moreover, there is limited guidance on the optimal management of such infections. We present the case of a 76-year-old male who developed a left hip PJI due to C. difficile six weeks after undergoing surgical revision for a periprosthetic fracture. Given the complexity of the case, curative surgical intervention was not considered feasible. The patient was treated with repeated debridement, intravenous vancomycin and oral metronidazole, followed by successful suppression with oral doxycycline – a novel therapeutic approach not previously documented. To date, only seven cases of C. difficile-associated PJI have been reported in the literature; this is the first known instance where suppression of a C. difficile PJI has been achieved and the first to utilize whole genome sequencing for further analysis of the isolate.
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Please see reviewer comments for suggested minor amendments to your manuscript.
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Comments to Author
General comments: Overall, I found this manuscript to be well written and appropriately cited. The presence of whole-genome sequencing and bioinformatics analysis added much value to this case report. I was anticipating a small discussion about possible source(s) of the C. difficile bacteria after the mention of an unremarkable CT scan. It never materialized. This is an important aspect in prevention of surgical site infections (SSI) by healthcare-associated infection pathogens, even in rare cases like this one caused by C. difficile. A total white blood cell count of 30.1 x 109 cells/L was provided on lines 48-49. What did the WBC differential show (e.g., neutrophilia with shift-to-the-left)? This would be beneficial information to provide for the reader. Having ruled out C. difficile transfer by …
Comments to Author
General comments: Overall, I found this manuscript to be well written and appropriately cited. The presence of whole-genome sequencing and bioinformatics analysis added much value to this case report. I was anticipating a small discussion about possible source(s) of the C. difficile bacteria after the mention of an unremarkable CT scan. It never materialized. This is an important aspect in prevention of surgical site infections (SSI) by healthcare-associated infection pathogens, even in rare cases like this one caused by C. difficile. A total white blood cell count of 30.1 x 109 cells/L was provided on lines 48-49. What did the WBC differential show (e.g., neutrophilia with shift-to-the-left)? This would be beneficial information to provide for the reader. Having ruled out C. difficile transfer by hip joint/colon fistula by CT scan, was an investigation conducted by Infection Control personnel to determine the etiology of the C. difficile infection? Was the introduction of C. difficile spores into the surgical site incision during post-operative wound care coinciding with an episode of diarrhea considered? The relative proximity of anus to the hip appears to suggest possible spore introduction into the incision site by this route. This also considers that C. difficile spores are very resistant to many chemical agents, including iodine and low concentrations (e.g., 3%) of hydrogen peroxide. If a post-operative wound care antiseptic was used on this patient, would it be effective against C. difficile spores? Specific comments: Line 58 - Readers unfamiliar with Mass Spectrometry MALDI-TOF technology will not know what a score of 2.34 represents. I recommend adding a statement indicating that a score >2.3 means a high probability of species identification, as log scores >2.0 are considered as reliable identification to species level. Line 60 - The authors indicate "ongoing fevers". Where any blood cultures drawn (aerobic & anaerobic with antimicrobial neutralization additive)? Literature review information in the Discussion section indicates bacteremia associated with an extra-colonic infection (see line 130). Lines 199-213 - Italicize each use of C. difficile.
Please rate the quality of the presentation and structure of the manuscript
Very good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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Comments to Author
The case was well presented, with a clear description of the clinical course. The discussion effectively related the findings to the existing literature, and the literature review was thorough and relevant. The case highlighted important learning points on managing rare and complex consequences of C. difficile infection. The proposed route of acquisition of the infection was thoughtfully addressed and added valuable context. I have offered a few suggestions to improve the manuscript further, focusing on correcting minor grammatical errors and providing additional clinical details about the gastrointestinal C. difficile infection to enhance its clarity and completeness. ABSTRACT This abstract is highly commendable for its clarity and conciseness, effectively outlining the background, methodology, key …
Comments to Author
The case was well presented, with a clear description of the clinical course. The discussion effectively related the findings to the existing literature, and the literature review was thorough and relevant. The case highlighted important learning points on managing rare and complex consequences of C. difficile infection. The proposed route of acquisition of the infection was thoughtfully addressed and added valuable context. I have offered a few suggestions to improve the manuscript further, focusing on correcting minor grammatical errors and providing additional clinical details about the gastrointestinal C. difficile infection to enhance its clarity and completeness. ABSTRACT This abstract is highly commendable for its clarity and conciseness, effectively outlining the background, methodology, key findings and implications of the study. Line 23 - Please italicise C. difficile CASE PRESENTATION Line 43-44 - A few lines describing the actual process of C difficile testing and the operational principle or mode of action of GeneXpert Cepheid would be useful for readers unfamiliar with the platform. Also consider 'TM' and referencing the product. Line 55 - Can you provide reasoning for the empiric choice of cefazolin? Is this part of local guidelines for the treatment of prosthetic joint infections? Line 65 - Please provide the full form of EUCAST and MIC in this first instance. More clinical information related to the C. difficile infection would be welcomed. Are C. difficile infections classified by severity in your institution? Did the patient have any predisposing factors for contracting a C. difficile infection? Prolonged antimicrobials? Close contact with other cases? Any proposals on how the patient acquired C. difficile? LITERATURE REVIEW Line 106 - Consider starting a new sentence, Despite this… Line 108 - Consider starting a new sentence, In this instance… DISCUSSION Lines 134-137 - I appreciate the proposed route of acquisition of C. difficile into the joint. However, it raises some questions. Was the patient mobile to any degree or bed bound? Were pads/diapers worn? Was the wound dressed? Your report of extensive faecal contamination to the surgical site is concerning. I note the patient is significantly co-morbid but was he completely dependent? Some social and functional context would be valuable here. If the wound was in fact grossly contaminated, you should emphasize the importance of wound care and hygiene to prevent such a case. Line 149 - Spelling of diarrhoea, please maintain the same version throughout the manuscript. Line 150 - Consider starting a new sentence, While its exact role… Line 152 - Please provide the full form of CDI in this first instance. Line 157 - Consider, '…toxins in disease, yet numerous…' Line 161 - Consider, '…strains acquired additional…' Lines 170-172 - Has this hypothesis been tested in other instances? Can vancomycin and metronidazole cause a loss of gene mutation? If so, consider some references of same. Line 177-178 - You have mentioned the absence of RT027 as a reason for the low prevalence of antimicrobial resistance; but forgive me as I cannot see how can the absence of an epidemic strain can influence antimicrobial resistance. Clarify please. Also, consider stating what 'RT' refers to in the first instance, as with all acronyms. Lines 178-180 - These lines need to be better explained. Antimicrobial resistance here is referring to which? Globally or in relation to C. difficile isolates in particular? Are you saying that those particular RTs have evolved due to resistance to the stated antimicrobials? If so, how was resistance among C. difficile isolates to these agents established? CONCLUSION Line 199-200, 205, 209 - Please italicise C. difficile
Please rate the quality of the presentation and structure of the manuscript
Very good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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