Structure-activity relationships of actively FhuE transported rifabutin derivatives with potent activity against Acinetobacter baumannii.

Hospital-acquired infections are on the rise and represent both, a clinical and financial burden. With resistance emerging and an ever-dwindling armamentarium at hand, infections caused by Acinetobacter baumannii are particularly problematic, since these bacteria have a high level of resistance and resilience to traditional and even last-resort antibiotics. The antibiotic rifabutin was recently found to show potent in vitro and in vivo activity against extensively drug resistant A. baumannii. Building on this discovery, we report on the synthesis and activity of rifabutin analogs, with a focus on N-functionalization of the piperidine ring. The antimicrobial testing uncovered structure activity relationships (SAR) for A. baumannii that were not reflected in Staphylococcus aureus. The cellular activity did not correlate with cell-free transcription inhibition, but with bacterial intracellular compound accumulation. Mass spectrometry-based accumulation studies confirmed the involvement of the siderophore receptor FhuE in active compound translocation at low concentrations, and they showed a strong impact of the culture medium on the accumulation of rifabutin. Overall, the study underlines the structural feature required for strong accumulation of rifabutin in A. baumannii and identifies analogs as or more potent than rifabutin against A. baumannii.

[Use of vitamins and minerals all food supplements from the MONICA cross-sectional study of 1994/95 from the Augsburg study region]. / Zufuhr an Vitaminen und Mineralstoffen aus Nahrungsergänzungspräparaten in der MONICA-Querschnittsstudie 1994/95 der Studienregion Augsburg.

The intake of vitamin and mineral supplements was examined in a southern German population. Analyses are based on data from the 3rd survey of the MONICA Project Augsburg which took place from 1994 to 1995. The study population were 4,856 persons aged 25 to 74 years of a representative sample (net response 74.9%). During a standardized interview, participants were asked about their intake of vitamin or mineral supplments in the previous week (information available from 4,854 persons). To evaluate this information, a database on vitamin and mineral contents of about 500 supplements was established. The prevalence of supplement users is significantly higher among women than among men: more than a quarter of women (27.5%) versus nearly a fifth of men (18.1%). With increasing age women take supplements more frequently, especially minerals. Male supplement usage increases up to the age group 35-44 years and then remains constant. Vitamin C (women 12.8%, men 9.4%), magnesium (women 12.4%, men 8.7%), vitamin E (women 9.8%, men 7.8%), and calcium (women 10.7%, men 4.9%) are the vitamins and minerals supplemented most often. Among supplement users, 46.5% of women and 52.1% of men reported taking vitamin C. The median daily intake of vitamins--except biotin and niacin in men and folic acid and biotin in women--is at least 100% of the recommendations of the German Society for Nutrition for both men and women. All of the median intake values for minerals were less or equal than 100% of the recommendations.