神经内科患者难辨梭菌感染的报告

目的:了解住院老年病人难辨梭菌小区域暴发流行的情况。方法:对我院神经内科一起暴发流行难辨梭状芽胞杆菌相关性腹泻(CDAD)的5例老年患者进行回顾调查。结果5例难辨梭状芽胞杆菌相关性腹泻的病人占同期神经内科住院病人的3.57％(5/140);其中轻型1例,重型1例,暴发型3例;痊愈3例,死亡2例。结论:①老年住院患者、抗生素使用及严重的基础疾病、气管切开和胃管进食是导致难辨梭菌感染的高危因素。②区域性丛集分布的患病人群提示有外源性交叉感染的可能。③暴发型难辨梭状芽胞杆菌感染病情进展迅猛,并发症严重,预后极差。     

Changes in laboratory and clinical workload for Clostridium difficile infection from 2003 to 2007 in hospitals in Edinburgh

Clostridium difficile infection (CDI) is a growing concern with regard to increases in incidence and its associated financial burden. A retrospective analysis of patients admitted to Hospitals in Edinburgh from 2003 to 2007 and tested for C. difficile toxins was performed. A total of 45 412 faecal samples were tested and 6286 (13.8%) were positive. Overall CDI was identified in 1.7 cases/1000 in-patient occupied bed days (OBD). The incidence of CDI fell from 1.98 cases/1000 OBD in 2006 to 1.48 cases/1000 OBD in 2007. Renal Medicine, including Transplant Surgery, and Intensive Care had the highest incidence, with >6.2 cases/1000 OBD each, followed by Infectious Diseases and Gastrointestinal Medicine, with rates of 5.5 and 4.42 cases/1000 OBD, respectively. Medicine of the Elderly had an incidence of 1.69 cases/1000 OBD. Incidence increased with age, from 0.45 cases/1000 OBD in the 0–20-year-old age group to 2.02 cases/1000 OBD in the 61–80-year-old age group. Twelve percent of all toxin-positive patients were transferred through a minimum of two specialties when they remained positive for C. difficile toxins. Estimated costs over the study period for toxin testing were approximately £126 500 and the minimal potential hospitalization costs for patients with CDI was £20 000 000. The overall incidence of patients identified with CDI fell in 2007 compared to 2006. The incidence has increased with age; however, patients in Medicine of the Elderly had a much lower incidence than in several other specialties and therefore risk assessment of CDI should also be targeted within other specialties. Judicious application of infection control measures remains important for preventing CDI.     

Distal landing zone optimization before endovascular repair of aortic dissection

Background

The general goals of endovascular management in chronic distal thoracic aortic dissection are optimizing the true lumen, maintaining branch patency, and promoting false lumen (FL) thrombosis. Distal seal can be challenging in chronic distal thoracic aortic dissection due to the well-established secondary fenestrations and fibrotic septum. We describe our approach of distal landing zone optimization (DLZO) to enable full-diameter contact of the distal endoprosthesis.

Clostridium difficile toxoid vaccine in recurrent C. difficile-associated diarrhea

BACKGROUND & AIMS: Recurrent C difficile -associated diarrhea (CDAD) is associated with a lack of protective immunity to C difficile toxins. A parenteral C difficile vaccine containing toxoid A and toxoid B was reported previously to be safe and immunogenic in healthy volunteers. Our aim was to examine whether the vaccine is also well tolerated and immunogenic in patients with recurrent CDAD. METHODS: Subjects received 4, 50-microg intramuscular inoculations of the C difficile vaccine over an 8-week period. Serum antitoxin antibodies were measured by ELISA, and toxin neutralizing activity was evaluated using the tissue culture cytotoxin assay. RESULTS: Three patients with multiple episodes of recurrent CDAD were vaccinated. Two of the 3 showed an increase in serum IgG antitoxin A antibodies (3-fold and 4-fold increases, respectively) and in serum IgG antitoxin B antibodies (52-fold and 20-fold, respectively). Both also developed cytotoxin neutralizing activity against toxin A and toxin B. Prior to vaccination, the subjects had required nearly continuous treatment with oral vancomycin for 7, 9, and 22 months, respectively, to treat recurrent episodes of CDAD. After vaccination, all 3 subjects discontinued treatment with oral vancomycin without any further recurrence. CONCLUSIONS: A C difficile toxoid vaccine induced immune responses to toxins A and B in patients with CDAD and was associated with resolution of recurrent diarrhea. The results of this study support the feasibility of active vaccination against C difficile and its toxins in high-risk individuals but must be validated in larger, randomized, controlled trials.     

Clostridium difficile: recent epidemiologic findings and advances in therapy

Clostridium difficile-associated disease (CDAD) has become an important public health problem. The causative organism is acquired by the oral route from an environmental source or by contact with an infected person or a health care worker who serves as a vector. Disruption of the bowel microflora, generally by antibiotics, creates an environment that allows C. difficile to proliferate. Organisms produce toxins A and B, which cause intense inflammation of the colonic mucosa. The syndrome that results includes severe diarrhea, fever, abdominal pain, and leukocytosis. A new strain of C. difficile has become prevalent in the United States, Canada, and the United Kingdom. Identified by pulsed-field gel electrophoresis (PFGE), this strain is called North America PFGE type 1, abbreviated as NAP-1. Clostridium difficile NAP-1 characteristically generates large amounts of toxins A and B, as well as an additional binary toxin and is associated with enhanced morbidity and a poor response to antibiotic therapy. Mild cases of CDAD may respond to cessation of antibiotic therapy, perhaps related to antibody production by the infected person, but most infected persons require antimicrobial therapy. Vancomycin has been approved by the United States Food and Drug Administration for treatment of CDAD, but reluctance to use this antibiotic in the hospital setting has led to reliance on metronidazole as first-line therapy. Recent studies show a high rate of failure, due either to infection by NAP-1 or to the presence, in hospitals, of older and sicker adults who have been treated with many broad-spectrum antibiotics. Nitazoxanide, bacitracin, teicoplanin, and fusidic acid are additional agents that have published efficacy for this indication in humans. Rifaximin and PAR-101 are under investigation. Other therapies, including polymers that bind C. difficile toxin and monoclonal antibodies to toxins, and preventive measures such as toxoid vaccines are also under study.     

PPI引起艰难梭状芽孢杆菌性腹泻的危险因素

目的:评价治疗酸相关性疾病患者的质子泵抑制剂是引起艰难梭状芽孢杆菌性腹泻的另类危险因素。方法:查阅近期文献进行评价和分析。结果:队列研究表明艰难梭状芽孢杆菌性腹泻发生于约6.8%用过抗生素的住院患者,多自变量因素分析表明艰难梭状芽孢菌性腹泻与质子泵抑制剂的应用明显相关。结论:抗生素破坏了正常肠道菌群,公认是引起艰难梭状芽孢杆菌性腹泻的危险因素,而胃酸度降低一直被认为是其危险因素,质子泵抑制剂因为其强力的抑酸作用,可能是致艰难梭状芽孢杆菌性腹泻的独立危险因素。     

A novel fusion protein containing the receptor binding domains of C. difficile toxin A and toxin B elicits protective immunity against lethal toxin and spore challenge in preclinical efficacy models

Antibodies targeting the Clostridium difficile toxin A and toxin B confer protective immunity to C. difficile associated disease in animal models and provided protection against recurrent C. difficile disease in human subjects. These antibodies are directed against the receptor binding domains (RBD) located in the carboxy-terminal portion of both toxins and inhibit binding of the toxins to their receptors. We have constructed a recombinant fusion protein containing portions of the RBD from both toxin A and toxin B and expressed it in Escherichia coli. The fusion protein induced high levels of serum antibodies to both toxins A and B capable of neutralizing toxin activity both in vitro and in vivo. In a hamster C. difficile infection model, immunization with the fusion protein reduced disease severity and conferred significant protection against a lethal dose of C. difficile spores. Our studies demonstrate the potential of the fusion protein as a vaccine that could provide protection from C. difficile disease in humans.     

Costs of nosocomial Clostridium difficile-associated diarrhoea

Nosocomial Clostridium difficile-associated disease (CDAD) is a common infection in hospitals. A matched case-control study was carried out to determine hospital-wide excess costs due to CDAD. Cases were assessed by prospective hospital-wide surveillance in a tertiary care university hospital in 2006. Nosocomial cases of CDAD (>72h after admission) were matched to control patients without CDAD in a ratio 1:3 using the same diagnosis-related group in the same year, for a hospital stay at least as long as the time of risk of the CDAD cases before infection and a Charlson comorbidity index +/-1. Data on overall costs per case were provided by the finance department. Matching was possible for 45 nosocomial CDAD cases. The difference in the length of stay showed that CDAD cases stayed significantly longer (median 7 days; P=0.006) than their matched controls. The average cost per CDAD patient was euro33,840. The difference in the cost per patient showed that the cost for CDAD patients was significantly more than for their matched controls (median euro7,147; 95% confidence interval: 4,067-9,276). Nosocomial CDAD is associated with high costs for healthcare systems. Clinicians should be aware of the financial impact of this disease and the application of appropriate infection control measures is recommended to reduce spread.