Nosocomial acquisition of Clostridium difficile infection

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 empyema caused by Clostridium difficile.

Pleural infection with Clostridium difficile is extremely rare. A case of nosocomial empyema following chest drain insertion in a 46 year old man is described. The potential of C difficile to cause extra-intestinal infections should be recognised and its isolation from other sites should not be ignored.     

Intestinal colonization of infant hamsters with Clostridium difficile

Infant hamsters of different ages were examined for their susceptibility to enteric Clostridium difficile colonization. Intragastric administration of C. difficile to infant hamsters resulted in multiplication of the organism in the intestinal tracts of animals 4 to 12 days old; hamsters younger or older were resistant to C. difficile intestinal colonization. Toxicity to the colonized animals could not be demonstrated despite cytotoxin titers in some infant hamsters comparable to titers found in the intestinal tracts of adult hamsters with C. difficile-associated intestinal disease. When introduced into 4-day-old hamsters, C. difficile colonized the intestinal tract and remained at high levels until the animals were 13 days old, at which time the presence of intestinal C. difficile could no longer be demonstrated. The number of C. difficile required to colonize the intestinal tracts of 50% of 7-day-old hamsters was 18 viable cells. On the other hand, 10(8) viable cells of C. difficile failed to colonize the intestinal tracts of healthy, non-antibiotic-treated adult hamsters.     

Clostridium difficile Infection: A Comprehensive Review

Clostridium difficile is one of the most important causes of healthcare acquired diarrhea. The disease spectrum caused by C. difficile infection ranges from mild, self-limited, illness to a severe, life-threatening colitis. The incidence of C. difficile associated disease has risen dramatically over the last decade, leading to increased research interest aiming at the discovery of new virulence factors and the development of new treatment and prevention regimens. This review summarizes the pathogenesis and changing epidemiology of C. difficile associated disease, the clinical spectrum and laboratory methods to diagnose C. difficile infection, and current treatment strategies.     

Nosocomial diarrhea in adults due to microorganisms other than Clostridium difficile

Nosocomial diarrhea of the adult is to the largest extend caused by Clostridium difficile. However, one must not underestimate the importance of other bacteria such as Salmonella or Shigella, which are most common in developing countries. Other viruses and parasites can equally be responsible for causing such infections.     

Clostridium difficile Toxin B Induces Apoptosis in Intestinal Cultured Cells

Toxigenic strains of the anaerobic bacterium Clostridium difficile produce at least two large, single-chain protein exotoxins involved in the pathogenesis of antibiotic-associated diarrhea and colitis. Toxin A (CdA) is a cytotoxic enterotoxin, while toxin B (CdB) is a more potent cytotoxin lacking enterotoxic activity. This study dealt with CdB, providing the first evidence that intestinal cells exposed to this toxin exhibit typical features of apoptosis in that a significant proportion of the treated cells displayed nuclear fragmentation and chromatin condensation. In keeping with ultrastructural data, CdB-treated cells showed the typical flow cytometric hallmark of apoptosis consisting of a distinct sub-G₁ peak. The CdB-induced apoptotic response was dose and time dependent and not simply due to the actin-disrupting effect of the toxin or to the subsequent impairment of cell anchorage. Rather, the inhibition of proteins belonging to the Rho family due to CdB seems to play a role in the induction of apoptosis in intestinal cells. The origin of cells and the growth rate may also be cofactors relevant to such a response.     

Nosocomial infection with Clostridium difficile investigated by pyrolysis mass spectrometry.

Fifty-eight isolates of Clostridium difficile from two distinct outbreaks were examined for inter-strain similarity by pyrolysis mass spectrometry (PMS). The first outbreak began on a geriatric acute unit and spread to a long stay geriatric facility. PMS analysis showed that most isolates from both sites were indistinguishable. Isolates obtained in the preceding year from the long stay facility were found to be closely similar to these outbreak isolates. In the second, smaller outbreak on a female medical ward in another general hospital, PMS again showed that a single strain was probably responsible. Representative isolates from these two different outbreaks were shown to be distinct. The ability to compare rapidly large numbers of isolates of C. difficile makes PMS attractive for initial screening in suspected outbreaks, providing important information for outbreak management and allowing conventional typing methods to be concentrated on relevant isolates.     

医院感染的耐药菌分布特点与药物应用

目的 分析我院医院感染的耐药菌分布特点以及抗生素的应用情况。方法 选择2017年7月~2018年7月我院住院治疗的多重耐药菌感染者的生物标本进行细菌检测和药敏试验,并对结果进行分析。结果 检出多重耐药菌的为962株,检出率为14.70%（962/6542）;多重耐药菌株感染的发生率为21.74%（962/4425）;其中有478株（49.69%）为产超广谱β-内酰胺酶（ESBLs）大肠埃希菌;科室分布主要以普外科（186株,19.33%）最高;大肠埃希菌和肺炎克雷伯菌对于头孢西丁、头孢哌酮-舒巴坦、美罗培南、亚胺培南、哌拉西林-他唑巴坦和阿米卡星的耐药率较低;金黄色葡萄球菌对于替考拉林、阿米卡星、庆大霉素、万古霉素和利奈唑胺的耐药率均为0,对于左氧氟沙星和莫西沙星的耐药率较低。结论 细菌耐药的形势严峻,临床应用时要首选敏感度较高的抗生素,以防细菌耐药进一步发生。医院要严格加强防控举措,切实避免医院感染的发生。     

Dynamics and Establishment of Clostridium difficile Infection in the Murine Gastrointestinal Tract

Clostridium difficile infection (CDI) following antibiotic therapy is a major public health threat. While antibiotic disruption of the indigenous microbiota underlies the majority of cases of CDI, the early dynamics of infection in the disturbed intestinal ecosystem are poorly characterized. This study defines the dynamics of infection with C. difficile strain VPI 10463 throughout the gastrointestinal (GI) tract using a murine model of infection. After inducing susceptibility to C. difficile colonization via antibiotic administration, we followed the dynamics of spore germination, colonization, sporulation, toxin activity, and disease progression throughout the GI tract. C. difficile spores were able to germinate within 6 h postchallenge, resulting in the establishment of vegetative bacteria in the distal GI tract. Spores and cytotoxin activity were detected by 24 h postchallenge, and histopathologic colitis developed by 30 h. Within 36 h, all infected mice succumbed to infection. We correlated the establishment of infection with changes in the microbiota and bile acid profile of the small and large intestines. Antibiotic administration resulted in significant changes to the microbiota in the small and large intestines, as well as a significant shift in the abundance of primary and secondary bile acids. Ex vivo analysis suggested the small intestine as the site of spore germination. This study provides an integrated understanding of the timing and location of the events surrounding C. difficile colonization and identifies potential targets for the development of new therapeutic strategies.     

The Bristol Stool Scale and Its Relationship to Clostridium difficile Infection

The Bristol stool form scale classifies the relative density of stool samples. In a prospective cohort study, we investigated the associations between stool density, C. difficile assay positivity, hospital-onset C. difficile infection, complications, and severity of C. difficile. We describe associations between the Bristol score, assay positivity, and clinical C. difficile infection.     

Survey of Incidence of Clostridium difficile Infection in Canadian Hospitals and Diagnostic Approaches

A questionnaire relating to Clostridium difficile disease incidence and diagnostic practices was sent to 380 Canadian hospitals (all with >50 beds). The national questionnaire response rate was 63%. In-house testing was performed in 17.6, 61.5, and 74.2% of the hospitals with <300, 300 to 500, and >500 beds, respectively. The average test positivity rates were 17.2, 15.3, and 13.2% for hospitals with <300, 300 to 500, and >500 beds, respectively. The average disease incidences were 23.5, 30.8, and 40.3 cases per 100,000 patient days in the hospitals with <300, 300 to 500, and >500 beds, respectively. In the 81 hospitals where in-house testing was performed, cytotoxin testing utilizing tissue culture was most common (44.4%), followed by enzyme-linked immunosorbent assay (38.3%), culture for toxigenic C. difficile (32.1%), and latex agglutination (13.6%). The clinical criteria for C. difficile testing were variable, with 85% of hospitals indicating that a test was done automatically if ordered by a doctor. Our results show that C. difficile-associated diarrhea is a major problem in hospitals with ≥200 beds. Despite a lower disease incidence in smaller hospitals, there was a higher diagnostic test positivity rate. This may reflect the preference of smaller hospitals for culture and latex agglutination tests.     

High Frequency of Antibiotic-Associated Diarrhea due to Toxin A-Negative, Toxin B-Positive Clostridium difficile in a Hospital in Japan and Risk Factors for Infection

Patients hospitalized in a hospital with a high incidence of antibiotic-associated diarrhea due to toxin A-negative, toxin B-positive (A–/B+) Clostridium difficile were retrospectively investigated to determine the clinical manifestations and risk factors for infection. Of 77 Clostridium difficile isolates obtained from 77 patients during the 1-year investigation period, 30 were A–/B+ and 47 were toxin A-positive, toxin B-positive (A+/B+). By pulsed-field gel electrophoresis analysis, 23 of the 30 A–/B+ strains were outbreak-related, suggesting nosocomial spread of a single type of bacterium, which mainly affected patients in the wards of respiratory medicine, hematology and neurology. Using regression analysis, three factors were found to be associated with infection by A–/B+ isolates: (i) exposure to antineoplastic agents (P=0.01, odds ratio [OR]=5.1), (ii) the use of nasal feeding tubes (P=0.008, OR=5.2), and (iii) assignment to a certain internal medicine ward (P=0.05, OR=3.0). Between patients with Clostridium difficile-associated diarrhea caused by A–/B+ strains and those with A+/B+ strains, no statistically significant difference was found in body temperature, serum concentration of C-reactive protein, leukocyte count in whole blood, frequency of diarrhea, or type of underlying disease. These results indicate that A–/B+ strains of Clostridium difficile can cause intestinal infection in humans and they spread nosocomially in the same manner as A+/B+ strains.     

Contribution of Adenosine A2B Receptors in Clostridium difficile Intoxication and Infection

Clostridium difficile toxins A (TcdA) and B (TcdB) induce a pronounced systemic and intestinal inflammatory response. A_2B adenosine receptors (A_2BARs) are the predominant adenosine receptors in the intestinal epithelium. We investigated whether A_2BARs are upregulated in human intestinal cells by TcdA or TcdB and whether blockade of A_2BARs can ameliorate C. difficile TcdA-induced enteritis and alter the outcome of C. difficile infection (CDI). Adenosine receptor subtype (A₁, A_2A, A_2B, and A₃) mRNAs were assayed in HCT-8 cells. Ileal loops from wild-type rabbits and mice and A_2BAR^−/− mice were treated with TcdA, with or without the selective A_2BAR antagonist ATL692 or PSB1115. A murine model of CDI was used to determine the effect of A_2BAR deletion or blockade with the orally available agent ATL801, on clinical outcome, histopathology and intestinal interleukin-6 (IL-6) expression from infection. TcdA and TcdB upregulated A_2BAR gene expression in HCT-8 cells. ATL692 decreased TcdA-induced secretion and epithelial injury in rabbit ileum. Deletion of A_2BARs reduced secretion and histopathology in TcdA-challenged mouse ileum. Deletion or blockade of A_2BARs reduced histopathology, IL-6 expression, weight loss, diarrhea, and mortality in C. difficile-infected mice. A_2BARs mediate C. difficile toxin-induced enteritis and disease. Inhibition of A_2BAR activation may be a potential strategy to limit morbidity and mortality from CDI.     

Economic Evaluation of Laboratory Testing Strategies for Hospital-Associated Clostridium difficile Infection

Clostridium difficile infection (CDI) is the most common cause of infectious diarrhea in health care settings, and for patients presumed to have CDI, their isolation while awaiting laboratory results is costly. Newer rapid tests for CDI may reduce this burden, but the economic consequences of different testing algorithms remain unexplored. We used decision analysis from the hospital perspective to compare multiple CDI testing algorithms for adult inpatients with suspected CDI, assuming patient management according to laboratory results. CDI testing strategies included combinations of on-demand PCR (odPCR), batch PCR, lateral-flow diagnostics, plate-reader enzyme immunoassay, and direct tissue culture cytotoxicity. In the reference scenario, algorithms incorporating rapid testing were cost-effective relative to nonrapid algorithms. For every 10,000 symptomatic adults, relative to a strategy of treating nobody, lateral-flow glutamate dehydrogenase (GDH)/odPCR generated 831 true-positive results and cost $1,600 per additional true-positive case treated. Stand-alone odPCR was more effective and more expensive, identifying 174 additional true-positive cases at $6,900 per additional case treated. All other testing strategies were dominated by (i.e., more costly and less effective than) stand-alone odPCR or odPCR preceded by lateral-flow screening. A cost-benefit analysis (including estimated costs of missed cases) favored stand-alone odPCR in most settings but favored odPCR preceded by lateral-flow testing if a missed CDI case resulted in less than $5,000 of extended hospital stay costs and <2 transmissions, if lateral-flow GDH diagnostic sensitivity was >93%, or if the symptomatic carrier proportion among the toxigenic culture-positive cases was >80%. These results can aid guideline developers and laboratory directors who are considering rapid testing algorithms for diagnosing CDI.