Severe Clostridium difficile-associated disease in populations previously at low risk--four states, 2005

Clostridium difficile is a spore-forming, gram-positive bacillus that produces exotoxins that are pathogenic to humans. C. difficile-associated disease (CDAD) ranges in severity from mild diarrhea to fulminant colitis and death. Antimicrobial use is the primary risk factor for development of CDAD because it disrupts normal bowel flora and promotes C. difficile overgrowth. C. difficile typically has affected older or severely ill patients who are hospital inpatients or residents of long-term-care facilities. Recently, however, both the frequency and severity of health-care-associated CDAD has increased; from 2000 to 2001, the rate of U.S. hospital discharge diagnoses of CDAD increased by 26%. One possible explanation for these increases is the emergence of a previously uncommon strain of C. difficile responsible for severe hospital outbreaks. Although individual cases of CDAD are not nationally reportable, in 2005, the Pennsylvania Department of Health (PADOH) and CDC received several case reports of serious CDAD in otherwise healthy patients with minimal or no exposure to a health-care setting. An investigation was initiated by the Philadelphia Department of Public Health (PDPH), PADOH, and CDC to determine the scope of the problem and explore a possible change in CDAD epidemiology. This report summarizes the results of the investigation in Pennsylvania and three other states, which indicated the presence of severe CDAD in healthy persons living in the community and peripartum women, two populations previously thought to be at low risk. The findings underscore the importance of judicious antimicrobial use, the need for community clinicians to maintain a higher index of suspicion for CDAD, and the need for surveillance to better understand the changing epidemiology of CDAD.     

Clinical features of Clostridium difficile-associated infections and molecular characterization of strains: results of a retrospective study, 2000-2004.

BACKGROUND: Recent outbreaks of severe cases of Clostridium difficile-associated diarrhea (CDAD) reported in North America, the United Kingdom, and The Netherlands have emphasized the importance of an ongoing epidemiological surveillance of CDAD. OBJECTIVE: To determine the epidemiology of CDAD over the years 2000-2004 and the rate of nosocomial transmission of C. difficile. DESIGN: Retrospective survey of inpatients with CDAD and molecular characterization of the strains isolated. SETTING: A 760-bed teaching hospital. METHODS: All CDAD cases diagnosed from January 1, 2000, to December 31, 2004, were reviewed. A CDAD case was defined as diarrhea in a hospitalized patient who had a stool specimen that tested positive for C. difficile cytotoxin or had a positive toxigenic culture result. CDAD was considered to be severe if a patient fulfilled at least 1 of the following 3 criteria: (1) presence of a fever (defined as temperature higher than 38.5 degrees C), abdominal pain, and leukocyte count greater than 10,000 cells/mm(3); (2) endoscopically or histologically proven pseudomembranous colitis; or (3) complications (defined as death with C. difficile infection as the primary or a contributing cause, toxic megacolon, perforation, toxic shock, and/or colectomy). CDAD was considered community-acquired if the diarrhea occurred in the patient within 72 hours after admission and if the patient had no history of hospitalization in the previous month; otherwise, CDAD was considered healthcare-associated. All the strains isolated were serogrouped and were characterized by toxinotyping and PCR ribotyping. Detection of toxin A, toxin B, and binary toxin was performed by PCR. RESULTS: One hundred fifty-one cases of CDAD were diagnosed; 147 clinical records could be reviewed, and 131 strains were studied. The overall incidence of CDAD was 1.1 cases per 1,000 patients admitted, but incidence rates were higher in 2003-2004, compared with 2000-2002 (P=.017). Diarrhea was community acquired in 28 patients (19%). For patients with healthcare-associated CDAD, transmission of the strain from patient to patient (ie, infection with a strain of the same serogroup and PCR ribotype as the strain isolated from another patient hospitalized in the same ward or in a linked ward in the previous 2 months) was demonstrated in 12 cases (10.1%). Eleven percent of strains were positive for binary toxin. Binary toxin-positive strains were associated with more-severe diarrhea (P=.01) and with a higher case-fatality rate (P=.03). A specific clone of C. difficile (serogroup H, PCR ribotype sa026) accounted for 35 (26.7%) of all the strains isolated, but this clone was found both in healthcare-associated and community-acquired cases. Three strains belonged to toxinotype III, but only 1 was related to the hypervirulent clone involved in recent outbreaks. CONCLUSION: The incidence of CDAD is low in our hospital, and cross-infection is limited. These results also suggest that strains with binary toxin might be more virulent.     

Morbidity, mortality, and healthcare burden of nosocomial Clostridium difficile-associated diarrhea in Canadian hospitals.

OBJECTIVE: To assess the healthcare burden, morbidity, and mortality of nosocomial Clostridium difficile-associated diarrhea (N-CDAD) in Canadian hospitals. DESIGN: Laboratory-based prevalence study. SETTING: Nineteen acute-care Canadian hospitals belonging to the Canadian Hospital Epidemiology Committee surveillance program. PATIENTS: Hospitalized patients in the participating centers. METHODS: Laboratory-based surveillance was conducted for C. difficile toxin in stool among 19 Canadian hospitals from January to April 1997, for 6 continuous weeks or until 200 consecutive diarrhea stool samples had been tested at each site. Patients with N-CDAD had to fulfill the case definition. Data collected for each case included patient demographics, length of stay, extent of diarrhea, complications of CDAD, CDAD-related medical interventions, patient outcome, and details of death. RESULTS: We found that 371 (18%) of 2,062 tested patients had stools with positive results for C difficile toxin, of whom 269 (13%) met the case definition for nosocomial CDAD. Of these, 250 patients (93%) had CDAD during their hospitalization, and 19 (7%) were readmitted because of CDAD (average readmission stay, 13.6 days). Forty-one patients (15.2%) died, of whom 4 (1.5% of the total) were considered to have died directly or indirectly of N-CDAD. The following N-CDAD-related morbidity was noted: dehydration, 3%; hypokalemia, 2%; gastrointestinal hemorrhage requiring transfusion, 1%; bowel perforation, 0.4%; and secondary sepsis, 0.4%. The cost of N-CDAD readmissions alone was estimated to be a minimum of $128,200 (Canadian dollars) per year per facility. CONCLUSION: N-CDAD is a common and serious nosocomial infectious complication in Canada, is associated with substantial morbidity and mortality, and imposes an important financial burden on healthcare institutions.     

Clostridium difficile in the long-term care setting

The incidence of Clostridium difficile-associated disease (CDAD) has increased over the past few years and more severe cases of CDAD have been reported. This changing epidemiology is possibly a result of the emergence of a more virulent strain of C difficile that is more resistant to fluoroquinolones and is associated with increased morbidity and mortality. Because of advanced age and frequent courses of antibiotic therapy, patients in long-term care facilities are at increased risk of C difficile infection. In addition to beta-lactams and clindamycin, the fluoroquinolones have recently been associated with increased rates of CDAD. Early identification of C difficile infection and prompt initiation of therapy with the most appropriate agent are critical to minimize morbidity and mortality in this era of increasingly severe CDAD. Metronidazole and vancomycin have been the mainstays of therapy, and recent data support the expanding role of vancomycin in the treatment of severe CDAD. Adjunctive therapy with probiotics, intravenous immunoglobulin, or rifampin has been used in refractory or recurrent CDAD. Adherence to the recommended infection control measures and the judicious use of antibiotics should also be part of the global management of CDAD in long-term care facilities.     

Predicting Clostridium difficile toxin in hospitalized patients with antibiotic-associated diarrhea.

OBJECTIVE: Clostridium difficile infection is implicated in 20%-30% of cases of antibiotic-associated diarrhea. Studying hospitalized patients who received antibiotic therapy and developed diarrhea, our objective was to compare the clinical characteristics of patients who developed C. difficile-associated diarrhea (CDAD) with those of patients with a negative result of a stool assay for C. difficile toxin. METHODS: A prospective study was done with a cohort of 217 hospitalized patients who had received antibiotics and developed diarrhea. Patients with CDAD were defined as patients who had diarrhea and a positive result for C. difficile toxin A/B by an enzyme immunoassay of stool. The variables that yielded a significant difference on univariate analysis between patients with a positive assay result and patients with a negative assay result were entered into a logistic regression model for prediction of C. difficile toxin.Setting. A 900-bed tertiary care medical center. RESULTS: Of 217 patients, 52 (24%) had a positive result of assay for C. difficile toxin A/B in their stool. The logistic regression model included impaired functional capacity, watery diarrhea, use of a proton pump inhibitor, use of a histamine receptor blocker, leukocytosis, and hypoalbuminemia. The area under the receiver operating characteristic curve for the model as a predictor of a positive result for the stool toxin assay was 0.896 (95% confidence interval, 0.661-1.000; P<.001), with 95% specificity and 68% sensitivity. CONCLUSIONS: Our results may help clinicians to predict the risk of CDAD in hospitalized patients with antibiotic-associated diarrhea, to guide careful, specific empirical therapy, and to direct early attention to infection control issues.     

The role of Clostridium difficile and viruses as causes of nosocomial diarrhea in children.

OBJECTIVE: We report surveillance of nosocomial diarrhea in children at our institution during the past decade and note different epidemiology of diarrhea due to viruses and Clostridium difficile. DESIGN: A prospective cohort study. SETTING: A university-affiliated pediatric hospital with 180 beds serving an urban area and providing referral care for the Maritime Provinces of Canada. PARTICIPANTS: Children younger than 18 years. METHODS: Surveillance was conducted from 1991 to 1999 using personal contact with personnel and review of microbiology and medical records. Nosocomial diarrhea was defined as loose stools occurring more than 48 hours after admission, with at least two loose stools in 12 hours and no likely non-infectious cause. RESULTS: Nosocomial diarrhea was the third most common nosocomial infection (217 of 1,466; 15%), after bloodstream and respiratory infections, with from 0.5 to 1 episode per 1,000 patient-days. Of 217 nosocomial diarrhea episodes, 122 (56%) had identified pathogens: C. difficile (39 of 122; 32%), rotavirus (38 of 122; 31%), adenovirus (36 of 122; 30%), and other viral (9 of 122; 7%). The median age was 1.3 years (range, 11 days to 17.9 years), 0.80 year for children with viral diarrhea, 3.9 years for children with C. difficile, and 1.5 years for children with diarrhea without a causative organism identified (P< .0001). Most children with nosocomial diarrhea were incontinent (diapered) at the time of their first episode (138 of 185; 75%), but preexisting incontinence was more common in those with viral diarrhea (93%) compared with those with no organism identified (71%) or those with C. difficile-associated diarrhea (CDAD) (49%) (P <.0001). CONCLUSIONS: C. difficile is the single most common cause of nosocomial diarrhea in our tertiary-care center, although all viral pathogens account for 69% of cases. Diapered status appears to be a risk factor for CDAD in children, and CDAD occurs more often in older children than viral nosocomial diarrhea. Further characterization of risk factors for, and morbidity associated with, nosocomial CDAD in children is warranted.     

Recommendations for surveillance of Clostridium difficile-associated disease.

BACKGROUND: The epidemiology of Clostridium difficile-associated disease (CDAD) is changing, with evidence of increased incidence and severity. However, the understanding of the magnitude of and reasons for this change is currently hampered by the lack of standardized surveillance methods. OBJECTIVE AND METHODS: An ad hoc C. difficile surveillance working group was formed to develop interim surveillance definitions and recommendations based on existing literature and expert opinion that can help to improve CDAD surveillance and prevention efforts. DEFINITIONS AND RECOMMENDATIONS: A CDAD case patient was defined as a patient with symptoms of diarrhea or toxic megacolon combined with a positive result of a laboratory assay and/or endoscopic or histopathologic evidence of pseudomembranous colitis. Recurrent CDAD was defined as repeated episodes within 8 weeks of each other. Severe CDAD was defined by CDAD-associated admission to an intensive care unit, colectomy, or death within 30 days after onset. Case patients were categorized by the setting in which C. difficile was likely acquired, to account for recent evidence that suggests that healthcare facility-associated CDAD may have its onset in the community up to 4 weeks after discharge. Tracking of healthcare facility-onset, healthcare facility-associated CDAD is the minimum surveillance required for healthcare settings; tracking of community-onset, healthcare facility-associated CDAD should be performed only in conjunction with tracking of healthcare facility-onset, healthcare facility-associated CDAD. Community-associated CDAD was defined by symptom onset more than 12 weeks after the last discharge from a healthcare facility. Rates of both healthcare facility-onset, healthcare facility-associated CDAD and community-onset, healthcare facility-associated CDAD should be expressed as case patients per 10,000 patient-days; rates of community-associated CDAD should be expressed as case patients per 100,000 person-years.     

Clostridium difficile infection in outpatients, Maryland and Connecticut, USA, 2002-2007

Clostridium difficile, the most commonly recognized diarrheagenic pathogen among hospitalized persons, can cause outpatient diarrhea. Of 1,091 outpatients with diarrhea, we found 43 (3.9%) who were positive for C. difficile toxin. Only 7 had no recognized risk factors, and 3 had neither risk factors nor co-infection with another enteric pathogen.     

Adenovirus-based vaccination against Clostridium difficile toxin A allows for rapid humoral immunity and complete protection from toxin A lethal challenge in mice

Clostridium difficile associated diarrhea (CDAD) is a critical public health problem worldwide with over 300,000 cases every year in the United States alone. Clearly, a potent vaccine preventing the morbidity and mortality caused by this detrimental pathogen is urgently required. However, vaccine efforts to combat C. difficile infections have been limited both in scope as well as to efficacy, as such there is not a vaccine approved for use against C. difficile to date. In this study, we have used a highly potent Adenovirus (Ad) based platform to create a vaccine against C. difficile. The Ad-based vaccine was able to generate rapid and robust humoral as well as cellular (T-cell) immune responses in mice that correlated with provision of 100% protection from lethal challenge with C. difficile toxin A. Most relevant to the clinical utility of this vaccine formulation was our result that toxin A specific IgGs were readily detected in plasma of Ad immunized mice as early as 3 days post vaccination. In addition, we found that several major immuno-dominant T cell epitopes were identified in toxin A, suggesting that the role of the cellular arm in protection from C. difficile infections may be more significant than previously appreciated. Therefore, our studies confirm that an Adenovirus based-C. difficile vaccine could be a promising candidate for prophylactic vaccination both for use in high risk patients and in high-risk environments.     

Changing epidemiology of Clostridium difficile-associated disease in children.

OBJECTIVE: To determine temporal trends in the incidence rate for Clostridium difficile-associated disease (CDAD) in a pediatric patient population. METHODS: We performed an observational, retrospective cohort study that included children who visited or were admitted to Children's National Medical Center during the period from July 2001 through June 2006. The CDAD incidence rates were determined and examined for changes over time using the Poisson regression method. RESULTS: A total of 513 patients whose stool specimens tested positive for C. difficile toxin were identified. Of these patients, 61% were children aged 2 years or older. The proportion of patients with CDAD in this age group has steadily increased from 46% in 2001 to 64% in 2006. Largely as a result of an increasing number of cases of community-associated CDAD, the incidence of CDAD increased significantly in the outpatient setting, particularly in the emergency department (1.18 cases per 1,000 visits in 2001 vs 2.47 cases per 1,000 visits in 2006; P=.02). The incidence among inpatients decreased during the study period (1.024 cases per 1,000 patient-days in 2001 vs 0.680 cases per 1,000 patient-days in 2006; P=.004). In the neonatal intensive care unit, C. difficile toxin was detected in stool specimens collected from 22 patients aged from 15 days to 6 months. CONCLUSION: This study revealed a steady increase in the number of patients seen in the emergency department with community-acquired CDAD. Findings from this study suggest that the characteristics of CDAD in children--a population that has not been considered to be at high risk for this disease in the past--are changing. Further investigations are warranted to explore deviations from the established burdens of the disease and patient risk factors.     

Management of an outbreak of Clostridium difficile-associated disease among geriatric patients.

OBJECTIVE: To describe a nosocomial outbreak of Clostridium difficile-associated disease (CDAD). DESIGN: A traditional outbreak investigation. SETTING: Geriatric department of a tertiary care teaching hospital from March through April 2003. METHODS: The outbreak was detected by the C. difficile surveillance program of the infection control unit. CDAD was diagnosed by stool culture and fecal toxin A detection with a qualitative rapid immunoassay. Isolates of C. difficile were serotyped and genotyped using pulsed-field gel electrophoresis. RESULTS: The incidence of CDAD increased from 27 cases per 100,000 patient-days in the 6-month period before the outbreak to 99 cases per 100,000 patient-days during the outbreak. This outbreak involved 21 of 92 patients in 4 geriatric wards, which were located at 2 geographically distinct sites and staffed by the same medical team. The mean age of patients was 83 years (range, 71-100 years). Five (24%) of the 21 patients had community-acquired diarrhea, and secondary hospital transmission resulted in 3 clusters involving 16 patients. Serotyping and genotyping were performed on isolates in stool specimens from 19 different patients; 16 of these isolates were serotype A1, whereas 3 displayed profiles different from the outbreak strain. Management of this outbreak consisted in reinforcement of contact isolation precautions for patients with diarrhea, cohorting of infected patients in the same ward, and promotion of hand hygiene. Relapses occurred in 6 (29%) of 21 patients. CONCLUSION: Control of this rapidly developing outbreak of CDAD was obtained with early implementation of cohorting and ward closure and reinforcement of environmental disinfection, hand hygiene, and enteric isolation precautions.     

Toxinotype V Clostridium difficile in humans and food animals

Clostridium difficile is a recognized pathogen in neonatal pigs and may contribute to enteritis in calves. Toxinotype V strains have been rare causes of human C. difficile-associated disease (CDAD). We examined toxinotype V in human disease, the genetic relationship of animal and human toxinotype V strains, and in vitro toxin production of these strains. From 2001 through 2006, 8 (1.3%) of 620 patient isolates were identified as toxinotype V; before 2001, 7 (<0.02%) of approximately 6,000 isolates were identified as toxinotype V. Six (46.2%) of 13 case-patients for whom information was available had community-associated CDAD. Molecular characterization showed a high degree of similarity between human and animal toxinotype V isolates; all contained a 39-bp tcdC deletion and most produced binary toxin. Further study is needed to understand the epidemiology of CDAD caused by toxinotype V C. difficile, including the potential of foodborne transmission to humans.     

Clostridium difficile-associated diarrhea in a VA medical center: clustering of cases, association with antibiotic usage, and impact on HIV-infected patients.

A case-control study of patients with stools assayed for Clostridium difficile toxin over a 24-month period at a Veterans Affairs hospital found that the majority of cases (70.6%) occurred in temporal clusters. Clustering was particularly evident on a designated human immunodeficiency virus (HIV) unit. Thirty-four (75.5%) of 45 HIV-infected patients with C difficile-associated diarrhea (CDAD) died during their hospitalization. Third-generation cephalosporins were the antibiotics most strongly associated with CDAD.     

Recurrence of Clostridium difficile-associated diarrhoea prevented by the administration of a whey concentrate from specifically immunised cows; prospective study

OBJECTIVE: To try to prevent recurrences of Clostridium difficile-associated diarrhoea (CDAD) by treatment with a specific neutralising secretory IgA-enriched whey-protein concentrate (40%) made from the milk of cows immunised with C. difficile and its toxins. DESIGN: Prospective, non-blinded, clinical cohort study. METHOD: In 2005-2006, 100 consecutive patients with CDAD received the whey concentrate for 2 weeks after completion of standard antibiotic therapy. For a period of 60 days after the start of the administration, the safety and preliminary efficacy of the whey concentrate were evaluated by means of a diary, blood determinations, active surveillance for adverse events, and the recurrence of CDAD. RESULTS: The whey concentrate was well tolerated and no safety issues were raised. Eleven out of 109 episodes (10%) were followed by a recurrence. After completion of the whey concentrate therapy, a positive test for faecal toxins or culture of C. difficile was predictive for the recurrence of CDAD (relative risk: 8.2 (95% CI: 1.04-64), and 4.7 (95% CI: 0.5-47), respectively). A positive faeces toxin during administration of the whey concentrate was also associated with an early recurrence of CDAD. CONCLUSION: Compared to historical and contemporary findings in control groups, the whey concentrate appeared to reduce the recurrence of CDAD by about 50%. However, the standard dose of the whey concentrate was probably not sufficient to fully neutralise the C. difficile toxins in faeces in all episodes.     

"Second-look" cytotoxicity: an evaluation of culture plus cytotoxin assay of Clostridium difficile isolates in the laboratory diagnosis of CDAD.

Clostridium difficile is one of the most frequent causes of hospital-acquired diarrhoea. Our objective was to prove that some stool samples with a direct negative cytotoxicity assay may indeed harbour toxigenic C. difficile and that this can be demonstrated by performing a "second-look" cytotoxicity assay using the isolated C. difficile strains. Over an eight-year period (1992-1999), the 8241 stool samples submitted for direct cell culture from patients with suspected C. difficile-associated diarrhoea (CDAD) were simultaneously plated on cycloserine cefoxitin fructose agar. C. difficile strains isolated from samples with a negative direct cell culture assay were re-tested for toxin production "second-look" cell culture assay). Using both methods 6423 samples (78%) were negative. Of the remaining 1818 samples, 127 (7%) yielded C. difficile isolates which were confirmed as non-producers of toxin by both methods, 1437 (85%) were positive in direct cell culture assay, and 254 were positive only after the "second-look" cell culture assay. Thus, our approach allowed us to detect an extra 15% of toxin-producing strains that could have gone undetected otherwise.The combination of direct-cell culture assay, culture for toxigenic C. difficile and "second-look" cell culture assay enhances the potential for diagnosis of CDAD and enables us to be more efficient with our patient care resources.     

Clinical inquiry: what risk factors contribute to C difficile diarrhea?

Certain antibiotics and using 3 or more antibiotics at one time are associated with Clostridium difficile-associated diarrhea. Hospital risk factors include proximity to other patients with C difficile and longer length of stay. Patient risk factors include advanced age and comorbid conditions. Acid suppression medication is also a risk factor for CDAD.     

Clostridium difficile among hospitalized patients receiving antibiotics: a case-control study.

OBJECTIVES: Clostridium difficile is the most common cause of infectious nosocomial diarrhea and can be found in up to 30% of asymptomatic hospitalized patients. Our primary aim was to compare the clinical characteristics of hospitalized patients who received antibiotics and developed C. difficile-associated diarrhea (CDAD) with those of hospitalized patients who received antibiotics and did not develop the disease. DESIGN: Case-control study comprising inpatients at a single institution. PATIENTS: Case-patients were defined as patients who had diarrhea and tested positive for C. difficile. Control-patients (matched 4:1 to case-patients) were defined as patients who received antibiotics for at least 5 days and did not develop CDAD. RESULTS: On univariate analysis, nine variables were associated with CDAD. Only three of the variables, need for intensive care, length of stay, and macrolide antibiotic use, were found to be significant (P < .05) on logistic regression analysis. The odds ratios for status as a CDAD case were 3.68 (CI95, 1.44 to 9.40) for stay in the intensive care unit and 1.03 (CI95, 1.02 to 1.05) for each day of hospital stay. Receipt of macrolide antibiotics reduced risk significantly; the odds ratio was 0.23 (CI95, 0.19 to 0.87). CONCLUSIONS: We identified need for intensive care and length of stay as important risk factors for the development of CDAD. We also identified macrolide antibiotic use as protective against its development. Patients receiving intensive care may represent a population to study for targeted prophylaxis.     

Risk factors for nosocomial Clostridium difficile diarrhoea in an infectious and tropical diseases department

FOREWORD: Clostridium difficile associated diarrhea (CDAD) accounts for 25% of all cases of diarrhea occurring in hospital. Infectious diseases departments are considered as presenting with an important risk of CDAD because of the large quantity of antibiotics used. OBJECTIVES AND METHOD: The authors made a prospective study in the first 6 months of 2001, in order to identify the risk factors of CDAD in their department. One hundred and fifty-two patients hospitalized for at least 6 days were included in this study. The studied factors were: age, mean number of days of hospitalization (MDH), antibiotic therapy, WHO scale of reduced mobility of patients, recent hospitalization (less than 3 months before). RESULTS: MDH was 36 (IC95%: 23-48). Beta-lactam antibiotics were found as significant risk factors, as reported in the literature. However, age and a recent hospitalization were not related to the CDAD as described in the literature. A reduced mobility of patients was identified as a significant risk factor for developing a CDAD in our department.     

Clostridium difficile: development of a novel candidate vaccine

Clostridium difficile has become the most frequent hospital-acquired infection in North America and the EU. C. difficile infection (CDI) is present worldwide and disease awareness is increasing. In the US, EU, and Canada, in addition to hospital diagnosed disease, CDI has also been reported with increasing frequency in the community. Hypervirulent strains have increased the morbidity and mortality associated with CDI. Current treatment options are suboptimal. Of all patients treated for CDI, 20% relapse and 65% of those experiencing a second relapse become chronic cases. An association between increased serum levels of IgG antibody against toxin A and asymptomatic carriage of C. difficile provides a rationale for vaccine development. Sanofi Pasteur's C. difficile candidate vaccine is being developed for the prevention of primary disease. The target population is adults at risk of CDI, those with planned hospitalization, long-term care/nursing home residents, and adults with co-morbidities requiring frequent/prolonged antibiotic use.     

Clostridium difficile in long-term-care facilities for the elderly.

Antimicrobial agents are among the most frequently prescribed medications in long-term-care facilities (LTCFs). Therefore, it is not surprising that Clostridium difficile colonization and C. difficile-associated diarrhea (CDAD) occur commonly in elderly LTCF residents. C. difficile has been identified as the most common cause of non-epidemic acute diarrheal illness in nursing homes, and outbreaks of CDAD in LTCFs have also been recognized. This position paper reviews the epidemiology and clinical features of CDAD in elderly residents of LTCFs and, using available evidence, provides recommendations for the management of C. difficile in this setting.