MAPK-activated protein kinase 2 contributes to Clostridium difficile-associated inflammation.

Clostridium difficile infection (CDI) results in toxin-induced epithelial injury and marked intestinal inflammation. Fecal markers of intestinal inflammation correlate with CDI disease severity, but regulation of the inflammatory response is poorly understood. Previous studies demonstrated that C. difficile toxin TcdA activates p38 kinase in tissue culture cells and mouse ilium, resulting in interleukin-8 (IL-8) release. Here, we investigated the role of phosphorylated mitogen-activated protein kinase (MAPK)-activated protein kinase (MK2 kinase, pMK2), a key mediator of p38-dependent inflammation, in CDI. Exposure of cultured intestinal epithelial cells to the C. difficile toxins TcdA and TcdB resulted in p38-dependent MK2 activation. Toxin-induced IL-8 and GROα release required MK2 activity. We found that p38 and MK2 are activated in response to other actin-disrupting agents, suggesting that toxin-induced cytoskeleton disruption is the trigger for kinase-dependent cytokine response. Phosphorylated MK2 was detected in the intestines of C. difficile-infected hamsters and mice, demonstrating for the first time that the pathway is activated in infected animals. Furthermore, we found that elevated pMK2 correlated with the presence of toxigenic C. difficile among 100 patient stool samples submitted for C. difficile testing. In conclusion, we find that MK2 kinase is activated by TcdA and TcdB and regulates the expression of proinflammatory cytokines. Activation of p38-MK2 in infected animals and humans suggests that this pathway is a key driver of intestinal inflammation in patients with CDI.

Genome sequence of Listeria monocytogenes 07PF0776, a cardiotropic serovar 4b strain.

Listeria monocytogenes is a food-borne bacterial pathogen commonly associated with serious invasive infections of the central nervous system or of the developing fetus. We present the genome sequence of Listeria monocytogenes 07PF0776, a serovar 4b isolate from a human myocardial abscess that exhibits enhanced invasion of cardiac tissue.

Recognition and prevention of hospital-associated enteric infections in the intensive care unit.

The objectives of this article were to review the causes and extent of hospital-associated infectious diarrhea and associated risks in the general hospital ward and intensive care unit (ICU), to compare microorganisms with similar symptoms to aid in recognition that will lead to timely and appropriate treatment and control measures, and to propose infection prevention protocols that could decrease human process errors in the ICU. This literature review describes epidemiology, comparison of microbial characteristics for potential hospital-associated enteric pathogens, diagnosis, and prevention, especially if important in the ICU, and particularly in regard to Clostridium difficile. Enteric organisms that most commonly cause hospital-associated infectious diarrhea in acute care settings and the ICU are C. difficile, rotavirus, and norovirus, although others may also be important, particularly in developing countries. To recognize and control infectious diarrhea successfully in the ICU, intensivists should be aware that epidemiology, risks, and prevention measures may differ between these microorganisms. In addition, intensivists should be ready to implement systems changes related to notification, isolation precautions and prevention, and environmental cleaning in the ICU.

Clostridium difficile in the ICU: the struggle continues.

Clostridium difficile infection (CDI) management has become more daunting over the past decade because of alarming increases in CDI incidence and severity both in the hospital and in the community. This increase has concomitantly caused significant escalation of the health-care economic burden caused by CDI, and it will likely be translated to increased ICU admission and attributable mortality. Some possible causes for difficulty in management of CDI are as follows: (1) inability to predict and prevent development of severe/complicated or relapsing CDI in patients who initially present with mild symptoms; (2) lack of a method to determine who would have benefited a priori from initiating vancomycin treatment first instead of treatment with metronidazole; (3) lack of sensitive and specific CDI diagnostics; (4) changing epidemiology of CDI, including the emergence of a hypervirulent, epidemic C difficile strain associated with increased morbidity and mortality; (5) association of certain high-usage nonantimicrobial medications with CDI; and (6) lack of treatment regimens that leave the normal intestinal flora undisturbed while treating the primary infection. The objective of this article is to present current management and prevention guidelines for CDI based on recommendations by the Society for Healthcare Epidemiology of America and Infectious Diseases Society of America and potential new clinical management strategies on the horizon.

Evidence for subpopulations of Listeria monocytogenes with enhanced invasion of cardiac cells.

Cardiac infections caused by the foodborne bacterium Listeria monocytogenes represent a significant but poorly studied facet of disease. It is not known whether L. monocytogenes cardiac infections stem solely from host susceptibility, or whether bacterial isolates exist that exhibit a tropism for cardiac tissue. Here we examine the cardio-invasive capacity of a recent L. monocytogenes cardiac case strain (07PF0776) as well as nine additional outbreak and clinical isolates. Mice infected with the cardiac isolate 07PF0776 had 10-fold more bacteria recovered from heart tissue than those infected with L. monocytogenes strain 10403S, a well-characterized clinical isolate originally obtained from a human skin lesion. Additional L. monocytogenes isolates exhibited varied capacities to colonize the hearts of mice; however, those with the highest efficiency of mouse cardiac invasion also demonstrated the highest levels of bacterial invasion in cultured myoblast cells. Our findings strongly suggest that subpopulations of L. monocytogenes strains have acquired an enhanced ability to target and invade the myocardium.

Human leukocyte antigen (HLA)-B, DRB1, and DQB1 allotypes associated with disease and protection of trachoma endemic villagers.

PURPOSE: Trachoma remains the leading preventable infectious cause of blindness in developing countries. Human leukocyte antigen (HLA) associations with ocular disease severity and persistent Chlamydia trachomatis infection of Tanzanians living in trachoma-endemic villages were examined to determine possible protective candidate allotypes for vaccine development. METHODS: Buccal swab scrapes were taken from subjects in the Trichiasis Study Group (TSG), which studied females only, and the Family Trachoma Study (FTS), which compared persistently infected probands who had severe disease with disease-free siblings and parents. DNA was purified for polymerase chain reaction sequence-specific oligonucleotide identification of HLA-DRB1, DQB1, and B allotypes. Infection was detected from conjunctival scrapes using a C. trachomatis-specific PCR-enzyme immunoassay for the MOMP-1 gene. RESULTS: In the TSG, DR*B11 (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.90; P=0.02) was significantly associated with lack of trichiasis, whereas HLA-B*07 (OR, 3.26; 95% CI, 1.42-7.49; P=0.004) and HLA-B*08 (OR, 5.12; 95% CI, 1.74-15.05; P=0.001) were associated with trichiasis. In addition, HLA-B*14 was significantly associated with inflammatory trachoma + follicular trachoma (OR, 3.76; 95% CI, 1.70-8.33; P=0.04). There were no significant allele frequencies for the FTS. CONCLUSIONS: The data suggest that HLA-DRB*11 may offer protection from trichiasis in trachoma hyperendemic villages. Complete allotype identification and designation of its respective protective CD4(+) T-cell antigens could provide a testable candidate vaccine for blindness prevention. Additionally, buccal swab DNA was sufficiently stable when acquired under harsh field conditions and stored long term in the freezer for low-resolution HLA typing.

Wine drinking and risk of non-Hodgkin's lymphoma among men in the United States: a population-based case-control study.

The relation between wine consumption and non-Hodgkin's lymphoma (NHL) was investigated using data from the Selected Cancers Study. Cases (n = 960) were men aged 32-60 years diagnosed with NHL from 1984 to 1988 and identified from eight US population-based cancer registries. Controls (n = 1,717) were men recruited by random digit dialing and frequency matched to cases by age and registry. Logistic regression was used to calculate odds ratios and 95% confidence intervals adjusted for age, registry, race/ethnicity, education, and smoking. Odds ratios for men who consumed less than one and those who consumed one or more wine drinks per day were 0.8 (95% confidence interval: 0.5, 1.3) and 0.4 (95% confidence interval: 0.2, 0.9) compared with nondrinkers, respectively (p for trend = 0.02). Among wine drinkers who consumed alcohol beverages from ages 16 years or less, odds ratios for intakes of less than one and one or more wine drinks per day were 0.4 (95% confidence interval: 0.2, 0.97) and 0.3 (95% confidence interval: 0.1, 0.8), respectively (p for trend = 0.004). No associations were evident for beer or spirits. These data show that consumption of wine, but not of beer or spirits, is associated with a reduced NHL risk.