Prevention Of Clostridium Difficile Infection Research Articles

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.

496. Secondary Prophylaxis for Clostridium difficile Infection: A Physician Practice Assessment

BackgroundRecurrent Clostridium difficile infection (CDI) is associated with significant morbidity, mortality and healthcare related costs. Up to 30% of CDI cases recur, resulting in 83,000 cases of recurrent CDI per year. Although agents for primary and secondary prophylaxis for CDI including the use of probiotics, antibiotics, fecal microbiota transplantations, and newer therapies such as bezlotoxumab have been reported, there is no consensus guidelines regarding their use. The purpose of this study was to assess physician practices regarding secondary prophylaxis for CDI.MethodsThis cross-sectional study using Qualtrics electronic survey (24 questions) assessed physician practice preferences. The survey was distributed through institutional emails and through the Infectious Disease Society of America “IDea Exchange” forum. Responses were collected and analyzed using descriptive statistics.ResultsA total of 246 surveys were completed. Physicians were surveyed from greater than 100 locations (see Figure 1). Most (229, 93%) of the physicians practiced in an inpatient setting. Respondent specialties were primarily infectious diseases (138, 56%) followed by internal medicine (72, 29%). Most physicians (173, 71%) use secondary prophylaxis for CDI prevention (see Figure 2). Vancomycin (121, 70%) and probiotics (114, 66%) were most commonly used for CDI secondary prophylaxis, (see Figure 3). Of 164 physicians who used secondary prophylaxis half of them (89, 54.2%), used prophylaxis only for patients with a history of recurrent CDI receiving antibiotics and about a third, (49, 29.9%) utilized it for patients with a history of CDI who were receiving antibiotics. ID physicians were more likely to prescribe secondary prophylaxis as compared with non-ID physicians (85% of 127 respondents vs. 75% of 85 respondents, P = 0.052). The use of secondary prophylaxis was similar among private practice and academic physicians (84% of 39 vs. 80% of 157 respondents, P = 0.591).ConclusionThe majority of the physicians who responded to this survey use secondary prophylaxis to prevent recurrent CDI, hence future CDI guidelines need to address the role of secondary prophylaxis in clinical practice. Disclosures All authors: No reported disclosures.

492. Long-Term Outcomes of Clostridium difficile Infection Among Medicare Beneficiaries

Background Clostridium difficile infection (CDI) is a common healthcare-associated infection, particularly among older adults. We used laboratory-confirmed CDI surveillance data from 8 states participating in the Centers for Disease Control and Prevention’s Emerging Infections Program linked to claims data for Centers for Medicare and Medicaid Services (CMS) beneficiaries to measure variation in 1-year outcomes associated with CDI.MethodsA CDI case was defined as a positive C. difficile stool test in 2014 in a person without a positive test in the prior 8 weeks. Cases aged ≥65 years were linked to their CMS beneficiary ID using unique combinations of date of birth, sex, and zip code. Each case was matched to five control beneficiaries who did not link to any case and were residents of the same catchment area. Inclusion criteria were continuous fee-for-service Medicare for the entire study period (1 year before and after event date), and no hospitalization or skilled nursing facility stay with an ICD-9-CM code for CDI in the year prior to their match date. Multivariable logistic regression models were used to compare mortality and hospitalization for 1 year following the event date between beneficiaries with and without CDI, adjusting for age, sex, race, catchment area, chronic conditions, number of hospitalizations in the prior year, and hospitalization status at the time of and 7 days preceding the event date.ResultsOf 5,097 cases aged ≥65, 3,082 (60%) were linked to a CMS ID, and 1,832 (59%) met inclusion criteria. In crude analysis, 34% of beneficiaries with CDI died within 1 year, compared with 5% of beneficiaries without CDI. Beneficiaries with CDI were also more likely to be hospitalized in the subsequent year (54% vs. 17%). Beneficiaries with CDI had a higher adjusted odds of death (adjusted OR 3.01, 95% CI: 2.46, 3.69) and hospitalization within 1 year (adjusted OR 1.93, 95% CI: 1.65, 2.25) than those without CDI.ConclusionOlder adults with CDI were three times more likely to die in the year following infection and nearly two times more likely to be hospitalized compared with those without CDI, revealing independent long-term risk of poor outcomes. This excess morbidity and mortality supports the need to develop novel CDI prevention strategies for this population.Disclosures All authors: No reported disclosures.

Lactobacillus plantarum 299v Reduces the Incidence of Clostridium difficile Infection in Nephrology and Transplantation Ward-Results of One Year Extended Study.

Background:Lactobacillus plantarum 299v (LP299v) is a probiotic strain which influences on the intestinal bacterial flora. This is why, it has been introduced into clinical practice for the prevention and treatment of diarrheal disorders and alleviation of their symptoms in patients during antibiotic therapy. However, the use of probiotics in the prophylaxis of Clostridium difficile infections (CDI) in these patients is problematic. The aim of this clinical, retrospective, single-centre study was to analyse the incidence of CDI among patients hospitalized in the nephrology and transplantation ward in the period before, during and after stopping of LP299v prophylaxis. Methods: Among 5341 patients hospitalized in the nephrology and transplantation ward over a three year period, 34 patients with CDI were diagnosed and included in this analysis. From December 2013 to December 2014 all patients under antibiotic and immunosuppressive therapies received LP299v as a prophylaxis of CDI. The observation period consisted of three twelve-months periods: before, during LP299v use and after stopping of such method of CDI prevention. Results: A significant (p = 0.0003) reduction of CDI incidence during LP299v use (0.11%) was observed compared to two other periods, that is, before and after LP299v use (1.03% and 0.77%, respectively). Conclusions: Routine use of LP299v as a CDI prophylaxis may prevent CDI during antibiotics therapy in patients treated with immunosuppressive agents in nephrology and transplantation ward.

Development of a risk prediction model for hospital-onset Clostridium difficile infection in patients receiving systemic antibiotics

Clostridium difficile infection (CDI) is recognized as a significant challenge in health care. Identification of high-risk individuals is essential for the development of CDI prevention strategies. The objective of this study was to develop an easily implementable risk prediction model for hospital-onset CDI in patients receiving systemic antimicrobials. This retrospective, case-control, multicenter study included adult patients admitted to Novant Health Forsyth Medical Center and Novant Health Presbyterian Medical Center from July 1, 2015, to July 1, 2017, who received systemic antibiotics. Cases were subjects with hospital-onset CDI; controls were subjects without a CDI diagnosis. Cases were matched 1:1 with controls by admitted medical unit type. Variables significantly associated with CDI were incorporated into a multivariate analysis. A logistic regression model was used to formulate a point-based risk prediction model. Positive predictive value, negative predictive value, sensitivity, specificity, and accuracy were determined at various point cutoffs of the model. A receiver operating characteristic-area under the curve was created to assess the discrimination of the model. A total of 200 subjects (100 cases and 100 controls) were included. Most patients were Caucasian and female. Risk factors for CDI identified and incorporated into the model included age ≥70 years (adjusted odds ratio, 1.89; 95% confidence interval 1.05-3.43; P = .0326) and recent hospitalization in the past 90 days (adjusted odds ratio, 3.55; 95% confidence interval 1.90-6.83; P < .0001). Sensitivity and specificity were 76% and 49%, respectively, for scores ≥2 and 20% and 93%, respectively, for a score of 6. Diagnostic performance of various score cutoffs for the model indicated that a score ≥2 was associated with the highest accuracy (63%). The receiver operating characteristic-area under the curve was 0.7. We developed a simple-to-implement hospital-onset CDI risk model that included only independent risks that can be obtained immediately on presentation to the health care facility. Despite this, the model had fair discriminatory power. Similar risk factors were found in previously developed models; however, the utility of these models is limited owing to the difficulty of assessing other included risk factors and the inclusion of risk factors that cannot be evaluated until the patient is discharged from the health care facility. Identification of hospitalized patients who are receiving systemic antibiotics, are ≥70 years old, and were recently admitted to the hospital in the past 90 days may allow for an easily implementable hospital-onset CDI risk prevention strategy.

Efficacy of Fecal Microbiota Transplantation for Clostridium difficile Infection in Immunocompromised Patients: A Systematic Review and Meta-Analysis

Introduction: Fecal microbiota transplantation (FMT) is a safe and effective therapy for recurrent Clostridium difficile infection (CDI). Although immunocompromised patients are at high risk of CDI, the use of FMT may be limited owing to safety concerns. Since most FMT clinical trials exclude these patients, data on efficacy and safety of FMT in these patients are limited. We report results from a systematicreview and meta-analysis to evaluate the efficacy and safety of FMT in immunocompromised patients. Methods: A systematic search of MEDLINE, Embase and Web of Science was performed up to April 2018, followed by manual search of identified studies. We included case series, case-control or cohort studies, and clinical trials of FMT for CDI in immunocompromised patients with prevention of recurrent CDI as the primary outcome. Our primary analysis focused on calculating weighted pooled cure rate after one or more FMT. Results: A total of 18 studies were included. Among these, 566 immunocompromised patients underwent FMT for recurrent CDI. The various reason for immunosuppression included inflammatory bowel diseases, solid organ transplant (SOT), cancer, human immunodeficiency virus infection, graft versus host disease and hematopoietic stem cell transplants. Of the 566 patients, 430 had clinical cure of CDI with a pooled resolution rate after one FMT of 77.4% (95% CI, 71.6%-83.2%, I2= 57%).The pooled resolution rate increased to 91.5% (95% CI, 87.6%-95.4%, I2=21%) with multiple FMTs. No serious adverse events attributed to FMT were reported in any of the studies. On separating the 9 studies with immunosuppressed IBD patients, resolution after 1 FMT was reported in 328/412 patients, the pooled resolution rate 80.7% (95% CI, 76.6%-84.8%). In three studies with 103 SOT patients, FMT cured 58, with pooled cure rate of 50.2% (95% CI, 29.7%-70.6%). Conclusion: FMT appears to be safe and effective therapy for preventing recurrent CDI in immunocompromised patients. However, efficacy is lower in these patients compared to reported rates in immunocompetent patients. Efficacy improves with multiple FMTs. Although data were not available, repeat non-CDI antibiotic exposure in this population could potentially explain these findings. Studies are needed to explore best treatment practices in these patients including predictors of failed FMT which may identify patients who would benefit from early pre-emptive repeat FMT to prevent recurrent CDI

Oral Vancomycin Prophylaxis Is Highly Effective in Preventing Clostridium difficile Infection in Allogeneic Hematopoietic Cell Transplant Recipients.

Clostridium difficile infection (CDI) is a leading cause of infectious complications in allogeneic hematopoietic cell transplant recipients (alloHCT). We sought to evaluate whether prophylactic oral vancomycin reduces the incidence of CDI in alloHCT recipients. We conducted a retrospective cohort study to examine the effectiveness of CDI prophylaxis with oral vancomycin, as compared to no prophylaxis, in 145 consecutive adult alloHCT recipients at the University of Pennsylvania between April 2015 and November 2016. Patients received oral vancomycin 125 mg twice daily, starting on admission and continuing until discharge. The primary outcome of interest was the association between oral vancomycin prophylaxis and CDI diagnosis. Secondary outcomes included graft-versus-host disease (GVHD) and relapse. There were no cases of CDI in patients that received prophylaxis (0/90, 0%), whereas 11/55 (20%) patients who did not receive prophylaxis developed CDI (P < .001). Oral vancomycin prophylaxis was not associated with a higher risk of acute, grades 2-4 GVHD (subhazard ratio [sHR] 1.59; 95% confidence interval [CI] 0.88-2.89; P = .12), acute, grades 3-4 GVHD (sHR 0.65; 95% CI 0.25-1.66; P = .36), or acute, grades 2-4 gastrointestinal GVHD (sHR 1.95; 95% CI 0.93-4.07; P = .08) at day 180 post-transplant. No associations between oral vancomycin and relapse or survival were observed. Prophylaxis with oral vancomycin is highly effective in preventing CDI in alloHCT recipients without increasing the risk of graft-versus-host disease or disease relapse. Further evaluation via a prospective study is warranted.

Meta-analysis comparing the effects of statins on the risk of Clostridium difficile diarrhea

A literature search was performed through May 2017. Studies that compared the risk of developing Clostridium difficile infection (CDI) and/or the clinical outcomes of CDI in patients who received statin treatment versus those who did not receive statins were included. Ten observational studies with 37,109 patients were included. Compared to no treatment, statins reduced the risk of CDI development (odds ratio [OR] = 0.66, 95% confidence interval [CI], 0.44–0.99). However, among patients who developed CDI, the use of statins did not significantly reduce recurrent CDI risk (OR = 0.69, 95% CI, 0.28–1.71) or 30-day mortality (OR = 0.77, 95% CI, 0.51–1.14). In conclusion, our study demonstrates a significant association between statin use and a reduced risk of CDI development. However, the findings of our study suggest no significant associations between statin use and improvement in clinical outcomes of CDI. These findings might impact the clinical management and primary prevention of CDI.

Clostridium difficile-related hospitalizations and risk factors for in-hospital mortality in Spain between 2001 and 2015

To examine trends in the incidence, characteristics and in-hospital outcomes of Clostridium difficile infection (CDI) hospitalizations from 2001 to 2015, to compare clinical variables among patients according to the diagnosis position (primary or secondary) of CDI, and to identify factors associated with in-hospital mortality (IHM). A retrospective study was performed using the Spanish National Hospital Discharge Database, 2001-2015. The study population included patients who had CDI as the primary or secondary diagnosis in their discharge report. Annual hospitalization rates were calculated and trends were assessed using Poisson regression models and Jointpoint analysis. Multi-variate logistic regression models were performed to identify variables associated with IHM. In total, 49,347 hospital discharges were identified (52.31% females, 33.69% with CDI as the primary diagnosis). The rate of hospitalization increased from 3.9 cases per 100,000 inhabitants in 2001-2003 to 12.97 cases per 100,000 inhabitants in 2013-2015. Severity of CDI and mean cost per patient increased from 6.36% and 3750.11€ to 11.19% and 4340.91€, respectively, while IHM decreased from 12.66% to 10.66%. Age, Charlson Comorbidity Index, severity, length of hospital stay and mean cost were significantly higher in patients with a primary diagnosis of CDI. Irrespective of the CDI diagnosis position, IHM was associated with male sex, older age, comorbidities, readmission and severity of CDI. Primary diagnosis of CDI was associated with lower IHM (odds ratio 0.60; 95% confidence interval 0.56-0.65). CDI-related hospitalization rates are increasing, leading to a high cost burden, although IHM has decreased in recent years. Factors associated with IHM should be considered in strategies for the prevention and management of CDI.

Guideline for the Management of Clostridium Difficile Infection in Children and Adolescents With Cancer and Pediatric Hematopoietic Stem-Cell Transplantation Recipients.

PurposeThe aim of this work was to develop a clinical practice guideline for the prevention and treatment of Clostridium difficile infection (CDI) in children and adolescents with cancer and pediatric hematopoietic stem-cell transplantation (HSCT) patients.MethodsAn international multidisciplinary panel of experts in pediatric oncology and infectious diseases with patient advocate representation was convened. We performed systematic reviews of randomized controlled trials for the prevention or treatment of CDI in any population and considered the directness of the evidence to children with cancer and pediatric HSCT patients. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to generate recommendations.ResultsThe panel made strong recommendations to administer either oral metronidazole or oral vancomycin for the initial treatment of nonsevere CDI and oral vancomycin for the initial treatment of severe CDI. Fidaxomicin may be considered in the setting of recurrent CDI. The panel suggested that probiotics not be routinely used for the prevention of CDI, and that monoclonal antibodies and probiotics not be routinely used for the treatment of CDI. A strong recommendation to not use fecal microbiota transplantation was made in this population. We identified key knowledge gaps and suggested directions for future research.ConclusionWe present a guideline for the prevention and treatment of CDI in children and adolescents with cancer and pediatric HSCT patients. Future research should include randomized controlled trials that involve children with cancer and pediatric HSCT patients to improve the management of CDI in this population.

Combination probiotics may prevent Clostridium difficile infection among elderly patients undergoing an orthopedic surgery.

The incidence of Clostridium difficile infection (CDI) is greater in elderly orthopedic patients. We conducted a retrospective case-control study by selecting elderly patients who underwent proximal femoral fracture surgery to investigate the effect of probiotics on CDI prevention. Cases were diagnosed with CDI by an enzyme-linked immunosorbent assay for C. difficile toxins using frozen stool specimens. The primary method of exposure was receipt of combination probiotics such as Streptococcus faecalis, Bacillus mesentericus, and Clostridium butyricum. The crude odds ratio between developing CDI and receiving combination probiotics was 0.074 (95% CI: 0.010–0.565; p=0.002). Adjunctive combination probiotics among elderly patients who undergo proximal femoral fracture surgery likely reduces the probability of CDI.

Outcomes of Clostridium difficile-suspected diarrhea in a French university hospital.

Clostridium difficile infection (CDI) produces a variety of clinical presentations ranging from mild diarrhea to severe infection with fulminant colitis, septic shock, and death. CDI puts a heavy burden on healthcare systems due to increased morbidity and mortality, and higher costs. We evaluated the clinical impact of CDI in terms of complications and mortality in a French university hospital compared with patients with diarrhea unrelated to CDI. A 3-year prospective, observational, cohort study was conducted in a French university hospital. Inpatients aged 18years or older with CDI-suspected diarrhea were eligible to participate in the study and were followed for up to 60days after CDI testing. Among the 945 patients with diarrhea included, 233 had confirmed CDI. Overall, 106 patients (11.2%) developed at least one of the following complications: colectomy, colitis, ileitis/rectitis, ileus, intestinal perforation, megacolon, multiorgan failure, pancolitis, peritonitis, pseudomembranous colitis, renal failure, and sepsis/septic shock. The complication rate was significantly higher in patients with diarrhea related to C. difficile than in non-CDI patients (26.6% vs 6.2%, P < 0.001). At day 60, 137 (14.5%) patients had died, with 37 deaths among the CDI group (15.9%). Death was attributable to CDI in 15 patients (6.4%). Complications are more frequent among CDI cases than in patients with diarrhea not related to C. difficile. Assessment of CDI is necessary to ensure allocation of sufficient resources to CDI prevention.

SYN-004 (Ribaxamase), an Orally Administered β-Lactamase for Prevention of Clostridium Difficile Infection in Patients Treated with Intravenous β-Lactam Antibiotics: A Randomized, Double-Blind, Placebo-Controlled Phase 2b Study

Background: Clostridium difficile infection (CDI) is an urgent public health threat, yet there is no product currently licensed for its prevention. The use of intravenous β-lactam antibiotics are considered high risk for the development of CDI due to their biliary excretion into the GI tract and disruption of the gut microbiome. SYN-004 (ribaxamase) is an orally-administered β-lactamase, designed to be given with IV β-lactam antibiotics to degrade excess antibiotics in the upper GI tract before they can disrupt the gut microbiome leading to CDI. Methods: A parallel-group, double-blind, placebo-controlled, multi-center, study evaluating the effectiveness of ribaxamase for prevention of CDI was conducted in 412 hospitalized patients > 50 years of age who received intravenous ceftriaxone for a lower respiratory tract infection (LRTI). Patients were randomized 1:1 to receive either 150 mg of ribaxamase or placebo four times per day during and for 72 hours after ceftriaxone treatment. The primary endpoint was the incidence of CDI through 4 weeks post-treatment in the ribaxamase vs. the placebo group. Secondary endpoints included resolution of the LRTI, new colonization by certain opportunistic pathogens, and microbiome-focused exploratory endpoints. Findings: Of 412 patients (mean age ~69·5), 206 each received ceftriaxone plus ribaxamase or ceftriaxone plus placebo. By 4 weeks post-antibiotics, the incidence of CDI in the placebo group was 3·4% while the incidence of C. difficile infection in the ribaxamase group was only 1·0% which corresponds to a 71% reduction in the incidence of C. difficile infection (one-sided, P=0·045). Patients who received ribaxamase also had a lower incidence of new fecal colonization with C. difficile and vancomycin resistant enterococci. Interpretation: In patients being treated with intravenous ceftriaxone for a LRTI, oral ribaxamase significantly reduced the incidence of CDI as compared with placebo. Ribaxamase has the potential to become the first product licensed for prevention of CDI. Trial registration number: The trial was registered at clinicaltrials.gov: NCT02563106. Funding: Synthetic Biologics, Inc. Declaration of Interest: All authors are employees or paid consultants of Synthetic Biologics, Inc. Ethical Approval: The study protocol was approved by the appropriate institutional review boards or ethics committees at the corresponding institutions or countries. All study patients provided written informed consent to participate in the study.

Clostridium difficile in the intensive care unit

Clostridium difficile infections (CDI) are encountered in about 1-2% of patients in the intensive care unit (ICU) and pose aspecial challenge to those who provide care. Only little data regarding severity and management of CDI in ICU patients in Europe are available. Extrapolation of results from one patient population to another is often difficult. The comorbidities of those patients often limit the application of general recommendations concerning diagnosis and therapy. In addition, there are arelevant percentage of patients (10-20%) with asymptomatic C.difficile colonization. The relevance for the patient and for the risk of patient to patient infection is not yet fully understood. Based on available data, we give an overview of current challenges in the diagnosis, assessment of disease course, primary management options, and alternatives in special cases and treatment failures of CDI. We also discuss prevention of new CDI in the intensive care unit.

Characterization of Clostridium difficile isolates collected during a phase 2b clinical study with SYN-004 (ribaxamase) for the prevention of C. difficile infection

During a Phase 2b study with SYN-004 (ribaxamase) for prevention of Clostridium difficile infection (CDI) conducted in North America and Eastern Europe, 45 C. difficile isolates from subjects with laboratory-confirmed CDI and or colonized with C. difficile were collected and characterized. Several C. difficile PCR ribotypes, including 027 and 198, were identified.

Safety and efficacy of encapsulated fecal microbiota transplantation for recurrent Clostridium difficile infection: a systematic review.

Fecal microbial transplantation (FMT) has been shown to be effective for the treatment of recurrent clostridium difficile infection (CDI). The efficacy and safety of freeze-dried encapsulated FMT for the treatment of recurrent CDI is unclear. We performed a systematic review to evaluate and analyze the current evidence in this respect. A systematic literature search was performed using the PubMed, Embase, and Medline databases until December 2017 to identify all original studies that investigated the role of administration of encapsulated FMT in recurrent CDI. The study included patients of all ages. Two independent reviewers extracted data and assessed the quality of publications; a third investigator resolved any discrepancies. A total of six studies, five case series and one randomized-controlled trial, were included in this review. Overall, 341 patients completed treatment with encapsulated FMT. Only three major adverse events were reported and no deaths occurred directly related to FMT. In all, 285 patients responded to the first treatment, with no recurrence during the specified follow-up period set to meet the primary endpoint. Forty-two patients underwent a second treatment, with resolution of symptoms in 28 patients. At least five patients were reported to undergo a third treatment, with resolution in three of them. Only one patient was reported to have received four treatments without long-term resolution of symptoms. Low-quality to moderate-quality evidence showed that encapsulated FMT is safe and cost-effective for the treatment and prevention of recurrent CDI. Its efficacy is not inferior to FMT performed through the nonoral route. Randomized-controlled trials are necessary to compare its efficacy with oral antimicrobial drugs and also to evaluate the potential adverse effects associated with the treatment.

Incidence, Epidemiology and Control of Clostridium difficile Infection in a Tertiary Care Private Hospital in India

Purpose:Clostridium difficile infection (CDI) is a serious healthcare-associated infection (HAI) now being increasingly reported from hospitals across India. However, there is a paucity of data on the incidence of and impact of control measures on CDI in India. Materials and Methods: This is a retrospective study conducted at a tertiary care hospital in Mumbai from January 2016 to December 2017. All patients with healthcare-onset diarrhoea were tested for C. difficile by glutamate dehydrogenase (GDH)/toxin assay or nucleic acid amplification test (NAAT). CDI was defined as either GDH and toxin positive or NAAT positive. The incidence of CDI was calculated per 1000 patient days. Demographic features of patients with CDI including age, sex, duration of hospitalisation before onset of CDI, antibiotic use and treatment administered were summarised. Results: A total of 67 patients had CDI in the study period with a mean incidence of 0.2/1000 patient days. A halving of the CDI incidence was seen after intensification of the CDI prevention bundle. The mean age of affected patients was 64 years and CDI occurred at a median duration of 2 weeks after hospitalisation. Eighty-seven per cent of the patients were on antibiotics at the time of diagnosis of CDI. The crude mortality rate was 22%. Conclusions: CDI is an emerging HAI in India. All hospitals need to set up policies for surveillance, testing, treatment and prevention of CDI based on recent international guidelines and local infrastructure/logistics.

Primary Prevention of Clostridium difficile-Associated Diarrhea: Current Controversies and Future Tools

Clostridium difficile infection (CDI) is a major cause of morbidity and mortality in hospitalized patients and rates in most places have not decreased significantly despite broad efforts by both hospitals and public health entities. This review aims to provide readers with a better understanding of the limitations of current prevention strategies. We also review potential future tools that may be available for the primary prevention of CDI in the next decade. Research over the last decade has expanded our appreciation of the role of asymptomatic shedding in the healthcare setting and in the community. This review demonstrates that poor quality data underlies even well-established guidance from national authorities on basic topics such as contact precautions, avoidance of alcohol-based hand hygiene products, CDI testing, supplemental cleaning modalities, and the use of bleach solutions. Additionally, we review research on novel preventative interventions such as identification of asymptomatic carriers, supplemental environmental cleaning technologies, vaccines, and the manipulation of the intestinal microbiome. While there is preliminary data that supports further research in all of these areas, the research is not yet robust enough on which to base local or national policy recommendations, though late-phase human clinical trials of CDI vaccine trials are ongoing. Over the last decade, researchers have begun to reassess the traditional infection prevention model for CDI. Data suggesting a greater role for asymptomatic shedders has increased our understanding of current vertical prevention techniques and is forcing researchers to look more at new processes and technologies to decrease disease incidence.

Application of Antibody-Mediated Therapy for Treatment and Prevention of Clostridium difficile Infection.

Clostridium difficile causes antibiotic- and healthcare-associated diarrhea, which is characterized by a high mortality rate (5–15%) and high recurrence rate of 20% or more. Therapeutic alternatives to antibiotics are urgently needed to improve the overall cure rate. Among these, therapeutic antibodies have shown promising results in clinical studies. Herein, the authors review current monoclonal and polyclonal anti- C. difficile antibodies that have entered the clinical development stage, either for systemic administration or by the oral route. The antibodies can be applied as monotherapy or in combination with standard-of-care to treat an infection with C. difficile or to protect from a recurrence. Bezlotoxumab is the first antibody for secondary prevention of recurrence of C. difficile infection approved by the regulatory agencies in US and Europe. The human monoclonal antibody is administered systemically to patients receiving oral standard-of–care antibiotics. Other antibodies are currently in the clinical pipeline, and some are intended for oral use. They show a good safety profile, high efficacy and low production costs, and can be considered promising therapies of the future. The most promising orally administered drug candidate is a bovine antibody from hyperimmune colostral milk, which is in an advanced clinical development stage. Which antibody will enter the market is dependent on its bioavailability at the site of infection as well as its activity against C. difficile toxins, protection against colonization and possible action on spore formation. The antibody must demonstrate a clear benefit in comparison with other available treatment options to be considered for use by clinicians.

New Guidelines and Data to Clostridium difficile - What's New?

The incidence of Clostridium difficile infections (CDI) remains on a high level globally. In Germany, the burden of disease and especially the number of severe or even lethal cases continue to increase. The main risk factor for the development of CDI is the exposure to broad-spectrum antibiotics, which disturb the intestinal microbiota and therefore enable the colonization with C. difficile. According to IDSA's and SHEA's updated US guidelines, vancomycin is the treatment of choice. Fidaxomicin is as effective as vancomycin, but its advantage is the lower rate of recurrence. For the treatment of multiple relapsing CDI, there are assured treatment successes of ≥ 90 % through a fecal microbiome transfer (FMT), whereby FMT in Germany currently only has the status of an individual therapeutic attempt. Thus, an evidence-based general recommendation for clinical practice is not possible. Currently, new antibiotics with narrow-spectrum activity and low intestinal resorption have been developed for the treatment of CDI, including surotomycin, cadazolid, and ridinilazol. Furthermore, recent clinical studies demonstrated that significantly fewer recurrences occurred in patients who additionally received the monoclonal antibody bezlotoxumab. Novel toxoid vaccines are expected to become an efficacious tool in the prevention of CDI. However, pivotal clinical trials have so far not been completed.