Sahil Khanna

The Epidemiology of Community-Acquired Clostridium difficile Infection: A Population-Based Study

OBJECTIVES:Clostridium difficile infection (CDI) is a common hospital-acquired infection with increasing incidence, severity, recurrence, and associated morbidity and mortality. There are emerging data on the occurrence of CDI in nonhospitalized patients. However, there is a relative lack of community-based CDI studies, as most of the existing studies are hospital based, potentially influencing the results by referral or hospitalization bias by missing cases of community-acquired CDI.METHODS:To better understand the epidemiology of community-acquired C. difficile infection, a population-based study was conducted in Olmsted County, Minnesota, using the resources of the Rochester Epidemiology Project. Data regarding severity, treatment response, and outcomes were compared in community-acquired vs. hospital-acquired cohorts, and changes in these parameters, as well as in incidence, were assessed over the study period.RESULTS:Community-acquired CDI cases accounted for 41% of 385 definite CDI cases. The incidence of both community-acquired and hospital-acquired CDI increased significantly over the study period. Compared with those with hospital-acquired infection, patients with community-acquired infection were younger (median age 50 years compared with 72 years), more likely to be female (76% vs. 60%), had lower comorbidity scores, and were less likely to have severe infection (20% vs. 31%) or have been exposed to antibiotics (78% vs. 94%). There were no differences in the rates of complicated or recurrent infection in patients with community-acquired compared with hospital-acquired infection.CONCLUSIONS:In this population-based cohort, a significant proportion of cases of CDI occurred in the community. These patients were younger and had less severe infection than those with hospital-acquired infection. Thus, reports of CDI in hospitalized patients likely underestimate the burden of disease and overestimate severity.

The growing incidence and severity of Clostridium difficile infection in inpatient and outpatient settings

Clostridium difficile infection (CDI) is a leading cause of nosocomial infections, with disease severity ranging from mild diarrhea to fulminant colitis. The incidence and severity of CDI has been on the rise over the last 10–20 years, with CDI being increasingly described outside healthcare settings and in populations previously thought to be at low risk. There has also been an increase in the morbidity, mortality and economic burden associated with CDI in the last several years. This increasing incidence and severity is thought to be at least partially due to frequent antibiotic use and the emergence of a hypervirulent C. difficile strain.

Community-acquired Clostridium difficile infection: an increasing public health threat.

There has been a startling shift in the epidemiology of Clostridium difficile infection over the last decade worldwide, and it is now increasingly recognized as a cause of diarrhea in the community. Classically considered a hospital-acquired infection, it has now emerged in populations previously considered to be low-risk and lacking the traditional risk factors for C. difficile infection, such as increased age, hospitalization, and antibiotic exposure. Recent studies have demonstrated great genetic diversity for C. difficile, pointing toward diverse sources and a fluid genome. Environmental sources like food, water, and animals may play an important role in these infections, apart from the role symptomatic patients and asymptomatic carriers play in spore dispersal. Prospective strain typing using highly discriminatory techniques is a possible way to explore the suspected diverse sources of C. difficile infection in the community. Patients with community-acquired C. difficile infection do not necessarily have a good outcome and clinicians should be aware of factors that predict worse outcomes in order to prevent them. This article summarizes the emerging epidemiology, risk factors, and outcomes for community-acquired C. difficile infection.

The Epidemiology of Clostridium difficile Infection in Children: A Population-Based Study

BACKGROUND The incidence of Clostridium difficile infection (CDI) is increasing, even in populations previously thought to be at low risk, including children. Most incidence studies have included only hospitalized patients and are thus potentially influenced by referral or hospitalization biases. METHODS We performed a population-based study of CDI in pediatric residents (aged 0-18 years) of Olmsted County, Minnesota, from 1991 through 2009 to assess the incidence, severity, treatment response, and outcomes of CDI. RESULTS We identified 92 patients with CDI, with a median age of 2.3 years (range, 1 month-17.6 years). The majority of cases (75%) were community-acquired. The overall age- and sex-adjusted CDI incidence was 13.8 per 100 000 persons, which increased 12.5-fold, from 2.6 (1991-1997) to 32.6 per 100 000 (2004-2009), over the study period (P < .0001). The incidence of community-acquired CDI was 10.3 per 100 000 persons and increased 10.5-fold, from 2.2 (1991-1997) to 23.4 per 100 000 (2004-2009) (P < .0001). Severe, severe-complicated, and recurrent CDI occurred in 9%, 3%, and 20% of patients, respectively. The initial treatment in 82% of patients was metronidazole, and 18% experienced treatment failure. In contrast, the initial treatment in 8% of patients was vancomycin and none of them failed therapy. CONCLUSIONS In this population-based cohort, CDI incidence in children increased significantly from 1991 through 2009. Given that the majority of cases were community-acquired, estimates of the incidence of CDI that include only hospitalized children may significantly underestimate the burden of disease in children.

A Novel Microbiome Therapeutic Increases Gut Microbial Diversity and Prevents Recurrent Clostridium difficile Infection

BACKGROUND Patients with recurrent Clostridium difficile infection (CDI) have a ≥60% risk of relapse, as conventional therapies do not address the underlying gastrointestinal dysbiosis. This exploratory study evaluated the safety and efficacy of bacterial spores for preventing recurrent CDI. METHODS Stool specimens from healthy donors were treated with ethanol to eliminate pathogens. The resulting spores were fractionated and encapsulated for oral delivery as SER-109. Following their response to standard-of-care antibiotics, patients in cohort 1 were treated with SER-109 on 2 consecutive days (geometric mean dose, 1.7 × 10(9) spores), and those in cohort 2 were treated on 1 day (geometric mean dose, 1.1 × 10(8) spores). The primary efficacy end point was absence of C. difficile-positive diarrhea during an 8-week follow-up period. Microbiome alterations were assessed. RESULTS Thirty patients (median age, 66.5 years; 67% female) were enrolled, and 26 (86.7%) met the primary efficacy end point. Three patients with early, self-limiting C. difficile-positive diarrhea did not require antibiotics and tested negative for C. difficile at 8 weeks; thus, 96.7% (29 of 30) achieved clinical resolution. In parallel, gut microbiota rapidly diversified, with durable engraftment of spores and no outgrowth of non-spore-forming bacteria found after SER-109 treatment. Adverse events included mild diarrhea, abdominal pain, and nausea. CONCLUSIONS SER-109 successfully prevented CDI and had a favorable safety profile, supporting a novel microbiome-based intervention as a potential therapy for recurrent CDI.

Clostridium difficile Infection: New Insights Into Management

Clostridium difficile was first described as a cause of diarrhea in 1978 and is now among the leading 3 hospital-acquired infections in the United States, along with methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. In the past 2 decades, there has been an increase in the incidence, severity, and recurrence rates of C difficile infection, all of which are associated with poor outcomes. In addition, several novel risk factors and newer treatment methods are emerging, including fidaxomicin therapy, treatment using monoclonal antibodies, and fecal microbiota transplantation, that have shown promise for the treatment of C difficile infection. This review focuses on the changing epidemiology, risk factors, and newer methods for treatment of C difficile infection.

A Clinician's Primer on the Role of the Microbiome in Human Health and Disease

The importance of the commensal microbiota that colonizes the skin, gut, and mucosal surfaces of the human body is being increasingly recognized through a rapidly expanding body of science studying the human microbiome. Although, at first glance, these discoveries may seem esoteric, the clinical implications of the microbiome in human health and disease are becoming clear. As such, it will soon be important for practicing clinicians to have an understanding of the basic concepts of the human microbiome and its relation to human health and disease. In this Concise Review, we provide a brief introduction to clinicians of the concepts underlying this burgeoning scientific field and briefly explore specific disease states for which the potential role of the human microbiome is becoming increasingly evident, including Clostridium difficile infection, inflammatory bowel disease, colonization with multidrug-resistant organisms, obesity, allergic diseases, autoimmune diseases, and neuropsychiatric illnesses, and we also discuss current and future roles of microbiome restorative therapies.

“Outcomes in community–acquired clostridium difficile infection”

Community‐acquired Clostridium difficile infection (CA‐CDI) is an increasingly appreciated condition. It is being described in populations lacking traditional predisposing factors that have been previously considered at low‐risk for this infection. As most studies of CDI are hospital‐based, outcomes in these patients are not well known.

Systematic review: colitis associated with anti-CTLA-4 therapy

Cytotoxic T‐lymphocyte‐associated protein‐4 (CTLA‐4) has an important role in T‐cell regulation, proliferation and tolerance. Anti‐CTLA‐4 agents, such as ipilimumab and tremelimumab, have been shown to prolong overall survival in patients with metastatic melanoma, and their use is being investigated in the treatment of other malignancies. Their novel immunostimulatory mechanism, however, predisposes patients to immune‐related adverse effects, of which gastrointestinal effects such as diarrhoea and colitis are the most common.

The Epidemiology of Microscopic Colitis in Olmsted County From 2002 to 2010: A Population-Based Study

BACKGROUND & AIMS The increasing incidence of microscopic colitis has been partly attributed to detection bias. We aimed to ascertain recent incidence trends and the overall prevalence of microscopic colitis in a population-based study. METHODS Using data from the Rochester Epidemiology Project, we identified residents of Olmsted County, Minnesota, who were diagnosed with collagenous colitis or lymphocytic colitis from January 1, 2002, through December 31, 2010, based on biopsy results and the presence of diarrhea (N = 182; mean age at diagnosis, 65.8 years; 76.4% women). Poisson regression analyses were performed to evaluate associations between incidence and age, sex, and calendar period. RESULTS The age- and sex-adjusted incidence of microscopic colitis was 21.0 cases per 100,000 person-years (95% confidence interval [CI], 18.0-24.1 cases per 100,000 person-years). The incidence of lymphocytic colitis was 12.0 per 100,000 person-years (95% CI, 9.6-14.3 per 100,000 person-years) and collagenous colitis was 9.1 per 100,000 person-years (95% CI, 7.0-11.1 per 100,000 person-years). The incidence of microscopic colitis and its subtypes remained stable over the study period (P = .63). Increasing age (P < .001) and female sex (P < .001) were associated with increasing incidence. On December 31, 2010, the prevalence of microscopic colitis was 219 cases per 100,000 persons (90.4 per 100,000 persons for collagenous colitis and 128.6 per 100,000 persons for lymphocytic colitis). CONCLUSION The incidence of microscopic colitis in Olmsted County residents has stabilized and remains associated with female sex and increasing age.