Life-threatening infections with a new strain of Clostridium difficile

Three men, aged 39, 73, and 66 years, respectively, developed an infection with a new strain ofClostridium difficile, ribotype 027.C.difficile-associated diarrhoea (CDAD) occurred in two patients after multiple abdominal surgery and in the third patient one week after autologous haematopoietic cell transplantation. Within a few days, despite antibiotic therapy, all three patients developed severe (pseudomembranous) colitis with sepsis for which admission to the Intensive Care Unit was required. Two patients underwent (sub)total colectomy and received an intensive course of oral and/or rectal vancomycin. In all patients who develop diarrhoea in hospital, especially during or after treatment with antibiotics or chemotherapeutic agents, an infection with C. difficile ribotype 027 should be suspected. Recent outbreaks of this hypervirulent strain of C. difficile have been reported in Canada, the United States, United Kingdom, and The Netherlands. Demonstration of C. difficile toxin in faeces confirms the clinical suspicion of CDAD and ribotyping of the strain may reveal whether the 027 strain is present. For treatment of these 027 infections, vancomycin is preferred to metronidazole. After a severe course of colitis or in case of recurrence a 'tapering and pulse' course ofvancomycin can be prescribed; alternatively, treatment with bovine antibody-enriched whey may be considered. The introduction of this hypervirulent strain has led to reinforcement of the hygienic measures in accordance with the recommendations of the Dutch Working Party on Infection Prevention and a policy to deter the use of fluoroquinolones.     

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.     

Infection control policies and practices for Iowa long-term care facility residents with Clostridium difficile infection.

OBJECTIVE: To identify infection control policies and practices used by Iowa long-term care facilities (LTCFs) for residents with Clostridium difficile infection or C. difficile-associated diarrhea and to assess use of antimicrobial agents. DESIGN: Survey. SETTING: LTCFs in Iowa that responded between March 25, 2005 (ie, when surveys were mailed), and July 2005. RESULTS: Of the 418 LTCFs in Iowa, 263 (62.9%) responded. Most facilities (94.3%) reported that they accept persons known to have C. difficile infection. Few LTCFs reported that clusters of C. difficile infection had been identified. However, only 111 facilities (42.2%) had a protocol to identify residents with C. difficile infection, and most (77.5%) did not test for C. difficile unless a resident had severe diarrhea. Only 58.5% of the facilities placed residents with C. difficile infection in private rooms, and 60.9% cohorted residents infected with C. difficile with other residents with C. difficile colonization or infection. Only 66 facilities (25.1%) have a program to control the use of antimicrobial agents. Staff could use alcohol-based hand gel products after contact with residents known to have C. difficile infection (in 188 facilities [71.5%]) or diarrhea (in 173 [65.8%]). However, the survey did not ask whether the staff used alcohol-based products instead of soap and water. CONCLUSIONS: C. difficile is present in Iowa LTCFs, but many C. difficile infections probably remain undiagnosed. Staff in LTCFs should be educated about this organism so that they can implement appropriate testing and preventive strategies.     

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.     

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.     

Risk factors for acquisition of Clostridium difficile-associated diarrhea among outpatients at a cancer hospital.

BACKGROUND: Clostridium difficile-associated diarrhea (CDAD) is an important infection in hospital settings. Its impact on outpatient care has not been well defined. OBJECTIVE: To examine risk factors of ambulatory cancer patients with CDAD. DESIGN: Case-control study. SETTING: Memorial Sloan-Kettering Cancer Center, a tertiary-care hospital. METHODS: Cases of CDAD among oncology outpatients from January 1999 through December 2000 were'identified via positive C. difficile toxin assay results on stool specimens sent from clinics or the emergency department. A 1:3 matched case-control study examined exposures associated with CDAD. RESULTS: Forty-eight episodes of CDAD were identified in cancer outpatients. The mean age was 51 years; 44% were female. Forty-one (85%) had received antibiotics within 60 days of diagnosis, completing courses a median of 16.5 days prior to diagnosis. Case-patients received longer courses of first-generation cephalosporins (4.8 vs 3.2 days; P = .03) and fluoroquinolones (23.6 vs 8 days; P < .01) than did control-patients. Those receiving clindamycin were 3.9-fold more likely to develop CDAD (P < .01). For each additional day of clindamycin or third-generation cephalosporin exposure, patients were 1.29- and 1.26-fold more likely to develop CDAD (P < .01 and .04, respectively). The 38 CDAD patients hospitalized during the risk period (79.2%) spent more time as inpatients than did control-patients (19.3 vs 9.7 days; P < .001). CONCLUSIONS: Antibiotic use, especially with cephalosporins and clindamycin, and prolonged hospitalization contributed to the development of CDAD. Outpatient CDAD appears to be most strongly related to inpatient exposures; reasons for the delayed development of symptoms are unknown.     

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.     

Mortality of patients with antibiotic-associated diarrhoea: the impact of Clostridium difficile

Previous studies have shown conflicting results concerning mortality related to Clostridium difficile infection. The objective of this study was to determine the impact of C. difficile infection on short- and long-term mortality in hospitalised patients with antibiotic-associated diarrhoea. We therefore undertook a prospective case-control study of 217 hospitalised patients who received antibiotics, developed diarrhoea and underwent stool enzyme immunoassay for C. difficile TOX A/B. The Kaplan-Meier and the log-rank test were used to determine univariate survival analysis and a Cox regression model for multivariate analysis of 28 day and long-term mortality. Fifty-two (24%) of the 217 patients who met the study criteria were positive for C. difficile TOX A/B. The crude 28 day and long-term mortality rates of the entire cohort were 12.4% and 56%, respectively. On Cox regression analysis, hypoalbuminaemia, impaired functional capacity and elevated serum urea levels were found to be the only independent and statistically significant variables associated with long-term mortality. C. difficile toxin positivity per se was not associated with increased short- or long-term mortality rates. In conclusion, hypoalbuminaemia, renal failure, and impaired function capacity predict mortality due to antibiotic-associated diarrhoea, but C. difficile involvement by itself does not further increase the risk of death in these patients.     

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.     

Clostridium difficile in the intensive care unit: epidemiology, costs, and colonization pressure.

OBJECTIVE: To evaluate the epidemiology, outcomes, and importance of Clostridium difficile colonization pressure (CCP) as a risk factor for C. difficile-associated disease (CDAD) acquisition in intensive care unit (ICU) patients. DESIGN: Secondary analysis of data from a 30-month retrospective cohort study. SETTING: A 19-bed medical ICU in a midwestern tertiary care referral center. PATIENTS: Consecutive sample of adult patients with a length of stay of 24 hours or more between July 1, 1997, and December 31, 1999. RESULTS: Seventy-six (4%) of 1,872 patients were identified with CDAD; 40 (53%) acquired CDAD in the ICU, for an incidence of 3.2 cases per 1,000 patient-days. Antimicrobial therapy, enteral feeding, mechanical ventilation, vancomycin-resistant enterococci (VRE) colonization or infection, and CCP (5.5 vs 2.0 CDAD case-days of exposure for patients with acquired CDAD vs no CDAD; P=.001) were associated with CDAD acquisition in the univariate analysis. Only VRE colonization or infection (45% of patients with acquired CDAD vs 16% of patients without CDAD; adjusted odds ratio, 2.76 [95% confidence interval, 1.36-5.59]) and a CCP of more than 30 case-days of exposure (20% with acquired CDAD vs 2% with no CDAD; adjusted odds ratio, 3.77 [95% confidence interval, 1.14-12.49]) remained statistically significant in the multivariable analysis. Lengths of stay (6.1 vs 3.0 days; P<.001 by univariate analysis) and ICU costs ($11,353 vs $6,028; P<.001 by univariate analysis) were higher for patients with any CDAD than for patients with no CDAD. CONCLUSIONS: In this nonoutbreak setting, the CCP was an independent risk factor for acquisition of CDAD in the ICU at the upper range of exposure duration. Having CDAD in the ICU was a marker of excess healthcare use.     

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.     

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.     

Treatment of recurrent Clostridium difficile-associated diarrhoea with a suspension of donor faeces

OBJECTIVE: To study the effect of treating recurrent Clostridium difficile-associated diarrhoea (CDAD) with a suspension of donor faeces. DESIGN: Uncontrolled interventional study. METHOD: Patients that, despite adequate antibiotic therapy, had developed at least 2 recurrences ofCDAD, including at least one recurrence that had been treated with a vancomycin tapering regimen, were included in the study. Relatives or volunteers served as faeces donor. All donors were previously examined for the presence of HIV, hepatitis B- and C-virus, and acute infection with cytomegalovirus or Epstein-Barr virus. The donor faeces were examined for the presence of C. difficile, Yersinia, Campylobacter, Shigella, Salmonella, and parasites. Before the infusion of donor faeces, the patients were treated for 4 days with vancomycin 500 mg q.i.d., followed by colon lavage. The suspension of 150 g of donor faeces dissolved in 300-400 ml of NaCl was infused into the jejunum via a duodenal catheter or into the caecum via colonoscopy. RESULTS: 7 CDAD patients were included and treated, including 2 with the hypervirulent C. difficile-strain PCR ribotype 027, toxinotype III. In 5 patients, the defaecation frequency returned to normal almost immediately after treatment and the cultures and toxin tests for C. difficile were repeatedly negative. In the remaining 2 patients, the treatment was successful after a repeated infusion of faeces from a different donor. CONCLUSION: Treatment with donor faeces seems promising for patients who develop repeated recurrences despite adequate therapy and could be valuable in the future during (local) epidemics of the PCR ribotype 027 strain. A randomised nationwide study (FECAL trial) has been started in order to determine the efficacy of this treatment.     

Epidemiology and incidence of Clostridium difficile-associated diarrhoea diagnosed upon admission to a university hospital

Patients with Clostridium difficile-associated diarrhoea (CDAD) may initially develop symptoms in the community and be subsequently diagnosed at hospital admission. At the present time there is no national surveillance system and no standardized case definition of CDAD in the USA, and baseline data on the incidence and epidemiology of CDAD are scarce. The objective of this study was to report the incidence of CDAD at a tertiary care hospital, and to determine the epidemiology of cases diagnosed within 48h of hospital admission, compared with cases of nosocomial CDAD diagnosed 48h or more after hospitalization. The average incidence was 4.0 cases/10 000 patient-days for CDAD on admission and 7.0 cases/10 000 patient-days for nosocomial CDAD. A significant difference was observed in CDAD rates on admission compared with nosocomial CDAD rates (P=0.017), but no differences were observed over time for either rate. Overall, 44% of cases had CDAD on admission and 56% of cases had nosocomial CDAD. Fifty-six (62%) patients with CDAD on admission had been admitted to the same hospital and 24 (27%) had been admitted to another hospital within the previous 90 days. Only eight (9%) patients had not been exposed to any healthcare services in the 90 days preceding hospital admission. A standardized case definition of healthcare-associated CDAD should include previous hospitalizations. Admitting physicians should consider C. difficile in the differential diagnosis of patients admitted with diarrhoea, with or without a history of admission to healthcare facilities.     

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.     

Relapsing infections with Clostridium difficile

Two women, aged 78 and 85 years, presented with watery diarrhoea and fever after a course of antibiotic therapy. Pseudo-membranous colitis was diagnosed, which was adequately treated. In both patients the C. difficile colitis relapsed, which was successfully treated with a pulse and tapering scheme of vancomycin. C. difficile infection is a frequent cause of antibiotic-associated diarrhoea. Clinical presentation can vary in severity. Cytotoxin testing, immunoassay and endoscopy are important tools in diagnosing C. difficile colitis. Like the first infection, the first relapse must be treated with metronidazole or vancomycin. To treat a second relapse, a pulse and tapering dose of vancomycin has been recommended. Nevertheless, multiple recurrences may occur, which are difficult to treat.     

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.     

Clostridium difficile: a questionnaire survey of laboratory practice in England, Wales, and Northern Ireland

Since January 2004, the incidence of Clostridium difficile associated disease (CDAD) has been monitored by a systematic, national, laboratory surveillance system. This system incorporates the recommendations of a body of experts, the National Clostridium difficile Standards Group, which was convened in 2002 to advise the Department of Health (DoH). The recommendations of the group were informed by a questionnaire survey of current practice, and the results of that survey have been used to assess the implications of the recommendations on laboratory practice. Large variability was found as to the specimens selected, tested, and reported on for C. difficile. Standardisation of the diagnosis and reporting of CDAD is desirable and necessary to increase understanding of its epidemiology.