Original Article
Asymptomatic Carriage of Clostridium difficile and Serum Levels of IgG Antibody against Toxin A
N Engl J Med 2000; 342:390-397February 10, 2000
- Abstract
Background
Clostridium difficile infection can result in asymptomatic carriage, mild diarrhea, or fulminant pseudomembranous colitis. We studied whether antibody responses to C. difficile toxins affect the risks of colonization, diarrhea, and asymptomatic carriage.
Methods
We prospectively studied C. difficile infections in hospitalized patients who were receiv-ing antibiotics. Serial stool samples were tested for C. difficile colonization by cytotoxin assay and culture. Serum antibody (IgA, IgG, and IgM) levels and fecal antibody (IgA and IgG) levels against C. difficile toxin A, toxin B, and nontoxin antigens were measured by an enzyme-linked immunosorbent assay (ELISA).
Results
Of 271 patients, 37 (14 percent) were colonized with C. difficile at the time of admission, 18 of whom were asymptomatic carriers. An additional 47 patients (17 percent) became infected in the hospital, 19 of whom remained asymptomatic. The base-line antibody levels were similar in the patients who later became colonized and those who did not. After colonization, those who became asymptomatic carriers had significantly greater increases in serum levels of IgG antibody against toxin A than did the patients in whom C. difficile diarrhea developed (P<0.001). The adjusted odds ratio for diarrhea was 48.0 (95 percent confidence interval, 3.4 to 678) among patients with colonization who had a serum level of IgG antibody against toxin A of 3.00 ELISA units or less, as compared with patients with colonization who had a level of more than 3.00 ELISA units.
Conclusions
We find no evidence of immune protection against colonization by C. difficile. Howev-er, after colonization there is an association between a systemic anamnestic response to toxin A, as evidenced by increased serum levels of IgG antibody against toxin A, and asymptomatic carriage of C. difficile.
Media in This Article
Figure 1
Results of Screening, Reasons for Nonenrollment, and Results of Serial Cultures of Stool Specimens and Rectal Swabs for Clostridium difficile and Stool Cytotoxin Assays.Figure 2
Serum Levels of IgG Antibodies against Toxin A, Toxin B, and Nontoxin Antigens at the Time of Colonization in 28 Patients in Whom Clostridium difficile Diarrhea Developed and in 19 Asymptomatic Carriers.Article Activity
- Article
Clostridium difficile is the leading infectious cause of nosocomial diarrhea in developed countries.1-4 In one study, 21 percent of patients admitted to a general medical ward became colonized with C. difficile and diarrhea developed in 8 percent.5 C. difficile diarrhea and colitis result from the actions of protein exotoxins released by pathogenic strains of the organism.1,6 Toxin A and toxin B are proinflammatory and cytotoxic. Toxin A is also enterotoxic to both animal and human intestine, whereas toxin B may have enterotoxic activity in the human colon.1,6,7
The clinical outcome of infection with toxigenic C. difficile ranges from asymptomatic carriage to mild diarrhea to fulminant pseudomembranous colitis.1,5,8,9 Host, rather than bacterial, factors appear to determine these differences in clinical presentation.10,11 Serum and colonic antibody responses to C. difficile toxins are evident in more than 60 percent of the general population.12,13 There is some evidence, albeit inconclusive, that the immune response to C. difficile and its toxins contributes to the wide spectrum of disease presentation.14-19 In one study, for example, serum levels of IgG antibody against toxin A and fecal levels of IgA antibody against toxin A were higher in patients with mild C. difficile–associated disease than in those with prolonged or severe diarrhea.19
We hypothesized that acquired antibody responses to C. difficile can protect against diarrhea induced by C. difficile toxins. To test this hypothesis, we conducted a prospective study of hospitalized patients who were receiving antibiotics to determine whether antibody responses to C. difficile and its toxins are associated with a lower risk of colonization with hospital-acquired C. difficile and a lower risk of diarrhea in patients with nosocomial C. difficile infection.
Methods
Study Protocol
Consecutive patients who were admitted to either of two general medical wards at our institution between January 5, 1998, and May 22, 1998, were screened for enrollment. Patients were eligible for the study if they were receiving antimicrobial therapy and if their expected length of stay was more than two days. The study was approved by the institutional review board, and informed consent was obtained from all patients or their health care proxies.
At study entry we recorded age, sex, race, and information on known risk factors for C. difficile diarrhea and on potential confounding factors, including transfer from another health care facility; history of C. difficile diarrhea within the preceding year; antibiotic agents received; use of acid antisecretory drugs; type of feeding regimen (oral, tube [nasogastric, gastrostomy, or jejunostomy], or total parenteral nutrition); immunosuppression, including that induced by corticosteroid or immunosuppressive therapy; presence of renal disease, diabetes, dementia, or metastatic disease; a history of stroke; serum albumin level; score on the Charlson comorbidity index; and severity of the condition that led to hospitalization.20 The last factor was assessed with use of a modified Horn's index in which the severity of disease is rated as mild (1 point), moderate (2 points), severe (3 points), or extremely severe (4 points).5,21-23
We obtained a stool specimen for C. difficile culture and cytotoxin assay (or in some cases, a rectal swab for C. difficile culture) and a serum sample for antibody measurements at the time of enrollment, every three days during hospitalization, and on the day of discharge. Patients were monitored daily for the development of diarrhea, and if diarrhea occurred, an additional serum sample was obtained on the first day that the patient had symptoms.
Definitions of Outcomes
Colonization with C. difficile was considered to have occurred during hospitalization if the culture and cytotoxin tests of stool (or rectal swabs) obtained at the time of admission were negative for C. difficile and any subsequent stool culture or cytotoxin test was positive. Among patients with hospital-acquired C. difficile infection, asymptomatic carriage was defined as a positive stool culture or cytotoxin test and the absence of diarrhea during hospitalization and during a 30-day period after discharge. Diarrhea was defined as the passage of three or more unformed stools for at least two consecutive days.5 C. difficile diarrhea was defined as diarrhea that was not attributed to any other cause and that was associated with a positive stool cytotoxin test.
Laboratory Studies
All laboratory studies were performed on coded specimens by investigators who were unaware of the patients' base-line characteristics, colonization status, and clinical outcome. Stool specimens and rectal swabs were transported and then stored at –80°C as previously described.24 They were later thawed, heated briefly, and then cultured for 72 hours under anaerobic conditions in selective (cycloserine, cefoxitin, fructose) broth medium.25,26 Presumptive identification of C. difficile was made by subculturing of specimens on solid medium, examination of colony morphology, Gram's staining, and the use of a system of rapid identification based on enzymatic activity (Rapid-Ana, Innovative Diagnostics, Atlanta).
We assessed cytotoxin activity in filter-sterilized fecal supernatants using the tissue-culture cytotoxin assay.27 To confirm that a cytotoxin effect was caused by C. difficile toxins, we mixed the fecal filtrate with neutralizing antibodies against C. difficile toxins according to the manufacturer's instructions (Techlab, Blacksburg, Va.). An aliquot of the fecal filtrate was supplemented with protease inhibitors (complete protease inhibitors, Boehringer Mannhein, Mannheim, Germany) and used for antibody testing.28
Toxin A and toxin B were purified from the supernatant of a culture of strain VPI 10463 (American Type Culture Collection 43255) as previously described.29,30 Nontoxin antigens were prepared from a sonicate of two nontoxigenic strains of C. difficile (American Type Culture Collection 43597 and 43593). Levels of antibody against C. difficile toxin A, toxin B, and the nontoxin antigen preparation were measured by an enzyme-linked immunosorbent assay (ELISA) as previously described.13,17,19 Serum samples or filter-sterilized fecal samples from a different population of patients, with high levels of antitoxin immunoglobulin (IgG, IgA, or IgM) were pooled, assigned an arbitrary value that was expressed in ELISA units, and used in all assays as standards.
Statistical Analysis
All cutoff points for categories of variables were determined before we examined the study data. We separated antibody levels in patients with colonization into four categories on the basis of the distribution of antibody levels in the group of patients without colonization, as follows: levels below the 25th percentile were defined as low, levels ranging from the 25th to 75th percentile were defined as medium, levels ranging from the 76th to 90th percentile were defined as high, and levels above the 90th percentile were defined as very high. Age was categorized into three groups, on the basis of our knowledge of the age distribution of patients admitted to the study wards: 65 years of age or younger, 66 to 84 years of age, and 85 years of age or older. The severity of disease was dichotomized as mild to moderate (a score of 1 or 2 on Horn's index) or severe to extremely severe (a score of 3 or 4).
Antibody measurements were not distributed normally; therefore, we calculated the median levels and used Wilcoxon's rank-sum tests to assess the significance of any differences in median values between patients with colonization and patients without colonization and between patients with C. difficile diarrhea and asymptomatic carriers. We examined associations between other potentially predictive variables and the outcomes using chi-square tests or two-tailed Fisher's exact tests for categorical variables and Student's t-tests for continuous variables. We used Wilcoxon's rank-sum tests, the Kruskal–Wallis test, or Spearman correlation coefficients to assess associations between antibody levels and other variables.
Our main variables of interest were the C. difficile antibody levels at the time of admission and at the time of colonization. If these variables were significant in univariate analyses, we entered antibody levels (dichotomized as low, medium, or high vs. very high) into a multivariable logistic-regression model, along with age, sex, severity of disease, and the scores on the Charlson comorbidity index, since we hypothesized a priori that these might confound the immune response. Other variables associated with the outcome in univariate analyses (P<0.10) were also included in the multivariable model, and the adjusted odds ratios and 95 percent confidence intervals were calculated. Only confounders of antibody levels (variables that resulted in a change of more than 10 percent in the odds ratio for C. difficile diarrhea as compared with asymptomatic carriage) were included in the final model.
All analyses were performed with the SAS software system (version 6.12, SAS Institute, Cary, N.C.). The alpha level was set at 0.05. All P values were two-sided.
Results
Characteristics of the Patients
The results of screening for enrollment, the reasons for nonenrollment, and the results of serial cultures of stool specimens and rectal swabs for C. difficile and stool cytotoxin assays are summarized in Figure 1Figure 1
Results of Screening, Reasons for Nonenrollment, and Results of Serial Cultures of Stool Specimens and Rectal Swabs for Clostridium difficile and Stool Cytotoxin Assays.. Of 586 consecutive patients who were hospitalized, 333 were eligible for the study and 271 of these patients were enrolled; all 271 completed the study.Forty-seven patients (17 percent) acquired C. difficile infection while in the hospital. An addition-al 37 patients (14 percent) were found to be colonized with C. difficile at the time of admission. These 37 patients were excluded from all subsequent data analyses because our study was designed to examine prospectively the immune response to colonization. Cytotoxin activity was detected in the stools of all patients with C. difficile diarrhea and in 15 of the 19 asymptomatic carriers (79 percent). Three of the four asymptomatic carriers with negative stool cytotoxin assays were colonized with nontoxigenic strains of C. difficile. The C. difficile isolate of the fourth patient could not be recultured for the toxin assay.
The base-line characteristics of the patients are shown in Table 1Table 1
Base-Line Characteristics of the Patients and the Results of Univariate Analyses of Factors Associated with Diarrhea in 47 Patients with Hospital-Acquired Clostridium difficile Infection.. The majority were white and were older than 65 years of age; approximately one third had been admitted from nursing homes or other institutions. Most patients had serious coexisting conditions, and one third had severe or extremely severe disease (as indicated by a score of 3 or 4 on Horn's index) at the time of admission.Serum Levels of Antibody against Toxin A, Toxin B, and Nontoxin Antigens
There were no statistically significant differences in median serum IgA, IgG, or IgM antibody levels against toxin A, toxin B, or nontoxin antigens at the time of admission between 47 patients who subsequently became colonized with C. difficile and 187 who did not become colonized.
Among the 47 patients who acquired C. difficile infection in the hospital, C. difficile diarrhea developed in 28 (60 percent) (Figure 1). The 19 patients who were asymptomatic after infection remained so during the 30-day follow-up period after discharge.
At the time of colonization, the median serum level of IgG antibody against toxin A was significantly higher in asymptomatic carriers than in patients in whom C. difficile diarrhea developed (P<0.001) (Figure 2Figure 2
Serum Levels of IgG Antibodies against Toxin A, Toxin B, and Nontoxin Antigens at the Time of Colonization in 28 Patients in Whom Clostridium difficile Diarrhea Developed and in 19 Asymptomatic Carriers.). Median serum levels of IgG antibody against toxin B and against nontoxin antigens were also higher in the asymptomatic carriers than in the patients with diarrhea, but these differences were not statistically significant (Figure 2). The median serum level of IgM antibody against nontoxin antigens was also slightly higher in asymptomatic carriers than in the patients with diarrhea (0.29 vs. 0.21 ELISA unit, P=0.03). There were no significant differences between asymptomatic carriers and patients in whom C. difficile diarrhea developed in the median serum levels of IgA antibody against toxin A, toxin B, or nontoxin antigens; in the median serum levels of IgM antibody against toxin A or toxin B; or in the median fecal levels of IgA or IgG antibody against toxin A, toxin B, or nontoxin antigens.Among asymptomatic carriers, but not among patients with diarrhea, serum levels of IgG antibody against toxin A were significantly correlated with serum levels of IgG antibody against toxin B (R=0.49, P=0.03) and with serum levels of IgG antibody against nontoxin antigens (R=0.70, P<0.001). Serum levels of IgG antibody against toxin A at the time of admission were also highly correlated with the levels at the time of colonization (R=0.67, P= 0.001). There was no apparent association between serum levels of IgG antibody against toxin A and age, sex, score on the Charlson comorbidity index, severity of disease, presence or absence of immunosuppression, or serum albumin level.
Other Variables Associated with C. difficile Diarrhea
Among patients with colonization, other variables that were significantly associated with C. difficile diarrhea included increasing severity of disease and admission to the intensive care unit (Table 1). There was a trend for patients who were 65 years of age or younger and for those who had received acid antisecretory therapy to be more likely to have C. difficile diarrhea. There was no significant association between C. difficile diarrhea and the other variables examined.
For the multivariable logistic-regression analyses, we constructed a model to compare the risk of C. difficile diarrhea associated with a serum level of IgG antibody against toxin A of 3.00 ELISA units or less and a very high level (more than 3.00 ELISA units). Although admission to the intensive care unit was significantly associated with C. difficile diarrhea in the univariate analysis, we excluded this variable from the model because it was correlated with severe or extremely severe disease (P=0.001). In the final model, severe or extremely severe disease, as compared with mild or moderate disease, was found to be an independent predictor of C. difficile diarrhea (odds ratio, 7.7; 95 percent confidence interval, 1.5 to 39.9). Among patients with colonization and severe or extremely severe disease at admission, diarrhea occurred in 88 percent of those with a serum level of IgG antibody against toxin A of 3.00 ELISA units or less and in 20 percent of those with a level of more than 3.00 ELISA units (P=0.007) (Figure 3Figure 3
Relation between Serum Levels of IgG Antibody against Toxin A and Clostridium difficile Diarrhea in 47 Patients with Colonization, According to the Severity of Disease at Admission.). Among patients with mild or moderate disease at admission, diarrhea occurred in 43 percent of those with a serum level of IgG antibody against toxin A of 3.00 ELISA units or less and in none of those with a level of more than 3.00 ELISA units (P= 0.25). After adjustment for the severity of disease, age, and sex, the odds of C. difficile diarrhea associated with a serum level of IgG antibody against toxin A of 3.00 ELISA units or less increased from 19.6 (95 percent confidence interval, 2.2 to 176) to 48.0 (95 percent confidence interval, 3.4 to 678; chi-square for the model, 23.3; P<0.001). We did not identify any other independent predictors for C. difficile diarrhea or potential confounding factors among patients with colonization.Serum Levels of IgG Antibody against Toxin A during Hospitalization
Figure 4Figure 4
Median Levels of IgG Antibody against Toxin A during Hospitalization. shows the median serum levels of IgG antibody against toxin A during the course of hospitalization in patients with hospital-acquired C. difficile diarrhea, asymptomatic carriers, and the patients without colonization. At the time of admission, there was a trend (P=0.06) for patients who subsequently became asymptomatic carriers of C. difficile to have higher serum levels of IgG antibody against toxin A (median level, 1.43 ELISA units; range, 0.05 to 41.92) than patients in whom C. difficile diarrhea developed (0.93 ELISA unit; range, 0.45 to 7.96) or those who did not become infected with the organism (1.01 ELISA units; range, 0.00 to 25.47). At the time of colonization, the levels increased in patients who became asymptomatic carriers and dropped significantly in patients in whom C. difficile diarrhea subsequently developed (mean decrease, –0.6 ELISA unit; P=0.02). At this point the median serum level of IgG antibody against toxin A was three times as high in asymptomatic carriers (2.24 ELISA units; range, 0.04 to 42.50) as in patients in whom C. difficile diarrhea developed (0.75 ELISA unit; range, 0.20 to 5.07; P<0.001). Thereafter, there continued to be significant differences in the levels among the three groups. The serum levels of IgG antibody against toxin A did not change significantly in patients who were not colonized with C. difficile during hospitalization.Discussion
We found that asymptomatic carriage of C. difficile was strongly associated with an immune response to C. difficile toxins that was manifested by high serum levels of IgG antibody against toxin A. Conversely, patients who became colonized by C. difficile but who had low levels of serum IgG antibody against toxin A had a much greater risk of C. difficile diarrhea. The presence of severe disease on admission to the hospital was also independently associated with the risk of C. difficile diarrhea. The risk of diarrhea among patients with colonization who had severe or extremely severe disease was eight times that of patients who were less severely ill. All patients who were colonized with C. difficile but who had high serum levels of IgG antibody against toxin A and less severe disease were asymptomatic carriers, whereas all patients with colonization who had low antibody levels and severe disease had C. difficile diarrhea.
Shim et al. reported that asymptomatic colonization with C. difficile was associated with a decreased risk of subsequent C. difficile diarrhea.31 However, the mechanism of this protective effect was not identified. Our study shows that asymptomatic carriers mount an effective immune response to C. difficile toxins. The findings that asymptomatic carriage was associated with high levels of IgG antibody and that serum levels of IgG antibody against toxin A increased rapidly after colonization both indicate the occurrence of a systemic anamnestic response to C. diffi-cile toxin A.
Our findings advance the understanding of the pathophysiology of nosocomial C. difficile diarrhea.1,5,6,31-33 Antibiotic therapy alters the normal colonic microflora, permitting opportunistic infection by C. difficile. If antibiotic therapy is administered in an environment where C. difficile and its spores are prevalent, such as a hospital or nursing home, colonization by toxigenic C. difficile is more likely to occur. We suspect that patients with colonization who have a serum IgG response to C. difficile enterotoxin usually become asymptomatic carriers; patients who lack protective immunity have diarrhea and colitis.
We studied the immune response to C. difficile in a cohort of elderly hospitalized patients, many of whom had severe coexisting disease. These are the patients at highest risk for C. difficile diarrhea.5,21,34-38 We were able to determine the time of acquisition of C. difficile and to measure antibody levels at the time of colonization, before the onset of diarrhea. We examined a variety of relevant markers of immune response (serum IgA, IgM, and IgG and fecal IgA and IgG) to biologically important C. difficile antigens (toxin A, toxin B, and nontoxin antigens) and prospectively examined potential confounding variables. However, our study also had some limitations. The severity of disease was measured at base line but was not reassessed at the time of colonization. More important, the power of the study to detect differences in median antibody levels other than serum IgG antibody against toxin A was limited because of the relatively small number of patients with colonization. This lack of power may account for the absence of any statistically significant differences in fecal levels of antibody against C. difficile. The significant correlations between serum levels of IgG antibody against toxin A, toxin B, and nontoxin antigens indicate that asymptomatic carriers have humoral immune responses to toxin A and toxin B as well as to nontoxin antigens. However, whether immune responses to antigens other than toxin A are important with respect to protection against diarrhea is not clear.
Two previous studies examined antibody levels in asymptomatic carriers and patients with C. difficile diarrhea. Johnson et al. found that serum and fecal levels of IgA antibody against toxin A were significantly higher in 21 patients with C. difficile diarrhea than in 9 asymptomatic carriers.15 In contrast, Mulligan et al. reported that serum levels of IgA, IgM, and polyvalent immunoglobulins against somatic-cell antigens of C. difficile were higher in 5 asymptomatic carriers than in 21 patients with C. difficile diarrhea.18 However, in both studies, antibody levels, the putative marker of protection, were measured after the outcome (i.e., the onset of diarrhea or established asymptomatic carriage), the total number of patients studied was small, and potential confounding variables were not examined.
Approximately one third of the patients in our study (31 percent) were colonized with C. difficile, either at the time of admission to the hospital or during hospitalization. This high rate of C. difficile infection is similar to that reported in previous prospective studies of similar populations of patients.5,35-38 In this prospective study, we found no evidence that antibody responses to C. difficile or its toxins influence colonization.
Previous studies indicate that an inadequate immune response to C. difficile toxins predisposes patients to severe, prolonged, and recurrent C. difficile diarrhea.16,39 We have reported previously that passive immunotherapy using pooled normal human immune globulin (which contains IgG antibody against toxin A) is effective in treating recurrent or refractory C. difficile diarrhea.17,40 Clinical studies of the safety and immunogenicity of a candidate vaccine against C. difficile toxins are now under way.16,39 Our findings support the appropriateness of the use of vaccines and hyperimmune globulin by providing evidence that the host immune response to C. difficile has a substantial role in determining the clinical outcome of infection. It also highlights a potential marker of immune protection (very high serum levels of IgG antibody against toxin A) that can be used as a surrogate marker of vaccine efficacy. Ultimately, passive or active immunization against C. difficile toxins may prove to be an effective way to prevent and control nosocomial C. difficile diarrhea.
Supported by grants from the National Institutes of Health (AG16956, to Drs. Kyne and Kelly; AG08812, to Dr. Kyne; and RR-01032). Dr. Kyne was the recipient of a Fellowship Award from the John A. Hartford Foundation, and Dr. Warny was the recipient of a Fellowship Award from the Crohn's and Colitis Foundation of America.
We are indebted to Drs. M. Samore and K. Sands for their helpful comments on the design of the study; to Dr. A. Fatimi for assistance in processing samples; to Dr. E.J. Orav for statistical advice; to Drs. J.T. LaMont and E.F. Cook for their helpful comments and review of the manuscript; and to Dr. J.Y. Wei for her support, encouragement, and advice.
Source Information
From the Divisions of Gerontology (L.K.) and Gastroenterology (M.W., A.Q., C.P.K.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston.
Address reprint requests to Dr. Kelly at the Gastroenterology Division, Dana 601, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215, or at ciaran_kelly@caregroup.harvard.edu.
- References
References
1
Kelly CP ,Pothoulakis C ,LaMont JT . Clostridium difficile colitis. N Engl J Med 1994;330:257-262
Full Text | Web of Science | Medline2
Kyne L ,Moran A ,Keane C ,O'Neill D . Hospital-acquired diarrhoea in elderly patients: epidemiology and staff awareness. Age Ageing 1998;27:339-343
CrossRef | Web of Science3
Guerrant RL ,Hughes JM ,Lima NL ,Crane J . Diarrhea in developed and developing countries: magnitude, special settings, and etiologies. Rev Infect Dis 1990;12:Suppl 1:S41-S50
CrossRef | Medline4
McFarland LV . Epidemiology of infectious and iatrogenic nosocomial diarrhea in a cohort of general medicine patients. Am J Infect Control 1995;23:295-305
CrossRef | Web of Science | Medline5
McFarland LV ,Mulligan ME ,Kwok RYY ,Stamm WE . Nosocomial acquisition of Clostridium difficile infection. N Engl J Med 1989;320:204-210
Full Text | Web of Science | Medline6
Pothoulakis C . Pathogenesis of Clostridium difficile-associated diarrhoea. Eur J Gastroenterol Hepatol 1996;8:1041-1047
CrossRef | Web of Science | Medline7
Riegler M ,Sedivy R ,Pothoulakis C , et al. Clostridium difficile toxin B is more potent than toxin A in damaging human colonic epithelium in vitro. J Clin Invest 1995;95:2004-2011
CrossRef | Web of Science | Medline8
Rubin MS ,Bodenstein LE ,Kent KC . Severe Clostridium difficile colitis. Dis Colon Rectum 1995;38:350-354
CrossRef | Web of Science | Medline9
Kyne L ,Merry C ,O'Connell B ,Keane C ,O'Neill D . Factors associated with prolonged symptoms and severe disease due to Clostridium difficile. Age Ageing 1999;28:107-113
CrossRef | Web of Science | Medline10
McFarland LV ,Elmer GW ,Stamm WE ,Mulligan ME . Correlation of immunoblot type, enterotoxin production, and cytotoxin production with clinical manifestations of Clostridium difficile infection in a cohort of hospitalized patients. Infect Immun 1991;59:2456-2462
Web of Science | Medline11
Cheng SH ,Lu JJ ,Young TG ,Perng CL ,Chi WM . Clostridium difficile-associated diseases: comparison of symptomatic infection versus carriage on the basis of risk factors, toxin production, and genotyping results. Clin Infect Dis 1997;25:157-158
CrossRef | Web of Science | Medline12
Viscidi R ,Laughon BE ,Yolken R , et al. Serum antibody response to toxins A and B of Clostridium difficile. J Infect Dis 1983;148:93-100
CrossRef | Web of Science | Medline13
Kelly CP ,Pothoulakis C ,Orellana J ,LaMont JT . Human colonic aspirates containing immunoglobulin A antibody to Clostridium difficile toxin A inhibit toxin A-receptor binding. Gastroenterology 1992;102:35-40
Web of Science | Medline14
Bacon AE III ,Fekety R . Immunoglobulin G directed against toxins A and B of Clostridium difficile in the general population and patients with antibiotic-associated diarrhea. Diagn Microbiol Infect Dis 1994;18:205-209
CrossRef | Web of Science | Medline15
Johnson S ,Gerding DN ,Janoff EN . Systemic and mucosal antibody responses to toxin A in patients infected with Clostridium difficile. J Infect Dis 1992;166:1287-1294
CrossRef | Web of Science | Medline16
Kelly CP . Immune response to Clostridium difficile infection. Eur J Gastroenterol Hepatol 1996;8:1048-1053
CrossRef | Web of Science | Medline17
Leung DY ,Kelly CP ,Boguniewicz M ,Pothoulakis C ,LaMont JT ,Flores A . Treatment with intravenously administered gamma globulin of chronic relapsing colitis induced by Clostridium difficile toxin. J Pediatr 1991;118:633-637
CrossRef | Web of Science | Medline18
Mulligan ME ,Miller SD ,McFarland LV ,Fung HC ,Kwok RY . Elevated levels of serum immunoglobulins in asymptomatic carriers of Clostridium difficile. Clin Infect Dis 1993;16:Suppl 4:S239-S244
CrossRef | Web of Science | Medline19
Warny M ,Vaerman JP ,Avesani V ,Delmee M . Human antibody response to Clostridium difficile toxin A in relation to clinical course of infection. Infect Immun 1994;62:384-389
Web of Science | Medline20
Charlson ME ,Pompei P ,Ales KL ,MacKenzie CR . A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40:373-383
CrossRef | Medline21
McFarland LV ,Surawicz CM ,Stamm WE . Risk factors for Clostridium difficile carriage and C. difficile-associated diarrhea in a cohort of hospitalized patients. J Infect Dis 1990;162:678-684
CrossRef | Web of Science | Medline22
Horn SD ,Sharkey PD ,Bertram DA . Measuring severity of illness: homogeneous case mix groups. Med Care 1983;21:14-30
CrossRef | Web of Science | Medline23
Charlson ME ,Sax FL ,MacKenzie CR ,Fields SD ,Braham RL ,Douglas RG Jr . Assessing illness severity: does clinical judgment work? J Chronic Dis 1986;39:439-452
CrossRef | Medline24
McFarland LV ,Coyle MB ,Kremer WH ,Stamm WE . Rectal swab cultures for Clostridium difficile surveillance studies. J Clin Microbiol 1987;25:2241-2242
Web of Science | Medline25
Hanff PA ,Zaleznik DF ,Kent KC , et al. Use of heat shock for culturing Clostridium difficile from rectal swabs. Clin Infect Dis 1993;16:Suppl 4:S245-S247
CrossRef | Web of Science | Medline26
George WL ,Sutter VL ,Citron D ,Finegold SM . Selective and differential medium for isolation of Clostridium difficile. J Clin Microbiol 1979;9:214-219
Web of Science | Medline27
Kelly CP ,Pothoulakis C ,Vavva F , et al. Anti-Clostridium difficile bovine immunoglobulin concentrate inhibits cytotoxicity and enterotoxicity of C. difficile toxins. Antimicrob Agents Chemother 1996;40:373-379
Web of Science | Medline28
Hohmann A ,LaBrooy J ,Davidson GP ,Shearman DJ . Measurement of specific antibodies in human intestinal aspirate: effect of the protease inhibitor phenylmethylsulphonyl fluoride. J Immunol Methods 1983;64:199-204
CrossRef | Web of Science | Medline29
Sullivan NM ,Pellet S ,Wilkins TD . Purification and characterization of toxins A and B of Clostridium difficile. Infect Immun 1982;35:1032-1040
Web of Science | Medline30
von Eichel-Streiber C ,Harperath U ,Bosse D ,Hadding U . Purification of two high molecular weight toxins of Clostridium difficile which are antigenically related. Microb Pathog 1987;2:307-318
CrossRef | Web of Science | Medline31
Shim JK ,Johnson S ,Samore MH ,Bliss DZ ,Gerding DN . Primary symptomless colonisation by Clostridium difficile and decreased risk of subsequent diarrhoea. Lancet 1998;351:633-636
CrossRef | Web of Science | Medline32
Starr JM ,Rogers TR ,Impallomeni M . Hospital-acquired C. difficile diarrhoea and herd immunity. Lancet 1997;349:426-428
CrossRef | Web of Science | Medline33
Gerding DN ,Johnson S ,Peterson LR ,Mulligan ME ,Silva J Jr . Clostridium difficile-associated diarrhea and colitis. Infect Control Hosp Epidemiol 1995;16:459-477
CrossRef | Web of Science | Medline34
Kent KC ,Rubin MS ,Wroblewski L ,Hanff PA ,Silen W . The impact of Clostridium difficile on a surgical service: a prospective study of 374 patients. Ann Surg 1998;227:296-301
CrossRef | Web of Science | Medline35
Johnson S ,Clabots CR ,Linn FV ,Olson MM ,Peterson LR ,Gerding DN . Nosocomial Clostridium difficile colonisation and disease. Lancet 1990;336:97-100
CrossRef | Web of Science | Medline36
Clabots CR ,Johnson S ,Olson MM ,Peterson LR ,Gerding DN . Acquisition of Clostridium difficile by hospitalized patients: evidence for colonized new admissions as a source of infection. J Infect Dis 1992;166:561-567
CrossRef | Web of Science | Medline37
Samore MH ,DeGirolami PC ,Tlucko A ,Lichtenberg DA ,Melvin ZA ,Karchmer AW . Clostridium difficile colonization and diarrhea at a tertiary care hospital. Clin Infect Dis 1994;18:181-187
CrossRef | Web of Science | Medline38
Bliss DZ ,Johnson S ,Savik K ,Clabots CR ,Willard K ,Gerding DN . Acquisition of Clostridium difficile and Clostridium difficile-associated diarrhea in hospitalized patients receiving tube feeding. Ann Intern Med 1998;129:1012-1019
Web of Science | Medline39
Kyne L ,Kelly CP . Prospect for a vaccine for Clostridium difficile. BioDrugs 1998;10:173-181
CrossRef | Web of Science | Medline40
Salcedo J ,Keates S ,Pothoulakis C , et al. Intravenous immunoglobulin therapy for severe Clostridium difficile colitis. Gut 1997;41:366-370
CrossRef | Web of Science | Medline
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Citing Articles
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E. Jong, A. S. Jong, C. J. M. Bartels, C. van der Rijt-van den Biggelaar, W. J. G. Melchers, P. D. J. Sturm. (2012) Clinical and laboratory evaluation of a real-time PCR for Clostridium difficile toxin A and B genes. European Journal of Clinical Microbiology & Infectious Diseases
CrossRef2
Richard N. Greenberg, Thomas C. Marbury, Ginamarie Foglia, Michel Warny. (2012) Phase I dose finding studies of an adjuvanted Clostridium difficile toxoid vaccine. Vaccine
CrossRef3
M. FURR, N. D. COHEN, J. E. AXON, L. C. SANCHEZ, L. PANTALEON, E. HAGGETT, R. CAMPBELL, B. TENNENT-BROWN. (2012) Treatment with histamine-type 2 receptor antagonists and omeprazole increase the risk of diarrhoea in neonatal foals treated in intensive care units. Equine Veterinary Journal 44, 80-86
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John P. Flaherty, Michael P. Angarone. 2012. Acute Diarrhea and Vomiting. , 72-83.
CrossRef5
Jennifer L. Hsu, Nasia Safdar. (2011) Polyclonal Immunoglobulins and Hyperimmune Globulins in Prevention and Management of Infectious Diseases. Infectious Disease Clinics of North America 25:4, 773-788
CrossRef6
Paul J. Collini, Martijn Bauer, Ed Kuijper, David H. Dockrell. (2011) Clostridium difficile infection in HIV-seropositive individuals and transplant recipients. Journal of Infection
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Gene Y. Im, Rani J. Modayil, Cheng T. Lin, Steven J. Geier, Douglas S. Katz, Martin Feuerman, James H. Grendell. (2011) The Appendix May Protect Against Clostridium difficile Recurrence. Clinical Gastroenterology and Hepatology 9:12, 1072-1077
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Sergey S. Seregin, Yasser A. Aldhamen, David P.W. Rastall, Sarah Godbehere, Andrea Amalfitano. (2011) Adenovirus-based vaccination against Clostridium difficile toxin A allows for rapid humoral immunity and complete protection from toxin A lethal challenge in mice. Vaccine
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F. Barbut, A. Monnier, C. Eckert. (2011) Infections à Clostridium difficile : aspects cliniques épidémiologiques et thérapeutiques. Réanimation
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Loo, Vivian G., Bourgault, Anne-Marie, Poirier, Louise, Lamothe, François, Michaud, Sophie, Turgeon, Nathalie, Toye, Baldwin, Beaudoin, Axelle, Frost, Eric H., Gilca, Rodica, Brassard, Paul, Dendukuri, Nandini, Béliveau, Claire, Oughton, Matthew, Brukner, Ivan, Dascal, Andre, . (2011) Host and Pathogen Factors for Clostridium difficile Infection and Colonization. New England Journal of Medicine 365:18, 1693-1703
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V. C. C. Cheng, W. C. Yam, O. T. C. Lam, J. L. Y. Tsang, E. Y. F. Tse, G. K. H. Siu, J. F. W. Chan, H. Tse, K. K. W. To, J. W. M. Tai, P. L. Ho, K. Y. Yuen. (2011) Clostridium difficile isolates with increased sporulation: emergence of PCR ribotype 002 in Hong Kong. European Journal of Clinical Microbiology & Infectious Diseases 30:11, 1371-1381
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F.J. Sanz Santaeufemia, T. del Rosal Rabes, J. Zapardiel Ferrero, M.E. García Talavera, F.J. González-Valcárcel Sánchez-Puelles. (2011) Infección por Clostridium difficile en niño sin riesgo previo. Anales de Pediatría
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Frédéric Barbut, Gabrielle Jones, Catherine Eckert. (2011) Epidemiology and control of Clostridium difficile infections in healthcare settings. Current Opinion in Infectious Diseases 24:4, 370-376
CrossRef14
C. P. Kelly, L. Kyne. (2011) The host immune response to Clostridium difficile. Journal of Medical Microbiology 60:8, 1070-1079
CrossRef15
Daniel L. Raines, Fred A. Lopez. (2011) Clostridium Difficile Infection in Non–HIV-Immunocompromised Patients and in HIV-Infected Patients. Current Gastroenterology Reports 13:4, 344-350
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David A. Enoch, Matthew J. Butler, Sumita Pai, Sani H. Aliyu, J. Andreas Karas. (2011) Clostridium difficile in children: Colonisation and disease. Journal of Infection 63:2, 105-113
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(2011) Chapter 2-12-7. Anaerobic infections (individual fields): antibiotic-associated diarrhea and enterocolitis. Journal of Infection and Chemotherapy 17:S1, 137-139
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Caitlin R. Musgrave, P. Brandon Bookstaver, S. Scott Sutton, April D. Miller. (2011) Use of alternative or adjuvant pharmacologic treatment strategies in the prevention and treatment of Clostridium difficile infection. International Journal of Infectious Diseases 15:7, e438-e448
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A. M. Kufelnicka, T. J. Kirn. (2011) Effective Utilization of Evolving Methods for the Laboratory Diagnosis of Clostridium difficile Infection. Clinical Infectious Diseases 52:12, 1451-1457
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C. Eckert, V. Lalande, F. Barbut. (2011) Diagnostic des infections à Clostridium difficile. Journal des Anti-infectieux 13:2, 67-73
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C. Lanzas, E. R. Dubberke, Z. Lu, K. A. Reske, Y. T. Gröhn. (2011) Epidemiological Model for Clostridium difficile Transmission in Healthcare Settings. Infection Control and Hospital Epidemiology 32:6, 553-561
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F. Barbut, J.-L. Meynard, C. Eckert. (2011) Traitement des infections digestives à Clostridium difficile : anciennes et nouvelles approches. Journal des Anti-infectieux 13:2, 74-86
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Mamoon A. Aldeyab, James C. McElnay, Michael G. Scott, Elizabeth Davies, Collette Edwards, Feras W. Darwish Elhajji, Geraldine Conlon, Fidelma A. Magee, Paul J. Barr, Mary P. Kearney. (2011) An Evaluation of the Impact of a Single-Dose Intravenous Immunoglobulin Regimen in the Treatment of Clostridium difficile Infections. Infection Control and Hospital Epidemiology 32:6, 631-633
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Claire M.F. van Nispen tot Pannerden, Annelies Verbon, Ernst J. Kuipers. (2011) Recurrent Clostridium difficile Infection. Drugs 71:7, 853-868
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J.H. Kim, R.R. Muder. (2011) Clostridium difficile enteritis: A review and pooled analysis of the cases. Anaerobe 17:2, 52-55
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David C. Kaslow, John W. Shiver. (2011) Clostridium difficile and Methicillin-Resistant Staphylococcus aureus: Emerging Concepts in Vaccine Development. Annual Review of Medicine 62:1, 201-215
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E. R. Dubberke, D. B. Haslam, C. Lanzas, L. D. Bobo, C.-A. D. Burnham, Y. T. Gröhn, P. I. Tarr. (2011) The Ecology and Pathobiology of Clostridium difficile Infections: An Interdisciplinary Challenge. Zoonoses and Public Health 58:1, 4-20
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Ellie JC Goldstein. (2011) Beyond the target pathogen: ecological effects of the hospital formulary. Current Opinion in Infectious Diseases 24:Suppl 1, S21-S31
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Jieun Kim, Hyunjoo Pai, Mi-ran Seo, Jung Oak Kang. (2011) Epidemiology and Clinical Characteristics of Clostridium difficile Infection in a Korean Tertiary Hospital. Journal of Korean Medical Science 26:10, 1258
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Caoilfhionn OʼDonoghue, Lorraine Kyne. (2011) Update on Clostridium difficile infection. Current Opinion in Gastroenterology 27:1, 38-47
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Marwan S. Abougergi, John H. Kwon. (2011) Intravenous Immunoglobulin for the Treatment of Clostridium difficile Infection: A Review. Digestive Diseases and Sciences 56:1, 19-26
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Ashwin N. Ananthakrishnan. (2011) Clostridium difficile infection: epidemiology, risk factors and management. Nature Reviews Gastroenterology & Hepatology 8:1, 17-26
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A. H. W. Bruns, J. J. Oosterheert, E. J. Kuijper, J. W. J. Lammers, S. Thijsen, A. Troelstra, A. I. M. Hoepelman. (2010) Impact of different empirical antibiotic treatment regimens for community-acquired pneumonia on the emergence of Clostridium difficile. Journal of Antimicrobial Chemotherapy 65:11, 2464-2471
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Ashwin N Ananthakrishnan, David G Binion. (2010) Impact of Clostridium difficile on inflammatory bowel disease. Expert Review of Gastroenterology & Hepatology 4:5, 589-600
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Alan C. Moss, John Thomas LaMont. 2010. Clostridium difficile Infection and Pseudomembranous Colitis. , 361-366.
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Latisha Heinlen, Jimmy D. Ballard. (2010) Clostridium difficile Infection. The American Journal of the Medical Sciences 340:3, 247-252
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J. B. Rosen, M. G. Schecter, J. S. Heinle, E. D. McKenzie, D. L. Morales, M. K. Dishop, L. Danziger-Isakov, G. B. Mallory, O. Elidemir. (2010) Clostridium difficile colitis in children following lung transplantation. Pediatric Transplantation 14:5, 651-656
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Andrew E. Simor. (2010) Diagnosis, Management, and Prevention of Clostridium difficile Infection in Long-Term Care Facilities: A Review. Journal of the American Geriatrics Society 58:8, 1556-1564
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Bruce Y. Lee, Michael J. Popovich, Ye Tian, Rachel R. Bailey, Paul J. Ufberg, Ann E. Wiringa, Robert R. Muder. (2010) The potential value of Clostridium difficile vaccine: An economic computer simulation model. Vaccine 28:32, 5245-5253
CrossRef40
Sushrut Jangi, J Thomas Lamont. (2010) Asymptomatic Colonization by Clostridium difficile in Infants: Implications for Disease in Later Life. Journal of Pediatric Gastroenterology and Nutrition 51:1, 2-7
CrossRef41
B. Faris, A. Blackmore, N. Haboubi. (2010) Review of medical and surgical management of Clostridium difficile infection. Techniques in Coloproctology 14:2, 97-105
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Jennifer S. Hardesty, Paul Juang. (2010) Administering Intravenous Immune Globulin for a Patient With Clostridium difficile Infection and Acute Renal Failure. Infectious Diseases in Clinical Practice 18:3, 211-215
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Naomi G Diggs, Christina M Surawicz. (2010) Clostridium difficile infection: still principally a disease of the elderly. Therapy 7:3, 295-301
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Rosemarie Metzger, Brian R. Swenson, Hugo Bonatti, Traci L. Hedrick, Tjasa Hranjec, Kimberley A. Popovsky, Timothy L. Pruett, Robert G. Sawyer. (2010) Identification of Risk Factors for the Development of Clostridium difficile-Associated Diarrhea Following Treatment of Polymicrobial Surgical Infections. Annals of Surgery 251:4, 722-727
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Sukhminderjit Kaur, Chetana Vaishnavi, Pallab Ray, Rakesh Kochhar, Kaushal Kishor Prasad. (2010) Effect of biotherapeutics on cyclosporin-induced Clostridium difficile infection in mice. Journal of Gastroenterology and Hepatology 25:4, 832-838
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Scott Curry. (2010) Clostridium difficile. Clinics in Laboratory Medicine 30:1, 329-342
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Kyne, Lorraine, . (2010) Clostridium difficile — Beyond Antibiotics. New England Journal of Medicine 362:3, 264-265
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Lowy, Israel, Molrine, Deborah C., Leav, Brett A., Blair, Barbra M., Baxter, Roger, Gerding, Dale N., Nichol, Geoffrey, Thomas, William D. Jr., Leney, Mark, Sloan, Susan, Hay, Catherine A., Ambrosino, Donna M., . (2010) Treatment with Monoclonal Antibodies against Clostridium difficile Toxins. New England Journal of Medicine 362:3, 197-205
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Ashwin N. Ananthakrishnan, Mazen Issa, David G. Binion. (2010) Clostridium Difficile and Inflammatory Bowel Disease. Medical Clinics of North America 94:1, 135-153
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Udayakumar Navaneethan, Bo Shen. (2010) Secondary Pouchitis: Those With Identifiable Etiopathogenetic or Triggering Factors. The American Journal of Gastroenterology 105:1, 51-64
CrossRef51
Hyunjoo Pai. (2010) Current epidemiology and treatment of Clostridium difficile infection. Infection and Chemotherapy 42:6, 362
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Brett A. Leav, Barbra Blair, Mark Leney, Michael Knauber, Courtney Reilly, Israel Lowy, Dale N. Gerding, Ciarán P. Kelly, Kia Katchar, Roger Baxter, Donna Ambrosino, Deborah Molrine. (2010) Serum anti-toxin B antibody correlates with protection from recurrent Clostridium difficile infection (CDI). Vaccine 28:4, 965-969
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Marwan S. Abougergi, Apoorv Broor, Wei Cui, Bernard G. Jaar. (2010) Intravenous immunoglobulin for the treatment of severe Clostridium difficile colitis: An observational study and review of the literature. Journal of Hospital Medicine 5:1, E1-E9
CrossRef54
Martijn P Bauer, Jaap T van Dissel, Ed J Kuijper. (2009) Clostridium difficile: controversies and approaches to management. Current Opinion in Infectious Diseases 22:6, 517-524
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Ashwin N. Ananthakrishnan, Mazen Issa, David G. Binion. (2009) Clostridium Difficile and Inflammatory Bowel Disease. Gastroenterology Clinics of North America 38:4, 711-728
CrossRef56
E. R. Dubberke, D. J. Riddle, . (2009) Clostridium difficile in Solid Organ Transplant Recipients. American Journal of Transplantation 9, S35-S40
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John O’Horo, Nasia Safdar. (2009) The role of immunoglobulin for the treatment of Clostridium difficile infection: a systematic review. International Journal of Infectious Diseases 13:6, 663-667
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Karin I. Hjalmarson, Sherwood L. Gorbach. 2009. Clostridium difficile Infection in Critical Care. , 271-287.
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Naomi G. Diggs, Christina M. Surawicz. (2009) Evolving concepts in Clostridium difficile colitis. Current Gastroenterology Reports 11:5, 400-405
CrossRef60
C. POTHOULAKIS. (2009) Review article: anti-inflammatory mechanisms of action of Saccharomyces boulardii. Alimentary Pharmacology & Therapeutics 30:8, 826-833
CrossRef61
O. M. Williams, R. C. Spencer. (2009) The management of Clostridium difficile infection. British Medical Bulletin 91:1, 87-110
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David J. Riddle, Erik R. Dubberke. (2009) Clostridium difficile Infection in the Intensive Care Unit. Infectious Disease Clinics of North America 23:3, 727-743
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Jeffrey Cloud, Laura Noddin, Amanda Pressman, Mary Hu, Ciaran Kelly. (2009) Clostridium difficile Strain NAP-1 Is Not Associated With Severe Disease in a Nonepidemic Setting. Clinical Gastroenterology and Hepatology 7:8, 868-873.e2
CrossRef64
Teresa Pareja Sierra. (2009) Clostridium difficile en el anciano: actualización epidemiológica y terapéutica. Medicina Clínica 133:5, 180-183
CrossRef65
Maja Rupnik, Mark H. Wilcox, Dale N. Gerding. (2009) Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nature Reviews Microbiology 7:7, 526-536
CrossRef66
Robin B. McFee, George G. Abdelsayed. (2009) Clostridium difficile. Disease-a-Month 55:7, 439-470
CrossRef67
Stuart Johnson. (2009) Recurrent Clostridium difficile infection: A review of risk factors, treatments, and outcomes. Journal of Infection 58:6, 403-410
CrossRef68
Daniel A. Leffler, J. Thomas Lamont. (2009) Treatment of Clostridium difficile-Associated Disease. Gastroenterology 136:6, 1899-1912
CrossRef69
Evelyn M Clayton, Mary C Rea, Fergus Shanahan, Eamonn M M Quigley, Barry Kiely, Colin Hill, R Paul Ross. (2009) The Vexed Relationship Between Clostridium Difficile and Inflammatory Bowel Disease: An Assessment of Carriage in an Outpatient Setting Among Patients in Remission. The American Journal of Gastroenterology 104:5, 1162-1169
CrossRef70
Gareth C Parkes, Jeremy D Sanderson, Kevin Whelan. (2009) The mechanisms and efficacy of probiotics in the prevention of Clostridium difficile-associated diarrhoea. The Lancet Infectious Diseases 9:4, 237-244
CrossRef71
Mary Y. Hu, Kianoosh Katchar, Lorraine Kyne, Seema Maroo, Sanjeev Tummala, Valley Dreisbach, Hua Xu, Daniel A. Leffler, Ciarán P. Kelly. (2009) Prospective Derivation and Validation of a Clinical Prediction Rule for Recurrent Clostridium difficile Infection. Gastroenterology 136:4, 1206-1214
CrossRef72
Dale N. Gerding. (2009) Clostridium difficile 30 years on: what has, or has not, changed and why?. International Journal of Antimicrobial Agents 33, S2-S8
CrossRef73
Michelle M. Merrigan, Susan P. Sambol, Stuart Johnson, Dale N. Gerding. (2009) New approach to the management of Clostridium difficile infection: colonisation with non-toxigenic C. difficile during daily ampicillin or ceftriaxone administration. International Journal of Antimicrobial Agents 33, S46-S50
CrossRef74
Stuart Johnson. (2009) Recurrent Clostridium difficile infection: causality and therapeutic approaches. International Journal of Antimicrobial Agents 33, S33-S36
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M Sandra Dial. (2009) Proton Pump Inhibitor Use and Enteric Infections. The American Journal of Gastroenterology 104, S10-S16
CrossRef76
Christopher W. Seder, Mario R. Villalba, James Robbins, Felicia A. Ivascu, Christopher F. Carpenter, Mary Dietrich, Mario R. Villalba. (2009) Early colectomy may be associated with improved survival in fulminant Clostridium difficile colitis: an 8-year experience. The American Journal of Surgery 197:3, 302-307
CrossRef77
R. V. FENGER, A. LINNEBERG, M. TVEDE, C. ØSTERGAARD. (2009) Increasing seroprevalence of Clostridium difficile in an adult Danish general population. Epidemiology and Infection 137:02, 278
CrossRef78
Hye Sun Park, Dong Soo Han. (2009) Management of Antibiotics-Associated Diarrhea. The Korean Journal of Gastroenterology 54:1, 5
CrossRef79
Xinhua Chen, Kianoosh Katchar, Jeffrey D. Goldsmith, Nanda Nanthakumar, Adam Cheknis, Dale N. Gerding, Ciarán P. Kelly. (2008) A Mouse Model of Clostridium difficile–Associated Disease. Gastroenterology 135:6, 1984-1992
CrossRef80
Jaime Belmares, Dale N Gerding, Glenn Tillotson, Stuart Johnson. (2008) Measuring the severity of Clostridium difficile infection: implications for management and drug development. Expert Review of Anti-infective Therapy 6:6, 897-908
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Mary Y. Hu, Seema Maroo, Lorraine Kyne, Jeffrey Cloud, Sanjeev Tummala, Kianoosh Katchar, Valley Dreisbach, Laura Noddin, Ciarán P. Kelly. (2008) A Prospective Study of Risk Factors and Historical Trends in Metronidazole Failure for Clostridium difficile Infection. Clinical Gastroenterology and Hepatology 6:12, 1354-1360
CrossRef82
David J Riddle, Erik R Dubberke. (2008) Clostridium difficile infection in solid organ transplant recipients. Current Opinion in Organ Transplantation 13:6, 592-600
CrossRef83
Chin Wee Ang, Graham Heyes, Paul Morrison, Bryan Carr. (2008) The acquisition and outcome of ICU-acquired Clostridium difficile infection in a single centre in the UK. Journal of Infection 57:6, 435-440
CrossRef84
M. Raffat Jaber, Snorri Olafsson, Wesley L. Fung, Mark E. Reeves. (2008) Clinical Review of the Management of Fulminant Clostridium difficile Infection. The American Journal of Gastroenterology 103:12, 3195-3203
CrossRef85
Herbert L DuPont, Kevin Garey, Juan-Pablo Caeiro, Zhi-Dong Jiang. (2008) New advances in Clostridium difficile infection: changing epidemiology, diagnosis, treatment and control. Current Opinion in Internal Medicine 7:6, 591-598
CrossRef86
J. M. Blondeau. (2008) What have we learned about antimicrobial use and the risks for Clostridium difficile-associated diarrhoea?. Journal of Antimicrobial Chemotherapy 63:2, 238-242
CrossRef87
Kelly, Ciarán P., LaMont, J. Thomas, . (2008) Clostridium difficile — More Difficult Than Ever. New England Journal of Medicine 359:18, 1932-1940
Full Text88
Herbert L DuPont, Kevin Garey, Juan-Pablo Caeiro, Zhi-Dong Jiang. (2008) New advances in Clostridium difficile infection: changing epidemiology, diagnosis, treatment and control. Current Opinion in Infectious Diseases 21:5, 500-507
CrossRef89
Kimberly Lumpkins, Grant V. Bochicchio, Manjari Joshi, Ryan Gens, Kelly Bochicchio, Anne Conway, Stacey Schaub, Thomas Scalea. (2008) Clostridium difficile Infection in Critically Injured Trauma Patients. Surgical Infections 9:5, 497-501
CrossRef90
K.W. Garey, T.K. Dao-Tran, Z.D. Jiang, M.P. Price, L.O. Gentry, H.L. DuPont. (2008) A clinical risk index for Clostridium difficile infection in hospitalised patients receiving broad-spectrum antibiotics. Journal of Hospital Infection 70:2, 142-147
CrossRef91
P. A. Sutton, S. Li, J. Webb, K. Solomon, J. Brazier, Y. R. Mahida. (2008) Essential role of toxin A in C. difficile 027 and reference strain supernatant-mediated disruption of Caco-2 intestinal epithelial barrier function. Clinical & Experimental Immunology 153:3, 439-447
CrossRef92
H.C. Barker, C.S. Haworth, D. Williams, P. Roberts, D. Bilton. (2008) Clostridium difficile pancolitis in adults with cystic fibrosis. Journal of Cystic Fibrosis 7:5, 444-447
CrossRef93
Thomas Mathew, Philip A. Higginbottom. (2008) Clostridium difficile infection: Emerging concepts and treatments. Current Gastroenterology Reports 10:4, 404-408
CrossRef94
Alex Carignan, Catherine Allard, Jacques Pépin, Benoit Cossette, Vincent Nault, Louis Valiquette. (2008) Risk of Clostridium difficile Infection after Perioperative Antibacterial Prophylaxis before and during an Outbreak of Infection due to a Hypervirulent Strain. Clinical Infectious Diseases 46:12, 1838-1843
CrossRef95
Nadine G. Rouphael, Judith A. O'Donnell, Julu Bhatnagar, Felicia Lewis, Philip M. Polgreen, Susan Beekmann, Jeannette Guarner, George E. Killgore, Becky Coffman, Jennifer Campbell, Sherif R. Zaki, L. Clifford McDonald. (2008) Clostridium difficile–associated diarrhea: an emerging threat to pregnant women. American Journal of Obstetrics and Gynecology 198:6, 635.e1-635.e6
CrossRef96
K. Sanchez-Hurtado, M. Corretge, E. Mutlu, R. McIlhagger, J. M. Starr, I. R. Poxton. (2008) Systemic antibody response to Clostridium difficile in colonized patients with and without symptoms and matched controls. Journal of Medical Microbiology 57:6, 717-724
CrossRef97
A. Wright, D. Drudy, L. Kyne, K. Brown, N. F. Fairweather. (2008) Immunoreactive cell wall proteins of Clostridium difficile identified by human sera. Journal of Medical Microbiology 57:6, 750-756
CrossRef98
P. Brun, M. Scarpa, A. Grillo, G. Palu, C. Mengoli, A. Zecconi, P. Spigaglia, P. Mastrantonio, I. Castagliuolo. (2008) Clostridium difficile TxAC314 and SLP-36kDa enhance the immune response toward a co-administered antigen. Journal of Medical Microbiology 57:6, 725-731
CrossRef99
B. Dupuy, R. Govind, A. Antunes, S. Matamouros. (2008) Clostridium difficile toxin synthesis is negatively regulated by TcdC. Journal of Medical Microbiology 57:6, 685-689
CrossRef100
Claribel P. Taylor, Sanjeev Tummala, Deborah Molrine, Lisa Davidson, Richard J. Farrell, Anthony Lembo, Patricia L. Hibberd, Israel Lowy, Ciaran P. Kelly. (2008) Open-label, dose escalation phase I study in healthy volunteers to evaluate the safety and pharmacokinetics of a human monoclonal antibody to Clostridium difficile toxin A. Vaccine 26:27-28, 3404-3409
CrossRef101
Ernst J Kuipers, Christina M Surawicz. (2008) Clostridium difficile infection. The Lancet 371:9623, 1486-1488
CrossRef102
Jennifer Clooten, Stephen Kruth, Luis Arroyo, J. Scott Weese. (2008) Prevalence and risk factors for Clostridium difficile colonization in dogs and cats hospitalized in an intensive care unit. Veterinary Microbiology 129:1-2, 209-214
CrossRef103
A. R. F. Barreto, I. C. Cavalcante, M. V. Castro, A. F. T. A. Junqueira, M. R. Vale, R. A. Ribeiro, M. H. L. P. Souza, G. A. C. Brito. (2008) Fucoidin Prevents Clostridium difficile Toxin-A-Induced Ileal Enteritis in Mice. Digestive Diseases and Sciences 53:4, 990-996
CrossRef104
J. Bishara, N. Peled, S. Pitlik, Z. Samra. (2008) Mortality of patients with antibiotic-associated diarrhoea: the impact of Clostridium difficile. Journal of Hospital Infection 68:4, 308-314
CrossRef105
Preeta K. Kutty, Stephen R. Benoit, Christopher W. Woods, Arlene C. Sena, Susanna Naggie, Joyce Frederick, John Engemann, Sharon Evans, Brian C. Pien, Shailendra N. Banerjee, Jeffery Engel, L. Clifford McDonald. (2008) Assessment of Clostridium difficile –Associated Disease Surveillance Definitions, North Carolina, 2005 • . Infection Control and Hospital Epidemiology 29:3, 197-202
CrossRef106
Danielle Scheurer. (2008) Diagnostic and treatment delays in recurrentclostridium difficile–associated disease. Journal of Hospital Medicine 3:2, 156-159
CrossRef107
Abhishek Deshpande, Chaitanya Pant, Anil Jain, Thomas G. Fraser, David D. K. Rolston. (2008) Do fluoroquinolones predispose patients to Clostridium difficile associated disease? A review of the evidence. Current Medical Research and Opinion 24:2, 329-333
CrossRef108
Crenguta Stepan, Christina M Surawicz. (2007) Treatment strategies for recurrent and refractory Clostridium difficile -associated diarrhea. Expert Review of Gastroenterology & Hepatology 1:2, 295-305
CrossRef109
Robert C. Owens, August J. Valenti, Mark H. Wilcox. 2007. Clostridium difficile Infection: Overview and Update with a Focus on Antimicrobial Resistance as a Risk Factor. , 183-218.
CrossRef110
Edie P. Shen, M. Surawicz Christina. (2007) The Changing Face of Clostridium difficile: What Treatment Options Remain?. The American Journal of Gastroenterology 102:12, 2789-2792
CrossRef111
John R. Rodney, Philip S. Barie. (2007) Difficulties with Clostridium difficile. Surgical Infections 8:6, 553-556
CrossRef112
Z.F. Gellad, B.D. Alexander, J.K. Liu, B.C. Griffith, A.M. Meyer, J.L. Johnson, A.J. Muir. (2007) Severity of Clostridium difficile-associated diarrhea in solid organ transplant patients. Transplant Infectious Disease 9:4, 276-280
CrossRef113
Luis A. Marcos, Herbert L. DuPont. (2007) Advances in defining etiology and new therapeutic approaches in acute diarrhea. Journal of Infection 55:5, 385-393
CrossRef114
Chantri Trinh, Kavita Prabhakar. (2007) Diarrheal Diseases in the Elderly. Clinics in Geriatric Medicine 23:4, 833-856
CrossRef115
M. M. Riggs, A. K. Sethi, T. F. Zabarsky, E. C. Eckstein, R. L. P. Jump, C. J. Donskey. (2007) Asymptomatic Carriers Are a Potential Source for Transmission of Epidemic and Nonepidemic Clostridium difficile Strains among Long-Term Care Facility Residents. Clinical Infectious Diseases 45:8, 992-998
CrossRef116
Christos Gougoulias, Kieran M. Tuohy, Glenn R. Gibson. (2007) Dietary-based gut flora modulation against Clostridium difficile onset. Food Science & Technology Bulletin: Functional Foods 4:4, 31-41
CrossRef117
B. Razavi, A. Apisarnthanarak, L. M. Mundy. (2007) Clostridium difficile: Emergence of Hypervirulence and Fluoroquinolone Resistance. Infection 35:5, 300-307
CrossRef118
Robert C. Owens, August J. Valenti. (2007) Clostridium difficile-Associated Disease in the New Millennium. Infectious Diseases in Clinical Practice 15:5, 299-315
CrossRef119
Patricia Muñoz, Maddalena Giannella, Luís Alcalá, Elisabeth Sarmiento, Juan Fernandez Yañez, Jesus Palomo, Pilar Catalán, Javier Carbone, Emilio Bouza. (2007) Clostridium difficile–associated Diarrhea in Heart Transplant Recipients: Is Hypogammaglobulinemia the Answer?. The Journal of Heart and Lung Transplantation 26:9, 907-914
CrossRef120
Zhi–Dong Jiang, Kevin W. Garey, Margaret Price, Gail Graham, Pablo Okhuysen, Thanh Dao–Tran, Mark LaRocco, Herbert L. DuPont. (2007) Association of Interleukin-8 Polymorphism and Immunoglobulin G Anti–Toxin A in Patients With Clostridium difficile–Associated Diarrhea. Clinical Gastroenterology and Hepatology 5:8, 964-968
CrossRef121
M. Wilcox, W. Fawley. (2007) Viral gastroenteritis increases the reports of Clostridium difficile infection. Journal of Hospital Infection 66:4, 395-396
CrossRef122
Heidi T. Chang, Dorota Krezolek, Stuart Johnson, Jorge P. Parada, Charlesnika T. Evans, Dale N. Gerding. (2007) Onset of Symptoms and Time to Diagnosis of Clostridium difficile –Associated Disease Following Discharge From an Acute Care Hospital • . Infection Control and Hospital Epidemiology 28:8, 926-931
CrossRef123
B. Elliott, B. J. Chang, C. L. Golledge, T. V. Riley. (2007) Clostridium difficile-associated diarrhoea. Internal Medicine Journal 37:8, 561-568
CrossRef124
D. B. SCHEURER, L. S. HICKS, E. F. COOK, J. L. SCHNIPPER. (2007) Accuracy of ICD-9 coding for Clostridium difficile infections: a retrospective cohort. Epidemiology and Infection 135:06, 1010
CrossRef125
Denise Drudy, Norma Harnedy, Seamus Fanning, Margaret Hannan, Lorraine Kyne. (2007) Emergence and Control of Fluoroquinolone‐Resistant, Toxin A–Negative, Toxin B–Positive Clostridium difficile • . Infection Control and Hospital Epidemiology 28:8, 932-940
CrossRef126
Ciaran P. Kelly. (2007) Playing Host to the Difficult Clostridium. Clinical Gastroenterology and Hepatology 5:8, 912-914
CrossRef127
D. B. Blossom, L. C. McDonald. (2007) The Challenges Posed by Reemerging Clostridium difficile Infection. Clinical Infectious Diseases 45:2, 222-227
CrossRef128
Kiup A. Kim, Philip Wry, Eugene Hughes, Jeffrey Butcher, Donna Barbot. (2007) Clostridium difficile Small-Bowel Enteritis After Total Proctocolectomy: A Rare But Fatal, Easily Missed Diagnosis. Report of a Case. Diseases of the Colon & Rectum 50:6, 920-923
CrossRef129
Darrell S. Pardi. (2007) Recurrent Clostridium Difficile Infection: An Immunodeficiency State?. Clinical Gastroenterology and Hepatology 5:6, 672-673
CrossRef130
Kianoosh Katchar, Claribel P. Taylor, Sanjeev Tummala, Xinhua Chen, Javed Sheikh, Ciarán P. Kelly. (2007) Association Between IgG2 and IgG3 Subclass Responses to Toxin A and Recurrent Clostridium difficile–Associated Disease. Clinical Gastroenterology and Hepatology 5:6, 707-713
CrossRef131
John G. Bartlett. (2007) Clostridium difficile. Journal of Clinical Gastroenterology 41:Supplement 1, S24-S29
CrossRef132
Jeffrey Cloud, Ciaran P Kelly. (2007) Update on Clostridium difficile associated disease. Current Opinion in Internal Medicine 6:2, 131-136
CrossRef133
Nir Peled, Silvio Pitlik, Zmira Samra, Arkadi Kazakov, Yoram Bloch, Jihad Bishara. (2007) Predicting Clostridium difficile Toxin in Hospitalized Patients With Antibiotic‐Associated Diarrhea • . Infection Control and Hospital Epidemiology 28:4, 377-381
CrossRef134
Paul Juang, Susan J. Skledar, Nathalie K. Zgheib, David L. Paterson, Emanuel N. Vergis, William D. Shannon, Nicole T. Ansani, Robert A. Branch. (2007) Clinical outcomes of intravenous immune globulin in severe clostridium difficile-associated diarrhea. American Journal of Infection Control 35:2, 131-137
CrossRef135
Dominique Vanjak, Guillaume Girault, Catherine Branger, Pierre Rufat, Dominique‐Charles Valla, Bruno Fantin. (2007) Risk Factors for Clostridium difficile Infection in a Hepatology Ward • . Infection Control and Hospital Epidemiology 28:2, 202-204
CrossRef136
L. Clifford McDonald, Bruno Coignard, Erik Dubberke, Xiaoyan Song, Teresa Horan, Preeta K. Kutty, . (2007) Recommendations for Surveillance of Clostridium difficile –Associated Disease • . Infection Control and Hospital Epidemiology 28:2, 140-145
CrossRef137
Denise Drudy, Séamus Fanning, Lorraine Kyne. (2007) Toxin A-negative, toxin B-positive Clostridium difficile. International Journal of Infectious Diseases 11:1, 5-10
CrossRef138
Gertrude Seiberl, Elisabeth Bischof, Christoph Wenisch. (2006) Akute infektiöse Diarrhoe. Wiener klinische Wochenschrift Education 1:3, 137-152
CrossRef139
Emilio Bouza, Almudena Burillo, Patricia Muñoz. (2006) Antimicrobial Therapy of Clostridium difficile-Associated Diarrhea. Medical Clinics of North America 90:6, 1141-1163
CrossRef140
Lawrence A. Cone, Carlos Lopez, Harold L. Tarleton, V. Douglas Jodoin, Murray Taylor, Radikha Gade-Andavolu, Luke P. Dreisbach. (2006) A Durable Response to Relapsing Clostridium difficile Colitis May Require Combined Therapy with High-dose Oral Vancomycin and Intravenous Immune Globulin. Infectious Diseases in Clinical Practice 14:4, 217-220
CrossRef141
Saima Aslam, Daniel M. Musher. (2006) An Update on Diagnosis, Treatment, and Prevention of Clostridium difficile–Associated Disease. Gastroenterology Clinics of North America 35:2, 315-335
CrossRef142
Cheleste M. Thorpe, Sherwood L. Gorbach. (2006) Update on Clostridium difficile. Current Treatment Options in Gastroenterology 9:3, 265-271
CrossRef143
Stuart McPherson, Colin J. Rees, Richard Ellis, Shelly Soo, Simon J. Panter. (2006) Intravenous Immunoglobulin for the Treatment of Severe, Refractory, and Recurrent Clostridium difficile Diarrhea. Diseases of the Colon & Rectum 49:5, 640-645
CrossRef144
Zhi-Dong Jiang, Herbert L. DuPont, Kevin Garey, Margaret Price, Gail Graham, Pablo Okhuysen, Thanh Dao-Tran, Mark LaRocco. (2006) A Common Polymorphism in the Interleukin 8 Gene Promoter Is Associated with Clostridium difficile Diarrhea. The American Journal of Gastroenterology 101:5, 1112-1116
CrossRef145
Seema Maroo, J. Thomas Lamont. (2006) Recurrent Clostridium Difficile. Gastroenterology 130:4, 1311-1316
CrossRef146
J I Arango, A Restrepo, D L Schneider, N S Callander, J L Ochoa-Bayona, M I Restrepo, P Bradshaw, J Patterson, C O Freytes. (2006) Incidence of Clostridium difficile-associated diarrhea before and after autologous peripheral blood stem cell transplantation for lymphoma and multiple myeloma. Bone Marrow Transplantation 37:5, 517-521
CrossRef147
L. Clifford McDonald, Maria Owings, Daniel B. Jernigan. (2006) Clostridium difficile Infection in Patients Discharged from US Short-stay Hospitals, 1996–20031. Emerging Infectious Diseases 12:3, 409-415
CrossRef148
K. Koss, M. A. Clark, D. S. A. Sanders, D. Morton, M. R. B. Keighley, J. Goh. (2006) The outcome of surgery in fulminant Clostridium difficile colitis. Colorectal Disease 8:2, 149-154
CrossRef149
Jihad Bishara, Yoram Bloch, Moshe Garty, Jaqueline Behor, Zmira Samra. (2006) Antimicrobial resistance of Clostridium difficile isolates in a tertiary medical center, Israel. Diagnostic Microbiology and Infectious Disease 54:2, 141-144
CrossRef150
S. Sivapalasingam, M. J. Blaser. (2005) Bacterial Diarrhea in HIV-Infected Patients: Why Clostridium difficile, and Why Now?. Clinical Infectious Diseases 41:11, 1628-1630
CrossRef151
J. Pepin, N. Saheb, M.-A. Coulombe, M.-E. Alary, M.-P. Corriveau, S. Authier, M. Leblanc, G. Rivard, M. Bettez, V. Primeau, M. Nguyen, C.-E. Jacob, L. Lanthier. (2005) Emergence of Fluoroquinolones as the Predominant Risk Factor for Clostridium difficile-Associated Diarrhea: A Cohort Study during an Epidemic in Quebec. Clinical Infectious Diseases 41:9, 1254-1260
CrossRef152
N. González-García, J. Gómez-Pavón, J.L. Martínez-Porras. (2005) Diagnóstico, tratamiento y control de la infección causada por Clostridium difficile. Revista Española de Geriatría y Gerontología 40:5, 310-319
CrossRef153
Saima Aslam, Richard J Hamill, Daniel M Musher. (2005) Treatment of Clostridium difficile-associated disease: old therapies and new strategies. The Lancet Infectious Diseases 5:9, 549-557
CrossRef154
Scott Modena, Dilip Bearelly, Kenneth Swartz, Frank K. Friedenberg. (2005) Clostridium difficile Among Hospitalized Patients Receiving Antibiotics: A Case–Control Study • . Infection Control and Hospital Epidemiology 26:8, 685-690
CrossRef155
L. Clifford McDonald. (2005) Clostridium difficile : Responding to a New Threat From an Old Enemy • . Infection Control and Hospital Epidemiology 26:8, 672-675
CrossRef156
John M. Boyce, Nancy L. Havill. (2005) Nosocomial Antibiotic-Associated Diarrhea Associated with Enterotoxin-Producing Strains of Methicillin-Resistant Staphylococcus Aureus. The American Journal of Gastroenterology 100:8, 1828-1834
CrossRef157
D. M. Musher, S. Aslam, N. Logan, S. Nallacheru, I. Bhaila, F. Borchert, R. J. Hamill. (2005) Relatively Poor Outcome after Treatment of Clostridium difficile Colitis with Metronidazole. Clinical Infectious Diseases 40:11, 1586-1590
CrossRef158
J. Pepin, M.-E. Alary, L. Valiquette, E. Raiche, J. Ruel, K. Fulop, D. Godin, C. Bourassa. (2005) Increasing Risk of Relapse after Treatment of Clostridium difficile Colitis in Quebec, Canada. Clinical Infectious Diseases 40:11, 1591-1597
CrossRef159
R. M. Mc Loughlin, H. J. O’Connor. (2005) Diarrhoea developing in hospital patients. Irish Journal of Medical Science 174:1, 5-7
CrossRef160
Stavros Sougioultzis, Lorraine Kyne, Denise Drudy, Sarah Keates, Seema Maroo, Charalabos Pothoulakis, Paul J. Giannasca, Cynthia K. Lee, Michel Warny, Thomas P. Monath, Ciarán P. Kelly. (2005) Clostridium difficile toxoid vaccine in recurrent C. difficile-associated diarrhea. Gastroenterology 128:3, 764-770
CrossRef161
Jill A. Rebuck, Ryan J. Daley, Lynda S. Welage. (2005) Caution and Patient Safety Concerns Should Guide Us. Critical Care Medicine 33:2, 472
CrossRef162
J. Glenn Songer. (2004) The emergence of Clostridium difficile as a pathogen of food animals. Animal Health Research Reviews 5:02, 321-326
CrossRef163
Jonathan Gonenne, Darrell S. Pardi. (2004) Clostridium difficile: An update. Comprehensive Therapy 30:3, 134-140
CrossRef164
C. Hernandez, O. Meunier, F. Audeoud, P. Lutz, M. Bientz. (2004) Use of Pulsed‐Field Gel Electrophoresis for a Pseudoepidemic of Clostridium difficile Infections in a Pediatric Oncology and Hematology Department • . Infection Control and Hospital Epidemiology 25:9, 708-709
CrossRef165
B. M. Hafed, E. Bilikova, J. Kovarnova, G. Kovacicova, I. Svetlansky, V. Krcmery. (2004) Infections Due to Group B Streptococci in Neonates Are Not Associated With Higher Mortality Than Infections Due to Other Organisms • . Infection Control and Hospital Epidemiology 25:9, 709-712
CrossRef166
Luis G. Arroyo, J. Scott Weese, Henry R. Staempfli. (2004) Experimental Clostridium difficile Enterocolitis in Foals. Journal of Veterinary Internal Medicine 18:5, 734-738
CrossRef167
Thomas V Riley. (2004) Nosocomial diarrhoea due to Clostridium difficile. Current Opinion in Infectious Diseases 17:4, 323-327
CrossRef168
M. Iizuka, H. Itou, S. Konno, J. Chihara, M. Tobita, H. Oyamada, I. Toyoshima, K. Sasaki, A. Sato, Y. Horie, S. Watanabe. (2004) Elemental diet modulates the growth of Clostridium difficile in the gut flora. Alimentary Pharmacology and Therapeutics 20:s1, 151-157
CrossRef169
Denise Drudy, Emanuela Calabi, Lorraine Kyne, Stavros Sougioultzis, Eoin Kelly, Neil Fairweather, Ciarán P Kelly. (2004) Human antibody response to surface layer proteins in Clostridium difficile infection. FEMS Immunology & Medical Microbiology 41:3, 237-242
CrossRef170
Laurent Beaugerie, Jean-Claude Petit. (2004) Antibiotic-associated diarrhoea. Best Practice & Research Clinical Gastroenterology 18:2, 337-352
CrossRef171
Robert Gaynes, David Rimland, Edna Killum, H. Ken Lowery, Theodore M. Johnson II, George Killgore, Fred C. Tenover. (2004) Outbreak of Clostridium difficile Infection in a Long‐Term Care Facility: Association with Gatifloxacin Use. Clinical Infectious Diseases 38:5, 640-645
CrossRef172
Paul J Giannasca, Michel Warny. (2004) Active and passive immunization against Clostridium difficile diarrhea and colitis. Vaccine 22:7, 848-856
CrossRef173
(2004) National Clostridium difficile Standards Group: Report to the Department of Health. Journal of Hospital Infection 56, 1-38
CrossRef174
Stavros Sougioultzis, Charalabos Pothoulakis. 2004. Antibiotic-Associated Diarrhea. , 89-93.
CrossRef175
Sue Eng, Christina M. Surawicz. 2004. Colitis Pseudomembranous. , 379-381.
CrossRef176
Richard Koehler, Mary Mone, Edward Kimball, Daniel Vargo, Nick Lonardo, Richard Barton. (2003) Clostridium difficile Pericarditis Complicating Pseudomembranous Colitis in a Trauma Patient. The Journal of Trauma: Injury, Infection, and Critical Care 55:4, 771
CrossRef177
Tor C Savidge, Wei-hua Pan, Paul Newman, Michael O’Brien, Pauline M Anton, Charalabos Pothoulakis. (2003) Clostridium difficile toxin B is an inflammatory enterotoxin in human intestine. Gastroenterology 125:2, 413-420
CrossRef178
Mark H Wilcox. (2003) Clostridium difficile infection and pseudomembranous colitis. Best Practice & Research Clinical Gastroenterology 17:3, 475-493
CrossRef179
L. Beaugerie, A. Flahault, F. Barbut, P. Atlan, V. Lalande, P. Cousin, M. Cadilhac, J.-C. Petit, . (2003) Antibiotic-associated diarrhoea and Clostridium difficile> in the community. Alimentary Pharmacology and Therapeutics 17:7, 905-912
CrossRef180
Johannes Aas, Charles E. Gessert, Johan S. Bakken. (2003) Recurrent Clostridium difficile Colitis: Case Series Involving 18 Patients Treated with Donor Stool Administered via a Nasogastric Tube. Clinical Infectious Diseases 36:5, 580-585
CrossRef181
Jeffrey James Glasheen. (2003) Clostridium Difficile-Associated Diseases. Primary Care Case Reviews 6:1, 2-11
CrossRef182
Stavros Sougioultzis, Charalabos Pothoulakis. (2003) Bacterial infections: small intestine and colon. Current Opinion in Gastroenterology 19:1, 23-30
CrossRef183
John G. Bartlett. (2002) Clostridium difficile-associated enteric disease. Current Infectious Disease Reports 4:6, 477-483
CrossRef184
Andrew E. Simor, Suzanne F. Bradley, Larry J. Strausbaugh, Kent Crossley, Lindsay E. Nicolle, . (2002) Clostridium difficile in Long‐Term–Care Facilities for the Elderly • . Infection Control and Hospital Epidemiology 23:11, 696-703
CrossRef185
Lorraine Kyne, Stavros Sougioultzis, Lynne V. McFarland, Ciaran P. Kelly. (2002) Underlying Disease Severity as a Major Risk Factor for Nosocomial Clostridium difficile Diarrhea • . Infection Control and Hospital Epidemiology 23:11, 653-659
CrossRef186
John G. Bartlett. (2002) Top Ten Publications of 2001. Clinical Infectious Diseases 35:s1, S88-S92
CrossRef187
Munshi Moyenuddin, John C. Williamson, Cristopher A. Ohl. (2002) Clostridium difficile — associated diarrhea: Current strategies for diagnosis and therapy. Current Gastroenterology Reports 4:4, 279-286
CrossRef188
Ramsey M. Dallal, Brian G. Harbrecht, Arthur J. Boujoukas, Carl A. Sirio, Linda M. Farkas, Kenneth K. Lee, Richard L. Simmons. (2002) Fulminant Clostridium difficile: An Underappreciated and Increasing Cause of Death and Complications. Annals of Surgery 235:3, 363-372
CrossRef189
L. Kyne, M. B. Hamel, R. Polavaram, C. P. Kelly. (2002) Health Care Costs and Mortality Associated with Nosocomial Diarrhea Due to Clostridium difficile. Clinical Infectious Diseases 34:3, 346-353
CrossRef190
Bartlett, John G., . (2002) Antibiotic-Associated Diarrhea. New England Journal of Medicine 346:5, 334-339
Full Text191
P. Verity, M.H. Wilcox, W. Fawley, P. Parnell. (2001) Prospective evaluation of environmental contamination by Clostridium difficile in isolation side rooms. Journal of Hospital Infection 49:3, 204-209
CrossRef192
R. Balfour Sartor. (2001) Induction of mucosal immune responses by bacteria and bacterial components. Current Opinion in Gastroenterology 17:6, 555-561
CrossRef193
Lorraine Kyne, Richard J. Farrell, Ciarán P. Kelly. (2001) Clostridium difficile. Gastroenterology Clinics of North America 30:3, 753-777
CrossRef194
M. Delmee. (2001) Laboratory diagnosis of Clostridium difficile disease. Clinical Microbiology and Infection 7:8, 411-416
CrossRef195
J. M. Starr, A. Campbell. (2001) Mathematical modeling of Clostridium difficile infection. Clinical Microbiology and Infection 7:8, 432-437
CrossRef196
J. Scott Weese, Henry R. Staempfli, John F. Prescott, Steven A. Kruth, Spencer J. Greenwood, Heather E. Weese. (2001) The Roles of Clostridium difficile and Enterotoxigenic Clostridium perfringens in Diarrhea in Dogs. Journal of Veterinary Internal Medicine 15:4, 374-378
CrossRef197
Peter R. Holt. (2001) DIARRHEA AND MALABSORPTION IN THE ELDERLY. Gastroenterology Clinics of North America 30:2, 427-444
CrossRef198
William P. Ciesla, David A. Bobak. (2001) Management and prevention of Clostridium difficile-associated diarrhea. Current Infectious Disease Reports 3:2, 109-115
CrossRef199
Sunil G. Sheth, J. Thomas LaMont. (2001) Gastrointetinal Problems in the Chronically Critically Ill Patient. Clinics in Chest Medicine 22:1, 135-147
CrossRef200
Lorraine Kyne, Michel Warny, Amir Qamar, Ciarán P Kelly. (2001) Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. The Lancet 357:9251, 189-193
CrossRef201
Mark Wilcox, Jane Minton. (2001) Role of antibody response in outcome of antibiotic-associated diarrhoea. The Lancet 357:9251, 158-159
CrossRef202
Lynne V. McFarland, Sally A. Brandmarker, Stefano Guandalini. (2000) Pediatric Clostridium difficile: A Phantom Menace or Clinical Reality?. Journal of Pediatric Gastroenterology and Nutrition 31:3, 220-231
CrossRef203
Subhas Banerjee, J. Thomas Lamont. (2000) Non-antibiotic therapy for Clostridium difficile infection. Current Opinion in Infectious Diseases 13:3, 215-219
CrossRef
