Studies of microbial pathogens and the toxins they produce are important for determining the mechanisms by which they cause disease and spread throughout a population. Some bacteria produce secretory enterotoxins (such as choleratoxin or the heat-labile or stable enterotoxins produced by E. coli) that invade cells directly. Others produce cytotoxins (such as those produced by Shigella, enteroinvasive E. coli, or C. difficile) that damage cells or trigger host responses that cause small or large bowel diseases (such as enteroaggregative or enteropathogenic E. coli or Salmonella). Viruses (such as noroviruses and rotaviruses) and protozoa (such as Cryptosporidium, Giardia or Entameba histolytica) disrupt cell functions and cause short-or long-term disease. Much epidemiological data about these pathogens have been collected from community-and hospital-acquired settings, as well from patients with traveler's or persistent diarrhea. These studies have led to practical approaches for prevention, diagnosis and treatment.

Increased CDI incidence and severity in older adults corresponds with the emergence of the BI/NAP1 strain, making elucidation of the host immune response extremely important. We therefore infected germ-free, aged C57BL/6 mice with a BI strain and monitored for response. Infected mice were moribund 48–72 hours post infection, developed gross and histologic cecitis and colitis, elevated concentrations of KC, IL-1β, MCP-1, and G-CSF, and decreased IFN-γ, IL-12(p40), IL-12(p70), and IL-10 vs. controls. Aged, germ-free C57BL/6 mice are susceptible to fulminant CDI from a BI strain and represent a novel model to further elucidate the host immune response to acute CDI.

Objective Hospitalizations for acute bacterial skin and skin structure infection (ABSSSI) are common. Optimizing antibiotic use for ABSSSIs requires an understanding of current management. The objective of this study was to evaluate antibiotic prescribing practices and factors affecting prescribing in a diverse group of hospitals. Design Multicenter, retrospective cohort study Setting Seven community and academic hospitals Methods Children and adults hospitalized between June 2010 and May 2012 for cellulitis, wound infection, or cutaneous abscess were eligible. The primary endpoint was a composite of two prescribing practices representing potentially avoidable antibiotic exposure: 1) use of antibiotics with a broad spectrum of activity against gram-negative bacteria; or 2) treatment duration >10 days. Results 533 cases were included: 320 with non-purulent cellulitis, 44 with wound infection or purulent cellulitis, and 169 with abscess. Of 492 cases with complete prescribing data, the primary endpoint occurred in 394 (80%) cases and varied significantly across hospitals (64 – 97%, p<.001). By logistic regression, independent predictors of the primary endpoint included wound infection or purulent cellulitis (odds ratio [OR] 5.12, 95% confidence interval [CI] 1.46 – 17.88), head or neck involvement (OR 2.83, 95%CI 1.17 – 6.82), adult cases (OR 2.20, 95%CI 1.18 – 4.11), and admission to a community hospital (OR 1.90, 95%CI 1.05 – 3.44). Conclusions Among patients hospitalized for ABSSSI, use of antibiotics with broad gram-negative activity or treatment courses longer than 10 days were common. There may be substantial opportunity to reduce antibiotic exposure through shorter courses of therapy targeting gram-positive bacteria.

BackgroundSevere Clostridium difficile toxin-induced enteritis is characterized by exuberant intestinal tissue inflammation, epithelial disruption and diarrhea. Adenosine, through its action on the adenosine A2A receptor, prevents neutrophillic adhesion and oxidative burst and inhibits inflammatory cytokine production. Alanyl-glutamine enhances intestinal mucosal repair and decreases apoptosis of enterocytes. This study investigates the protection from enteritis by combination therapy with ATL 370, an adenosine A2A receptor agonist, and alanyl-glutamine in a rabbit and murine intestinal loop models of C. difficile toxin A-induced epithelial injury.MethodsToxin A with or without alanyl-glutamine was administered intraluminally to rabbit ileal or murine cecal loops. Animals were also given either PBS or ATL 370 parenterally. Ileal tissues were examined for secretion, histopathology, apoptosis, Cxcl1/KC and IL-10.ResultsATL 370 decreased ileal secretion and histopathologic changes in loops treated with Toxin A. These effects were reversed by the A2A receptor antagonist, SCH 58261, in a dose-dependent manner. The combination of ATL 370 and alanyl-glutamine significantly further decreased ileal secretion, mucosal injury and apoptosis more than loops treated with either drug alone. ATL 370 and alanyl-glutamine also decreased intestinal tissue KC and IL-10.ConclusionsCombination therapy with an adenosine A2A receptor agonist and alanyl-glutamine is effective in reversing C. difficile toxin A-induced epithelial injury, inflammation, secretion and apoptosis in animals and has therapeutic potential for the management of C. difficile infection.