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.     

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.     

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.     

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.     

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 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.     

Hospital-associated measles outbreak - Pennsylvania, March-April 2009

Although endemic measles transmission has been interrupted in the United States, importations of this highly infectious virus continue. On March 28, 2009, a physician notified the Pennsylvania Department of Health (PADOH) of a measles case involving an unvaccinated child. Within 5 days, four additional cases were reported to PADOH and the Allegheny County Health Department. All five infected persons had been in the same hospital emergency department (ED) on March 10; one of them was a physician who worked in the ED. To find the source patient, PADOH reviewed electronic records of patients evaluated in the ED on March 10 for fever and rash. This identified a child who arrived recently from India, was treated for viral exanthema, and discharged. On April 3, PADOH obtained serum from this child and confirmed a diagnosis of measles. After an extensive regional search and investigation of the six patients' 4,000 contacts, no additional cases were identified. The hospital reviewed employee health records to identify any exposed personnel who did not have serologic evidence of measles immunity. Among 168 potentially exposed employees, 72 (43%) had no documented measles immunity, thus requiring serologic testing and subsequent vaccination if they lacked serologic evidence of immunity. This outbreak highlights the potential for measles transmission in health-care settings. To decrease transmission, clinicians should know the signs and symptoms of measles, request travel histories of patients suspected of any infectious disease, and isolate potentially infectious patients. Hospital employees should have documented immunity to measles, and employees without evidence of measles immunity should be offered vaccination in accordance with Advisory Committee on Immunization Practices (ACIP) and Hospital Infection Control Practices Advisory Committee (HICPAC) recommendations.     

Incidence of Clostridium difficile infection: a prospective study in an Indian hospital

Clostridium difficile is the commonest cause of hospital-acquired diarrhoea. A prospective study comprising of 156 patients and 54 healthy controls was undertaken to assess C. difficile associated diarrhoea (CDAD) incidence in an Indian hospital. Methods used included C. difficile culture and enzyme linked immunosorbent assay (ELISA) for Toxin A. Attempts were made to type isolates by antibiogram and SDS-PAGE. Of the 210 stool samples tested, 12 gave positive results in at least one assay. Of these, 11 were positive by the ELISA method, eight by culture, and seven by both methods. Neither the organisms nor the toxin was found in healthy controls or neonates. The average disease incidence of CDAD estimated by using both methods was 15%. Two antibiotypes of the isolates were obtained and of the isolates characterized by SDS-PAGE, two had identical patterns. This study shows that CDAD is an emerging problem in Indian hospitals. Monitoring should enable the development and implementation of policies and procedures that minimize the risk of this nosocomial pathogen.     

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 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.     

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.     

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.     

Clostridium difficile-associated diarrhoea: epidemiological data from Western Australia.

The incidence of Clostridium difficile-associated diarrhoea (CDAD) was investigated retrospectively at a 690-bed teaching hospital for the period 1983-92. Our aims were to determine: (i) the distribution by age and sex of patients with CDAD, (ii) the possibility of a seasonal trend and, (iii) the influence of infection control procedures, contamination of the hospital environment and the use of third-generation cephalosporins. The laboratory diagnosis of CDAD was based on demonstration of the organism by stool culture and/or detection of specific cytotoxin in stool filtrates. C. difficile was detected in 917 patients who were being investigated for diarrhoeal illness. Yearly isolations varied from a low of 49 in 1983 to a high of 120 in 1990 (Chi square for linear trend 128.8; P < 0.005). Most patients were elderly, with 63% aged 60 years or more; the majority (59%) were female. The relationship between culture of C. difficile and detection of cytotoxin in faecal extracts was also examined. Sixty percent of a sample of 132 isolates from patients in whom faecal cytotoxin was not detected produced cytotoxin in vitro, suggesting that culture is a more sensitive indicator of infection with C. difficile than cytotoxin detection. When the total number of faecal specimens received in the laboratory was used as a denominator there was an increase in the number of incident cases of CDAD between 1983 and 1990, apart from 1986. When occupied bed days was used as the denominator a similar trend was observed with a peak in 1990.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of AP-PCR typing and PCR-ribotyping for estimation of nosocomial transmission of Clostridium difficile

We recently attempted to clarify an increased incidence of Clostridium difficile-associated diarrhoea (CDAD) in our hospital by arbitrarily primed polymerase chain reaction (AP-PCR) typing of isolates from 147 consecutive patients collected during a 12 month period (Wullt et al. J Hosp Infect 1999;43:265-273). In the present study we compared the results based on previous AP-PCR data with those based on recent PCR ribotyping of the same isolates and re-analysis of a subset of isolates by AP-PCR typing. The pattern of PCR ribotypes was similar among inpatients and outpatients. A cluster of three closely related PCR ribotypes, related to those of the serogroup H and A8 type strains, dominated and comprised 31% of inpatient and 28% of outpatient C. difficile isolates. The apparent nosocomial transmission rate among inpatients with CDAD was only 9% by AP-PCR typing compared with 18 or 36% by PCR ribotyping depending on the definition used (proportion of patients sharing C. difficile type and ward within two or 12 months). Corresponding rates for all CDAD patients were 5% by AP-PCR and 11 or 21% by PCR ribotyping. Thus, most CDAD patients apparently became ill due to their endogenous strain of C. difficile. Because of the low concordance between the two typing methods the proportion of patients fulfilling the criteria for nosocomial transmission by both methods was only 1%. Re-examination of isolates from patients with recurrences revealed a reproducibility problem with AP-PCR typing. We conclude, that of these two PCR-based options for typing of C. difficile PCR ribotyping offers a superior experimental robustness compared with AP-PCR typing.     

Inhalation anthrax associated with dried animal hides--Pennsylvania and New York City, 2006

On February 21, 2006, the Pennsylvania Department of Health (PDOH) reported to CDC and the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) a case of inhalation anthrax in a man who resided in New York City. This report summarizes the joint epidemiologic and environmental investigation conducted by local, state, and federal public health, animal health, and law enforcement authorities in Pennsylvania and NYC to determine the source of exposure and identify other persons who were potentially at risk.     

Underlying disease severity as a major risk factor for nosocomial Clostridium difficile diarrhea.

OBJECTIVE: To determine the diagnostic accuracy of an index of underlying disease severity (Horn's index) in identifying patients with a high probability of having nosocomial Clostridium difficile diarrhea as a complication of antimicrobial therapy. DESIGN: A prospective cohort study of 252 adult patients admitted to the hospital and receiving antibiotics. Risk facctors for C. difficile diarrhea were first determined retrospectively in a different cohort of 300 hospitalized patients (primary cohort) and then prospectively in this cohort of 252 hospitalized patients receiving antibiotics (secondary cohort). At the time of hospital admission, disease was rated by clinicians as mild (1), moderate (2), severe (3), or extremely severe (4) using a modified Horn's index. Multivariable logistic regression analysis was used to determine the odds ratio (OR) for C. difficile diarrhea associated with increasing levels of disease severity. SETTING: An urban teaching hospital affiliated with a medical school in Boston, Massachusetts. RESULTS: The incidence of nosocomial C. difficile diarrhea was 8.7% in the primary cohort and 11% in the secondary cohort In the prospective cohort study (secondary cohort), the OR for C. difficile diarrhea associated with extremely severe disease was 17.6 (95% confidence interval, 5.8 to 53.5). The sensitivity, specificity, and positive and negative predictive values of a Horn's index score of 3 or more (severe to extremely severe disease) as a predictor of nosocomial C. difficile diarrhea were 79%, 73%, 27%, and 96%, respectively. CONCLUSIONS: These findings provide a means of early stratification of hospitalized patients receiving antibiotics according to their risk for nosocomial C. difficile diarrhea. Patients with severe to extremely severe disease at the time of admission may benefit from careful monitoring of antibiotic prescribing and early attention to infection control issues. In the future, these "high-risk" patients may benefit from prophylaxis studies of novel agents being developed to prevent C. difficile diarrhea.     

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.     

Lack of association between the increased incidence of Clostridium difficile-associated disease and the increasing use of alcohol-based hand rubs.

OBJECTIVE: To determine whether there is an association between the increasing use of alcohol-based hand rubs (ABHRs) and the increased incidence of Clostridium difficile-associated disease (CDAD). SETTING: A 500-bed university-affiliated community teaching hospital. METHODS: Use of ABHRs during the period 2000-2003 was expressed as the number of liters of ABHR used per 1000 patient-days. The proportion of hand hygiene episodes performed by using an ABHR was determined by periodic observational surveys. CDAD was defined as a physician-ordered stool assay positive for C. difficile toxin A or A/B. The incidence of CDAD was expressed as the number of unique patients who had 1 or more positive CDAD test results per 1,000 patient-days. RESULTS: During 2000-2003, the use of ABHR increased 10-fold, from 3 to greater than 30 L/1,000 patient-days (P<.001). The proportion of hand hygiene episodes performed using an ABHR increased from 10% to 85% (P<.001). The incidence of CDAD in 2000, 2001, 2002, and 2003 was 1.74, 2.33, 1.14, and 1.18 cases/1,000 patient-days, respectively. CONCLUSION: Despite a significant and progressive increase in the use of ABHRs in our facility during a 3-year period, there was no evidence that the incidence of CDAD increased. These findings suggest that factors other than the increased use of ABHRs are responsible for the increasing incidence of CDAD noted since 2000 in other facilities.     

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.