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Reviews of "Combination of Mitomycin C and low-dose Metronidazole Synergistically against Clostridioides Difficile Infection and Recurrence Prevention"

Reviewers: E Kuijper (Leiden University) | πŸ“’πŸ“’πŸ“’ ◻️◻️ β€’ T Eubank (University of Houston) | πŸ“’πŸ“’πŸ“’β—»οΈβ—»οΈ

Published onDec 06, 2024
Reviews of "Combination of Mitomycin C and low-dose Metronidazole Synergistically against Clostridioides Difficile Infection and Recurrence Prevention"
key-enterThis Pub is a Review of
Combination of mitomycin C and low-dose metronidazole synergistically against Clostridioides difficile infection and recurrence prevention
Combination of mitomycin C and low-dose metronidazole synergistically against Clostridioides difficile infection and recurrence prevention
Description

Abstract Clostridioides difficile is an anaerobic, spore-forming, Gram-positive pathogen responsible for various conditions from mild diarrhea to severe toxic megacolon and potentially death. Current treatments for C. difficile infection (CDI) rely on antibiotics like vancomycin and metronidazole (MTZ); however, the high doses required often disrupt gut microbiota, leading to a high recurrence rate. Mitomycin C (MMC), a chemotherapy drug approved by the FDA, is known for inducing phage production in lysogenic bacterial strains, effectively targeting the host bacteria. Given that 70% of C. difficile strains harbor prophages, this study investigates MMC’s potential to enhance antibiotic efficacy against CDI. Our in vitro experiments indicate that MMC acts synergistically with MTZ to inhibit the growth of C. difficile strain R20291. Furthermore, this combination decreases biofilm-resident vegetative cell resistance and reduces the MTZ concentration needed to kill C. difficile in stool samples ex vivo. In a CDI mouse relapse model, in vivo results show that MMC combined with a low dose of MTZ significantly improves survival rates and reduces fecal spore counts after antibiotic treatment. Overall, these findings suggest that a low-dose combination of MMC and MTZ offers enhanced therapeutic efficacy for CDI, both in vitro and in vivo, and may provide a promising new approach for treatment.

To read the original manuscript, click the link above.

Summary of Reviews: This study investigates the synergistic effects of mitomycin C and metronidazole in treating C. diff infections, using both in vitro assays and a mouse model. The authors present evidence that the combination improves survival in a mouse model infected with the hypervirulent RT 027 strain. However, the study's clinical relevance remains uncertain, as mitomycin C is not currently used in clinical practice for C. diff infections. Additionally, the generalizability of the results to other C. diff strains or antibiotic combinations is unclear. Reviewers raised concerns about methodological issues, including the choice of assays, the lack of histological analysis in tissue studies, and the need for further investigation into the mechanisms of metronidazole resistance. Additionally, the manuscript would benefit from a more balanced discussion on the broader implications of the findings, especially regarding the uncertain clinical applicability of the combination therapy.

Reviewer 1 (Ed K…) | πŸ“’πŸ“’πŸ“’ ◻️◻️

Reviewer 2 (Taryn E…) | πŸ“’πŸ“’πŸ“’ ◻️◻️

RR\ID Strength of Evidence Scale Key

πŸ“• ◻️◻️◻️◻️ = Misleading

πŸ“™πŸ“™ ◻️◻️◻️ = Not Informative

πŸ“’πŸ“’πŸ“’ ◻️◻️ = Potentially Informative

πŸ“—πŸ“—πŸ“—πŸ“—β—»οΈ = Reliable

πŸ“˜πŸ“˜πŸ“˜πŸ“˜πŸ“˜ = Strong

To read the reviews, click the links below.Β 

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