This proof-of-concept study demonstrates that no longer routinely reporting urine culture results from noncatheterized medical and surgical inpatients can greatly reduce unnecessary antimicrobial therapy for asymptomatic bacteriuria without significant additional laboratory workload. Larger studies are needed to confirm the generalizability, safety, and sustainability of this model of care.

Introduction Survival in uveal melanoma has remained unchanged since the early 1970s. Because outcomes are

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BackgroundClostridium difficile is the leading cause of hospital-borne infections occurring when the natural intestinal flora is depleted following antibiotic treatment. Current treatments for Clostridium difficile infections present high relapse rates and new hyper-virulent and multi-resistant strains are emerging, making the study of this nosocomial pathogen necessary to find novel therapeutic targets.ResultsWe present iMLTC806cdf, an extensively curated reconstructed metabolic network for the C. difficile pathogenic strain 630. iMLTC806cdf contains 806 genes, 703 metabolites and 769 metabolic, 117 exchange and 145 transport reactions. iMLTC806cdf is the most complete and accurate metabolic reconstruction of a gram-positive anaerobic bacteria to date. We validate the model with simulated growth assays in different media and carbon sources and use it to predict essential genes. We obtain 89.2% accuracy in the prediction of gene essentiality when compared to experimental data for B. subtilis homologs (the closest organism for which such data exists). We predict the existence of 76 essential genes and 39 essential gene pairs, a number of which are unique to C. difficile and have non-existing or predicted non-essential human homologs. For 29 of these potential therapeutic targets, we find 125 inhibitors of homologous proteins including approved drugs with the potential for drug repositioning, that when validated experimentally could serve as starting points in the development of new antibiotics.ConclusionsWe created a highly curated metabolic network model of C. difficile strain 630 and used it to predict essential genes as potential new therapeutic targets in the fight against Clostridium difficile infections.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-014-0117-z) contains supplementary material, which is available to authorized users.

Early improvements in eating behaviour and weight appear to have additive effects in the prediction of ongoing weight change. Future research is required to identify the optimal rate of weight loss, whether there are critical periods for behaviour change, and factors which influence the likelihood of early behaviour change.