Randomized clinical trial to evaluate the effect of fecal microbiota transplant for initial Clostridium difficile infection in intestinal microbiome

Adrián Camacho-Ortiz, Eva María Gutiérrez-Delgado, Jose F Garcia-Mazcorro, Soraya Mendoza-Olazarán, Adrián Martínez-Meléndez, Laura Palau-Davila, Simon D Baines, Héctor Maldonado-Garza, Elvira Garza-González

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Abstract

OBJECTIVE: The aim of this study was to evaluate the impact of fecal donor-unrelated donor mix (FMT-FURM) transplantation as first-line therapy for C. difficile infection (CDI) in intestinal microbiome.

METHODS: We designed an open, two-arm pilot study with oral vancomycin (250mg every 6 h for 10-14 days) or FMT-FURM as treatments for the first CDI episode in hospitalized adult patients in Hospital Universitario "Dr. Jose Eleuterio Gonzalez". Patients were randomized by a closed envelope method in a 1: 1 ratio to either oral vancomycin or FMT-FURM. CDI resolution was considered when there was a reduction on the Bristol scale of at least 2 points, a reduction of at least 50% in the number of bowel movements, absence of fever, and resolution of abdominal pain (at least two criteria). From each patient, a fecal sample was obtained at days 0, 3, and 7 after treatment. Specimens were cultured to isolate C. difficile, and isolates were characterized by PCR. Susceptibility testing of isolates was performed using the agar dilution method. Fecal samples and FMT-FURM were analyzed by 16S rRNA sequencing.

RESULTS: We included 19 patients; 10 in the vancomycin arm and 9 in the FMT-FURM arm. However, one of the patients in the vancomycin arm and two patients in the FMT-FURM arm were eliminated. Symptoms resolved in 8/9 patients (88.9%) in the vancomycin group, while symptoms resolved in 4/7 patients (57.1%) after the first FMT-FURM dose (P = 0.26) and in 5/7 patients (71.4%) after the second dose (P = 0.55). During the study, no adverse effects attributable to FMT-FURM were observed in patients. Twelve isolates were recovered, most isolates carried tcdB, tcdA, cdtA, and cdtB, with an 18-bp deletion in tcdC. All isolates were resistant to ciprofloxacin and moxifloxacin but susceptible to metronidazole, linezolid, fidaxomicin, and tetracycline. In the FMT-FURM group, the bacterial composition was dominated by Firmicutes, Bacteroidetes, and Proteobacteria at all-time points and the microbiota were remarkably stable over time. The vancomycin group showed a very different pattern of the microbial composition when comparing to the FMT-FURM group over time.

CONCLUSION: The results of this preliminary study showed that FMT-FURM for initial CDI is associated with specific bacterial communities that do not resemble the donors' sample.

Original languageEnglish
Pages (from-to)e0189768
JournalPLoS One
Volume12
Issue number12
DOIs
Publication statusPublished - 2017
Externally publishedYes

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Clostridium Infections
Clostridium difficile
Clostridium
Transplants
randomized clinical trials
Microbiota
Vancomycin
Randomized Controlled Trials
vancomycin
infection
Linezolid
Metronidazole
signs and symptoms (animals and humans)
Ciprofloxacin
Tetracycline
mouth
Chemical analysis
Dilution
Agar
Gastrointestinal Microbiome

Cite this

Camacho-Ortiz, A., Gutiérrez-Delgado, E. M., Garcia-Mazcorro, J. F., Mendoza-Olazarán, S., Martínez-Meléndez, A., Palau-Davila, L., ... Garza-González, E. (2017). Randomized clinical trial to evaluate the effect of fecal microbiota transplant for initial Clostridium difficile infection in intestinal microbiome. PLoS One, 12(12), e0189768. https://doi.org/10.1371/journal.pone.0189768
Camacho-Ortiz, Adrián ; Gutiérrez-Delgado, Eva María ; Garcia-Mazcorro, Jose F ; Mendoza-Olazarán, Soraya ; Martínez-Meléndez, Adrián ; Palau-Davila, Laura ; Baines, Simon D ; Maldonado-Garza, Héctor ; Garza-González, Elvira. / Randomized clinical trial to evaluate the effect of fecal microbiota transplant for initial Clostridium difficile infection in intestinal microbiome. In: PLoS One. 2017 ; Vol. 12, No. 12. pp. e0189768.
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abstract = "OBJECTIVE: The aim of this study was to evaluate the impact of fecal donor-unrelated donor mix (FMT-FURM) transplantation as first-line therapy for C. difficile infection (CDI) in intestinal microbiome.METHODS: We designed an open, two-arm pilot study with oral vancomycin (250mg every 6 h for 10-14 days) or FMT-FURM as treatments for the first CDI episode in hospitalized adult patients in Hospital Universitario {"}Dr. Jose Eleuterio Gonzalez{"}. Patients were randomized by a closed envelope method in a 1: 1 ratio to either oral vancomycin or FMT-FURM. CDI resolution was considered when there was a reduction on the Bristol scale of at least 2 points, a reduction of at least 50{\%} in the number of bowel movements, absence of fever, and resolution of abdominal pain (at least two criteria). From each patient, a fecal sample was obtained at days 0, 3, and 7 after treatment. Specimens were cultured to isolate C. difficile, and isolates were characterized by PCR. Susceptibility testing of isolates was performed using the agar dilution method. Fecal samples and FMT-FURM were analyzed by 16S rRNA sequencing.RESULTS: We included 19 patients; 10 in the vancomycin arm and 9 in the FMT-FURM arm. However, one of the patients in the vancomycin arm and two patients in the FMT-FURM arm were eliminated. Symptoms resolved in 8/9 patients (88.9{\%}) in the vancomycin group, while symptoms resolved in 4/7 patients (57.1{\%}) after the first FMT-FURM dose (P = 0.26) and in 5/7 patients (71.4{\%}) after the second dose (P = 0.55). During the study, no adverse effects attributable to FMT-FURM were observed in patients. Twelve isolates were recovered, most isolates carried tcdB, tcdA, cdtA, and cdtB, with an 18-bp deletion in tcdC. All isolates were resistant to ciprofloxacin and moxifloxacin but susceptible to metronidazole, linezolid, fidaxomicin, and tetracycline. In the FMT-FURM group, the bacterial composition was dominated by Firmicutes, Bacteroidetes, and Proteobacteria at all-time points and the microbiota were remarkably stable over time. The vancomycin group showed a very different pattern of the microbial composition when comparing to the FMT-FURM group over time.CONCLUSION: The results of this preliminary study showed that FMT-FURM for initial CDI is associated with specific bacterial communities that do not resemble the donors' sample.",
author = "Adri{\'a}n Camacho-Ortiz and Guti{\'e}rrez-Delgado, {Eva Mar{\'i}a} and Garcia-Mazcorro, {Jose F} and Soraya Mendoza-Olazar{\'a}n and Adri{\'a}n Mart{\'i}nez-Mel{\'e}ndez and Laura Palau-Davila and Baines, {Simon D} and H{\'e}ctor Maldonado-Garza and Elvira Garza-Gonz{\'a}lez",
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Camacho-Ortiz, A, Gutiérrez-Delgado, EM, Garcia-Mazcorro, JF, Mendoza-Olazarán, S, Martínez-Meléndez, A, Palau-Davila, L, Baines, SD, Maldonado-Garza, H & Garza-González, E 2017, 'Randomized clinical trial to evaluate the effect of fecal microbiota transplant for initial Clostridium difficile infection in intestinal microbiome', PLoS One, vol. 12, no. 12, pp. e0189768. https://doi.org/10.1371/journal.pone.0189768

Randomized clinical trial to evaluate the effect of fecal microbiota transplant for initial Clostridium difficile infection in intestinal microbiome. / Camacho-Ortiz, Adrián; Gutiérrez-Delgado, Eva María; Garcia-Mazcorro, Jose F; Mendoza-Olazarán, Soraya; Martínez-Meléndez, Adrián; Palau-Davila, Laura; Baines, Simon D; Maldonado-Garza, Héctor; Garza-González, Elvira.

In: PLoS One, Vol. 12, No. 12, 2017, p. e0189768.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Randomized clinical trial to evaluate the effect of fecal microbiota transplant for initial Clostridium difficile infection in intestinal microbiome

AU - Camacho-Ortiz, Adrián

AU - Gutiérrez-Delgado, Eva María

AU - Garcia-Mazcorro, Jose F

AU - Mendoza-Olazarán, Soraya

AU - Martínez-Meléndez, Adrián

AU - Palau-Davila, Laura

AU - Baines, Simon D

AU - Maldonado-Garza, Héctor

AU - Garza-González, Elvira

PY - 2017

Y1 - 2017

N2 - OBJECTIVE: The aim of this study was to evaluate the impact of fecal donor-unrelated donor mix (FMT-FURM) transplantation as first-line therapy for C. difficile infection (CDI) in intestinal microbiome.METHODS: We designed an open, two-arm pilot study with oral vancomycin (250mg every 6 h for 10-14 days) or FMT-FURM as treatments for the first CDI episode in hospitalized adult patients in Hospital Universitario "Dr. Jose Eleuterio Gonzalez". Patients were randomized by a closed envelope method in a 1: 1 ratio to either oral vancomycin or FMT-FURM. CDI resolution was considered when there was a reduction on the Bristol scale of at least 2 points, a reduction of at least 50% in the number of bowel movements, absence of fever, and resolution of abdominal pain (at least two criteria). From each patient, a fecal sample was obtained at days 0, 3, and 7 after treatment. Specimens were cultured to isolate C. difficile, and isolates were characterized by PCR. Susceptibility testing of isolates was performed using the agar dilution method. Fecal samples and FMT-FURM were analyzed by 16S rRNA sequencing.RESULTS: We included 19 patients; 10 in the vancomycin arm and 9 in the FMT-FURM arm. However, one of the patients in the vancomycin arm and two patients in the FMT-FURM arm were eliminated. Symptoms resolved in 8/9 patients (88.9%) in the vancomycin group, while symptoms resolved in 4/7 patients (57.1%) after the first FMT-FURM dose (P = 0.26) and in 5/7 patients (71.4%) after the second dose (P = 0.55). During the study, no adverse effects attributable to FMT-FURM were observed in patients. Twelve isolates were recovered, most isolates carried tcdB, tcdA, cdtA, and cdtB, with an 18-bp deletion in tcdC. All isolates were resistant to ciprofloxacin and moxifloxacin but susceptible to metronidazole, linezolid, fidaxomicin, and tetracycline. In the FMT-FURM group, the bacterial composition was dominated by Firmicutes, Bacteroidetes, and Proteobacteria at all-time points and the microbiota were remarkably stable over time. The vancomycin group showed a very different pattern of the microbial composition when comparing to the FMT-FURM group over time.CONCLUSION: The results of this preliminary study showed that FMT-FURM for initial CDI is associated with specific bacterial communities that do not resemble the donors' sample.

AB - OBJECTIVE: The aim of this study was to evaluate the impact of fecal donor-unrelated donor mix (FMT-FURM) transplantation as first-line therapy for C. difficile infection (CDI) in intestinal microbiome.METHODS: We designed an open, two-arm pilot study with oral vancomycin (250mg every 6 h for 10-14 days) or FMT-FURM as treatments for the first CDI episode in hospitalized adult patients in Hospital Universitario "Dr. Jose Eleuterio Gonzalez". Patients were randomized by a closed envelope method in a 1: 1 ratio to either oral vancomycin or FMT-FURM. CDI resolution was considered when there was a reduction on the Bristol scale of at least 2 points, a reduction of at least 50% in the number of bowel movements, absence of fever, and resolution of abdominal pain (at least two criteria). From each patient, a fecal sample was obtained at days 0, 3, and 7 after treatment. Specimens were cultured to isolate C. difficile, and isolates were characterized by PCR. Susceptibility testing of isolates was performed using the agar dilution method. Fecal samples and FMT-FURM were analyzed by 16S rRNA sequencing.RESULTS: We included 19 patients; 10 in the vancomycin arm and 9 in the FMT-FURM arm. However, one of the patients in the vancomycin arm and two patients in the FMT-FURM arm were eliminated. Symptoms resolved in 8/9 patients (88.9%) in the vancomycin group, while symptoms resolved in 4/7 patients (57.1%) after the first FMT-FURM dose (P = 0.26) and in 5/7 patients (71.4%) after the second dose (P = 0.55). During the study, no adverse effects attributable to FMT-FURM were observed in patients. Twelve isolates were recovered, most isolates carried tcdB, tcdA, cdtA, and cdtB, with an 18-bp deletion in tcdC. All isolates were resistant to ciprofloxacin and moxifloxacin but susceptible to metronidazole, linezolid, fidaxomicin, and tetracycline. In the FMT-FURM group, the bacterial composition was dominated by Firmicutes, Bacteroidetes, and Proteobacteria at all-time points and the microbiota were remarkably stable over time. The vancomycin group showed a very different pattern of the microbial composition when comparing to the FMT-FURM group over time.CONCLUSION: The results of this preliminary study showed that FMT-FURM for initial CDI is associated with specific bacterial communities that do not resemble the donors' sample.

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DO - 10.1371/journal.pone.0189768

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JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

ER -