Bacteraemia and obstructive pyelonephritis caused by Bifidobacterium breve in an elderly woman: a case report and literature review

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Abstract

Bifidobacterium spp. are non-spore-forming Gram-positive anaerobes that are indigenous to the human gastrointestinal tract and vagina. They are believed to be non-pathogenic organisms for humans and thus are widely used as probiotics. An 83-year-old woman taking cephalexin for 4 days was diagnosed with obstructive pyelonephritis. Y-branched Gram-positive rods were found in both anaerobic and aerobic blood culture bottles, and in an anaerobic urine culture. Bifidobacterium breve was finally identified. Ceftriaxone and metronidazole were administered to the patient, and she was discharged after intermittent catheterization for dysuria. Urinary tract infection caused by Bifidobacterium spp. is believed to be rare, but it can develop in patients with underlying urological conditions. Recognition of the characteristic morphology and conducting anaerobic urine culture may help in identifying more cases of Bifidobacterium urinary tract infections.

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  1. Comments to Author

    1. Description of the case(s): Case has been described in sequential manner with major and relevant findings. However, there are a few points as detailed below: in Case presentation Page 3 L16-20 opening statememt of case presentation can be rephrased eg. "An 83-year-old woman with diabetes mellitus and dementia presented in our hospital with Fever, loss of appetite, inability to move and impaired consciousness. As per available information, four days earlier, she had visited a local clinic with complaints of fever and was prescribed with cephalexin. She gradually developed loss of appetite and difficulty in ambulation. Fever & loss of appetite persisted even after four days and she could not move. She was then shifted to the hospital. Other details could not be found as the patient was having dementia and impaired consciousness." L23-24 "Neither abdominal tenderness nor costovertebral tenderness was noted in the patient " This sentence should be rephrased as "The patient did not have abdominal tenderness and costovertebral tenderness." To convey the message correctly. Page 3, L30 "however, neither ureteral nor kidney stones" to be rephrased as "with no kidney or ureter stones. L32- delete "therefore" page 4 L16- "Gram staining of the urine samples showed only numerous Y-branched GPRs" to be written as "Gram staining of the urine sample showed numerous Y-branched GPRs." (delete only and Urine sample instead of urine samples) Conclusion: page 6 L13- "Recognition of Y-branched GPR" to be written as Recognition of Y-branched GPR in Gram stain Page 6 L14- conducting anaerobic urine culture may lead to find more cases of Bifidobacterium UTIs ---- conducting anaerobis urine culture may lead to finding more cases of Bifidobacterium UTIs. 2. Presentation of results The results are now presented in sequential manner as per the order of events 3. How the style and organization of the paper communicates and represents key findings The organization and style is now sequential as per order of events with relevant significant clinical details, investigations, course of event during hospital stay etc. 4. Literature analysis or discussion literature has now been analysed and discussed well 5. Any other relevant comments The Case report

    Please rate the quality of the presentation and structure of the manuscript

    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?

    No: not applicable

  2. Comments to Author

    Thank you for the opportunity to re-review this case report of a rare Bifidobacterium breve infection. I think that you have answered all of the points that I suggested on your original submission and I therefore think this should now be accepted with no further revision.

    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

  3. This study would be a valuable contribution to the existing literature. This is a study that would be of interest to the field and community. The reviewers have highlighted major concerns with the work presented. Please ensure that you address their comments.

  4. Comments to Author

    [Delete this text before submitting your review. Please include comments to the author here, and include the below sections, where possible. All comments here will be posted publicly online alongside the article once the Editor has made a decision.] 1. Description of the case(s) Abstract to be rewritten- with brief introduction of Bifidobacterium spp , importance/ role in causing disease and then brief introduction of case being reported and its significance/importance. Page 1, L12-13: Presenting complaints in hospital to be written instead of "she presented to our hospital in an ambulance." Relevant clinical history & Physical examination findings with respect to urological complaints or disorders/pre-existing urinary tract structural abnormalities or obstructions etc. to be mentioned. Other relevant investigations and findings (even negative ones) to be mentioned eg. RBCs, casts & crystals in urine, X ray KUB, USG abdomen & pelvis, Page 1, L23: therefore to be deleted, Dose & route of administration of Ceftriaxone to be mentioned. Timing of collection of blood cultures and urine culture to be mentioned as per sequence of events Page 1 L26: "The patient's clinical course after admission was uneventful" clinical course in hospital, follow up investigations if any, duration of hospital stay & outcome etc to be mentioned in the case description. L30-31, gram staining from blood culture bottles 2. Presentation of results: should be seuential. Page 2, L-2: "The organism was identified as B. breve " - should be written as The organism was identified as Bifidobacterium breve. Page 2 L-11 to L-15: regarding urine sample, there is no mention of urine sample subjected to culture (aerobic &/or anaerobic), their numbers, timing etc. Antimicrobial sensitivity of aerobic and anaerobic isolates from urine to be mentioned. For Page2, L2-L5: "The organism was identified as B. breve based on matrix-assisted laser 3 desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS, microflex ® 4 LT/ST using MBT Compass Ver 4.1 and MBT Compass Library Ver 9.0.0.0. (8468 5 MSPs) (Bruker Daltonics, Bremen, Germany; score value 2.11)." and L21-24: "The bacterium was identified as Bifidobacterium spp. by MALDI-TOF-MS (VITEK MS 22 using the software 4.3.0 and VITEK MS Knowledge Base version 3.0, bioMérieux, Marcy. 23 Marcy-l'´Etoile, France). These should be linked and described together. Page 2, L17-18: dosage of ceftriaxone and metronidazole also to be mentioned. 3. How the style and organization of the paper communicates and represents key findings The organization and style to be sequential as per order of events with relevant significant clinical details, investigations, course of disease/event during hospital stay and outcome etc. as detailed above 4. Literature analysis or discussion Page 4, L-33: " bloodstream infections with B. Breve" should be written as bloodstream infections with Bifidobacterium breve Page 5, L17-L23: two commercial kits have been mentioned for identification of Bifidibacterium spp. However, their use or reason for not using in the present case is not discussed. Page 5, L24-L27: in discussion, experience in identification to species level in this case with MALDI-TOF (Microflex LT instrument, Bruker Daltonics) is not mentioned although the same is written in case description. " identification of B. breve was finally re-confirmed by 16s 24 rRNA sequencing" is not discussed with respect to literature. 5. Any other relevant comments Anaerobic culture are routinely not done in cases of pyelonephritis. possibility of anaerobic pathogen to be kept in mind. Anaerobic cultures to be done in patients with high index of suspicion especially in elderly patients with immunocompromised state or debilitating illness or underlying urological conditions for iidentification of anaerobic infections and appropriate treatment to improvei patient outcome. comment to this effect to be included in conclusion.

    Please rate the quality of the presentation and structure of the manuscript

    Satisfactory

    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

  5. Comments to Author

    Thank you for the opportunity to review this case report that is presenting a rare case of Bifibobacterium breve from blood cultures with a urinary origin. This is an interesting case and you have reported the clinical picture, laboratory diagnosis, and management of the patient. The language used overall is good, but in some places is too abrupt and does not elaborate on finer details. References in text need to be with the statement and not at the beginning of the following sentence. The key findings of the case report need to be highlighted in the conclusion. Introduction I think this should be longer, and some of the points you make should be elaborated. For example, in line 4 and line 6 it would be nice to know if these 10 species were infection or have been identified as part of microbiome studies, and what other infections have been reported. Can you please include further references. Case Presentation Line 11 - can you explain why she was prescribed cephalexin? What was the basis of this choice of empirical antibiotic? Were there any clinical signs of UTI? Lines 14-21 - as this is a Microbiology journal, and the audience will likely include non-clinicians, can you please state the relevance of these results as they appear (ie. Are they high/low/abnormal). Line 26 - "The patient's clinical course after admission was uneventful." this needs to be reworded, as a full clinical outcome is noted on page 4 line 16 onwards. Line 27 - you state she had 2 sets of blood cultures but you do not mention whether these were collected before or after the ceftriaxone - this is important and needs to be included. Line 36 - smaller colonies found on the BBL TSA - I presume these were also identified as the same organism? Can this be added if so. Lines 21-24 on page 4 - can you please put the 16S results after the initial MALDI-ToF result, and can you please state where the 16S sequencing was performed. Can you please write something to the effect of "100% sequence match" instead of just 100%. Discussion Overall, this is a decent discussion but it can be strengthened a great deal. The literature has obviously been reviewed by the authors, but the data hasn't been presented as well as it could in the text - it would benefit from some summarisation. Line 28 - "0-2 cases" - reword this; is it 2 cases from 2007-2012, is it 2 cases every year, or can you work out the total number of cases over that time period. Is Norway the only country to report cases? Table 1 and table 2 could easily be combined so that you are reviewing all reported cases, then refer to UTI separately and reference the articles. Line 7 page 5 - please clarify that this is a hypothesis for *this case* - make that clear. Did the patient say in the initial work up that she had been experiencing chronic cystitis, as you haven't mentioned this previously. Line 11-12 page 5 - was the urine sample taken at the same time as the blood cultures? Was this pre-ceftriaxone? Add "urine" to routine culture and state GPR were seen in the urine specimen Gram stain. Line 15 page 5 - "Few reports" how many is few? You've reviewed the literature so this number should be known? Line 23 page 5 - I think this is a really important point that you should definitely highlight with more gravitas. Diagnostic labs without a MALDI-ToF may struggle to identify these isolates if relying on Vitek, as API tests are becoming less common (from my experience in the UK). Conclusion The conclusion needs to be reworded, or the results section needs to clearly include that the two commercial kits mentioned in the discussion were also tested, as this information isn't stated. This is the final statement of the case report: "A greater compilation of Bifidobacterium infection reports is necessary to clarify the pathogenicity, clinical picture, and optimal management of infections, especially UTI." The final statement of your conclusion should be the importance of the case you have reported and the important points you have discovered and you think are important for clinicians and scientists to know. If you want to keep this statement it might be worth having this in the discussion instead.

    Please rate the quality of the presentation and structure of the manuscript

    Good

    To what extent are the conclusions supported by the data?

    Partially 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