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

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.

Predictors of severe outcomes in patients with Clostridium difficile infection from a Hispanic population.

BACKGROUND: Factors associated with complicated Clostridium difficile infection (CDI) may vary among populations, and predictors of severe outcomes in CDI have not been studied in Hispanic patients. The aim of this study was to identify factors associated with a higher risk of colectomy, all-cause mortality, and CDI-associated mortality in a Hispanic population. METHODS: We performed a retrospective study of all hospitalized patients with a diagnosis of CDI between January 1, 2011 and September 30, 2015 in a 450-bed teaching hospital in Monterrey, northeast Mexico. Three main outcomes were defined: fulminant colitis with subsequent colectomy, all-cause mortality within 30 days of diagnosis, and CDI-attributable mortality. RESULTS: Of 261 patients with diarrhea, 176 were diagnosed with CDI. For colectomy, Charlson comorbidity index, ICU stay and mechanical ventilation prior to CDI diagnosis, days with diarrhea prior to treatment, total days of hospital stay and days after CDI diagnosis, elevated ATLAS score, days of diarrhea post CDI treatment, and treatment failure significantly predicted the necessity of surgical treatment with colectomy. CONCLUSION: Treatment failure, persistent diarrhea, and a high ATLAS score were identified as risk factors for severe outcomes of CDI. A low albumin concentration and high creatinine were associated with higher overall mortality.

A case report of small bowel perforation secondary to cytomegalovirus related immune reconstitution inflammatory syndrome in an AIDS patient.

Non-traumatic small bowel perforation is rare in adults but carries a high morbidity and mortality. The diagnosis is made on clinical suspicion, and the most common causes in developing countries are infectious diseases, being cytomegalovirus infection in immunocompromised patients the main etiology. We describe a patient with a recently diagnosed advanced stage HIV infection and an intestinal perforation associated with cytomegalovirus immune reconstitution inflammatory syndrome after highly active antiretroviral therapy initiation.

Efficacy of computed tomography for the prediction of colectomy and mortality in patients with clostridium difficile infection.

AIM: To develop a CT predictor scale for the need for colectomy and to evaluate predictors of all-cause mortality within 30 days after diagnosis ofC. difficile infection (CDI). METHODS: We conducted a retrospective study of adult hospitalized patients whounderwent abdominal CT within 72 h of diagnosis of CDI. RESULTS: Presence of abnormal wall thickening in caecum (OR 8.0; CI 1.37-46.81; p = 0.021), transverse colon (OR 6.7; CI 1.15-35.60; p = 0.034), sigmoid colon (OR 12.6; CI 1.37-115.97; p = 0.025), pancolitis (OR 7.0; CI 1.36-36.01; p = 0.02) and bowel dilation (OR 16.5; CI 2.41-112.83; p = 0.004) predicted colectomy. With these values, a five parameter radiological scale from 0 to 24 was developed (sensitivity and NPV of 100%, cut-off of 6). Furthermore, wall thickening of caecum (OR 6.2; CI 1.06-35.57; p = 0.043), ascending colon (OR 12.0; CI 1.29-111.32; p = 0.029), descending colon (OR 17.0; CI 1.81-160.05; p = 0.013) and sigmoid (OR 10.2; CI 1.10-94.10; p = 0.041) independently predicted mortality within 30 days of CDI diagnosis. CONCLUSION: We designed a CT scale to predict colectomy, able to rule out the development of fulminant colitis and the need for surgical procedure. Patients with wall thickening of the caecum, ascending, descending or sigmoid colon were more likely to die within 30 days of CDI diagnosis.