Copyright ©The Author(s) 2021.
World J Gastroenterol. Nov 14, 2021; 27(42): 7210-7232
Published online Nov 14, 2021. doi: 10.3748/wjg.v27.i42.7210
Table 1 Representatives of anti-Clostridioides difficile chemical clusters from reported literature
Cluster No.
Compound class
21Antifungal imidazoles
42Metronidazole and its derivatives
61Benzalkonium cationic surfactants
98–99Tetracycline and its derivatives
Table 2 Recent clinical trials examining potential fecal microbiota transplantation for treatment of Clostridioides difficile infection
Current phase
Title Identifier
First posted
NAFecal microbiota transplantation for C. difficile infectionNCT01905709July 23, 2013
Immune response to FMT for C. difficileNCT02797288June 13, 2016
Outcomes and data collection for fecal microbiota transplantation for the treatment of recurrent C. difficileNCT03562741June 19, 2018
Fecal microbiota transplantation (FMT) for C. difficile (CEFTA)NCT03712722October 1, 2018
Rescue fecal microbiota transplantation for national refractory intestinal infectionNCT03895593March 29, 2019
Safety and efficacy of fecal microbiota transplantationNCT04014413July 10, 2019
1Fecal transplant for pediatric patients who have recurrent C. difficile infection (FMT)NCT02134392May 9, 2014
2Stool transplants to treat refractory C. difficileNCT02127398April 30, 2014
FMT versus antimicrobials for initial treatment of recurrent CDINCT02255305October 2, 2014
Fecal microbiota therapy for recurrent C. difficile infectionNCT02686645February 19, 2016
Phase II trial of fecal microbiota transplant (FMT) for VRE and CRE patientsNCT03643887August 23, 2018
Fecal microbiota transplantation (FMT) plus fidaxomicin for severe of fulminant C. difficileNCT03760484November 30, 2018
Multicentre blinded comparison of lyophilized sterile fecal filtrate to lyophilized fecal microbiota transplant in recurrent C. difficile infectionNCT03806803January 16, 2019
FMT and bezltoxumab compared to FMT and placebo for patients with IBD and CDI (ICON-2)NCT03829475February 4, 2019
PMT for severe-CDINCT03970200May 31, 2019
Penn microbiome therapy (PMT) for recurrent C. difficile infectionNCT03973697June 4, 2019
3Fecal transplantation for primary C. difficile infection (COLONIZE)NCT03796650January 8, 2019
Microbiota restoration therapy for recurrent C. difficile infection (PUNCH CD3-OLS) (CD3-OLS)NCT03931941April 30, 2019
Fecal microbiota transplantation for primary C. difficile diarrheaNCT02801656June 16, 2016
Table 3 Key experiments in bacteriophage for Clostridioides difficile infection treatment
phiCD140A single dose of phage treatment for C. difficile infection in hamstersSurviving of phage treated hamster [135]
phiCD27Phage treatment of CDI in an in vitro batch fermentation and human colon model (1) Reduction of both vegetative cell and toxin A and toxin B productions from C. difficile; and (2) No impact on others gut microbes[135]
phiCDHM1 to phiCDHM6, and phiCDHS1(1) Investigation for an effective phage combination; and (2) Phage delivered orally in hamster model every 8 h after C. difficile challenge(1) Discovery of phage-resistant colonies after a single phage treatment; and (2) Reduction of C. difficile amount and colonization using phage combination in vivo [124]
phiCDHM1, 2, 5, and 6 (1) Phage treatment before and after the biofilm formation; (2) First time using Galleria mellonella (wax moth) model for C. difficile phage; and (3) Using phage in combination with antibiotics (vancomycin)(1) Reduction and prevention of the biofilm establishment in vitro; and (2) Disease prevention in the prophylaxis group and increasing the wax moth survival rates [130]
phiCDHM1, 2, 5, and 6(1) Optimized temperate phage cocktail to treat in batch fermentation model; and (2) First metagenomic analysis of phage treatment on gut microbiome (1) C. difficile elimination after 24 h in prophylactic condition while maintain other microbiota components; and (2) No significant impact on other bacterial groups in human gut[127]
phiCDHS1 Measurement of planktonic and adhered C. difficile cells and free phage to human colon tumorigenic cell line HT-29(1) Reduction of planktonic and adhered C. difficile; and (2) No cytotoxicity to human cells[129]
phiCD24-2(1) Using engineered phage delivered Type 1-B CRISPR system as antimicrobial agent in vitro and in vivo; and (2) Mutation of phage lysogenic gene by the cI repressor and integrase gene deletion(1) C. difficile eradication effectively in engineered phage comparing with wild-type phage; and (2) Detection of lysogen due to potentially functional complements from C. difficile prophage [125]