Differences of the Fecal Microflora With Clostridium difficile Therapies.
BACKGROUND
During treatment of Clostridium difficile infection (CDI), patterns of pathogen reduction in relationship to changes in components of the normal microbiota are hypothesized to be predictive of response to treatment and subsequent sustained cure.


METHODS
At a single center, subjects enrolled into phase 2 and 3 C. difficile treatment clinical trials (2003-2008) provided fecal samples to assess killing of C. difficile and changes to components of the microbiome. Quantitative bacterial cultures, measurement of C. difficile toxin titers, quantitative polymerase chain reaction of fecal samples for Bacteroidetes, Clostridium clusters XIVa and IV, and C. difficile were performed.


RESULTS
Quantitative bacterial cultures showed a mean log10 C. difficile count (colony-forming units [CFU]) of 6.7 ± 2.0 at study entry; vancomycin treatment consistently reduced C. difficile counts to the limit of detection (2.0 log10 CFU/g), whereas metronidazole was associated with mean C. difficile counts 1.5-2 log10 higher at 10 days of treatment. In patients receiving tolevamer, C. difficile persisted in high counts during treatment; response to treatment was correlated with neutralization of toxin along with persistence of normal microbiota components. However, this was achieved in approximately half of subjects. Both vancomycin and metronidazole further suppressed microbiome components during treatment of CDI. Lactobacilli were observed to be a microbiome component that persisted during treatment of CDI.


CONCLUSIONS
Differences of pathogen clearance and microbiome perturbation during treatment of CDI appear to explain treatment outcomes. The hypothesis that probiotic microbes could help prevent onset of CDI is supported by the observation of persistence of lactobacilli during and after treatment of CDI.
Department of Medicine and Department of Microbiology, Immunology and Infectious Diseases, University of Calgary Infection Prevention and Control, Calgary Zone, Alberta Health Services, Canada.
Thomas J
TJ
Louie
Department of Medicine and Department of Microbiology, Immunology and Infectious Diseases, University of Calgary.
Brendan
B
Byrne
Department of Medicine and Department of Microbiology, Immunology and Infectious Diseases, University of Calgary.
Judith
J
Emery
Infection Prevention and Control, Calgary Zone, Alberta Health Services, Canada.
Linda
L
Ward
Infection Prevention and Control, Calgary Zone, Alberta Health Services, Canada.
Wally
W
Krulicki
Department of Medicine and Department of Microbiology, Immunology and Infectious Diseases, University of Calgary.
David
D
Nguyen
Department of Medicine and Department of Microbiology, Immunology and Infectious Diseases, University of Calgary.
Kaiyu
K
Wu
Department of Medicine and Department of Microbiology, Immunology and Infectious Diseases, University of Calgary Infection Prevention and Control, Calgary Zone, Alberta Health Services, Canada.
Kristine
K
Cannon
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D058491:Bacterial Load; D041963:Bacteroidetes / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification; D016360:Clostridioides difficile / Q000235:genetics / Q000254:growth & development* / Q000302:isolation & purification; D003015:Clostridium Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology*; D005243:Feces / Q000382:microbiology*; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007778:Lactobacillus / Q000254:growth & development / Q000302:isolation & purification; D008297:Male; D008795:Metronidazole / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011108:Polymers / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D019936:Probiotics / Q000627:therapeutic use; D013451:Sulfonic Acids; D013997:Time Factors; D016896:Treatment Outcome; D014640:Vancomycin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D011108:Polymers; D013451:Sulfonic Acids; D008795:Metronidazole; D014640:Vancomycin; C077114:styrenesulfonic acid polymer
C. difficile; lactobacilli; metronidazole; tolevamer; vancomycin