Sch 29482, laboratory evaluation of a new penem antibiotic

The antibacterial activity of a new penem antibiotic, Sch 29482 (SCH), was examined in comparison with appropriate cephalosporins and penicillins. The drug inhibited penicillinase-positive and negative staphylococci equally well, being 2-5 times more active than cephalothin or cefamandole and 10-20 times more active than methicillin. Staphylococci resistant to methicillin were susceptible to SCH in agar dilution tests. Staphylococci tolerant to methicillin were also tolerant to SCH. Streptococci and pneumococci were highly susceptible to the drug. The agent was of only moderate activity against enterococci, especially Streptococcus faecium strains. MICs of ampicillin and penicillin G against enterococci were 4-8 times lower than those of SCH. SCH was bactericidal. Neither the choice of the method used for susceptibility testing, nor the size of the inoculum nor various test media influenced the in-vitro activity of this drug against a representative collection of Gram-negative and Gram-positive bacteri

Comparative activity of the penem antibiotic Sch 34343 against Gram-negative and Gram-positive bacteria with special reference to multiresistant strains

A new penem antibiotic, Sch 34343, was shown to be active against a large number of Gram-positive bacteria. The drug inhibited penicillinase-positive and -negative staphylococci equally well, being five times more active than cefamandole and ten times more active than methiallin. Most methicillin-rcsistant staphylococci were inhibited by concentrations between 0.25 and 4 mg/1, but a small group of highly resistant strains were observed. Sch 34343 was eight times less active than ampicillin and penicillin G, but as active as piperacilhn against enterococci. The drug showed excellent activity against various streptococci. Sch 34343 was as bactericidal as flucloxacillin, ampicillin and penicillin G against staphylococci, enterococci and streptococci, respectively, in killing kinetic tests Enterobacteriaceae susceptible to third-generation cephalosporins were approximately five times less susceptible to Sch 34343, but MICs were far below the susceptibility breakpoint Sch 34343 was equally active against Citrobacter and Enterobacter strains that were highly resistant to third-generation cephalosporins and to aztreonam. Together with thienamycin, this drug seems to be a good alternative for the treatment of infections caused by bacteria resistant to third-generation cephalosporins and to aztreona

Natural methicillin resistance in comparison with that selected by in-vitro drug exposure in Staphylococcus aureus

Methicillin resistant staphylococci selected during serial passage in increasing concentrations of methicillin were compared with an isogenic methicillin resistant strain carrying the methicillin resistance determinant (mec) found in clinical isolates of Staphylococcus aureus. Selection for methicillin resistance was followed by changes in the binding characteristic of penicillin binding proteins (PBPs) 2 and 4. There was no immunological nor genetic relationship between the mec-determined low affinity PBP2′ and the PBPs of the in-vitro selected mutants. The Tn551 insertion Ω2003, which inactivates mec determined methicillin resistance, but which is not linked to mec, also partially reduced in-vitro selected methicillin resistance. This suggests that this methicillin resistance controlling factor contributes at least partially to methicillin resistance selected in vitr

Interactive and automated application of virtual microscopy

Virtual microscopy can be applied in an interactive and an automated manner. Interactive application is performed in close association to conventional microscopy. It includes image standardization suitable to the performance of an individual pathologist such as image colorization, white color balance, or individual adjusted brightness. The steering commands have to include selection of wanted magnification, easy navigation, notification, and simple measurements (distances, areas). The display of the histological image should be adjusted to the physical limits of the human eye, which are determined by a view angle of approximately 35 seconds. A more sophisticated performance should include acoustic commands that replace the corresponding visual commands. Automated virtual microscopy includes so-called microscopy assistants which can be defined similar to the developed assistants in computer based editing systems (Microsoft Word, etc.). These include an automated image standardization and correction algorithms that excludes images of poor quality (for example uni-colored or out-of-focus images), an automated selection of the most appropriate field of view, an automated selection of the best magnification, and finally proposals of the most probable diagnosis. A quality control of the final diagnosis, and feedback to the laboratory determine the proposed system. The already developed tools of such a system are described in detail, as well as the results of first trials. In order to enhance the speed of such a system, and to allow further user-independent development a distributed implementation probably based upon Grid technology seems to be appropriate. The advantages of such a system as well as the present pathology environment and its expectations will be discussed in detail

Gravitational lensing as folds in the sky

We revisit the gravitational lensing phenomenon using a new visualization technique. It consists in projecting the observers sky into the source plane, what gives rise to a folded and stretched surface. This provides a clear graphical tool to visualize some interesting well-known effects, such as the development of multiple images of a source, the structure of the caustic curves, the parity of the images and their magnification as a function of the source position.Comment: 11 pages, 8 figure

Activity of meropenem, against Gram-positive bacteria

A new carbapenem antibiotic, meropenem, was shown to be active against a large number of Gram-positive bacteria. The drug inhibited penicillinase-positive and -negative, methicillin-susceptible staphylococci equally well. Among the comparative antimicrobials examined, only N-fonnimidoyl-thienamycin (imipenem) was two to four times more active than meropenem. Compared with vancomycin or methicillin, meropenem was 10-20 times more active. Strains of 11 species of streptococci were highly susceptible to meropenem; the geometric mean MICs of the drug for these species ranged from 0.01 to 0.04mg/l. The agent, however, only had moderate activity against Enterococcus faecalis (mean MIC 5mg/l) and Ent. faecium (mean MIC 11.6 mg/l). Among Corynebacterium jeikeium, strains were encountered that showed susceptibility to meropenem but resistance to imipenem and other β-lactams. Strains of other corynebacteria, Rhodococcus equi, Erysopelothrix rhusio-pathiae, Listeria monocytogenes, and Bacillus spp. all were highly susceptible to meropenem (mean MICs 0.04-0.17 mg/l). Although methicillin-resistant staphylo-cocci were inhibited by concentrations of 1-2 mg/l of meropenem in agar dilution tests, such strains showed heteroresistance in population studies, as is typical for all β-lactam antibiotics. In addition, the biochemical correlate of methicillin-resistance, penicillin-binding protein 2′, showed low affinity for meropenem, similar to that for imipenem. Meropenem was as bactericidal as imipenem and comparative bactericidal antimicrobials in killing-curve experiments. Strains of Ent. faecium, C. jeikeium, and L. monocytogenes were killed at a slower rate than streptococci or staphylococc

Antibacterial properties of imipenem with special reference to the activity against methicillin-resistant staphylococci, cefotaxime-resistant Enterobacteriaceae and Pseudomonas aeruginosa

Imipenem was examined with standardized agar dilution procedures against a wide range of bacteria. Geometric mean MICs against the genera Escherichia, Klebsiella, Enterobacter, Citrobacter and Serratia were 0·1-0·4 mg/1, and Proteus and Providencia spp. were inhibited by 0·25-4 mg/1. Acinetobacter calcoaceticus var. anitratum strains were inhibited by concentrations ranging from 0·12-0·5 mg/1. Methicillin-susceptible staphylococci were highly susceptible to the drug (MICs: ⩾0·03 mg/1) and enterococci were inhibited by 0·25-16 mg/1. Most of the multi-resistant JK corynebacteria were resistant to imipenem. Imipenem was more active than any other ß-lactam against methicillin-resistant staphylococci; this was also demonstrated in a population analysis. Imipenem-resistant minorities in populations, however, were also observed. Cefotaxime-resistant and -intermediate Enterobacter and Citrobacter strains were inhibited by concentrations of 0·5 mg/1 or less. No third-generation cephalosporin nor any other ß-lactam showed similarly high activity against these groups of organisms. Among 20 ceftazidime-resistant and 20 ceftazidime-susceptible isolates of Pseudomonas aeruginosa, no strain was resistant and only five ceftazidime-resistant strains were intermediately susceptible (MIC, 8 mg/1) to imipene

Probing the Atmospheres of Planets Orbiting Microlensed Stars via Polarization Variability

We present a new method to identify and probe planetary companions of stars in the Galactic Bulge and Magellanic Clouds using gravitational microlensing. While spectroscopic studies of these planets is well beyond current observational techniques, monitoring polarization fluctuations during high magnification events induced by binary microlensing events will probe the composition of the planetary atmospheres, an observation which otherwise is currently unattainable even for nearby planetary systems.Comment: 7 pages, 2 figures. To appear in Astrophysical Journal Letter

Prognostic significance of endogenous adhesion/growth-regulatory lectins in lung cancer

Objective: To determine the expression of endogenous adhesion/growth-regulatory lectins and their binding sites using labeled tissue lectins as well as the binding profile of hyaluronic acid as an approach to define new prognostic markers. Methods: Sections of paraffin-embedded histological material of 481 lungs from lung tumor patients following radical lung excision processed by a routine immunohistochemical method (avidin-biotin labeling, DAB chromogen). Specific antibodies against galectins-1 and - 3 and the heparin-binding lectin were tested. Staining by labeled galectins and hyaluronic acid was similarly visualized by a routine protocol. After semiquantitative assessment of staining, the results were compared with the pT and pN stages and the histological type. Survival was calculated by univariate and multivariate methods. Results: Binding of galectin-1 and its expression tended to increase, whereas the parameters for galectin-3 decreased in advanced pT and pN stages at a statistically significant level. The number of positive cases was considerably smaller among the cases with small cell lung cancer than in the group with non-small-cell lung cancer, among which adenocarcinomas figured prominently with the exception of galectin-1 expression. Kaplan-Meier computations revealed that the survival rate of patients with galectin-3-binding or galectin-1-expressing tumors was significantly poorer than that of the negative cases. In the multivariate calculations of survival lymph node metastases ( p < 0.0001), histological type ( p = 0.003), galectin-3-binding capacity ( p = 0.01), galectin-3 expression ( p = 0.03) and pT status ( p = 0.003) proved to be independent prognostic factors, not correlated with the pN stage. Conclusion: The expression and the capacity to bind the adhesion/growth regulatory galectin-3 is defined as an unfavorable prognostic factor not correlated with the pTN stage. Copyright (C) 2005 S. Karger AG, Basel