Recurrent Clostridium Difficile Infection In Patients Research Articles

Efficacy and safety of fecal microbiota transplant for recurrent Clostridium difficile infection in inflammatory bowel disease: a systematic review and meta-analysis.

the objective of this systematic review and meta-analysis was to evaluate the outcomes of fecal microbiota transplantation (FMT) therapy for recurrent Clostridium difficile infection (CDI) in inflammatory bowel disease (IBD) patients. electronic databases were searched for studies reporting on the efficacy and/or safety of FMT therapy for recurrent CDI in IBD. The meta-prop command of the meta package in R was used to assess efficacy and safety. Subgroup analyses were performed to explore heterogeneity regarding all outcomes. eleven trials were included in the study. A pooled analysis showed that the initial cure rate of recurrent CDI among IBD patients was 80 % (95 % CI, 0.76, 0.84), and the overall cure rate after two or more FMT procedures was 90 % (95 % CI, 0.84, 0.94). The recurrence rate post-FMT therapy was 25 % (95 % CI: 0.20, 0.32). Sub-analyses suggested that the initial cure rate of CDI in ulcerative colitis (UC) patients was higher than in Crohn's disease (CD) patients (85 % vs. 79 %), with no statistically significant differences (p > 0.05). No serious adverse events were noted in any of the patients post-FMT. FMT is an effective and safe treatment for recurrent CDI in patients with IBD. FMT should be considered early in cases of recurrent or refractory CDI. Multiple FMT procedures can improve the cure rate of CDI.

S2941 Fecal Microbiota Transplant in Recurrent Clostridium difficile Enteritis Following Colectomy

Introduction: Fecal microbiota transplant (FMT) is well-known as treatment for recurrent Clostridium difficile infection (CDI). It is curative in 80% of severe or fulminant CDI cases. In this case, we explore the utility of FMT in a patient with recurrent C. diff enteritis (CDE) after colectomy with ileorectal anastomosis. Case Description/Methods: A 46 yr old woman underwent abdominal colectomy with ileostomy 05/2020 with ileorectal anastomosis 07/2020 for severe colonic inertia and h/o ligament release for Median Arcuate Ligament Syndrome in 2/2021. She initially presented with RUQ abdominal pain, nausea, vomiting and diarrhea during the 1st episode of CDI in 10/2020 which was treated with Vancomycin 125mg PO QID for 10 days. Symptoms recurred a month later, C. diff toxin (CDT)+, and this 2nd episode was treated with 3 weeks of Vancomycin 125mg PO QID. Symptoms resolved but recurred 5 months later with hospital admission, again CDT+. CBC and renal function were normal. CT abdomen/pelvis showed nonspecific prominent fluid-filled loops of proximal and mid small bowel consistent with focal ileus or enteritis. Patient was treated for the 3rd time on a prolonged Vancomycin taper (125mg QID x 10 days, 125mg TID x 7 days, 125mg BID x 7 days, 125mg QD x 7 days, 125mg QOD x 14 days) with plans for FMT. She was readmitted 2 months later for pain, nausea, vomiting and diarrhea, CDT-, and underwent planned FMT. FMT was performed via flexible sigmoidoscopy reaching 70cm proximal to the anus with 250cc of donor fecal material mixed with saline (Open Biome). Since FMT, patient has reported resolution of symptoms. Discussion: FMT for recurrent CDI in patients s/p colectomy is not well-documented. A small series of patients s/p colectomy over 20 years showed recurrent CDE does occur after colectomy, and results in severe disease in half of patients, requiring hospitalization in 81%. Risk factors for CDE were colectomy for IBD, colectomy for fulminant CDI, β-lactam use with enteral feeds, and acid suppression after colectomy. Cases of fulminant CDE with multiorgan failure and death have been reported (diagnosed post-mortem). A young man with UC s/p colectomy with IPAA with recurrent CDE was effectively treated with FMT. While rare, recurrent CDE is potentially fatal and warrants consideration of FMT as a treatment modality. Though our patient did not have IBD, was not immunosuppressed and underwent colectomy for reasons unrelated to IBD, the recurrent CDE was effectively treated with FMT.

2827 Fecal Microbiota Transplant for Recurrent Clostridium difficile Infection in Patients With Multiple Comorbidities: A Case Series From a Tertiary Care Community Hospital

INTRODUCTION: Cure rates of Clostridium difficile infection (CDI) with Fecal Microbioata Transplant (FMT) have been promising. However, there is debate regarding success of FMT in patients with co-morbidities. In this case series, we describe a tertiary care center’s experience with FMT for recurrent CDI in patients with varied clinical background including those with co-morbidities and IBD. METHODS: CDI was defined as diarrhea (≥3 loose stools in 24 hours) and stool test positive for C. difficile toxins by PCR. Early FMT failure was defined as diarrhea and positive stool test within 8 weeks, and recurrence/late FMT failure was defined as that after 8 weeks. Adults >18 years of age with 3 or more recurrences of CDI were included in the study. There were no specific exclusion criteria. Electronic chart review was done to collect data on patients who underwent FMT from January 2015 to August 2017. Charts were analyzed in November 2018 with a median follow up of 25.4 months (IQR 10.4). The study was approved by Institutional Review Board (IRB). Descriptive analyses like frequencies and measures of central tendencies were used for continuous variables. Due to low sample size, further statistical analysis could not be performed. RESULTS: 20 patients underwent FMT (Table 1). The primary success rate at our institution was 90% (Figure 1) and overall recurrence rate was 100%. 6 patients (43%) had FMT failure (early and late). 2 patients (10%), both of whom were immunosuppressed, had early FMT failure. 4 (20%) patients had late FMT failure or recurrence of CDI and had successful resolution either with repeat FMT or antibiotic treatment . None of the 20 patients reported side effects from FMT. All-cause mortality was noted in 2 (10%) patients unrelated to FMT. Charlson comorbidity index was not associated with failure of FMT. CONCLUSION: 50% FMT failure patients were immunosuppressed compared to 21% in the primary success group. Immunosuppression was due to medications in all patients. 33% of FMT failure patients had IBD (vs 7% in the FMT cure group), all of them had sustained cure after repeat treatments. Mean age of FMT failure patients was lower than those in the primary cure group (59 vs 64), while the subgroup of patients with early failure were older (65.5). PPI use was higher in late failure patients (75% vs 64%), but overall there was no difference between patients with failure and cure. Our case series reiterates the safety and efficacy of FMT for recurrent CDI in patients with comorbidities.

1593. Recurrence of Clostridium difficile Infection in Multiple Myeloma Patients Receiving Prophylactic Oral Vancomycin or Oral Metronidazole vs. No Prophylaxis

BackgroundMultiple myeloma (MM) patients are at increased risk of Clostridium difficile infection (CDI) compared with the general population. In prior studies, 12–14% were diagnosed with CDI, and ~16% had recurrent CDI during subsequent treatments. Recent studies have shown that oral vancomycin is effective secondary prophylaxis for the prevention of recurrent CDI in the general population. This retrospective study examined if secondary prophylaxis with oral vancomycin or metronidazole is effective to prevent recurrent CDI in MM patients.MethodsMM patients who tested positive for their first episode of CDI from January 2014–December 2016 were included, and the 3 months following the CDI diagnosis was reviewed. Patients who died, and those who did not receive additional chemotherapy or antibiotics during the 3-month review period were excluded. The patients were divided into 3 cohorts: (1) oral vancomycin as secondary prophylaxis, (2) oral metronidazole as secondary prophylaxis, and (3) no C. difficile prophylaxis.ResultsA total of 110 MM patients with a first episode of CDI were reviewed, six were excluded due to death and four were excluded due to no subsequent chemotherapy or antibiotics. This left 100 patients included for analysis. The median age was 62 years, range 34–81. 92 subjects (92%) had exposure to antibiotics and 76 (76%) received chemotherapy. A total of 38 (38%) received secondary prophylaxis: 16 (42%) with oral metronidazole and 22 (58%) with oral vancomycin. There was no significant difference in recurrent CDI in patients who received any secondary prophylaxis (7/38, 18.4%) and in those who received none (15/62, 24.2%), P = 0.46. Incidence of recurrent CDI in patients receiving oral vancomycin (3/22, 13.6%) was not significantly different from patients receiving oral metronidazole (4/16, 25%), P = 0.56. An analysis of risk factors for recurrent CDI showed no difference in recurrence in patients who received metronidazole vs. vancomycin as treatment for the initial CDI. Similar recurrent CDI occurred in patients who received antibiotics and those who received chemotherapy.ConclusionSecondary prophylaxis with either oral metronidazole or oral vancomycin did not reduce the incidence of recurrent CDI in MM patients.Disclosures All authors: No reported disclosures.

Cirrhotic Patients With Prior i>Clostridium difficile Infection (CDI) and Recent Hospitalization Are at High-Risk for Recurrent CDI (rCDI) Despite Frequent Use of Rifaximin

Introduction: Patients with cirrhosis have an increased risk of CDI and this is associated with increased mortality. However, few studies have examined the rates, outcomes, and predictors of rCDI among patients with cirrhosis. Methods: We retrospectively identified patients admitted to Yale-New Haven Hospital from 2008-2015 with the diagnosis of CDI based on stool toxin assay and presence of diarrhea. From this group, we identified a sub-group of those with cirrhosis defined by either liver biopsy or standard laboratory and imaging findings. Cirrhosis patients with recurrent CDI (Cirr+CDIR) were compared to a control group of cirrhosis patients with only one isolated episode of CDI (Cirr+CDIO). Demographics, medical comorbidities, prior medication exposures, serologic values, and outcomes (30-day, 90-day and 1-year mortality, 30-day readmission) were compared (IBM SPSS 23.0). Results: Of 1,309 patients with CDI, 49 had cirrhosis without history of liver transplant; 18 were Cirr+CDIR and 31 were Cirr+CDIO. The rate of CDI recurrence among cirrhotics was 37% and the majority (61%) had multiple recurrences. There were no significant differences in mortality, readmission, MELD or Charlson co-morbidity scores among Cirr+CDIR and Cirr+CDIO. Cirr+CDIR had higher rates of recent hospitalization (83% vs. 48%, p=0.02) with more frequent use of chronic rifaximin (72% vs. 39%, p=0.04) and lactulose (72% vs.39%, p=0.04) compared with Cirr+CDIO. Metronidazole was the most common antibiotic used to treat initial CDI (78% Cirr+CDIR vs. 71% Cirr+CDIO). Using the significant predictors of recurrence from univariate analysis (varices, recent hospitalization, rifaximin use), multivariate analysis revealed that recent hospitalization within the prior 12-weeks was the only significant predictor of recurrent CDI in patients with cirrhosis (OR 6.0, 95% CI 1.3-28.6, p=0.02). Conclusion: Our study shows that recent hospitalization was the strongest risk factor for recurrence in patients with cirrhosis, despite this cohort receiving chronic rifaximin more frequently than Cirr+CDIO. Inpatients with cirrhosis who develop CDI might benefit from more aggressive therapy to reduce their risk of future recurrence. Further study is needed to clarify the optimal treatment for inpatients with cirrhosis who get CDI to minimize their risk of recurrence.858 Figure 1 No Caption available.

Safety and Efficacy of Fecal Microbiota Transplant for Recurrent Clostridium difficile Infection in Patients With Cancer Treated With Cytotoxic Chemotherapy: A Single-Institution Retrospective Case Series

ObjectiveTo study the safety and efficacy of fecal microbiota transplant (FMT) for Clostridium difficile infection (CDI) in patients with cancer treated with cytotoxic chemotherapy in a single-institution retrospective case series. Patients and MethodsTwenty-three consecutive patients with underlying hematologic (n=13) or solid (n=10) malignancies who underwent FMT for recurrent CDI from August 1, 2012, through June 30, 2016, were studied. ResultsAll the patients had received cytotoxic chemotherapy a median of 12 months (range, 1-340 months) before FMT. Patients had experienced a median of 4 (range, 2-9) CDI episodes and had been treated with a median of 106 days (range, 42-495 days) of vancomycin, metronidazole, or fidaxomicin before FMT. Twelve patients (52%) had severe/severe-complicated CDI at some stage. Eight patients (35%) had active cancer and 5 (22%) had received chemotherapy within 12 weeks of FMT. Diarrhea resolved without recurrence within 60 days of FMT in all but 3 patients (13%) (all had negative C difficile results). Of the 22 patients who were alive 60 days or more after FMT, 11 (48%) underwent further chemotherapy and 10 (43%) received more antibiotics. Two patients (9%) developed recurrent CDI 14 and 22 months after FMT. One death occurred 5 days after FMT as a result of cardiac arrest unrelated to FMT. There were no other severe adverse events and no infectious complications directly attributable to FMT. ConclusionThis series demonstrates that FMT is a highly effective and safe therapeutic option for multiply recurrent CDI in patients with cancer treated with cytotoxic chemotherapy.

Association of Gastric Acid Suppression With Recurrent Clostridium difficile Infection

Gastric acid suppression has been associated with an increased risk of primary Clostridium difficile infection (CDI), but the risk of recurrent CDI in patients taking gastric acid suppressant medications is unclear. To perform a systematic review and meta-analysis to evaluate the association between gastric acid suppressants and recurrent CDI. MEDLINE, EMBASE, the Cochrane Central Register, the Cochrane Database, and Web of Science were searched from January 1, 1995, to September 30, 2015, for studies assessing the association between gastric acid suppressant exposure and recurrent CDI. Search terms included Clostridium difficile, pseudomembranous colitis, proton pump inhibitor, and histamine H2 blocker. Case-control studies, cohort studies, and clinical trials that included patients with CDI who did or did not receive gastric acid suppressant therapy and who were evaluated for recurrent CDI were included, with no restriction on study setting (inpatient or outpatient). The Newcastle-Ottawa scale was used to assess the methodologic quality of included studies. In this scale, case-control and cohort studies were scored on selection, comparability, and ascertainment of the outcome of interest. Data were independently abstracted to a predetermined collection form by 2 investigators. Summary odds ratio estimates with 95% CIs were calculated using the random-effects model and software to calculate the pooled effect size of studies reporting multivariate analyses. Risk of recurrent infection in patients with CDI and its association with use of gastric acid suppressant medication. Sixteen observational studies were included, together reporting 7703 patients with CDI; among these, 1525 patients (19.8%) developed recurrent CDI. The rate of recurrent CDI in patients with gastric acid suppression was 22.1% (892 of 4038 patients) compared with 17.3% (633 of 3665) in patients without gastric acid suppression, which indicated an increased risk by meta-analysis (odds ratio [OR], 1.52; 95% CI, 1.20-1.94; P < .001). There was significant heterogeneity among the studies, with an I2 value of 64%. Subgroup analyses of studies adjusting for age and potential confounders confirmed an increased risk of recurrent CDI with use of gastric acid suppressants (OR, 1.38; 95% CI, 1.08-1.76; P = .02). Meta-analyses of observational studies suggest that patients who receive gastric acid suppressants may be at increased risk for recurrent CDI. These data should be interpreted with caution because they may be confounded owing to the observational design of the individual studies. It may be reasonable to re-evaluate the need for these medications in patients with CDI.

Safety and Efficacy of Fecal Microbiota Transplantation for Recurrent Clostridium Infection in Patients with Hematologic Malignancies

Background:Patients with hematological malignancies are at an increased risk for developing both primary and recurrent Clostridium difficile Infection (RCDI) along with complications such as toxic mega colon and treatment failure likely due to underlying immunosuppression and frequent use of broad spectrum antibiotics that lead to altered gut microbiome. Fecal Microbiota Transplantation (FMT) is an effective treatment for RCDI (Brandt et. al; 2012). However, experience in patients with hematologic malignancies is sparse and most clinical trials exclude these patients due to potential complications. We report the largest case series to date from a single institution evaluating the safety and efficacy of FMT for RCDI in patients with hematologic malignancies.Methods:After IRB approval, a database of 452 RCDI patients treated with FMT between August 2012 and June 2016 was reviewed to identify those with an underlying hematologic malignancy. Data regarding demographics, hematologic disease, C. difficile history, treatments, and outcomes were retrospectively abstracted from the electronic medical record.Results:Sixteen patients (median age 74 years; male 50%) with known hematologic malignancies underwent FMT during the study period. The underlying diagnoses are outlined in Table 1. Five patients had received hematopoietic cell transplantation (3 allogeneic and 2 autologous) prior to FMT. Patients had a median of 4.5 (range 2-9) CDI episodes before FMT, and 4 of them had severe/severe-complicated CDI at some stage. Prior treatments included a median of 3 (range 1-5) standard vancomycin/metronidazole courses, median of 2 (range 0-4) vancomycin taper courses, fidaxomicin in 3 patients, and chronic vancomycin suppression in one patient. Diarrheal symptoms were in remission in all but 3 patients in the week before FMT.FMT was performed via colonoscopy in all patients. At the time of FMT, hematologic malignancies were in complete remission in 9 patients, stable on active treatment in 4, stable off treatment in 2, and relapsed awaiting treatment in 1 patient. Median time from last anti-neoplastic treatment (n = 14) and from last neutropenia (n = 8) to FMT were 10 (range 0-301) and 9.5 (0-68) months, respectively. One patient with hairy cell leukemia was still neutropenic and on prophylactic oral trimethoprim/sulfamethoxazole at the time of FMT. Five patients were on active immunosuppressive medications, including prednisone (n = 2), methotrexate (n = 2), sirolimus (n =1), and cyclosporine (n =1) for related comorbidities at the time of FMT (Table 2).At last follow up (median 12, range 0-32 months), 6 patients had active/relapsed hematological disease, 6 had received additional antineoplastic treatments, and 7 had received additional antibiotics. RCDI developed in two (12%) patients at 8 and 22 months post FMT secondary to exposure to broad spectrum antimicrobials. These patients were successfully treated with a second FMT and with metronidazole, respectively. Severe adverse events included death in one patient that occurred 3 days post FMT due to unexpected cardiac arrest and was deemed unrelated to the procedure. Another patient developed community-acquired pneumonia 15 days post FMT and was treated successfully with oral azithromycin. Minor adverse events within the first two weeks post FMT were noted in 6 (38%) patients (self-limited diarrhea in 3, fecal urgency in 2, abdominal cramps in 2, and constipation in one patient) (Table 3). Only one patient had persistent diarrhea shortly after FMT, with the cause attributed to underlying Crohn's disease. No complications related to the colonoscopy procedure were noted.Conclusion:FMT appears to be a safe and effective therapeutic option for RCDI in patients with hematological malignancies. Considering very few adverse events and particularly no infectious complications in our series, we conclude that immunosuppression should not preclude the use of FMT for treatment of RCDI in this high risk population. These results need prospective validation. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Fecal Microbiota Therapy: Ready for Prime Time?

Fecal Microbiota Therapy: Ready for Prime Time?

Gastric Acid Suppression and Recurrent Clostridium difficile Infection: A Systematic Review and Meta-analysis

Purpose:Clostridium difficile infection (CDI) is the most common cause of nosocomial diarrhea with the risk of recurrence ranging from 20-65%. Gastric acid suppression is associated with an increased risk of CDI, however, studies regarding the risk of recurrent CDI in patients on acid suppression have shown conflicting results. Up to 50% or more of patients with CDI are on concomitant gastric acid suppression medications. We performed a systematic review and meta-analysis to study the association between gastric acid suppression medications and the risk of recurrent CDI. Methods: A systematic search of Medline, Embase, and Web of Science was performed up to April 2012 and a manual review of the literature was performed. Studies were included if they assessed the association between exposure to gastric acid suppression medications (histamine 2 receptor blocker or proton pump inhibitor) and recurrent CDI as an outcome; and reported relative risks or odds ratio (OR) or provided data for their calculation. Summary OR estimates with 95% confidence intervals (CIs) were calculated using the random-effects model using Review Manager version 5.1 (Cochran Inc). Results: Eleven studies (10 observational and 1 post-hoc analysis of a randomized controlled trial) reporting 899 cases of recurrent CDI in 3,929 patients with CDI were included. Of the 3,929 patients with CDI, 1,983 (50.4%) were on acid suppression. The rate of recurrent CDI in patients on acid suppression was 24.1% (n=477/1,983), compared to 21.7% (n=422/1,946) in patients without acid suppression. Meta-analysis of studies using the random effects model did not show an increased risk of recurrent CDI in patients on gastric acid suppression medications (OR 1.40, 95% Cl 0.92 - 2.13, p=0.24). There was significant heterogeneity among the studies with I2 of 77% and Cochran's Q p<0.0001. Sensitivity analyses based on the definition of recurrent CDI revealed that acid suppression medication use was associated with increased risk of recurrence in studies defining recurrent CDI within 90 days (OR 1.75, 95% Cl 1.06 - 2.87, p=0.03) but not in studies defining recurrent CDI up to 60 days (OR 1.32, 95% Cl 0.58 - 2.98, p=0.67). Conclusion: Meta-analyses of existing studies does not indicate that concomitant use of gastric acid suppression medications is associated with an increased risk of recurrent CDI within 60 days, but may be associated with reinfection through 90 days.

Standardized Frozen Preparation for Transplantation of Fecal Microbiota for Recurrent Clostridium difficile Infection

While fecal microbiota transplantation (FMT) is historically known to be an effective means to treat recurrent Clostridium difficile infection (CDI) refractory to standard antibiotic therapies, the procedure is rarely performed. At least some of the reasons for limited availability are those of practicality, including aesthetic concerns and costs of donor screening. The objective of this study was to overcome these barriers in our clinical FMT program. We report clinical experience with 43 consecutive patients who were treated with FMT for recurrent CDI since inception of this program at the University of Minnesota. During this time, we simplified donor identification and screening by moving from patient-identified individual donors to standard volunteer donors. Material preparation shifted from the endoscopy suite to a standardized process in the laboratory, and ultimately to banking frozen processed fecal material that is ready to use when needed. Standardization of material preparation significantly simplified the practical aspects of FMT without loss of apparent efficacy in clearing recurrent CDI. Approximately 30% of the patients had underlying inflammatory bowel disease, and FMT was equally effective in this group. Several key steps in the standardization of donor material preparation significantly simplified the clinical practice of FMT for recurrent CDI in patients failing antibiotic therapy.