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Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2.

Toll-like receptors (TLRs) mediate recognition of a wide range of microbial products including lipopolysaccharides, lipoproteins, flagellin, and bacterial DNA, and signaling through TLRs leads to the production of inflammatory mediators. In addition to TLRs, many other surface receptors have been proposed to participate in innate immunity and microbial recognition, and signaling through some of these receptors is likely to cooperate with TLR signaling in defining inflammatory responses. In this report we have examined how dectin-1, a lectin family receptor for beta-glucans, collaborates with TLRs in recognizing microbes. Dectin-1, which is expressed at low levels on macrophages and high levels on dendritic cells, contains an immunoreceptor tyrosine-based activation motif-like signaling motif that is tyrosine phosphorylated upon activation. The receptor is recruited to phagosomes containing zymosan particles but not to phagosomes containing immunoglobulin G-opsonized particles. Dectin-1 expression enhances TLR-mediated activation of nuclear factor kappa B by beta-glucan-containing particles, and in macrophages and dendritic cells dectin-1 and TLRs are synergistic in mediating production of cytokines such as interleukin 12 and tumor necrosis factor alpha. Additionally, dectin-1 triggers production of reactive oxygen species, an inflammatory response that is primed by TLR activation. The data demonstrate that collaborative recognition of distinct microbial components by different classes of innate immune receptors is crucial in orchestrating inflammatory responses.

3T3 Cells↗

Role of bile in non-specific defence mechanisms of the gut.

The effect of depriving the intestine of bile for 48 hours was studied to determine any influence on various parameters of innate immunity in the gastrointestinal tract. Groups of rats were prepared by bile duct cannulation (with or without fluid replacement) or bile duct ligation. Normal and sham operated animals were used for comparing the thickness of the mucus layer and the cells contained therein, enumeration of goblet cells, and measurement of villus size. Histological examination indicated that the intestinal tissues of treated and control rats were similar. Though villus size and numbers of goblet cells were unaffected, a significant reduction occurred in the thickness of the mucus blanket in the duodenal regions of rats deprived of bile, and there were significantly lower numbers of mucus associated enterocytes and lymphocytes, suggesting a lower turnover rate of the epithelium. The balance of the bacterial populations in the caecum and intestine was altered by bile deprivation-increased numbers of coliform organisms were found in both regions. The range of factors, including antibodies and other known constituents, present in bile may contribute to the maintenance of tissue integrity and influence the balance in indigenous bacterial populations in the intestine. Disturbance of the host's biliary system and concomitant effects on the microbial flora may weaken the overall processes of defence in the intestine.

Animals↗

Environmental surface cleanliness and the potential for contamination during handwashing.

Effective handwashing (including drying) is important in infection control. The ability of the various stages of handwashing to decrease skin-surface microbial counts has been documented. However, an important element, environmental surface cleanliness, and the potential for contamination of hands during the process has not been well studied or quantified. An examination of the adenosine triphosphate (a measure of residual organic soil), bacterial, and staphylococcal load on ward handwash station surfaces, which could be touched during handwashing, is reported. Hand contact surfaces tested consisted of approximately 620 each of: faucet handles, soap dispenser activator mechanisms, and folded paper-towel dispenser exits. Failure rates in excess of benchmark clean values were higher with adenosine triphosphate assays than microbial counts. This could indicate the presence of a higher level of general organic debris (eg, skin cells) as opposed to microbial contamination or could reflect greater assay sensitivity. Faucet handles were more likely to be contaminated and be in excess of benchmark values than paper-towel dispenser exits. However, the latter are likely to be the final surface touched during the handwashing process and overall nearly 20% were above microbiologic benchmark values. Many of the organisms isolated were staphylococci and the results are discussed within the context of microbial cross-contamination and potential pathogen spread.

Adenosine Triphosphate↗

Anaerobic ammonium oxidation by marine and freshwater planctomycete-like bacteria.

Recently, two fresh water species, " Candidatus Brocadia anammoxidans" and " Candidatus Kuenenia stuttgartiensis", and one marine species, " Candidatus Scalindua sorokinii", of planctomycete anammox bacteria have been identified. " Candidatus Scalindua sorokinii" was discovered in the Black Sea, and contributed substantially to the loss of fixed nitrogen. All three species contain a unique organelle--the anammoxosome--in their cytoplasm. The anammoxosome contains the hydrazine/hydroxylamine oxidoreductase enzyme, and is thus the site of anammox catabolism. The anammoxosome is surrounded by a very dense membrane composed almost exclusively of linearly concatenated cyclobutane-containing lipids. These so-called 'ladderanes' are connected to the glycerol moiety via both ester and ether bonds. In natural and man-made ecosystems, anammox bacteria can cooperate with aerobic ammonium-oxidising bacteria, which protect them from harmful oxygen, and provide the necessary nitrite. The cooperation of these two groups of ammonium-oxidising bacteria is the microbial basis for a sustainable one reactor system, CANON (completely autotrophic nitrogen-removal over nitrite) to remove ammonia from high strength wastewater.

Anaerobiosis↗

Stewardship of antibiotic use and resistance surveillance: the international scene.

Audit is all about education and changing practice. It is well known that doctors are both difficult to target with educational initiatives and those who need educating are the most difficult to target! Changing established practice is even harder and maintaining change in practice is often considered just a dream. This emphasises the importance of the cycle of audit, feedback (education), re-audit etc. This process has been developed over a twelve-year period in Aberdeen while the antibiotic policy has evolved from a 15-page booklet on hospital antibiotic prescribing into a 90-page book combining both hospital and general practice prescribing. Both successes and failures of the audit process will be described in the context of Strategic Goals. The next phase is assessment of performance against other policies in Europe to establish the best methods of antibiotic stewardship. A European group has recently been formed to begin this process. Parameters that can be used to assess the comparative performance of policies will be discussed and include antibiotic resistance rates. Several international resistance surveillance and quality of antibiotic use programmes are highlighted.

Anti-Bacterial Agents↗

Improving inpatient antibiotic prescribing: insights from participation in a national collaborative.

BACKGROUND: Increasing rates of antimicrobial resistance and the role antibiotic overuse plays in contributing to this problem have been widely documented and have prompted appeals to change prescribing practices. How to actually achieve such changes represents a major challenge. As part of the Institute for Healthcare Improvement (IHI) Breakthrough Series project Improving Prescribing Practices (IPP), in 1997-1998, Cook County Hospital (Chicago) worked with other institutions that chose antibiotics as their focus in this national collaborative. PRACTICAL SUGGESTIONS: Practical suggestions are offered within six categories--adopting a general approach to improving antibiotic prescribing (marshalling credible evidence, addressing physician concerns and skepticism, and removing barriers to make it easier for prescribers to change); rethinking guidelines (providing syndrome-based guidance, revising national guidelines for local use, defining scenarios in which drug(s) can be safely withheld, offering alternatives, prospectively resolving conflicts over drug of choice and empiric regimens, and defining situations in which immediate treatment is and is not critical); getting the message out and changes implemented (using antibiotic order forms, computer order entry, and infectious disease specialist consultation); building viable linkages to leverage change (bridging disciplines); improving measurement; and promoting nondrug strategies and patients' roles in treating and preventing infection. CONCLUSION: Antimicrobials are unique, being the only class of drug therapy that affects not only the patient to whom it is prescribed but other current and future patients as well. Institutions therefore have a special responsibility to ensure their efficient and judicious use. It is often easier to prescribe antibiotics than to exercise restraint.

Academies and Institutes↗

Global surveillance through PROTEKT: the first year.

The increasing antimicrobial resistance amongst bacterial pathogens causing community-acquired respiratory tract infections (CARTIs) necessitates surveillance at the local, regional, national and international levels to provide information to guide empiric antimicrobial therapy. PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) is a longitudinal, global, multicenter surveillance study designed to monitor the worldwide development of antimicrobial resistance and disseminate up-to-date information via the internet to assist in the choice of empiric therapy at the local level. In this paper, the results for the first year of PROTEKT are presented from a global perspective. Streptococcus pneumoniae, followed by Haemophilus influenzae and Moraxella catarrhalis, are the principal organisms responsible for the majority of CARTIs. The global prevalence of penicillin G resistance in S. pneumoniae has risen to an alarming 36.3% (high-level resistance 22.1%, intermediate-level 14.2%) with the highest prevalence found in Asia (68%). In all regions, macrolide resistance is greater than penicillin G resistance with a global prevalence rate of 31.2%. High resistance rates were also found for tetracycline (30.5%) and co-trimoxazole (43.9%), and multiresistance was found between penicillin G, macrolides, tetracycline and co-trimoxazole. The prevalence of beta-lactamase-producing H. influenzae and M. catarrhalis was found to be similar to previous reports. Macrolide resistance in S. pyogenes was 0.3% overall. Telithromycin demonstrated excellent in vitro activity against all organisms and is a potential new candidate for the empiric therapy of CARTIs. The first year of PROTEKT has provided valuable information on the prevalence of antimicrobial resistance of bacterial agents causing CARTIs that can be used for guiding empiric therapy and policies. The rapidly developing and geographically varying resistance observed in this study further emphasizes the need for accurate up-to-date surveillance data.

Acute Disease↗

Recovery of vancomycin-resistant enterococci on fingertips and environmental surfaces.

OBJECTIVE: To determine the recovery of vancomycin-resistant enterococci (VRE) on fingertips, gloved fingertips, and environmental surfaces commonly encountered in the healthcare setting, and to examine the importance of handwashing on the removal of these organisms. DESIGN: Two clinical isolates of VRE (Enterococcus faecalis and Enterococcus faecium) were inoculated onto the hands of healthy human volunteers and the following environmental surfaces: countertops, bedrails, telephones, and stethoscopes. Following inoculation, samples were obtained at various time intervals to determine rates of recovery of organisms. To evaluate the effects of handwashing on enterococcal recovery, two different soap preparations were tested. Hands were washed with water alone or with one of the soaps and water. The soap and water studies were performed with a 5-second and a 30-second wash. RESULTS: Both enterococcal strains survived for at least 60 minutes on gloved and ungloved fingertips. The E faecalis was recoverable from countertops for 5 days; the E faecium persisted for 7 days. For bedrails, both enterococcal species survived for 24 hours without significant reduction in colony counts. The bacteria persisted for 60 minutes on the telephone handpiece and for 30 minutes on the diaphragmatic surface of the stethoscope. A 5-second wash with water alone resulted in virtually no change in recovery of enterococci; a 30-second wash with water plus either soap was necessary to eradicate the bacteria from hands completely. CONCLUSION: VRE are capable of prolonged survival on hands, gloves, and environmental surfaces. Hands should be washed thoroughly and gloves removed following contact with patients infected or colonized with these multidrug-resistant bacteria. Finally, environmental surfaces may serve as potential reservoirs for nosocomial transmission of VRE and need to be considered when formulating institutional infection control policies.

Drug Resistance, Microbial↗

Evolution of lamivudine-resistant hepatitis B virus and HIV-1 in co-infected individuals: an analysis of the CAESAR study. CAESAR co-ordinating committee.

OBJECTIVES: Lamivudine has potent activity against HIV-1 and hepatitis B virus (HBV). Co-infection with these two viruses is common, and this may therefore influence the choice of antiretroviral therapies. A cohort of co-infected patients treated with lamivudine were studied in order to evaluate the differential effects of lamivudine on the two viral populations within the same individual after 44-52 weeks of therapy. DESIGN AND METHODS: Retrospective virological analysis of an HIV-1/HBV co-infected lamivudine cohort derived from a randomized, placebo-controlled study of lamivudine in HIV infection, the CAESAR study. RESULTS: Five of thirteen patients with HBV viral load > 10,000 copies/ml after 44-52 weeks of lamivudine therapy had genotypic drug resistance. Four of these five had a rebound of viral replication over the period of study and in one case this was associated with an alanine transaminase serum elevation. Ten of the thirteen patients had a 44-52 week HIV viral load > 1000 copies/ml, all of whom also had HIV reverse transcriptase M184V or M184I mutations. CONCLUSIONS: Extrapolating these results to the population yields an estimated 1-year incidence of drug-resistant HBV of at least 14% in lamivudine-treated HIV-1/HBV co-infected patients. The clinical and virological benefit of HBV lamivudine monotherapy in co-infected patients should be balanced against the potential for emergence of drug resistance. Further, these data suggest that the determinants of HIV and HBV drug resistance are different and that parallel evolution, rather than co-evolution of HBV and HIV-1 in co-infected individuals occurs.

CD4 Lymphocyte Count↗

Antibiotic rotation.

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Anti-Bacterial Agents↗

Microbial biofilms.

Direct observations have clearly shown that biofilm bacteria predominate, numerically and metabolically, in virtually all nutrient-sufficient ecosystems. Therefore, these sessile organisms predominate in most of the environmental, industrial, and medical problems and processes of interest to microbiologists. If biofilm bacteria were simply planktonic cells that had adhered to a surface, this revelation would be unimportant, but they are demonstrably and profoundly different. We first noted that biofilm cells are at least 500 times more resistant to antibacterial agents. Now we have discovered that adhesion triggers the expression of a sigma factor that derepresses a large number of genes so that biofilm cells are clearly phenotypically distinct from their planktonic counterparts. Each biofilm bacterium lives in a customized microniche in a complex microbial community that has primitive homeostasis, a primitive circulatory system, and metabolic cooperativity, and each of these sessile cells reacts to its special environment so that it differs fundamentally from a planktonic cell of the same species.

Bacteria↗

[Antibiotic resistance: recommendations from the Advisory Council for Health Research].

The Advisory Council for Health Research (RGO) advised the Dutch Minister of Health on research into the epidemiology, prevention and research of antibiotic resistance in the Netherlands. Good antimicrobial practice, insight into antibiotic use, implementation of measures to prevent development of resistance and fundamental research on resistance should be promoted. It was concluded that there is very little extramural surveillance and that only a few existing intramural surveillance programmes appear useful for long-term monitoring, inclusion into international databases and comparison purposes. The initiatives taken by the Working Party on Antibiotic Policy (SWAB) and the National Institute of Public Health and the Environment (RIVM), including the development of a standard for susceptibility testing and the coordination of surveillance studies according to international standards, should be supported and continued. The RGO committee is impressed by central and integrated national surveillance programmes such as those in Denmark or Finland. This approach however seems not necessary for good medical practice and not currently feasible. Priority should now be given to specific projects which focus on specific resistance problems among well-defined patient groups, and on indicator-organisms and indicator-antibiotics.

Animals↗