Penicillin-resistant clinical isolates of Streptococcus pneumoniae contain mosaic penicillin-binding protein (PBP) genes that encode PBPs with decreased affinity for beta-lactam antibiotics. The mosaic blocks are believed to be the result of gene transfer of homologous PBP genes from related penicillin-resistant species. We have now identified a gene homologous to the pneumococcal PBP2x gene (pbpX) in a penicillin-sensitive Streptococcus oralis isolate M3 from South Africa that diverged by almost 20% from pbpX of penicillin-sensitive pneumococci, and a central sequence block of a mosaic pbpX gene of Streptococcus mitis strain NCTC 10712. In contrast, it differed by only 2-4% of the 1 to 1.5 kb mosaic block in pbpX genes of three genetically unrelated penicillin-resistant S. pneumoniae isolates, two of them representing clones of serotype 6B and 23F, which are prevalent in Spain and are also already found in other countries. With low concentrations of cefotaxime, transformants of the sensitive S. pneumoniae R6 strain could be selected containing pbpX genes from either S. mitis NCTC 10712 or S. oralis M3, demonstrating that genetic exchange can already occur between beta-lactam-sensitive species. These data are in agreement with the assumption that PBPs as penicillin-resistance determinants have evolved by the accumulation of point mutations in genes of sensitive commensal species.

A derivative of quinolinecarboxylic acid, ciprofloxacin (BAY o 9867) was found to be an effective bactericidal agent against Pseudomonas aeruginosa and Escherichia coli. A bactericidal effect was achieved immediately after the addition of ciprofloxacin. At a concentration of 0.5 ,ug/ml, culture viability was reduced from 5 x 10 to about S x 103 CFU/ml within 15 min, and at 0.1 ,ug/ml, a >10-fold reduction in viability resulted during the first hour after exposure. This bactericidal activity observed during the lag phase in Mueller-Hinton broth was also demonstrated in a nongrowing system. The antibiotics used in comparative studies, i.e., tobramycin, aztreonam, cefotaxime, and azlocillin, did not show this initial bactericidal activity, and ciprofloxacin prevented culture regrowth at lower concentrations. Staphylococcus aureus was not as susceptible to ciprofloxacin; killing occurred at a concentration of 0.5 ,Ig/ml only after the onset of exponential growth in the control culture. Synergistic interactions were observed wtih ciprofloxacin in combination with tobramycin and azlociilin against P. aeruginosa and with cefotaxime and tobramycin against E. coli.

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Background/objectives:The emptying of the gall bladder in response to feeding is pivotal for the digestion of fat, but the role of various food ingredients in contracting the gall bladder postprandially is not well understood. We hypothesized that different food ingredients, when consumed, will have a different effect on stimulating gall bladder emptying. To investigate this we designed two randomized, investigator-blind, cross-over studies in healthy subjects using magnetic resonance imaging (MRI) to measure gall bladder volumes serially and non-invasively.Subjects/methods:Study 1: exploratory study evaluating the effects of 10 different food ingredients on gall bladder emptying in eight healthy subjects. The choice of ingredients varied from common items like coffee, tea and milk to actives like curcumin and potato protease inhibitor. Study 2: mechanistic study investigating the cholecystokinin (CCK) dose response to the best performer ingredient from Study 1 in 21 healthy subjects four ways.Results:The largest gall bladder volume change in Study 1 was observed with fat, which therefore became the dose-response ingredient in Study 2, where the maximum % gall bladder volume change correlated well with CCK.Conclusions:These serial test-retest studies showed that the fasted gall bladder volume varied remarkably between individuals and that individual day-to-day variability had wide coefficients of variation. Improved knowledge of how to stimulate bile release using food ingredients will be useful to improve in vitro–in vivo correlation of bioavailability testing of hydrophobic drugs. It could improve performance of cholesterol-lowering plant stanol and sterol products and possibly aid understanding of some cholesterol gallstone disease.