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Enteric infection in relapse of inflammatory bowel disease: importance of microbiological examination of stool.

OBJECTIVE: Previous reports have suggested that diarrhoeal relapses of inflammatory bowel disease (IBD) may be associated or confused with enteric infection, and that treatment of such infections with appropriate antibiotics may be beneficial. To re-evaluate the suggestion that enteric infection is rare and microbiological testing of stool not routinely necessary in patients presenting with relapse of IBD, we have reviewed the incidence of concurrent infection in patients presenting in relapse over a recent 5-year period. METHODS: Stool microbiology results relating to relapses of IBD during the period 1997-2001 were obtained retrospectively. Relapse was confirmed by standard clinical, sigmoidoscopic and laboratory criteria. RESULTS: During the period 1997-2001 there were 237 relapses in 213 patients. Enteric infection was found in 25 (10.5%) relapses in 24 patients; in seven patients, infection was associated with the initial presentation of their IBD. Clostridium difficile toxin was detected in 13 (5.5%) instances; the 12 other infections (5% relapses) were Campylobacter spp. (five), Entamoeba histolytica (three), Salmonella spp. (one), Plesiomonas shigelloides (one), Strongyloides stercoralis (one) and Blastocystis hominis (one). There was a significant association between infection and the need for hospital admission. Of the 13 relapses associated with C. difficile, ten were in outpatients, seven patients had undergone previous antibiotic treatment, and four patients were presenting with IBD for the first time. All relapses resolved satisfactorily after treatment with antibiotics with or without corticosteroids. CONCLUSIONS: The high prevalence of enteric infections, of which C. difficile was the most common, indicates that all patients presenting with relapse of IBD should have stool examined microbiologically.

Adolescent↗

Multilocus sequence analysis and comparative evolution of virulence-associated genes and housekeeping genes of Clostridium difficile.

A multilocus sequence analysis of ten virulence-associated genes was performed to study the genetic relationships between 29 Clostridium difficile isolates of various origins, hosts and clinical presentations, and selected from the main lineages previously defined by multilocus sequence typing (MLST) of housekeeping genes. Colonization-factor-encoding genes (cwp66, cwp84, fbp68, fliC, fliD, groEL and slpA), toxin A and B genes (tcdA and tcdB), and the toxin A and B positive regulator gene (tcdD) were investigated. Binary toxin genes (cdtA and cdtB) were also detected, and internal fragments were sequenced for positive isolates. Virulence-associated genes exhibited a moderate polymorphism, comparable to the polymorphism of housekeeping genes, whereas cwp66 and slpA genes appeared highly polymorphic. Isolates recovered from human pseudomembranous colitis cases did not define a specific lineage. The presence of binary toxin genes, detected in five of the 29 isolates (17 %), was also not linked to clinical presentation. Conversely, toxigenic A-B+ isolates defined a very homogeneous lineage, which is distantly related to other isolates. By clustering analysis, animal isolates were intermixed with human isolates. Multilocus sequence analysis of virulence-associated genes is consistent with a clonal population structure for C. difficile and with the lack of host specificity. The data suggest a co-evolution of several of the virulence-associated genes studied (including toxins A and B and the binary toxin genes) with housekeeping genes, reflecting the genetic background of C. difficile, whereas flagellin, cwp66 and slpA genes may undergo recombination events and/or environmental selective pressure.

Alleles↗

Novel evidence suggesting Clostridium difficile is present in human gut microbiota more frequently than previously suspected.

Prevalence rate of Clostridium difficile in healthy human adults is believed to be very low. Our RT-PCR system using glass powder, which can eliminate PCR inhibitors, detected C. difficile toxin B mRNA in 16 of 30 fecal samples (53.3%) from healthy human adults. In contrast, we failed to detect toxin B in the same fecal samples by PCR using DNA templates extracted with phenol-chloroform. Our results suggest that PCR inhibitors in feces carried through phenol-chloroform extraction procedure might suppress the sensitivity of PCR and that C. difficile is actually present in human gut microbiota more frequently than previously suspected.

Adult↗

Prospective study of oral teicoplanin versus oral vancomycin for therapy of pseudomembranous colitis and Clostridium difficile-associated diarrhea.

A prospective, randomized study comparing oral teicoplanin with oral vancomycin in the treatment of pseudomembranous colitis (PMC) and Clostridium difficile-associated diarrhea (CDAD) was performed. Teicoplanin was administered at a dosage of 100 mg twice a day for 10 days, and vancomycin was administered at a dosage of 500 mg four times a day for 10 days. CDAD was diagnosed by demonstrating both C. difficile and cytotoxin in the feces of symptomatic patients (more than three loose stools per day). The diagnosis of PMC was also based on colonoscopy. Cytotoxin assay and cultures were checked in all patients 7 to 10 days after discontinuation of therapy and 25 to 30 days thereafter. Of the 51 patients enrolled, 46 were judged to be assessable. Among these, 26 received teicoplanin and 20 received vancomycin. At enrollment, both groups were comparable in terms of age, sex, occurrence of PMC or CDAD, and previous antibiotic treatment. Eighteen of the 20 patients in the vancomycin group and 10 of the 26 patients in the teicoplanin group had previously undergone surgery (P = 0.0004). Treatment resulted in the clinical cure of 20 (100%) vancomycin and 25 (96.2%) teicoplanin patients (P = 0.56). After discontinuation of therapy, clinical symptoms recurred in four (20%) vancomycin patients and two (7.7%) teicoplanin patients (P = 0.21). Posttherapy asymptomatic C. difficile carriage (positive follow-up cultures without any clinical symptoms) occurred in five (25%) vancomycin patients and two (7.7%) teicoplanin patients (P = 0.11).Overall, 9 of 20 (45%) vancomycin patients and 5 of 26 (19.2%) teicoplanin patients (P=0.059) appeared not to be cleared of C. difficile after treatment. No adverse effects related to vancomycin or teicoplanin therapy were observed.

Administration, Oral↗

Multilocus variable-number tandem-repeat analysis for investigation of Clostridium difficile transmission in Hospitals.

Clostridium difficile is a major cause of antibiotic-associated gastrointestinal illness. Recently, an increased incidence of hospital-acquired infections with severe outcomes has been reported in North America and Europe. Current molecular-typing methods for detection of outbreaks and nosocomial transmission are labor-intensive, subjective, or insufficiently discriminatory to differentiate between closely related strains. This report describes the development of multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) for molecular subtyping of C. difficile. Seven VNTR loci were identified from the C. difficile 630 genome by screening an isolate collection of various restriction endonuclease analysis (REA) types. The stability of the loci for short-term epidemiologic investigations was determined by performing MLVA on consecutive isolates of the same REA type from individual patients collected over as many as 90 days. Validation of MLVA for molecular genotyping was performed by direct comparison with REA results obtained from Hines Veterans Affairs Hospital on a combined collection of 40 C. difficile isolates from two different sources. The ability of MLVA to detect outbreaks was demonstrated on a collection of tertiary-care hospital isolates from a defined C. difficile outbreak in 2001. MLVA successfully clustered C. difficile isolates of the same REA type and discriminated isolates of unique REA type. Thus, MLVA is an objective, portable genotyping method that permits reliable detection of C. difficile outbreaks and can aid epidemiologic investigations of nosocomial transmission.

Bacterial Typing Techniques↗

Development of a rapid and efficient restriction endonuclease analysis typing system for Clostridium difficile and correlation with other typing systems.

A HindIII restriction endonuclease analysis (REA) typing system for total genomic Clostridium difficile DNA including a rapid and efficient method of DNA extraction and a scheme for organizing unique electrophoretic DNA band patterns was developed. REA typing was performed by two extraction methods for 1,965 C. difficile isolates obtained from patients with symptomatic C. difficile disease, asymptomatic patients who were C. difficile culture positive, and environmental surfaces. This isolate collection yielded 206 unique REA types, which were organized into 75 groups. A reference strain representing each unique REA type was chosen for DNA band pattern comparisons, cytotoxin testing, and plasmid analysis. The DNA band patterns utilizing a guanidine thiocyanate-EDTA-Sarkosyl DNA extraction method were 94% reproducible, while the original and sporadically problematic diethyl pyrocarbonate-sodium dodecyl sulfate DNA extraction method was 98% reproducible when readable patterns were obtained. Reference strains from 43 of the 75 groups were cytotoxin positive, 28 groups were cytotoxin negative, and 4 groups included both toxigenic and nontoxigenic strains. Cytotoxicity of isolates with a particular REA type was always consistent with the toxicity of the reference strain for that type. REA typing was able to discriminate strain differences within types identified by the immunoblot (89 isolates), bacteriophage-bacteriocin (44 isolates), and ribotyping (23 isolates) methods. REA typing is a sensitive, discriminating, reproducible, and rapid method for differentiating C. difficile strains and is suitable for large-scale epidemiologic studies.

Bacterial Typing Techniques↗

Multicenter evaluation of four methods for Clostridium difficile detection: ImmunoCard C. difficile, cytotoxin assay, culture, and latex agglutination.

A three-center study was undertaken to compare several test methods for the detection of Clostridium difficile, associated toxin, or related markers by using 927 stool specimens. Methods included direct assay of cytotoxin in stool by tissue culture, C. difficile bacterial culture followed by cytotoxin assay, bacterial culture alone, latex agglutination assay, and the ImmunoCard C. difficile test (Meridian Diagnostics, Inc.). The sensitivities, as determined against direct cytotoxin assay results, of the ImmunoCard C. difficile and latex agglutination assays were 84 and 67%, respectively (92 and 77%, respectively, when adjusted for bacterial culture outcomes). Evaluation for C. difficile-associated disease (CDAD) among 864 patients was based on clinical criteria for antibiotic-associated diarrhea combined with laboratory evidence of toxin or toxin-producing C. difficile in stool specimens. The sensitivity of each test method for screening of CDAD was as follows: bacterial culture, 95%; culture with cytotoxin assay of isolates, 90%; ImmunoCard C. difficile test, 83%; cytotoxin assay 82%; and latex agglutination assay, 67% (P < or = 0.05 versus all other methods). The standard deviations of the test sensitivity statistics between study sites were ranked as follows: cytotoxin assay (+/- 3.1%) < ImmunoCard C. difficile test (+/- 5.7%) < latex agglutination assay (+/- 12.3%) < culture (+/- 24.7%) < culture with cytotoxin assay (+/- 28.0%). The data support the use of the ImmunoCard C. difficile test as an adjunct for the diagnosis of CDAD.

Bacterial Toxins↗

Prevalence and genetic characterization of toxin A variant strains of Clostridium difficile among adults and children with diarrhea in France.

Toxin A variant strains (toxin A-negative, toxin B-positive strains) of Clostridium difficile have been reported to be responsible for diarrhea or pseudomembranous colitis in humans. These strains lack parts of the repeating sequences of the toxin A gene (tcdA) and are toxin A negative by commercial enzyme immunoassays (EIA). Here, we report the prevalence of the toxin A variant strains in 334 patients with C. difficile-associated diarrhea in France. The repeating segment of the tcdA gene (1,200 bp) was amplified by PCR using the primers NK9 and NK11 (H. Kato et al., J. Clin. Microbiol. 36:2178-2182, 1998). In the case of amplified fragments of unexpected size, the entire tcdA gene was studied by PCRs A1, A2, and A3 (Rupnik et al., J. Clin. Microbiol. 36:2240-2247, 1998), and strains were characterized by serotyping, pulsed-field gel electrophoresis and PCR ribotyping. By PCR with primers NK9 and NK11, C. difficile variant strains were detected in 2.7% of patients. Several variant types were found. A deletion of approximately 1,700 bp was observed in six strains from five patients. These strains belonged to serotype F and were characterized by the same pulsotype and the same PCR ribotype. They were toxin A negative by EIA and exhibited an atypical cytopathic effect on MRC-5 cells. Two other tcdA variant types that exhibited a positive result for toxin A by EIA were identified: one from serotype H with a longer amplified fragment (insertion of 200 bp) and one with a deletion of 600 bp. Diagnosis of C. difficile-associated diseases would have been missed in five patients (1.5%) by laboratories that screen the stools only for the presence of toxin A. This result underlines the need for testing stool by the cytotoxicity assay in patients with a high suspicion of C. difficile-associated diarrhea but a negative immunoassay for toxin A.

Aged↗

Epidemiology and molecular characterization of Clostridium difficile strains from patients with diarrhea: low disease incidence and evidence of limited cross-infection in a Swedish teaching hospital.

We prospectively studied the epidemiology of Clostridium difficile-associated diarrhea (CDAD) in a 900-bed hospital over the course of 12 months by PCR-ribotyping of C. difficile isolates. A total of 304 cases were diagnosed, corresponding to an overall incidence of 7/1,000 admissions, with higher rates in nephrology, hematology, and organ transplantation wards (37, 30, and 21/1,000), and 72% were classified as hospital associated (onset in hospital or onset at home but after a hospital stay within 2 months). All 382 isolates from 227 of 304 (75%) patients available for PCR-ribotyping were typeable, yielding 70 PCR-ribotypes. The three most common types comprised 30% of hospital-associated and 34% of community-associated cases, indicating import via admitted patients as a major source of C. difficile strains occurring in the hospital. Of the 227 patients studied, 38% each contributed 2 to 13 fecal samples positive for C. difficile over the course of the study period. Repeat isolates of the same PCR-ribotype as the first isolate were found in 79% of these patients and in 95% of specimens delivered within 30 days, compared to 63% of those obtained at 31 to 204 days. Nosocomial acquisition of CDAD, defined as the proportion of cases sharing C. difficile type and admitted to the same ward within 2 or 12 months, was 20% and 32% of hospital-associated cases and 14% and 23% of all cases, respectively. Thus, most CDAD cases diagnosed over the course of the study period, including those associated with hospitalization, appeared to be caused by endogenous C. difficile strains rather than by strains truly being acquired in the hospital.

Adolescent↗

Bovine immunoglobulin concentrate-clostridium difficile retains C difficile toxin neutralising activity after passage through the human stomach and small intestine.

BACKGROUND: Bovine immunoglobulin concentrate (BIC)-Clostridium difficile is prepared from the colostrum of cows immunised against C difficile toxins and contains high concentrations of neutralising IgG antitoxin. AIMS: To determine the proportion of BIC-C difficile which survives passage through the human stomach and small intestine. METHODS: Six volunteers with an end ileostomy took 5 g of BIC-C difficile containing 2.1 g of bovine IgG on four occasions: alone, with an antacid, during treatment with omeprazole, and within enteric coated capsules. RESULTS: When BIC-C difficile was taken alone, a mean (SEM) of 1033 (232) mg of bovine IgG was recovered in the ileal fluid representing 49% of the total ingested dose. Bovine IgG recovery was not significantly increased by antacid (636 (129) mg) or omeprazole (1052 (268) mg). The enteric capsules frequently remained intact or only partially opened in the ileal effluent and free bovine IgG levels were low in this treatment group (89 (101) mg). Bovine IgG recovery was higher in volunteers with shorter (less than two hours) mouth to ileum transit times (68% versus 36%, p<0. 05). Specific bovine IgG against C difficile toxin A was detected in ileal fluid following oral BIC. Toxin neutralising activity was also present and correlated closely with bovine IgG levels (r=0.95, p<0. 001). CONCLUSION: BIC-C difficile resists digestion in the human upper gastrointestinal tract and specific anti-C difficile toxin A binding and neutralising activity was retained. Passive oral immunotherapy with anti-C difficile BIC may be a useful non-antibiotic approach to the prevention and treatment of C difficile antibiotic associated diarrhoea and colitis.

Administration, Oral↗

Infection control. Dazed and confused.

This research project aims to uncover the practical concerns of health care staff on a hospital ward while attempting to implement isolation precaution guidelines for patients with Clostridium difficile-associated diarrhoea (CDAD) and methicillin-resistant Staphylococcus aureus (MRSA). The project is still in progress so this article describes the research methods used and some preliminary findings.

Attitude of Health Personnel↗

[Clostridium difficile infection associated with pseudomembranous colitis in district hospitals].

At a regional hospital serving 150,000 inhabitants, the authors were tracking the occurrence of antibiotic-associated diarrhea caused by a nosocomial infection of the Clostridium difficile, especially its most serious form--pseudomembranous colitis. Six cases of the disease were found in a retrospective study in 2001, another 20 cases were diagnosed while actively searching for the disease from January till September of 2002. The patients suffered from many complications, were of an average age of 69.24 years, their hospitalization averaged 34 days and 15 (52%) of them underwent surgery during their hospitalization. It could be demonstrably proved that 25 cases of nosocomial infection occurred during hospitalization and 3 patients were admitted to hospital with the disease. However, 2 of them had been released from hospital less than 20 days before being admitted again. Twenty-five patients (96%) had been treated with antibiotics, often in combined therapy. Most often this involved penicillin with betalactamas activity (50%), clindamycin (42%) and cefalosporins (42%). We used methods for detecting enterotoxin A in the stool, rectoscopy and anaerobic cultivation of the stool in the diagnostic process. Rectoscopy discovered pseudomembranous colitis in 14 of 17 patients examined this way. The sensitivity for proving enterotoxin A in the stool using EIA, for patients with proven pseudomembranous colitis via rectoscopy, was 75%. Anaerobic cultivation of the stool was done in 12 patients and all the results were negative. The mortality rate of 38% for our group of patients testifies to the seriousness of this disease, which we consider to be the results of antibiotic therapy. In conclusion, nosocomial infection caused by Clostridium difficile is quite often a nosocomial disease, a prognosis that especially worsens for seriously ill patients.

Adolescent↗

The etiology and management of diarrhea in the gynecologic oncology patient.

PURPOSE: We determined the etiology and evaluated the usefulness of diagnostic tests in 42 gynecologic oncology patients with diarrhea. METHODS: All inpatients who developed diarrhea during treatment for gynecologic cancer were prospectively evaluated during the 12-month study period ending June 1992. Diarrhea was defined as five or more loose stools per 24 hr lasting for 48 hr or more. Diagnostic tests were complete blood cell count; electrolytes; stool for occult blood, white blood cells, and Clostridia difficile toxin; and stool culture for Shigella, Salmonella, Yersinia, and Campylobacter. RESULTS: During the study period 351 women with gynecologic cancer received inpatient care. Forty-two (12%) patients developed diarrhea. One patient had three episodes and another had two episodes of diarrhea. There were 39 evaluable patients; 3 patients were excluded due to incomplete tests. The only cause of bacterial-associated diarrhea was C. difficile, which occurred in 4 of 39 (10.3%) patients. No patient had community-acquired diarrhea, and 1 patient had diarrhea due to Crohn's Disease. Surgery was performed on 265 patients; 29 of 265 (10.9%) developed postoperative diarrhea. Eighty-six patients had medical treatment and 13 (15.1%) developed diarrhea. The distribution by admission status of patients with diarrhea did not differ statistically from the patients without diarrhea. The four patients with C. difficile-associated diarrhea received appropriate therapy at the time of diagnosis. Nevertheless, the mean (SD) duration of C. difficile-associated diarrhea (342 (103) hr) was significantly longer than the mean (SD) duration of diarrhea not associated with this pathogen (79 (32) hr). The difference between the sample means is 263 hr with a 95% confidence interval for the difference between the means of 218 and 308 hr. Electrolyte abnormalities occurred in 20 patients (51%). Fecal leukocytes were present in 11 (28%) patients and occult blood in 5 (12.8%) of the 39 patients. Neither study was predictive for the presence of C. difficile. CONCLUSION: Hospital-acquired diarrhea in gynecologic oncology patients is common, although specific bacterial pathogens requiring antibiotic therapy account for only 10% of cases. Diagnostic tests for infectious causes besides C. difficile are infrequently useful and may be omitted unless the condition persists more than 72 hr.

Anti-Bacterial Agents↗

Comparison of vidas Clostridium difficile toxin-A assay and premier C. difficile toxin-A assay to cytotoxin-B tissue culture assay for the detection of toxins of C. difficile.

Damage to the intestinal mucosa by Clostridium difficile (CD) is toxin mediated. Two enzyme immunoassays (EIAs) for toxin-A detection, the automated Vitek immunodiagnostic assay system CDA (Vidas CDA), and the Premier toxin A (Premier) were tested for their ability to detect toxin A in 301 stool samples and compared with an in-house tissue culture assay for toxin B (TCA). Of these 301 samples, 49 were TCA positive and 252 were TCA negative. Agreement between Vidas CDA and TCA on the initial run was 85% (255 of 301) and increased to 94% (278 of 296) when discordant samples were retested from available frozen specimens. Corresponding levels of agreement for Premier were 91% (272 of 301) and 98% (284 of 288), respectively. If tissue culture positivity at any titer was used as the sole criterion for positivity of the specimen, agreement with positive TCA before and after repeat testing was 57% (26 of 49) and 74% (34 of 46) for Vidas CDA and 65% (32 of 49) and 95% (36 of 38) for Premier. Agreement with negative TCA titers was good: 90% for Vidas CDA and 95% for Premier, and 98% for Vidas CDA and 99% for Premier after repeat testing. Predictive values positive and negative after repeat testing were, respectively, 88% and 96% for Vidas CDA, and 95% and 99% for Premier. Results for the automated and manual EIA methods for detection of C. difficile toxin A were obtained in 2.5 h as compared with 36-48 h for tissue culture.

Bacterial Proteins↗

Clinical application of polymerase chain reaction to diagnose Clostridium difficile in hospitalized patients with diarrhea.

BACKGROUND & AIMS: Clostridium difficile is a common cause of diarrhea in hospitalized patients and is associated with significant morbidity and cost. The current diagnostic standard, enzyme immunoassay (EIA), has low sensitivity, leading to duplicate testing and empiric treatment. We sought to show the usefulness and potential cost effectiveness of polymerase chain reaction (PCR) amplification of toxin B gene for diagnosis of C. difficile-induced diarrhea. METHODS: A total of 148 stool samples from academic and community-based hospitals were sent for EIA testing and were evaluated prospectively for the presence of toxin B gene by PCR. Results were compared with EIA regarding sensitivity, specificity, and predictive values. Medical charts were reviewed to determine the following: (1) number of EIAs sent per admission, (2) number sent within a 24-hour time period, and (3) how caregivers practiced based on EIA results. RESULTS: The mean age of 130 patients was 55 years. EIA and PCR were positive in 6.8% and 13.6% of patients, respectively. EIA sensitivity was 40%, specificity was 98%, and positive and negative predictive values were 80% and 91%, respectively. The cost of the PCR was $22/sample. Empiric treatment for C. difficile was given unnecessarily in 42% of EIA-negative results. Thirty percent of patients had 3 or more EIAs sent during their hospital admission. Of patients with multiple samples sent, 57% had more than 1 sample sent in a 24-hour period. CONCLUSIONS: Many physicians do not conform to practice guidelines regarding recommended diagnosis and empiric treatment of C. difficile. Toxin B gene PCR represents a more sensitive and potentially cost-effective method to diagnose C. difficile-induced diarrhea than EIA and should be considered for use as an alternative diagnostic standard.

Adult↗

[Nosocomial epidemiology and transmission of Clostridium difficile infection].

BACKGROUND: Clostridium difficile is of growing importance as a hospital-acquired pathogen. Pseudomembraneous colitis is the main clinical disease. Transmission and epidemiological features are not yet fully understood. PATIENTS AND METHODS: Stool samples from 1164 individuals (571 women and 593 men) attending were examined for the presence of C. difficile. Follow-up examinations and molecular typing methods were used for the detection nosocomial transmissions. Additionally, hospital-borne environmental samples as well as staff samples were tested. RESULTS: Incidence of C. difficile infection was 8.4%. Nearly all patients (92.9%) had antibiotics given. Using molecular typing nosocomial transmission was evident. Though, environmental samples in general had a low positivity, toilet chairs were contaminated in 15.4% and may be a potential source of transmission. Staff was positive in only one case. CONCLUSIONS: Prevention of infections with C. difficile becomes to be a major threat for the clinical and hygienic management.

Adolescent↗

Use of gene amplification to detect Clostridium difficile in clinical specimens.

The combined use of an enrichment broth and gene amplification following simple DNA extraction to detect toxigenic strains of Clostridium difficile in feces was investigated by examining feces from 329 cases of suspected C. difficile infection. DNA was extracted by heating the washed centrifuged deposit from the broth in a microwave oven. For comparison, specimens were tested concurrently using standard methods for culture and cytotoxin testing. Amplified fragments were identified by molecular weight estimation, restriction enzyme digestion patterns and Southern blot hybridization. The combination of an enrichment broth followed by gene amplification was shown to be a sensitive, specific and rapid method for detecting toxigenic strains of C. difficile in feces. Use of the method in diagnostic laboratories may require the development of improved detection and verification systems for the amplified gene fragment.

Bacterial Toxins↗

Bacteremia due to Clostridium difficile: case report and review of extraintestinal C. difficile infections.

We report the case of an 85-year-old woman who developed diarrhea and bacteremia caused by Clostridium difficile after a prolonged hospitalization. C. difficile is a major cause of antibiotic-associated diarrhea but only rarely has been reported to cause extraintestinal infection. Isolation of C. difficile from a wide range of specimens outside the intestinal tract has been reported and is not always associated with diarrhea or intestinal pathology.

Aged↗