Role of Amoxicillin Serum Levels for Successful Prophylaxis of Experimental Endocarditis Due to Tolerant Streptococci

The importance of amoxicillin serum profiles for successful prophylaxis of experimental endocarditis in rats was assessed. Animals with catheter-induced vegetations were challenged intravenously with large inocula of Streptococcus sanguis and received one of the following amoxicillin dosages: single or multiple bolus injection of 40 mg/kg; 40 mg/kg administered as a continuous infusion over 12 h; or either 9 or 18 mg/kg administered over 12 or 24 h, respectively. The regimen producing a single transient high peak serum level failed to prevent experimental endocarditis; in contrast, a second injection 6 h after the first resulted in successful prophylaxis. Likewise, the three regimens of continuous, relatively low-dose regimens prevented infections. Thus, the most important parameter for successful prophylaxis was the duration of inhibitory concentration of the drug in the serum. The total dose of antibiotic, the peak serum levels, or the area-under-the-curve values were not predictive of successful prophylaxi

Therapeutic drug monitoring of newer generation antiseizure medications at the point of treatment failure.

The benefit of therapeutic drug monitoring (TDM) of newer generation antiseizure medications (ASM) has been little studied. A recent randomized study suggested that TDM at each medical visit did not bring a significant benefit, but the study did not investigate TDM in cases of treatment failure. Accordingly, we realized a post hoc analysis of this trial. We analyzed 282 TDMs in 136 patients. We compared TDM performed at visits after treatment failure versus without treatment failure, reporting the proportion of drug levels out of range and the prescriber's adherence to dosage recommendations according to measured drug levels. There was no statistical difference in terms of proportion of out of range plasma drug levels (47% vs 50%, p = 0.7) or adherence of prescribers to the clinical pharmacologists' dosage recommendations (21% vs 30%, p = 0.6) between visits after treatment failure and visits without treatment failure, respectively. Knowledge of prior drug levels did not modify the results. Systematic TDM at appointments following treatment failure showed similar results to TDM at visits without treatment failure. The prescribers' adherence with dosage recommendations was low in both cases. It is not clear whether better prescriber adherence would improve patient outcome. Furthermore, the ability to detect poor patient compliance is limited in a planned outpatient appointment. The study setting does not reflect on the general usefulness of TDM

Development of the fast neutron imaging telescope

We report on the development of a next generation neutron telescope, with imaging and energy measurement capabilities, sensitive to neutrons in the 2-20 MeV energy range. The Fast Neutron Imaging Telescope (FNIT) was initially conceived to study solar neutrons as a candidate instrument for the Inner Heliosphere Sentinels (IHS) program under formulation at NASA. This detector is now being adapted to locate Special Nuclear Material (SNM) for homeland security purposes by detecting fission neutrons and reconstructing the image of their source. In either case, the detection principle is based on multiple elastic neutron-proton scatterings in organic scintillator. By reconstructing the scattering coordinates and measuring the recoil proton energy, the direction and energy of each neutron can be determined and discrete neutron sources identified. We describe the performance of the FNIT prototype, report on the current status of R&D efforts and present the results of recent laboratory measurements

Design optimization and performance capabilities of the fast neutron imaging telescope (FNIT)

We describe the design optimization process and performance characterization of a next generation neutron telescope, with imaging and energy measurement capabilities, sensitive to neutrons in the 1-20 MeV energy range. The response of the Fast Neutron Imaging Telescope (FNIT), its efficiency in neutron detection, energy resolution and imaging capabilities were characterized through a combination of lab tests and Monte Carlo simulations. Monte Carlo simulations, together with experimental data, are also being used in the development and testing of the image reconstruction algorithm. FNIT was initially conceived to study solar neutrons as a candidate instrument for the Inner Heliosphere Sentinel (IHS) spacecraft. However, the design of this detector was eventually adapted to locate Special Nuclear Material (SNM) sources for homeland security purposes, by detecting fission neutrons. In either case, the detection principle is based on multiple elastic neutron-proton scatterings in organic scintillator. By reconstructing event locations and measuring the recoil proton energies, the direction and energy spectrum of the primary neutron flux can be determined and neutron sources identified. This paper presents the most recent results arising from our efforts and outlines the performance of the FNIT detector

Ultra high energy cosmic rays and the large scale structure of the galactic magnetic field

We study the deflection of ultra high energy cosmic ray protons in different models of the regular galactic magnetic field. Such particles have gyroradii well in excess of 1 kpc and their propagation in the galaxy reflects only the large scale structure of the galactic magnetic field. A future large experimental statistics of cosmic rays of energy above 10$^{19}$ eV could be used for a study of the large scale structure of the galactic magnetic field if such cosmic rays are indeed charged nuclei accelerated at powerful astrophysical objects and if the distribution of their sources is not fully isotropic.Comment: 9 pages LaTeX file (AASTeX), 4 eps figures, submitted to The Astrophysical Journa

Galactomannan Does Not Precede Major Signs on a Pulmonary Computerized Tomographic Scan Suggestive of Invasive Aspergillosis in Patients with Hematological Malignancies

Background. Detection of serum galactomannan (GM) antigen and presence of the halo sign on a pulmonary computerized tomographic (CT) scan have a high specificity but a low sensitivity to diagnose invasive aspergillosis (IA) in patients at risk for this disease. To our knowledge, the relationship between the time at which pulmonary infiltrates are detected by CT and the time at which GM antigens are detected by enzyme immunoassay (EIA) has not been studied. Methods. In a prospective study, tests for detection of GM were performed twice weekly for patients with hematological malignancies who had undergone hematopoetic stem cell transplantation (HSCT) or had received induction and/or consolidation chemotherapy. A pulmonary CT scan was performed once weekly. Infiltrates were defined as either major or minor signs. IA was classified as proven, probable, or possible, in accordance with the definition stated by the European Organization for Research and Treatment of Cancer-Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group. Results. We analyzed 161 episodes of infection in 107 patients (65 allogeneic HSCT recipients, 30 autologous HSCT recipients, and 66 induction and/or consolidation chemotherapy recipients). A total of 109 episodes with no IA, 32 episodes with possible IA, and 20 episodes with probable or proven IA were identified. Minor pulmonary signs were detected by CT in 70 episodes (43%), and major pulmonary signs were detected by CT in 11 episodes (7%). Univariate and multivariate analyses revealed no significant association between detection of GM by EIA and detection of abnormal pulmonary signs by CT. A significant association was found between GM levels and receipt of piperacillin-tazobactam. GM test results were not positive before major signs were seen on CT images. Only 7 (10%) of 70 patients with minor pulmonary signs had positive GM test results before detection of the greatest pathologic change by CT. Conclusions. We show that detection of GM by EIA does not precede detection of major lesions by pulmonary CT. In the clinical setting, the decision to administer mold-active treatment should based on detection of new pulmonary infiltrates on CT performed early during infection, rather than on results of EIA for detection of G

Open Problems on Central Simple Algebras

We provide a survey of past research and a list of open problems regarding central simple algebras and the Brauer group over a field, intended both for experts and for beginners.Comment: v2 has some small revisions to the text. Some items are re-numbered, compared to v

Epidemiology of candidemia in Swiss tertiary care hospitals: secular trends, 1991-2000

Candida species are among the most common bloodstream pathogens in the United States, where the emergence of azole-resistant Candida glabrata and Candida krusei are major concerns. Recent comprehensive longitudinal data from Europe are lacking. We conducted a nationwide survey of candidemia during 1991-2000 in 17 university and university-affiliated hospitals representing 79% of all tertiary care hospital beds in Switzerland. The number of transplantations and bloodstream infections increased significantly (P<.001). A total of 1137 episodes of candidemia were observed: Candida species ranked seventh among etiologic agents (2.9% of all bloodstream isolates). The incidence of candidemia was stable over a 10-year period. C. albicans remained the predominant Candida species recovered (66%), followed by C. glabrata (15%). Candida tropicalis emerged (9%), the incidence of Candida parapsilosis decreased (1%), and recovery of C. krusei remained rare (2%). Fluconazole consumption increased significantly (P<.001). Despite increasing high-risk activities, the incidence of candidemia remained unchanged, and no shift to resistant species occurred