ArticleAntimicrobial agents and chemotherapy2016
Bacteriophage Combinations Significantly Reduce Clostridium difficile Growth In Vitro and Proliferation In Vivo.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
148 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Nonmammalian models to study Clostridioides difficile infection; a systematic review.Anaerobe · 2023Pooled it
- Prophage-encoding engineered bacteria enable prophylactic lytic phage therapy for enteric infection in mice.Nature microbiology · 2026Article
- Bacteriophages Control Epiphytic Pseudomonas syringae Populations in Highbush Blueberry Leaves.Microbial biotechnology · 2026Article
- Synergistic potential of probiotics and bacteriophages in combating multidrug-resistant microbial infections: A novel therapeutic strategy for the post-antibiotic era.New microbes and new infections · 2026Review
- Review
- Advances in Ciprofloxacin Derivatives: Emerging Strategies to Combat Antimicrobial Resistance.Topics in current chemistry (Cham) · 2026Review
- Phage-Microbiota Interactions in the Gut: Implications for Health and Therapeutic Strategies.Probiotics and antimicrobial proteins · 2026Review
- Insight into Bacteriophage Therapy for Bacterial Infections and Cancer.Molecular biotechnology · 2026Review
- Modeling the Phage Properties Best for Therapy.Viruses · 2026Article
- Emerging Therapeutic Approaches for Modulating the Intestinal Microbiota.Pharmaceutics · 2026Review
- Bacteriophage Therapy: Overcoming Antimicrobial Resistance Through Advanced Delivery Methods.Molecules (Basel, Switzerland) · 2026Review
- Enhanced efficiency of virulent and temperate phage combination mediated through bacterial membrane vesicles.Journal of virology · 2025Article
- Modeling the phage properties best for therapy.bioRxiv : the preprint server for biology · 2025Article
- Synergy between ciprofloxacin and temperate phages overcomes therapeutic limitations caused by lysogen formation.Scientific reports · 2025Article
- Structural determinants of SlpA-mediated phage recognition in Clostridioides difficile.PLoS pathogens · 2025Article
- The Gut Microbiome and Colistin Resistance: A Hidden Driver of Antimicrobial Failure.International journal of molecular sciences · 2025Review
- Article
- Recent insights on challenges encountered with phage therapy against gastrointestinal-associated infections.Gut pathogens · 2025Review
- Combined Forces Against Bacteria: Phages and Antibiotics.Health science reports · 2025Article
- Phage-Microbiota Crosstalk: Implications for Central Nervous System Disorders.International journal of molecular sciences · 2025Review
88 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
The microbiome dysbiosis caused by antibiotic treatment has been associated with both susceptibility to and relapse of Clostridium difficile infection (CDI). Bacteriophage (phage) therapy offers target specificity and dose amplification in situ, but few studies have focused on its use in CDI treatment. This mainly reflects the lack of strictly virulent phages that target this pathogen. While it is widely accepted that temperate phages are unsuitable for therapeutic purposes due to their transduction potential, analysis of seven C. difficile phages confirmed that this impact could be curtailed by the application of multiple phage types. Here, host range analysis of six myoviruses and one siphovirus was conducted on 80 strains representing 21 major epidemic and clinically severe ribotypes. The phages had complementary coverage, lysing 18 and 62 of the ribotypes and strains tested, respectively. Single-phage treatments of ribotype 076, 014/020, and 027 strains showed an initial reduction in the bacterial load followed by the emergence of phage-resistant colonies. However, these colonies remained susceptible to infection with an unrelated phage. In contrast, specific phage combinations caused the complete lysis of C. difficile in vitro and prevented the appearance of resistant/lysogenic clones. Using a hamster model, the oral delivery of optimized phage combinations resulted in reduced C. difficile colonization at 36 h postinfection. Interestingly, free phages were recovered from the bowel at this time. In a challenge model of the disease, phage treatment delayed the onset of symptoms by 33 h compared to the time of onset of symptoms in untreated animals. These data demonstrate the therapeutic potential of phage combinations to treat CDI.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.