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Background: A number of strategies exist to reduce Clostridium difficile (C. difficile) transmission. We conducted an economic evaluation of "bundling" these strategies together., Methods: We constructed an agent-based computer simulation of nosocomial C. difficile transmission and infection in a hospital setting. This model included the following components: interactions between patients and health care workers; room contamination via C. difficile shedding; C. difficile hand carriage and removal via hand hygiene; patient acquisition of C. difficile via contact with contaminated rooms or health care workers; and patient antimicrobial use. Six interventions were introduced alone and "bundled" together: (a) aggressive C. difficile testing; (b) empiric isolation and treatment of symptomatic patients; (c) improved adherence to hand hygiene and (d) contact precautions; (e) improved use of soap and water for hand hygiene; and (f) improved environmental cleaning. Our analysis compared these interventions using values representing 3 different scenarios: (1) base-case (BASE) values that reflect typical hospital practice, (2) intervention (INT) values that represent implementation of hospital-wide efforts to reduce C. diff transmission, and (3) optimal (OPT) values representing the highest expected results from strong adherence to the interventions. Cost parameters for each intervention were obtained from published literature. We performed our analyses assuming low, normal, and high C. difficile importation prevalence and transmissibility of C. difficile., Results: INT levels of the "bundled" intervention were cost-effective at a willingness-to-pay threshold of $100,000/quality-adjusted life-year in all importation prevalence and transmissibility scenarios. OPT levels of intervention were cost-effective for normal and high importation prevalence and transmissibility scenarios. When analyzed separately, hand hygiene compliance, environmental decontamination, and empiric isolation and treatment were the interventions that had the greatest impact on both cost and effectiveness., Conclusions: A combination of available interventions to prevent CDI is likely to be cost-effective but the cost-effectiveness varies for different levels of intensity of the interventions depending on epidemiological conditions such as C. difficile importation prevalence and transmissibility.

In 2011 a surveillance study for the susceptibility to fidaxomicin and epidemiology of Clostridium difficile isolates in the United States was undertaken in seven geographically dispersed medical centers. This report encompasses baseline surveillance in 2011 and 2012 on 925 isolates. A convenience sample of C. difficile isolates or toxin positive stools from patients were referred to a central laboratory. Antimicrobial susceptibility was determined by agar dilution (CLSI M11-A8). Clinical and Laboratory Standards Institute (CLSI), Food and Drug Administration, or European Union of Clinical Antimicrobial Susceptibility Testing (EUCAST) breakpoints were applied where applicable. Toxin gene profiles were characterized by multiplex PCR on each isolate. A random sample of 322 strains, stratified by institution, underwent restriction endonuclease analysis (REA). The fidaxomicin MIC90 was 0.5 μg/ml for all isolates regardless of REA type or toxin gene profile, and all isolates were inhibited at ≤1.0 μg/ml. By REA typing, BI strains represented 25.5% of the isolates. The toxin gene profile of tcdA, tcdB, and cdtA/B positive with a tcdC 18-bp deletion correlated with BI REA group. Moxifloxacin and clindamycin resistance was increased among either BI or binary toxin-positive isolates. Metronidazole and vancomycin showed reduced susceptibility (EUCAST criteria) in these isolates. Geographic variations in susceptibility, REA group and binary toxin gene presence were observed. Fidaxomicin activity against C. difficile isolated in a national surveillance study did not change more than 1 year after licensure. This analysis provides baseline results for future comparisons., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Epidemic C. difficile (027/BI/NAP1) has rapidly emerged in the past decade as the leading cause of antibiotic-associated diarrhea worldwide. However, the key events in evolutionary history leading to its emergence and the subsequent patterns of global spread remain unknown. Here, we define the global population structure of C. difficile 027/BI/NAP1 using whole-genome sequencing and phylogenetic analysis. We show that two distinct epidemic lineages, FQR1 and FQR2, not one as previously thought, emerged in North America within a relatively short period after acquiring the same fluoroquinolone resistance-conferring mutation and a highly related conjugative transposon. The two epidemic lineages showed distinct patterns of global spread, and the FQR2 lineage spread more widely, leading to healthcare-associated outbreaks in the UK, continental Europe and Australia. Our analysis identifies key genetic changes linked to the rapid transcontinental dissemination of epidemic C. difficile 027/BI/NAP1 and highlights the routes by which it spreads through the global healthcare system.

Background: Clostridium difficile infection (CDI) has been increasing in incidence and severity in recent years, coincident with the spread of a "hypervirulent" strain, REA type BI (ribotype 027, PFGE NAP 1). Exacerbating the problem has been the observation that metronidazole may be showing decreased effectiveness, particularly in the more severe cases. Fidaxomicin is an 18-membered macrocycle currently in phase 3 trials for the treatment of C. difficile infection (CDI). An open-label, phase II study in CDI patients has been completed and the clinical results published. C. difficile organisms were isolated from patient stool specimens and typed by restriction endonuclease analysis (REA) in order to determine the frequency and susceptibility of the C. difficile isolates and their response to treatment., Methods: Fecal samples were plated on CCFA agar for isolation of C. difficile. These isolates were tested for susceptibility to fidaxomicin, vancomycin, and metronidazole using CLSI agar dilution methods and were typed by REA., Results: C. difficile was isolated from 38 of 49 subjects and 16 (42%) were the epidemic C. difficile BI group. The BI strain was distributed approximately equally in the three dosing groups. Overall antibiotic susceptibilities were consistent with the previously reported MIC(90) values for the three antibiotics tested, but the MIC(90) of BI strains was two dilutions higher than non-BI strains for metronidazole and vancomycin (for both antibiotics, MIC(90) was 2 microg/mL vs. 0.5 microg/mL, P<0.01 for metronidazole, P=NS for vancomycin). Clinical cure for BI isolates (11/14, 79%) was not significantly different from non-BI isolates (21/22, 95%)., Conclusion: These results underscore the high prevalence of the BI epidemic strain and demonstrate that mild to moderate CDI infection as well as severe disease can be caused by these strains. Fidaxomicin cure rates for subjects with BI and with non-BI strains are similar, although the small numbers of subjects preclude a robust statistical comparison.

Background: Many clinical laboratories use toxin A immunoassays to test for Clostridium difficile., Objective: To describe the clinical course of a patient infected with a toxin variant strain of C. difficile that was not detected by toxin A immunoassay; to genetically characterize this strain; and to estimate the number of laboratories that use only toxin A immunoassays., Design: Case report, molecular investigation, and laboratory survey., Setting: Tertiary care hospital in Chicago, Illinois., Patient: An 86-year-old man., Measurements: Restriction endonuclease analysis, polymerase chain reaction, and survey of regional clinical laboratories., Results: An elderly hospitalized man died of advanced pseudomembranous colitis. Four stool specimens submitted over a 2-month period had tested negative on toxin A immunoassay, but a strain of C. difficile with a 1.8-kb deletion of the toxin A gene was recovered from each specimen. This strain, identified as restriction endonuclease analysis type CF4, is closely related to a widely disseminated variant, toxinotype VIII. Toxin A immunoassay was the only test being performed for detection of C. difficile at 31 of 67 (46%) regional clinical laboratories., Conclusions: Toxin A variant strains of C. difficile cause serious disease and are undetectable in clinical laboratories that use only toxin A immunoassays for C. difficile testing.

Five different toxigenic strains of Clostridium difficile of known human epidemiologic importance were tested for virulence in hamsters. Three strains-types B1, J9, and K14-have caused hospital outbreaks. Type Y2 is associated with a high rate of asymptomatic colonization in patients. The fifth strain, type CF2, is a toxin A-negative, toxin B-positive strain implicated in multiple human cases of C. difficile-associated diarrhea. Groups of 10 hamsters per strain were given 1 dose of clindamycin, followed 5 days later with gastric inoculation of 100 cfu of C. difficile. Hamsters given types B1, J9, K14, or Y2 showed 90%-100% colonization (albeit at a slower rate with type Y2) and 100% mortality of colonized animals. Hamsters challenged with type CF2 showed 60% (P= .01) colonization and 30% mortality (P= .0003). The hamster model demonstrated pathogenicity differences between a toxin variant strain and standard toxigenic strains but no significant differences among the standard strains.

A toxin variant strain of Clostridium difficile was isolated from two patients with C. difficile-associated disease (CDAD), one of whom died from extensive pseudomembranous colitis. This strain, identified by restriction endonuclease analysis (REA) as type CF2, was not detected by an immunoassay for C. difficile toxin A. Culture supernatants of CF2 failed to elicit significant enterotoxic activity in the rabbit ileal loop assay but did produce atypical cytopathic effects in cell culture assay. Southern hybridization, PCR amplification, and DNA sequence analyses were performed on the toxin A (tcdA) and toxin B (tcdB) genes of type CF2 isolate 5340. Type CF2 5340 tcdA exhibited a 1,821-bp truncation, due to three deletions in the 3' end of the gene, and a point mutation in the 5' end of the gene, resulting in a premature stop codon at tcdA position 139. Type CF2 5340 tcdB exhibited multiple nucleotide base substitutions in the 5' end of the gene compared to tcdB of the standard toxigenic strain VPI 10463. Type CF2 5340 toxin gene nucleotide sequences and deduced amino acid sequences showed a strong resemblance to those of the previously described variant C. difficile strain 1470, a strain reported to have reduced pathogenicity and no association with clinical illness in humans. REA of strain 1470 identified this strain as a distinct type (CF1) within the same REA group as the closely related type CF2. A review of our clinical-isolate collection identified five additional patients infected with type CF2, three of whom had documented CDAD. PCR amplification of the 3' end of tcdA demonstrated identical 1. 8-kb deletions in all seven type CF2 isolates. REA type CF2 is a toxin variant strain of C. difficile that retains the ability to cause disease in humans but is not detected in clinical immunoassays for toxin A.

Background: Information about fecal incontinence experienced by patients in acute-care settings is lacking. The relationship of fecal incontinence to several well-known nosocomial or iatrogenic causes of diarrhea has not been determined., Objectives: To determine the cumulative incidence of fecal incontinence in hospitalized patients who are acutely ill, and to ascertain the relationship between fecal incontinence and stool consistency, and between diarrhea and two well-known nosocomial or iatrogenic etiologies of diarrhea: Clostridium difficile and tube feeding. The relationship of fecal incontinence and risk factors for diarrhea associated with C. difficile and tube feeding in hospitalized patients was examined., Methods: Fecal incontinence, stool frequency and consistency, administration of tube feeding and medications, severity of illness, and nutritional data were prospectively recorded in 152 patients on acute or critical care units of a university-affiliated Veterans' Affairs Medical Center. Rectal swabs and stool specimens from patients were obtained weekly for C. difficile culture. C. difficile culture and cytotoxin assay were performed on diarrheal stools. HindIII restriction endonuclease analysis (REA) was used for typing of C. difficile isolates., Results: In this study, 33% (50/152) of the patients had fecal incontinence. The proportion of total surveillance days with fecal incontinence in these patients was 0.50 +/- 0.06. A greater percentage of patients with diarrhea had fecal incontinence than patients without diarrhea (23/53 [43%] vs. 27/99 [27%]; p = 0.04). Incontinence was more frequent in patients with loose/liquid stool consistency than in patients with hard/soft stool consistency (48/50 [96%] vs. 71/100 [71%]; p < 0.001). The proportion of surveillance days with fecal incontinence was related to the proportion of surveillance days with diarrhea (r = 0.69; p < 0.001) and the proportion of surveillance days with loose/liquid stools (r = 0.64; p < 0.001). Multivariate risk factors for fecal incontinence were unformed/loose or liquid consistency of stool (RR = 11.1; 95% confidence interval [CI] = 2.2, 56.7), severity of illness (RR = 5.7; CI = 2.6, 12.3), and age (RR = 1.1; CI = 1, 1.1)., Conclusions: Fecal incontinence is common in hospitalized patients who are acutely ill, but the condition was not associated with any specific cause of diarrhea. Because loose or liquid stool consistency is a risk factor for fecal incontinence, use of treatments that result in a more formed stool may be beneficial in managing fecal incontinence. However, treatments that slow intestinal transit should be avoided in patients with C. difficile-associated diarrhea.

Background: Large outbreaks of diarrhea caused by a newly recognized strain of Clostridium difficile occurred in four hospitals located in different parts of the United States between 1989 and 1992. Since frequent use of clindamycin was associated with the outbreak in one of the hospitals, we examined the resistance genes of the epidemic-strain isolates and studied the role of clindamycin use in these outbreaks., Methods: Case-control studies were performed at three of the four hospitals to assess the relation of the use of clindamycin to C. difficile-associated diarrhea. All isolates of the epidemic strain and representative isolates of other strains identified during each outbreak were tested for susceptibility to clindamycin. Chromosomal DNA from these representative isolates was also analyzed by dot blot hybridization and amplification with the polymerase chain reaction (PCR) with the use of probes and primers from a previously described determinant of erythromycin resistance - the erythromycin ribosomal methylase B (ermB) gene - found in C. perfringens and C. difficile., Results: In a stratified analysis of the case-control studies with pooling of the results according to the Mantel-Haenszel method, we found that the use of clindamycin was significantly increased among patients with diarrhea due to the epidemic strain of C. difficile, as compared with patients whose diarrhea was due to nonepidemic strains (pooled odds ratio, 4.35; 95 percent confidence interval, 2.02 to 9.38; P<0.001). Exposure to other types of antibiotics or hospitalization in a surgical ward was not significantly associated with the risk of C. difficile-associated diarrhea due to the epidemic strain. All epidemic-strain isolates were highly resistant to clindamycin (minimal inhibitory concentration, >256 microg per milliliter). DNA hybridization and PCR analysis showed that all these isolates had an ermB gene, which encodes a 23S ribosomal RNA methylase that mediates resistance to macrolide, lincosamide, and streptogramin antibiotics. Only 15 percent of the nonepidemic strains were resistant to clindamycin., Conclusions: A strain of C. difficile that is highly resistant to clindamycin was responsible for large outbreaks of diarrhea in four hospitals in different states. The use of clindamycin is a specific risk factor for diarrhea due to this strain. Resistance to clindamycin further increases the risk of C. difficile-associated diarrhea, an established complication of antimicrobial use.

Background: Little is known about whether patients who develop Clostridium-difficile-associated diarrhoea (CDAD) are culture-positive or culture-negative before illness. The most important risk factor is antibiotic exposure. We aimed to find out whether patients identified as primary symptom-free C difficile carriers are at higher risk of developing CDAD than patients who are culture-negative., Method: We reviewed four longitudinal studies in which 810 patients admitted to hospital were followed up by prospective rectal-swab culture. At least two consecutive weekly cultures were obtained. We calculated the difference in risk of CDAD between colonised and non-colonised patients in each study and combined the results of the four studies in a random-effects model., Findings: Of 618 non-colonised patients (mean follow-up 1.7 weeks [SD 1.3]), 22 (3.6%) developed CDAD, whereas only two (1.0%) of 192 primary symptom-free carriers (1.5 [1.5]) developed CDAD (pooled risk difference -2.3% [95% CI 0.3-4.3], p=0.021). Of patients who received antibiotics, the risk difference was increased: 22 (4.5%) of 491 non-colonised patients compared with two (1.1%) of 176 colonised patients developed CDAD (-3.2% [0.4-6.0], p=0.024). Of the primary symptom-free C difficile carriers, 95 were colonised with toxigenic strains, 76 with non-toxigenic strains, 12 with both toxigenic and non-toxigenic strains (non-concurrently), and nine with strains of undetermined toxigenicity. Nine of the 12 toxogenic strains of C difficile isolates that cause CDAD were also recovered from stools of symptom-free patients., Interpretation: Primary symptomless C difficile colonisation is associated with a decreased risk of CDAD. Although the mechanism is unknown, risk reduction is found in colonisation with non-toxigenic and toxigenic strains.

The relationship between vancomycin or metronidazole treatment of Clostridium difficile-associated diarrhea (CDAD) and the occurrence of vancomycin-resistant enterococcus (VRE) infection was investigated by review of 18 case-control studies. Fifteen (83%) of 18 studies found vancomycin use, days of use, or grams used to be significantly associated with VRE infection or colonization. Intravenous vancomycin use was a significant risk in nine of 10 studies, and oral vancomycin use was a significant risk in three of four studies that stratified risk by route of administration. Although statistically associated, oral vancomycin use was so infrequent (25% in the study with the most use) that it is likely to have only a minor influence as a risk for VRE infection or colonization when compared with the much more widespread use of intravenous vancomycin. Metronidazole exposure was found to be a significant risk in four of five studies that specifically assessed this variable, but the indication for metronidazole use was not specified. Risk factors for both VRE infection and CDAD include antimicrobial exposure, number of antimicrobials, days of antimicrobial use, specific agents (third-generation cephalosporins, clindamycin, and imipenem), patient age, length of hospitalization, severity of underlying illness, use of electronic rectal thermometers, enteral feedings, environmental contamination, and contamination of the hands of health care workers.

Nosocomial Clostridium difficile infection was investigated at a hospital with 15 cases of C. difficile diarrhea per 1000 discharges. From January 1991 to May 1991, patients admitted or transferred to five wards or units had weekly rectal swabs taken for culture; in addition, all cytotoxin-positive stools were cultured. Restriction enzyme analysis (REA) was used for molecular typing. Among 205 isolates from 39 patients with C. difficile diarrhea and 67 asymptomatically colonized, 55 distinct REA banding patterns were identified. Evidence for patient-to-patient transmission was limited, in that numerous strains were found even among clustered cases of diarrhea. Patients who acquired C. difficile in the community or other hospitals constituted 32% of culture-positive patients and contributed 44% of the REA types. Diversity of C. difficile strains was in part the result of patients acquiring C. difficile in the community or other hospitals. High incidences of nosocomial C. difficile diarrhea do not necessarily indicate clonal epidemics.

Objectives: To understand the epidemiology, risks, and management of Clostridium difficile-associated disease (CDAD) and to establish and evaluate reliable methods of surveillance., Design: Case finding was done by daily ward and laboratory rounds. The criteria for CDAD diagnosis were: at least four unformed stools per day for 2 days and a positive culture or cytotoxin for C difficile, or positive endoscopy or autopsy for pseudomembranes., Setting: The surveillance covered all patients from 1982 through 1991 in the 820-bed Minneapolis Veterans Affairs Medical Center., Participants: The criteria were met by 908 patients. Medical service patients numbered 488; surgical patients, 420. Frequencies ranged from a high of 149 cases in 1982 to a low of 50 cases in 1989., Results: Stool specimens were obtained on 898 (99%) of the 908 CDAD patients. Stools were culture-positive in 864 (96%) of 898, cytotoxin-positive in 569 (63%) of 898. Endoscopy was performed on 196 (22%) of the 908 patients, and 80 (41%) of 196 patients had pseudomembranes. Ten (1%) of the 908 patients were diagnosed by endoscopy without a stool specimen, or at autopsy. No treatment was needed for 135 (15%) of the 908 CDAD patients, and 19 (2%) of the 908 died before treatment was started. Oral metronidazole was the treatment for 632 (70%) of 908 patients (1% intolerance, 2% failure, 7% relapse) and oral vancomycin was given to 122 (13%) of 908 patients (1% intolerance, 1% failure, 10% relapse). Twelve patients had pseudomembranous colitis at autopsy, and it was the primary cause of death in 5 (0.6%) of 908., Conclusions: CDAD usually responds to oral metronidazole or vancomycin but is nonetheless responsible for a high morbidity and occasional mortality in patients even when the diagnosis and treatment are pursued aggressively.

Objective: To report the investigation and effective control of a nosocomial epidemic of Clostridium difficile-associated diarrhea., Design: Concurrent surveillance for identification of new nosocomial cases, retrospective case-control analysis, and hospital formulary control of antibiotic use., Setting: University-affiliated Veterans Affairs Medical Center located in southwestern United States., Patients: Hospitalized patients who developed diarrhea submitted stool specimens for cytotoxin assay. Patients who were positive for cytotoxin were compared with control patients without infection., Measurements: Isolates of C. difficile were typed by restriction endonuclease analysis. Antimicrobial agent use from hospital pharmacy records and selected patient data from chart review were correlated with frequency of specific laboratory abnormalities., Results: For 13 months, the monthly incidence of C. difficile infection averaged more than five times that for the previous 21 months. Stool specimens from 34 patients (59%) contained a single strain (restriction enzyme analysis type J7). Clindamycin was statistically associated with the epidemic as shown by the following: clindamycin use at our center compared with national normal values, clindamycin use for years before compared with during the epidemic, monthly use of clindamycin compared with monthly frequency of infection, frequency of infection in patients receiving clindamycin compared with that in patients receiving other antimicrobial agents, and amount of clindamycin used by infected patients compared with that used by control patients. Restricting clindamycin use led to a prompt disease in infection rate and the type J7 organisms., Conclusion: A nosocomial epidemic of C. difficile diarrhea was controlled by analysis of antibiotic use patterns and by subsequent restriction of clindamycin.

The major controversy in the diagnosis of symptomatic gastrointestinal infection due to Clostridium difficile is whether laboratory evidence of the C. difficile organism in culture is sufficient or if evidence of one of the C. difficile toxins in stool should be required. Cultures performed properly on selective media currently are the most sensitive method for detection of C. difficile, whereas the cell cytotoxin assay for detection of toxin B is the most specific. Stool specimens from patients with clinical diarrhea are sometimes found to be culture-positive for C. difficile but assay-negative for cytotoxin. Samples from these patients can be viewed as false-positive by culture or false-negative by cytotoxin test. Evidence from endoscopy indicates that some patients whose stool is culture-positive for the organism but assay-negative for toxin do have pseudomembranous colitis, but its incidence among such patients (11%) is lower than that among patients whose stool is culture- and assay-positive (51%). Response to treatment with vancomycin or metronidazole is similar in the two groups of patients, and withholding treatment from patients whose stool contains C. difficile but not cytotoxin may result in increased morbidity and mortality. Up to one-third of C. difficile organisms from stool specimens that are culture-positive but assay-negative are incapable of producing cytotoxin in vitro, a finding that suggests these organisms may not be the cause of diarrhea.(ABSTRACT TRUNCATED AT 250 WORDS)

The systemic and mucosal humoral response to toxin A, the primary virulence factor of Clostridium difficile, was measured in sera and intestinal secretions from 21 patients with C. difficile diarrhea, 9 asymptomatic C. difficile fecal excretors, and 10 noncolonized control subjects. Toxin A-specific IgG was higher in convalescent sera of the patients with diarrhea (mean +/- SE, 990 +/- 260 ng/mL) than in acute sera (620 +/- 150 ng/mL), in sera from asymptomatic excretors (410 +/- 140 ng/mL), or control subjects (320 +/- 50 ng/mL; P < .05 convalescent vs. control). The pattern of toxin A-specific serum IgA and intestinal secretory IgA levels was similar to that of serum IgG in these groups. Neutralization of toxin A was demonstrated in 5 of 14 convalescent sera but only 1 of 13 acute sera (P = .04). However, the presence of neutralizing activity was independent of the subsequent clinical response. Therefore, most patients convalescent from C. difficile diarrhea demonstrate systemic and mucosal antibodies to toxin A, but these antibodies following natural infection do not appear to alter the clinical course of C. difficile infection.

To assess the risk of acquiring Clostridium difficile diarrhoea or colitis in patients colonised with C difficile, rectal swabs taken weekly for 9 weeks from patients with long-term (at least 7 days) hospital stays on three wards were cultured for C difficile. 60 (21%) of 282 patients were culture-positive for C difficile during their hospital stay, of whom 51 were symptom-free faecal excretors. C difficile diarrhoea developed in the other 9 patients; 2 were culture-positive for C difficile and had diarrhoea at the time of first culture, and 7 had diarrhoea or pseudomembranous colitis after 1-6 previously negative weekly rectal cultures. All patients with diarrhoea were on one ward, but symptom-free, excretors were found on all wards. HindIII chromosomal restriction endonuclease analysis (REA) of the C difficile isolates revealed 18 distinct types. All isolates from the patients with diarrhoea were one of two nearly identical REA types, B or B2. 26 of the 29 total B/B2 isolates were from patients on the same ward, which points to a nosocomial outbreak. The symptom-free excretors were not at increased risk of subsequent clinical illness.

Purpose: Despite recognition that Clostridium difficile diarrhea/colitis is a nosocomial infection, the manner in which this organism is transmitted is still not clear. Hands of health care workers have been shown to be contaminated with C. difficile and suggested as a vehicle of transmission. Therefore, we conducted a controlled trial of the use of disposable vinyl gloves by hospital personnel for all body substance contact (prior to the institution of universal body substance precautions) to study its effect on the incidence of C. difficile disease., Patients and Methods: The incidence of nosocomial C. difficile diarrhea was monitored by active surveillance for six months before and after an intensive education program regarding glove use on two hospital wards. The interventions included initial and periodic in-services, posters, and placement of boxes of gloves at every patient's bedside. Two comparable wards where no special intervention was instituted served as controls., Results: A decrease in the incidence of C. difficile diarrhea from 7.7 cases/1,000 patient discharges during the six months before intervention to 1.5/1,000 during the six months of intervention on the glove wards was observed (p = 0.015). No significant change in incidence was observed on the two control wards during the same period (5.7/1,000 versus 4.2/1,000). Point prevalence of asymptomatic C. difficile carriage was also reduced significantly on the glove wards but not on the control wards after the intervention period (glove wards, 10 of 37 to four of 43, p = 0.029; control wards, five of 30 to five of 49, p = 0.19). The cost of 61,500 gloves (4,505 gloves/100 patients) used was $2,768 on the glove wards, compared with $1,895 (42,100 gloves; 3,532 gloves/100 patients) on the control wards., Conclusions: Vinyl glove use was associated with a reduced incidence of C. difficile diarrhea and is indirect evidence for hand carriage as a means of nosocomial C. difficile spread.

Endoscopic and clinical features are reported for 39 patients detected early in the course of pseudomembranous colitis. Disease was detected early by virtue of careful surveillance in patients in whom diarrhea developed. Early proctosigmoidoscopic findings in pseudomembranous colitis are illustrated. Clinical presentation includes development of fever, leukocytosis, abdominal pain, and even an ileus picture on radiography in addition to diarrhea.

A large hospital outbreak of Clostridium difficile diarrhea at the Minneapolis Veterans Administration Medical Center (MVAMC) was studied by plasmid profile typing. Plasmids were obtained from 30 (37%) of 82 clinical isolates from MVAMC patients and 10 (67%) of 15 non-MVAMC isolates. While bacteriophage plus bacteriocin typing and polyacrylamide gel electrophoresis (PAGE) plus bacterial agglutination typing proved more universally applicable, plasmid profiles may be useful for tracing isolated epidemic outbreaks, reinfections and relapses caused by plasmid-bearing strains.

In a one-year period, 149 adult cases of Clostridium difficile-associated diarrhea and colitis were compared with 148 diarrhea-free controls. Eighty-seven percent were nosocomial and 75% were on surgical services. Endoscopy revealed pseudomembranes in 51% of the 109 cases in which stool cytotoxin was present, compared with 11% of the 40 cases that were culture-positive but cytotoxin-negative. Cases diagnosed only by stool culture showed essentially no differences from controls, 21% of whom had asymptomatic stool colonization. We estimate that only 20% of these cases had diarrhea due to C difficile. Compared with controls, cases diagnosed by the presence of cytotoxin or pseudomembranes were found to have been hospitalized longer at diarrhea onset, to have had more antecedent infections, and to have received clindamycin, multiple antimicrobials, and therapeutic antimicrobials more often than controls, but controls received prophylactic antimicrobials more frequently than cases. Cultures of the environment, patients, and personnel failed to detect a mechanism of acquisition.

The mean number of cases of Clostridium difficile diarrhea at the Minneapolis Veterans Administration Medical Center increased to 17.3 per month in June-August 1985, compared with 7.1 per month in the previous 17 mo. Plasmid profiles and clindamycin susceptibility were used as markers to evaluate the increase in cases. Ninety clindamycin-resistant and 22 clindamycin-susceptible isolates of C. difficile from 1985 were examined for plasmids. A clindamycin-resistant organism contained a cryptic plasmid of 3.1 kilobases (kb). None of the clindamycin-susceptible isolates contained the 3.1-kb plasmid, as compared with 40 of 90 clindamycin-resistant isolates (P less than .005). Restriction endonuclease digestion and Southern blot hybridization were used to confirm the identity of the 3.1-kb plasmid between strains. Isolates retained clindamycin resistance after plasmid curing. It could not be determined if the organism responsible was an indigenous C. difficile strain that acquired a plasmid or was a new strain introduced from outside the hospital.