We studied the acquisition and transmission of Clostridium difficile infection prospectively on a general medical ward by serially culturing rectal-swab specimens from 428 patients admitted over an 11-month period. Immunoblot typing was used to differentiate individual strains of C. difficile. Seven percent of the patients (29) had positive cultures at admission. Eighty-three (21 percent) of the 399 patients with negative cultures acquired C. difficile during their hospitalizations. Of these patients, 52 (63 percent) remained asymptomatic and 31 (37 percent) had diarrhea; none had colitis. Patient-to-patient transmission of C. difficile was evidenced by time-space clustering of incident cases with identical immunoblot types and by significantly more frequent and earlier acquisition of C. difficile among patients exposed to roommates with positive cultures. Of the hospital personnel caring for patients with positive cultures, 59 percent (20) had positive cultures for C. difficile from their hands. The hospital rooms occupied by symptomatic patients (49 percent) as well as those occupied by asymptomatic patients (29 percent) were frequently contaminated. Eighty-two percent of the infected cohort still had positive cultures at hospital discharge, and such patients were significantly more likely to be discharged to a long-term care facility. We conclude that nosocomial C. difficile infection, which was associated with diarrhea in about one third of cases, is frequently transmitted among hospitalized patients and that the organism is often present on the hands of hospital personnel caring for such patients. Effective preventive measures are needed to reduce nosocomial acquisition of C. difficile.

Nosocomial acquisition of Clostridium difficile infection

Developmental microbial ecology of the neonatal gastrointestinal tract

Background:Newborn infants in modern maternity hospitals are subject to numerous factors that affect normal intestinal colonization-for example, cesarean delivery and antimicrobial agents. To study the duration of the effect of external factors on intestinal colonization, two groups of infan

Fecal Microflora in Healthy Infants Born by Different Methods of Delivery: Permanent Changes in Intestinal Flora After Cesarean Delivery

Objectives To review and summarize the status of diagnosis, epidemiology, infection control, and treatment of Clostridium difficile-associated disease (CDAD). Diagnosis A case definition of CDAD should include the presence of symptoms (usually diarrhea) and at least one of the following positive tests: endoscopy revealing pseudomembranes, stool cytotoxicity test for toxin B, stool enzyme immunoassay for toxin A or B, or stool culture for C difficile (preferably with confirmation of organism toxicity if a direct stool toxin test is negative or not done). Testing of asymptomatic patients, including those who are asymptomatic after treatment, is not recommended other than for epidemiologic purposes. Lower gastrointestinal endoscopy is the only diagnostic test for pseudomembranous colitis, but it is expensive, invasive, and insensitive (51% to 55%) for the diagnosis of CDAD. Stool culture is the most sensitive laboratory test currently in clinical use, but it is not as specific as the cell cytotoxicity assay. Epidemiology C difficile is the most frequently identified cause of nosocomial diarrhea. The majority of C difficile infections are acquired nosocomially, and most patients remain asymptomatic following acquisition. Antimicrobial exposure is the greatest risk factor for patients, especially clindamycin, cephalosporins, and penicillins, although virtually every antimicrobial has been implicated. Cases of CDAD unassociated with prior antimicrobial or antineoplastic use are very rare. Hands of personnel, as well as a variety of environmental sites within institutions, have been found to be contaminated with C difficile, which can persist as spores for many months. Contaminated commodes, bathing tubs, and electronic thermometers have been implicated as sources of C difficile. Symptomatic and asymptomatic infected patients are the major reservoirs and sources for environmental contamination. Both genotypic and phenotypic typing systems for C difficile are available and have enhanced epidemiologic investigation greatly. Infection control Successful infection control measures designed to prevent horizontal transmission include the use of gloves in handling body substances and replacement of electronic thermometers with disposable devices. Isolation, cohorting, handwashing, environmental disinfection, and treatment of asymptomatic carriers are recommended practices for which convincing data of efficacy are not available. The most successful control measure directed at reduction in symptomatic disease has been antimicrobial restriction. Treatment Treatment of symptomatic (but not asymptomatic) patients with metronidazole or vancomycin for 10 days is effective; metronidazole may be preferred to reduce risk of vancomycin resistance among other organisms in hospitals. Recurrence of symptoms occurs in 7% to 20% of patients and is due to both relapse and reinfection. Over 90% of first recurrences can be treated successfully in the same manner as initial cases. Combination treatment with vancomycin plus rifampin or the addition orally of the yeast Saccharomyces boulardii to vancomycin or metronidazole treatment has been shown to prevent subsequent diarrhea in patients with recurrent disease.

Clostridium difficile-associated diarrhea and colitis

The prevalence of resistance in enterococci to antibiotics, commonly used for therapy in poultry or as antimicrobial growth promoters (AMGPs), was determined in faecal samples of two chicken populations: broilers in which antibiotic and AMGP use is common and laying-hens with a low antibiotic usage. In addition faecal samples were examined from three human populations: broiler farmers, laying-hen farmers and poultry slaughterers. MICs of an extended panel of antibiotics for a randomly chosen gentamicin- or vancomycin-resistant enterococcal isolate from each faecal specimen were also determined. The prevalence of resistance for all antibiotics tested was higher in broilers than in laying-hens. Resistance in faecal enterococci of broiler farmers was for nearly all antibiotics higher than those observed in laying-hen farmers and poultry slaughterers. The overall resistance in broilers was correlated with the resistance in broiler farmers and in poultry slaughterers. No correlation between the results obtained in the laying-hens with any of the other populations was found. The 27 gentamicin-resistant isolates all showed high-level resistance to gentamicin and two of these isolates, both Enterococcus faecium, were resistant to all antibiotics tested, except vancomycin. The 73 vancomycin-resistant enterococci (VRE) isolated from the five populations belonged to four different species and in all isolates the vanA gene cluster was detected by blot hybridization. The pulsed-field gel electrophoresis (PFGE) patterns of these vancomycin-resistant enterococci were quite heterogeneous, but Enterococcus hirae isolates with the same or a closely related PFGE pattern were isolated at two farms from the broiler farmer and from broilers. Molecular characterization of vanA-containing transposons of these isolates showed that similar transposon types, predominantly found in poultry, were present. Moreover, similar vanA elements were not only found in isolates with the same PFGE pattern but also in other VRE isolated from both humans and chickens. The results of this study suggest transmission of resistance in enterococci from animals to man. For VRE this might be clonal transmission of animal strains, but transposon transfer seems to occur more commonly.

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Antibiotic resistance of faecal Escherichia coli in poultry, poultry farmers and poultry slaughterers

Typing scheme for Clostridium difficile: its application in clinical and epidemiological studies.

A total of 2525 strains of Escherichia coli were isolated from the faeces of 33 mothers, the faeces of their babies and the mucus extracted from the babies' mouths after delivery. Of these strains 1832 could be O-serotyped with 150 O antisera. E. coli were isolated from 28 babies and the same serotypes as were found in their mothers were found in 22 of them. E. coli was isolated from only 14 of the mucus specimens but in 12 of these at least one of the serotypes present was subsequently found in the babies' stools.

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The origin of O serotypes of Escherichia coli in babies after normal delivery.

The epidemiology of Clostridium difficile with use of a typing scheme: nosocomial acquisition and cross-infection among immunocompromised patients.

A typing method for Clostridium difficile based on the incorporation of [35S]methionine into cellular proteins, their separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and their visualization by autoradiography is described. On analysis of the radiolabeled-protein profiles, nine distinct groups were observed (A to E and W to Z). The method, which is simple, reproducible, and readily expandable, has been applied in epidemiological studies to demonstrate cross-infection and hospital acquisition of C. difficile.

Method for the typing of Clostridium difficile based on polyacrylamide gel electrophoresis of [35S]methionine-labeled proteins.

Most babies are colonized by the predominant strains of Escherichia coli present in their own mother's faecal flora. Those babies who did not acquire their maternal faecal flora acquired strains of E. coli belonging to a small number of the possible serotypes. Moreover, the same serotypes were found in several babies and other mothers, suggesting spread within the ward. These few strains included some of the O groups which had previously commonly been found as urinary pathogens. These strains may have increased potentialities for colonization of human bowel. Antigenic and biochemical variation was observed among the strains.

Sheila M. O'farrell

Papers

Typing scheme for Clostridium difficile: its application in clinical and epidemiological studies.

The origin of O serotypes of Escherichia coli in babies after normal delivery.

The epidemiology of Clostridium difficile with use of a typing scheme: nosocomial acquisition and cross-infection among immunocompromised patients.

Method for the typing of Clostridium difficile based on polyacrylamide gel electrophoresis of [35S]methionine-labeled proteins.

Spread of Escherichia coli colonizing newborn babies and their mothers