Edgar C. Boedeker

Pathogenesis and treatment of Shiga toxin-producing Escherichia coli infections.

Purpose of review Shiga toxin-producing Escherichia coli cause hemorrhagic colitis and hemolytic uremic syndrome. We will summarize the literature on incidence and outcomes of these infections, and then review the pathogenesis to explain the current recommendations against antibiotic use and to suggest alternative therapies. Recent findings Shiga toxin-producing E. coli continue to be prevalent in the industrialized world because of dissemination in food products contaminated by ruminant feces. Declines in ground beef-related outbreaks have been matched by increased cases related to green vegetables. Fifteen percent of patients infected with E. coli O157:H7 progress to hemolytic uremic syndrome, but this figure may reach 50% if antibiotics are used. Mechanisms for bacteriophage induction causing Shiga toxin production, and for Shiga toxin dissemination to endothelium in gut, kidney and brain, may explain the negative effects of antibiotics and lead to rational therapies. Shiga toxin binders were not effective in clinical trials, but more avid binding agents may be. Current treatment recommendations are to maintain hydration to prevent thrombotic complications. Human vaccines are unlikely to be utilized. Cattle vaccines may prove the most significant approach to this disease. Summary Improved understanding of Shiga toxin-producing Escherichia coli pathophysiology and progression to hemolytic uremic syndrome provides the basis for prevention, prophylactic and treatment strategies.

Foodborne enteric infections

Foodborne infections are estimated to affect one in four Americans each year. Most these (67%) are caused by the Norwalk-like viruses, but Campylobacter and nontyphoidal Salmonellae together account for about one fourth of cases of illness in which a pathogen can be detected. Less common bacterial infections, such as with Listeria monocytogenes and the Shiga toxin-producing Escherichia coli, cause fewer infections but are important because of their severe complications or high mortality rate, or both. This review describes the recent development of a national surveillance system for foodborne illness, newer methods for molecular characterization of organisms for epidemiologic studies, and individual etiologic agents in the order of frequency of occurrence. Methods for decreasing the disease burden are discussed, including education of health care professionals and the public, modification of food-handling behaviors, the use of food irradiation, and the application of probiotics to foods.

Helicobacter pylori infection: treatment.

Current standard treatment regimens for Helicobacter pylori infection provide eradication rates 80 to 90%. These rates have been achieved with a variety of 1-week triple therapies using two antibiotics and an acid suppressant. Antibiotic resistance, which may develop during failed treatment, is becoming increasingly common and has led to studies of new regimens for primary therapy, and new strategies for salvage of failed therapy. Other regimens have been designed and tested with the aim of decreasing the cost of initial therapy or to improve compliance, but abbreviated regimens have high incidence of failure and may add to the problem of resistance. Increasing attention has been paid to the need for, and timing of, the determination of antibiotic resistance of H. pylori isolates either at the time of initial diagnosis or after treatment failure. New, simpler, and noninvasive methods are offered for follow-up to determine if eradication has been successful. Treatment regimens should be chosen based on local drug susceptibility patterns and the availability of approved therapeutic agents in each country. Established indications for testing for H. pylori and administering therapy include active or inactive peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, as well as hyperplastic polyps, hyperplastic gastropathy, postendoscopic resection for gastric malignancy, and acute H. pylori gastritis. It is now largely accepted that noninvestigated dyspepsia is an indication for testing for and treating H. pylori, but that dyspeptic symptoms shown not to be associated with ulcer (nonulcer dyspepsia) do not now provide an indication for testing. Controversial or unresolved indications for testing and treating include planned use of chronic antisecretory therapy, planned use of nonsteroidal anti-inflammatory drugs, and use as a general approach to the prevention of gastric cancer.

Gastrointestinal infections: an overview.

1. A functional outer membrane-associated inflammatory protein (oipA), which is an inducer of cytokine expression, was shown by regression analysis to be associated with duodenal ulcer, whereas its absence in infecting strains was likely to be associated with gastritis [1]. 2. The vacuolating cytotoxin (VacA) has been shown to associate with lipid raft [2] microdomains in epithelial cell membranes. Binding to protein tyrosine phosphatase receptors [3] by the cytotoxin was not sufficient for vacuolization if lipid rafts were not intact. 3. The introduction of the cytotoxin-associated gene product (cagA) into the cytoplasm of target cells requires a needlelike organelle, the type IV secretion system, encoded on the genes of the cag pathogenicity island. This organelle targets H. pylori to tight junction complexes [4], and the expression of the type IV secretion system is enhanced by the association with epithelial cells. Injection of cagA into host cells leads to phosphorylation, cytoskeletal rearrangement, and apoptosis. Genetic variations in the cagA gene sequence may alter kinase activation and phosphorylation.