28 research outputs found
Yeast from urinary nosocomial infection : biofilm and susceptibility to antifungal profile
Urinary infections caused by yeasts of Candida genus, in hospital environment, are frequent. The object of this work was to evaluate the susceptibility profile of yeasts isolated in patients with urinary infection to antifungal agents, comparing with broth methods microdilution and disk diffusion, and it was evaluated the capacity of these yeasts to form biofilm as well. There were used 98 samples isolated from hospitalized patients. Yeasts were isolated from urine culture with counting inferior to 105 CFU/ml although mixed cultures with bacteria, and cultures collected under the use of probe without previous changing were not selected. Susceptibility tests were evaluated using the following antifungals: amphotericin B, ketoconazole, fluconazole, itraconazole, voriconazole e caspofungin. The biofilm formation was carried out in polystyrene microtitration plate. Even though there were resistant isolates however most of them were susceptible for both methods. In this work, some discrepancies were observed between the susceptibility methods, suggesting that resistant cases for disk diffusion should be confirmed through the reference method (broth microdilution). C. tropicalis, had the higher capacity to form biofilm (91.7%) than C. albicans (82.5%) and C. glabrata (61.3%). In order to avoid biofilm formation, we suggest that the health professionals to be careful during the manipulation of urinary catheters, once the capacity of fungi to form biofilm upon foreign bodies is considered one of the main reasons for the antifungal treatment failure. We believe that the candiduria finding requires more attention and a better monitoring, especially in patients of high risk, considering the importance to avoid systemic infections with high mortality indices. It is also interesting the identification of yeasts isolated from patients with urinary infection, and the performance of susceptibility tests to antifungals as well, in order to avoid empiric therapy, and consequently the emergence of resistant isolates taking into consideration the variability of response to the antifungals evaluated
Synthesis of the Sterically Related Nickel Gallanediyl Complexes [Ni(CO)3(GaAr′)] (Ar′ = C6H3-2,6-(C6H3-2,6-iPr2)2) and [Ni(CO)3(GaL)] (L = HC[C(CH3)N(C6H3-2,6-iPr2)]2): Thermal Decomposition of [Ni(CO)3(GaAr′)] to give the Cluster [Ni4(CO)7(GaAr′)3]
Evaluation of the Effect of 5 QT-Positive Drugs on the JTpeak Interval — An Analysis of ECGs From the IQ-CSRC Study
The JTpeak interval has been proposed as a new biomarker to demonstrate mixed ion channel effects, potentially leading to reduced late-stage electrocardiogram (ECG) monitoring for mildly QT-prolonging drugs. ECG waveforms from the IQ-CSRC study were used. Twenty healthy subjects were enrolled with 6 subjects on placebo and 9 subjects on each of 5 mildly QT-prolonging drugs — moxifloxacin, dofetilide, ondansetron, dolasetron, and quinine — and 1 negative drug, levocetirizine. A vector magnitude lead was derived from 12-lead ECGs, and measurements were made on a median beat from three 10-second replicates. Data were analyzed using a linear concentration-response model with QTcF and heart rate corrected JTpeak (JTpeak_c) as dependent variables. For moxifloxacin, dofetilide, and ondansetron, all pure hERG blockers, slopes of the concentration (C)-QTcF and C-JTpeak_c relationships were positive and statistically significant. With the prespecified linear model, the predicted effects on ΔΔQTcF and ΔΔJTpeak_c were 11.4 and 9.4 milliseconds for moxifloxacin at the geometric mean Cmax on day 1, 9.0 and 11.7 milliseconds for dofetilide and 11.5, and 7.9 milliseconds for ondansetron, respectively. In contrast, dolasetron and quinine, both with additional ion channel effects, prolonged QTcF with a positive C-ΔQTcF slope and predicted ΔΔQTcF effect on day 1 of 6.2 and 11.4 milliseconds, whereas the C-ΔJTpeak_c slope and the predicted ΔΔJTpeak on day 1 were negative (−0.3 and −7.5 milliseconds per ng/mL). Pure hERG-blocking drugs prolonged both the QTc and the JTpeak_c intervals, whereas drugs with mixed ion channel effects, including peak sodium inhibition, prolonged QTcF but not the JTpeak_c interval
Evidências da metropolização do espaço no século XXI: elementos para identificação e delimitação do fenômeno
The IQ-CSRC Prospective Clinical Phase 1 Study: 'Can Early QT Assessment Using Exposure Response Analysis Replace the Thorough QT Study?'
A collaboration between the Consortium for Innovation and Quality in Pharmaceutical Development and the Cardiac Safety Research Consortium has been formed to design a clinical study in healthy subjects demonstrating that the thorough QT (TQT) study can be replaced by robust ECG monitoring and exposure-response (ER) analysis of data generated from First-in-Man single ascending dose (SAD) studies. Six marketed drugs with well-characterized QTc effects were identified in discussions with FDA; five have caused QT prolongation above the threshold of regulatory concern. Twenty healthy subjects will be enrolled in a randomized, placebo-controlled study designed with the intent to have similar power to exclude small QTc effects as a SAD study. Two doses (low and high) of each drug will be given on separate, consecutive days to 9 subjects. Six subjects will receive placebo. Data will be analyzed using linear mixed-effects ER models. Criteria for QT-positive drugs will be the demonstration of an upper bound (UB) of the 2-sided 90% confidence interval (CI) of the projected QTc effect at the peak plasma level of the lower dose above the threshold of regulatory concern (currently 10 ms) and a positive slope of ER relationship. The criterion for QT-negative drug will be an UB of the CI of the projected QTc effect of the higher dose <10 ms. It is expected that a successful outcome in this study will provide evidence supporting replacement of the TQT study with ECG assessments in standard early clinical development studies for a new chemical entit