Outbreaks Of Clostridium Difficile-associated Disease Research Articles

Statin Use Associated With a Decreased Length of Hospital Stay in Diabetic Patients With Clostridium difficile Infection

Clostridium difficile colitis has been gradually increasing in frequency in the United States, with worsening patient outcomes ( 1. Morris AM Jobe BA Stoney M Sheppard BC Deveney CW Deveney KE Clostridium difficile colitis: An increasingly aggressive iatrogenic disease?. Arch Surg. 2002; 137: 1096-1100 Crossref PubMed Google Scholar ). Diabetes mellitus has been shown to be a risk factor for C difficile colitis ( 2. Muto CA Pokrywka M Shutt K et al. A large outbreak of Clostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use. Infect Control Hosp Epidemiol. 2005; 26: 273-280 Crossref PubMed Scopus (549) Google Scholar ). We assessed factors associated with an increased length of hospital stay in diabetic patients with C difficile colitis.

Thuricin CD, a posttranslationally modified bacteriocin with a narrow spectrum of activity against Clostridium difficile

The last decade has seen numerous outbreaks of Clostridium difficile-associated disease (CDAD), which presented significant challenges for healthcare facilities worldwide. We have identified and purified thuricin CD, a two-component antimicrobial that shows activity against C. difficile in the nanomolar range. Thuricin CD is produced by Bacillus thuringiensis DPC 6431, a bacterial strain isolated from a human fecal sample, and it consists of two distinct peptides, Trn-alpha and Trn-beta, that act synergistically to kill a wide range of clinical C. difficile isolates, including ribotypes commonly associated with CDAD (e.g., ribotype 027). However, this bacteriocin thuricin CD has little impact on most other genera, including many gastrointestinal commensals. Complete amino acid sequencing using infusion tandem mass spectrometry indicated that each peptide is posttranslationally modified at its respective 21st, 25th, and 28th residues. Solution NMR studies on [(13)C,(15)N] Trn-alpha and [(13)C,(15)N]Trn-beta were used to characterize these modifications. Analysis of multidimensional NOESY data shows that specific cysteines are linked to the alpha-carbons of the modified residues, forming three sulfur to alpha-carbon bridges. Complete sequencing of the thuricin CD gene cluster revealed genes capable of encoding two S'-adenosylmethionine proteins that are characteristically associated with unusual posttranslational modifications. Thuricin CD is a two-component antimicrobial peptide system with sulfur to alpha-carbon linkages, and it may have potential as a targeted therapy in the treatment of CDAD while also reducing collateral impact on the commensal flora.

Association Between Use of Proton Pump Inhibitors and a <em>Clostridium difficile</em>– Associated Disease Outbreak: Case–Control Study

The use of proton pump inhibitors (PPIs) has been implicated as a potential contributor to the development of Clostridium difficile-associated disease (CDAD) because of the ability of these drugs to substantially reduce the bactericidal effect of gastric acid. This study focused on the impact of PPIs, among other known risk factors, during an outbreak of CDAD in a hospital setting. The primary objective was to determine whether there was an association between current use of a PPI and the CDAD outbreak. Secondary objectives were to evaluate any correlations between the CDAD outbreak and past use of PPIs, use of antibiotics, diabetes mellitus, enteral feeding, cancer, gastrointestinal surgery, inflammatory bowel disease, and previous care or residence in an institutional setting. A retrospective case-control study was conducted. One hundred and fifty cases of hospital-acquired Clostridium difficile were identified. Patients were individually matched to controls for age, sex, date of admission to hospital, and hospital unit. The groups were compared with respect to each exposure. Eight case patients could not be matched with suitable controls. Therefore, data from 142 cases and 142 controls were analyzed. There was no association between current use of a PPI and the CDAD outbreak (odds ratio [OR] 1.0, 95% confidence interval [CI] 0.99-1.01). Similarly, there was no correlation between the CDAD outbreak and diabetes, enteral feeding, cancer, gastrointestinal surgery, inflammatory bowel disease, or previous care or residence in an institution. However, the development of CDAD was positively associated with use of antibiotics within the 30 days preceding the infection (OR 12.0, 95% CI 4.0-35.7) and with past use of a PPI (OR 2.4, 95% CI 1.4-4.3). The development of CDAD during a hospital outbreak was associated with use of antibiotics and with past, not current, use of PPIs.

P289 Association between the use of proton pump inhibitors and a Clostridium difficile-associated disease outbreak: a case control study

Background: The use of proton pump inhibitors (PPIs) has been implicated as a potential contributor to the development of Clostridium difficile ‐associated disease (CDAD) because of the ability of these drugs to substantially reduce the bactericidal effect of gastric acid. This study focused on the impact of PPIs, among other known risk factors, during an outbreak of CDAD in a hospital setting. Objectives: The primary objective was to determine whether there was an association between current use of a PPI and the CDAD outbreak. Secondary objectives were to evaluate any correlations between the CDAD outbreak and past use of PPIs, use of antibiotics, diabetes mellitus, enteral feeding, cancer, gastrointestinal surgery, inflammatory bowel disease, and previous care or residence in an institutional setting. Methods: A retrospective case‐control study was conducted. One hundred and fifty cases of hospital-acquired Clostridium difficile were identified. Patients were individually matched to controls for age, sex, date of admission to hospital, and hospital unit. The groups were compared with respect to each exposure. Results: Eight case patients could not be matched with suitable controls. Therefore, data from 142 cases and 142 controls were analyzed. There was no association between current use of a PPI and the CDAD out break (odds ratio [OR] 1.0, 95% confidence interval [CI] 0.99‐1.01). Similarly, there was no correlation between the CDAD outbreak and diabetes, enteral feeding, cancer, gastrointestinal surgery, inflammatory bowel disease, or previous care or residence in an institution. However, the development of CDAD was positively associated with use of antibiotics within the 30 days preceding the infection (OR 12.0, 95% CI 4.0 ‐35.7) and with past use of a PPI (OR 2.4, 95% CI 1.4‐4.3). Conclusions: The development of CDAD during a hospital outbreak was associated with use of antibiotics and with past, not current, use of PPIs.

Germination of spores of Clostridium difficile strains, including isolates from a hospital outbreak of Clostridium difficile-associated disease (CDAD).

Clostridium difficile is an emerging nosocomial pathogen and one of the major causes of antibiotic-associated diarrhoea. Cases of Clostridium difficile-associated disease (CDAD) are likely initiated by the ingestion of dormant C. difficile spores, which then germinate, outgrow and rapidly proliferate to cause gastrointestinal (GI) infections. To understand the initial stages of CDAD pathogenesis, we have characterized the germination of spores from a collection of C. difficile strains, including some clinical isolates obtained from a CDAD outbreak (CDAD isolates). Spores of one laboratory strain and five CDAD isolates did not germinate with amino acids, but did germinate on a nutrient-rich medium. However, bile salts had little effect on spore germination, either alone or in a nutrient-rich medium. These spores also germinated with KCl, as well as the non-nutrient germinants dodecylamine and a 1 : 1 chelate of Ca(2+) and dipicolinic acid. An unexpected finding was that spores of most of the C. difficile strains also germinated with inorganic phosphate (P(i)) with a pH optimum of 6. The in vitro germination of spores of CDAD strains with KCl and P(i), two molecules present at significant levels in the GI tract, suggests that C. difficile spores germinate in the human body by sensing P(i) in the early segments of the duodenum and KCl in the colon.

An outbreak of Clostridium difficile-associated disease (CDAD) in a German university hospital

We investigated an outbreak of Clostridium difficile (CD)associated disease (CDAD) in a cardiac surgical department that took place between January 25th and April 28th 2007 at Hannover Medical School, Germany. Immediate infection control measures such as changing the surface disinfectant from an alcohol-based glucoprotamine to an oxygen-active disinfectant cleaner and the primary education of staff were proved to be insufficient to control the outbreak. Therefore, a “CD infection control bundle” was created consisting of: (a) implementation of a CDAD outbreak team; (b) education on hand hygiene; (c) the aim of early case finding as soon as clinical symptoms of CDAD were noticed; (d) daily control of microbiological results; (e) suggesting proper antimicrobial therapy of patients on the ward avoiding high-risk substances; (f) reinforcement of currently existing infection control measures, such as including the isolation of CDAD cases in single rooms; (g) and, finally, interim closure of the unit for any new admissions. For the treatment of CDAD, initially, metronidazole and, in the case of failure of initial therapy, oral vancomycin were used. A case–control study was performed. Cases were defined as proposed by the ECDC: (a) onset of diarrhoea ≥48 h after admission or ≥4 weeks after the most recent discharge and (b) positive enzyme-immunoassay (EIA) for CD toxins A or B in stool samples (RIDASCREEN® Clostridium difficile Toxin A/B test, R-Biopharm, Glasgow, United Kingdom) or the culturing of toxin-producing CD (Clostridium difficile-selective media, Oxoid, Hampshire, United Kingdom). The results of Gram strain, colony morphology and biochemical testing with the RapID II ANA System® (Remel, Lenexa, USA) were used for species determination. Cultured strains were examined by pulsed field gel electrophoresis (PFGE) using GelCompar II® software (Applied Maths NV, Sint-Martens-Latern, Belgium) and by polymerase chain reaction (PCR) ribotyping, as described by others [1]. Antimicrobial susceptibility testing was performed by E-test® (AB Biodisk, Solna, Sweden) on agar plates containing vitamin K1, haemin and 5% defibrinated sheep red blood cells (Inverness Medical Deutschland, Cologne, Germany). Breakpoint minimal inhibitory concentrations (MICs) were ≥8 μg/mL for fluoroquinolones (FQ) [2] and ≥4 μg/mL for erythromycin [3]. Severe CDAD was defined as readmission because of relapse, necessity of intensive care because of CDAD, surgical procedure due to CDAD or CDAD contributing to the patient’s death within 30 days after diagnosis [4–6]. Controls were diarrhoeal patients admitted to the same unit during the same time period but were negative for CD toxin EIA, including CD culture (= confirmed CD negative) and negative for other gastrointestinal infectious agents. Age, gender, co-morbidities, underlying diseases, endoscopic procedures, history of antimicrobial exposure, readmission and relapse of CDAD in both groups were Eur J Clin Microbiol Infect Dis (2009) 28:543–545 DOI 10.1007/s10096-008-0655-7

Germination of spores of Clostridium difficile strains, including isolates from a hospital outbreak of Clostridium difficile-associated disease (CDAD)

Clostridium difficile is an emerging nosocomial pathogen and one of the major causes of antibiotic-associated diarrhoea. Cases of Clostridium difficile-associated disease (CDAD) are likely initiated by the ingestion of dormant C. difficile spores, which then germinate, outgrow and rapidly proliferate to cause gastrointestinal (GI) infections. To understand the initial stages of CDAD pathogenesis, we have characterized the germination of spores from a collection of C. difficile strains, including some clinical isolates obtained from a CDAD outbreak (CDAD isolates). Spores of one laboratory strain and five CDAD isolates did not germinate with amino acids, but did germinate on a nutrient-rich medium. However, bile salts had little effect on spore germination, either alone or in a nutrient-rich medium. These spores also germinated with KCl, as well as the non-nutrient germinants dodecylamine and a 1 : 1 chelate of Ca(2+) and dipicolinic acid. An unexpected finding was that spores of most of the C. difficile strains also germinated with inorganic phosphate (P(i)) with a pH optimum of 6. The in vitro germination of spores of CDAD strains with KCl and P(i), two molecules present at significant levels in the GI tract, suggests that C. difficile spores germinate in the human body by sensing P(i) in the early segments of the duodenum and KCl in the colon.

Effect on diagnostic yield of repeated stool testing during outbreaks of Clostridium difficile-associated disease

The effect on diagnostic yield of testing sequential stools was assessed during two hospital epidemics of Clostridium difficile. Using a rapid immunoassay, C. difficile-associated disease was diagnosed in 237 diarrhoeal patients, of whom 204 (86%) were diagnosed from the first faeces sample and 12 (5%) were diagnosed from follow-up samples obtained within 1 week. The remaining 21 (9%) patients yielded a positive test from stools obtained >1 week after the initial negative sample. It was concluded that repeated testing of stools for C. difficile toxin is of value in controlling outbreaks of C. difficile infection.

The Economics of Clostridium difficile-Associated Disease for Providers and Payers

Outbreaks of Clostridium difficile-associated disease (CDAD), especially the hypervirulent North American pulsed field gel electrophoresis type 1 strain, have presented significant problems for patients, hospitals, long-term care facilities, and clinicians [1-3]. The important study by Dubberke et al. [4] in this issue of Clinical Infectious Diseases calls attention to the financial burden facing hospitals and, indirectly, to payers. As noted by Dubberke et al. [4], their findings are conservative, as we will discuss further.

Update on the changing epidemiology of Clostridium difficile-associated disease

In the past, Clostridium difficile-associated disease (CDAD) was thought of mainly as a nosocomial disease associated with the use of broad-spectrum antibiotics, but its epidemiology seems to be changing. Since 2002, outbreaks of severe CDAD associated with increased mortality and reduced effectiveness of treatment with metronidazole have focused attention on this challenging pathogen. A fluoroquinolone-resistant strain of C. difficile (BI/NAP1/027) has been predominantly associated with these outbreaks. Changes in the epidemiology of CDAD include the emergence of new at-risk populations and the increased incidence of the disease. Infection control programs and more effective treatments offer hope that future outbreaks of CDAD can be controlled.

Clostridium difficile--Associated Disease in a Setting of Endemicity: Identification of Novel Risk Factors

Previous studies of risk factors for Clostridium difficile-associated disease (CDAD) have been limited by small sample sizes and case-control study designs. Many of these studies were performed during outbreaks of CDAD. Colonization pressure and use of fluoroquinolones, vancomycin, and gastric acid suppressors have not been fully evaluated as risk factors for CDAD. The purpose of this study was to determine risk factors for endemic CDAD, including CDAD pressure, a modified version of colonization pressure. We performed a retrospective cohort study of 36,086 patients admitted to Barnes-Jewish Hospital (St. Louis, MO) during the period from 1 January 2003 through 31 December 2003. Administrative, laboratory, and pharmacy data were collected from electronic hospital databases. Colonization pressure was measured through a surrogate variable (i.e., CDAD pressure). Multivariable pooled logistic regression models were used to evaluate independent risk factors for CDAD. The analysis included 382 CDAD case patient admissions and 35,704 non-case patient admissions. Significant independent risk factors for CDAD included increasing age, admission(s) in the previous 60 days, hypoalbuminemia, leukemia and/or lymphoma, mechanical ventilation, and receipt of antimotility drugs, histamine-2 blockers, proton pump inhibitors, intravenous vancomycin, fluoroquinolones, and first-, third-, or fourth-generation cephalosporins. Increasing CDAD pressure was a strong risk factor for CDAD (for a CDAD pressure >1.4, the odds ratio was 4.0; 95% confidence interval, 2.9-5.6). Receipt of metronidazole was protective against CDAD (odds ratio, 0.5; 95% confidence interval, 0.3-0.6). This study identified the previously underrecognized CDAD risk factors of CDAD pressure and vancomycin. More studies are needed to evaluate the relationship between CDAD, these risk factors, and use of gastric acid suppressors and fluoroquinolones.

Infection of Hamsters with Historical and Epidemic BI Types ofClostridium difficile

North American and European hospitals have reported outbreaks of Clostridium difficile-associated disease with unexpectedly high mortality caused by a newly recognized group of C. difficile strains, group BI. Our objective was to compare, in hamsters, the virulence of a historical nonepidemic BI type, BI1, with that of 2 recent epidemic BI types, BI6 and BI17, and with that of 2 standard toxigenic strains, K14 and 630. For each strain, 10 hamsters were given 1 dose of clindamycin, followed 5 days later with 100 C. difficile spores administered by gastric inoculation. Outcomes were recorded. The hamster model demonstrated variations in mean times from inoculation to death (for BI6, 40 h; for BI1, 48 h; for K14, 49 h; for BI17, 69 h; for 630, 102 h; for BI6, BI1, and K14 vs. 630, P< .01; for BI17 vs. 630, P< .05) and from colonization to death (for BI1, 7 h; for BI17, 13 h; for BI6, 16 h; for K14, 17 h; for 630, 52 h; for BI1, BI17, BI6, and K14 vs. 630, P< .01). Group BI strains were not more rapidly fatal than the standard toxinotype 0 strain K14 but were more rapidly fatal than the standard toxinotype 0 strain 630. BI6, the most common BI type in our collection, was particularly virulent in hamsters, consistently causing death within 48 h of inoculation.

Spread and Epidemiology of Clostridium difficile Polymerase Chain Reaction Ribotype 027/Toxinotype III in The Netherlands

After reports of emerging outbreaks in Canada and the United States, Clostridium difficile-associated disease (CDAD) due to polymerase chain reaction ribotype 027 was detected in 2 medium-to-large hospitals in The Netherlands in 2005. National surveillance was initiated to investigate the spread and the epidemiology of CDAD. Microbiologists were asked to send strains recovered from patients with a severe course of CDAD or recovered when an increased incidence of CDAD was noted. A standardized questionnaire was used to collect demographic, clinical, and epidemiological patient data. Strains were characterized by polymerase chain reaction ribotyping, toxinotyping, the presence of toxin genes, and antimicrobial susceptibility. During the period from February 2005 through November 2006, 1175 stool samples from 863 patients were sent from 50 health care facilities. Of these patients, 218 (25.3%) had CDAD due to ribotype 027, and 645 patients (74.7%) had CDAD due to other ribotypes, mainly 001 (17.8%) and 014 (7.2%). Polymerase chain reaction ribotype 027 was more frequently present in general hospitals than in academic hospitals (odds ratio [OR], 4.38; 95% confidence interval [CI], 1.60-12.0). Outbreaks of CDAD were observed in 10 hospitals and in 1 nursing home. Patients infected with ribotype 027 were significantly older (OR, 2.18; 95% CI, 1.43-3.33), and significantly more patients used fluoroquinolones (OR, 2.88; 95% CI, 1.01-8.20), compared with those who were infected with other ribotypes. Clear trends were observed for more severe diarrhea (OR, 1.99; 95% CI, 0.83-4.73), higher attributable mortality (6.3% vs. 1.2%; OR, 3.30; 95% CI, 0.41-26.4), and more recurrences (OR, 1.44; 95% CI, 0.94-2.20). Ribotype 027 was found in 20 (18.3%) of 109 hospitals in The Netherlands, with a geographic concentration in the western and central parts of the country. The clinical syndrome in patients with CDAD differed on the basis of ribotype. Thus, early recognition of the ribotype has benefits.

Effect of Fluoroquinolone Treatment on Growth of and Toxin Production by Epidemic and Nonepidemic Clostridium difficile Strains in the Cecal Contents of Mice

Several recent outbreaks of Clostridium difficile-associated disease (CDAD) have been attributed to the emergence of an epidemic strain with increased resistance to fluoroquinolone antibiotics. Some clinical studies have suggested that fluoroquinolones with enhanced antianaerobic activity (i.e., gatifloxacin and moxifloxacin) may have a greater propensity to induce CDAD than ciprofloxacin and levofloxacin do. We examined the effects of subcutaneous fluoroquinolone treatment on in vitro growth of and toxin production by epidemic and nonepidemic C. difficile isolates in cecal contents of mice and evaluated the potential for these agents to inhibit fluoroquinolone-susceptible isolates during treatment. When C. difficile isolates were inoculated into cecal contents collected 2 days after the final antibiotic dose, gatifloxacin and moxifloxacin promoted significantly more growth and toxin production than ciprofloxacin and levofloxacin did. During treatment, gatifloxacin and moxifloxacin inhibited growth of fluoroquinolone-susceptible but not fluoroquinolone-resistant isolates. Ciprofloxacin and levofloxacin promoted growth of C. difficile when administered at higher doses (i.e., 20 times the human dose in mg/kg of body weight), and levofloxacin inhibited growth of fluoroquinolone-susceptible, but not fluoroquinolone-resistant, C. difficile isolates when administered in combination with ceftriaxone. Thus, fluoroquinolones with enhanced antianaerobic activity (i.e., gatifloxacin and moxifloxacin) promoted C. difficile growth to a greater extent than did ciprofloxacin and levofloxacin in this model. However, our findings suggest that fluoroquinolones may exert selective pressure favoring the emergence of epidemic fluoroquinolone-resistant C. difficile strains by inhibiting fluoroquinolone-susceptible but not fluoroquinolone-resistant isolates during treatment and that agents such as levofloxacin or ciprofloxacin can exert such selective pressure when administered in combination with antibiotics that disrupt the anaerobic microflora.

Incidence of Clostridium difficile Infection in Inflammatory Bowel Disease

Clostridium difficile-associated disease (CDAD) rates have been increasing. We sought to determine whether CDAD incidence has increased specifically in hospitalized patients with IBD. We also explored possible differences in the risk for and time to presentation of CDAD between IBD and non-IBD patients. We analyzed hospital admissions from 1998-2004 for demographics, length of stay, C difficile infections, and time from admission to a positive C difficile test. We calculated CDAD incidence for non-IBD, all IBD, CD, and UC admissions and used logistic regression to estimate the risk for CDAD. CDAD incidence increased in each group and was higher in all IBD than non-IBD groups. During the observation period, CDAD rates approximately doubled in CD (9.5 to 22.3/1000 admissions) and tripled in UC (18.4 to 57.6/1000). Length of stay was similar among the groups. For all years combined, the adjusted odds ratios for CDAD in all IBD, CD, and UC admissions were 2.9 (95% confidence interval, 2.1-4.1), 2.1 (1.3-3.4), and 4.0 (2.4-6.6), respectively. The median times from admission to a positive C difficile test result for non-IBD, CD, and UC were 4.0, 0.8, and 0.5 days, respectively. CDAD incidence in IBD has increased and is higher than in the non-IBD population. IBD and UC patients in particular have a higher risk for CDAD. C difficile infections in IBD are confirmed predominantly within 48 hours of admission, suggesting most were acquired before hospitalization.

Moxifloxacin Therapy as a Risk Factor forClostridium difficile–Associated Disease During an Outbreak: Attempts to Control a New Epidemic Strain

An outbreak of Clostridium difficile-associated disease (CDAD) caused by the epidemic North American pulsed-field gel electrophoresis type 1 (NAP1) strain began after a formulary change from levofloxacin to moxifloxacin. Cases of CDAD were associated with moxifloxacin use, but a formulary change back to levofloxacin failed to reduce rates of disease. Substituting use of one fluoroquinolone with use of another without also controlling the overall use of drugs from this class is unlikely to control outbreaks caused by the NAP1 strain of C. difficile.

A Hospital Outbreak of Diarrhea Due to an Emerging Epidemic Strain of Clostridium difficile

Increased Clostridium difficile-associated disease (CDAD) in a hospital and an affiliated long-term care facility continued despite infection control measures. We investigated this outbreak to determine risk factors and transmission settings. The CDAD cases were compared according to where the disease was likely acquired based on health care exposure and characterization of isolates from case patients, asymptomatic carriers, and the environment. Antimicrobial susceptibility testing, strain typing using pulsed-field gel electrophoresis, and toxinotyping were performed, and toxins A and B, binary toxin, and deletions in the tcdC gene were detected using polymerase chain reaction. Risk factors were examined in a case-control study, and overall antimicrobial use was compared at the hospital before and during the outbreak. Significant increases were observed in hospital-acquired (0.19 vs 0.86; P < .001) and long-term care facility-acquired (0.04 vs 0.31; P = .004) CDAD cases per 100 admissions as a result of transmission of a toxinotype III strain at the hospital and a toxinotype 0 strain at the long-term care facility. The toxinotype III strain was positive for binary toxin, an 18-base pair deletion in tcdC, and increased resistance to fluoroquinolones. Independent risk factors for CDAD included use of fluoroquinolones (odds ratio [OR], 3.22; P = .04), cephalosporins (OR, 5.19; P = .006), and proton pump inhibitors (OR, 5.02; P = .02). A significant increase in fluoroquinolone use at the hospital took place during the outbreak (185.5 defined daily doses per 1000 patient-days vs 200.9 defined daily doses per 1000 patient-days; P < .001). The hospital outbreak of CDAD was caused by transmission of a more virulent, fluoroquinolone-resistant strain of C difficile. More selective fluoroquinolone and proton pump inhibitor use may be important in controlling and preventing such outbreaks.

EpidemicClostridium difficileStrain in Hospital Visitation Dog

To the Editor: Rates of illness and death from Clostridium difficile–associated disease (CDAD) and reports of CDAD in persons without traditional risk factors (1) have been increasing. One particular strain of C. difficile has been implicated in outbreaks of CDAD in hospitals in North America and Europe and appears to be spreading internationally at an alarming rate. This strain is classified as ribotype 027, toxinotype III, and possesses genes encoding toxins A, B, and CDT (binary toxin) as well as a deletion in the tcdC gene, which is believed to increase virulence (2). We report this toxin-variant strain of C. difficile in a healthy, 4-year-old toy poodle that visits persons in hospitals and long-term care facilities in Ontario on a weekly basis. C. difficile was isolated from a fecal sample collected in the summer of 2004 as part of a cross-sectional study evaluating pathogen carriage by visitation dogs (3). The isolate was subsequently characterized by ribotyping (4) and by polymerase chain reaction (PCR) detection of genes that encode production of toxins A and B (5). Toxin CDT was confirmed by amplifying the portion of the gene (cdtB) that encodes for the receptor-binding component of the toxin, according to a previously reported protocol (6). As a result, the isolate was classified as ribotype 027, toxinotype III (7), and was found to possess all 3 toxin genes. The tcdC gene deletion was also confirmed with PCR (8). These results indicate that this canine isolate is indistinguishable from the major strain implicated in outbreaks of highly virulent CDAD around the world. According to the infection control practitioner at the hospital the dog visited, CDAD cases were occurring at increased frequency in the facility around the time the dog’s fecal specimen was collected. However, patient diagnosis was made solely through fecal toxin testing, and strains were not characterized. The facility has reported only sporadic cases of CDAD in the past few years. This is the first report of this human, epidemic strain of C. difficile in a dog. Many C. difficile strains isolated from animals, including dogs, are indistinguishable from strains associated with disease in humans (9). To date, no study, including this one, has shown that interspecies transmission occurs; however, that possibility exists, as is becoming apparent with other pathogens, such as methicillin-resistant Staphylococcus aureus. The recurrent exposure of this dog to human healthcare settings suggests that the animal acquired this strain during visits to the hospital or long-term care facility, either from the healthcare environment or contaminated hands of human contacts. We recommend that future studies evaluating the dissemination of this strain and investigations of the movement of C. difficile into the community consider the role of animals.

Controversies in Clostridium difficile testing

Recent reports of two nosocomial outbreaks of Clostridium difficile-associated disease caused by toxin A-deficient strains emphasize that these strains can cause disease. Laboratories using an assay that detects only toxin A as their primary diagnostic test risk misdiagnosis of cases or outbreaks in the institutions they serve. Repeat testing can account for a significant portion of a laboratory's C. difficile testing workload. Published data are available to support laboratory rules for rejection of repeat stool specimens within 7 days of an initial specimen. There are also substantial published data to support laboratory rejection of formed stools sent to the laboratory for C. difficile testing.

Community-acquired Clostridium difficile infection

Clostridium difficile-associated disease (CDAD) is primarily a nosocomial condition. Community-acquired disease has been reported but the incidence is felt to be low and the rate of disease resulting in hospitalization is reported as negligible. We recently experienced a 6-month outbreak of CDAD (January to June 1995): 139 patients were involved and four deaths were attributable to pseudomembranous colitis. Early in the outbreak period we were aware that many new admissions presented with C. difficile cytotoxin B positive diarrhoea: in some cases this was the sole reason for hospitalization. This observation forms the basis of this report.