CÓMO OPTIMIZAR LA FARMACODINAMIA ANTIMICROBIANA: UNA GUÍA PARA UN PROGRAMA DE OPTIMIZACIÓN DEL USO DE ANTIMICROBIANOS

RESUMENLos conceptos de farmacodinámica deberían aplicarse para optimizar los regímenes de dosificación antibiótica, especialmente de cara a algunas infecciones bacterianas resistentes a múltiples drogas. A pesar de que la farmacodinamia de la mayoría de las clases de antibióticos utilizadas en el ámbito hospitalario está bien descrita, las pautas acerca de cómo seleccionar regímenes y su implementación en un programa de administración antimicrobiana en la propia institución, son más limitadas. La función del antibiótico en concentraciones mínimas inhibitorias (MIC) es primordial para entender qué regímenes podrían beneficiarse de la implementación como un protocolo o como uso en los pacientes individuales. Este artículo destaca la farmacodinámica de aminoglucósidos, betalactámicos, fluoroquinolonas, tigeciclina, vancomicina, polimixinas, con el objetivo de proporcionar una base estratégica para seleccionar un régimen antibiótico optimizado en vuestro ámbito hospitalario

IT background of the medium-term storage of Martonvásár Cereal Genebank resources in phytotron cold rooms

Genebanks are storage facilities designed to maintain the plant genetic resources of crop varieties (and their wild relatives) and to ensure that they are made available and distributed for use by plant breeders, researchers and farmers. The Martonvásár Cereal Genebank (MV-CGB) collection evolved from the working collections of local breeders and consists predominantly of local and regional materials. Established in 1992 by the Agricultural Research Institute of the Hungarian Academy of Sciences (Bedő, 2009), MVCGB with its over 10,000 accessions of the major species (Triticum, Aegilops, Agropyron, Elymus, Thinopyrum, Pseudoroegneria, Secale, Hordeum, Avena, Zea mays), became one of the approx. 80 cereal germplasm collections that exist globally. In Martonvásár breeding is underway on a number of cereal species, and large numbers of genotypes are tested each year in the field and under laboratory conditions. The increasing size of the research programmes assisted by a modern genebank background involve an enormous increase in the quantity of data that must be handled during research activities such as traditional breeding, pre-breeding and organic breeding. A computerized system is of primary importance to synchronize breeding and genebank activities, to monitor the quality and quantity of seed accessions in cold storage, to assist the registration of samples, and to facilitate characterization, regeneration and germplasm distribution

Lung penetration, bronchopulmonary pharmacokinetic/pharmacodynamic profile and safety of 3 g of ceftolozane/tazobactam administered to ventilated, critically ill patients with pneumonia

Objectives: Ceftolozane/tazobactam is approved for hospital-acquired/ventilator-associated bacterial pneumonia at double the dose (i.e. 2 g/1 g) recommended for other indications. We evaluated the bronchopulmonary pharmacokinetic/pharmacodynamic profile of this 3 g ceftolozane/tazobactam regimen in ventilated pneumonia patients. Methods: This was an open-label, multicentre, Phase 1 trial (clinicaltrials.gov: NCT02387372). Mechanically ventilated patients with proven/suspected pneumonia received four to six doses of 3 g of ceftolozane/tazobactam (adjusted for renal function) q8h. Serial plasma samples were collected after the first and last doses. One bronchoalveolar lavage sample per patient was collected at 1, 2, 4, 6 or 8 h after the last dose and epithelial lining fluid (ELF) drug concentrations were determined. Pharmacokinetic parameters were estimated by noncompartmental analysis and pharmacodynamic analyses were conducted to graphically evaluate achievement of target exposures (plasma and ELF ceftolozane concentrations >4 mg/L and tazobactam concentrations >1 mg/L; target in plasma: similar to 30% and similar to 20% of the dosing interval, respectively). Results: Twenty-six patients received four to six doses of study drug; 22 were included in the ELF analyses. Ceftolozane and tazobactam T-max (6 and 2 h, respectively) were delayed in ELF compared with plasma (1h). Lung penetration, expressed as the ratio of mean drug exposure (AUC) in ELF to plasma, was 50% (ceftolozane) and 62% (tazobactam). Mean ceftolozane and tazobactam ELF concentrations remained >4 mg/L and >1mg/L, respectively, for 100% of the dosing interval. Therewere no deaths or adverse event-related study discontinuations. Conclusions: In ventilated pneumonia patients, 3 g of ceftolozane/tazobactam q8h yielded ELF exposures considered adequate to cover ceftolozane/tazobactam-susceptible respiratory pathogens

Observation of Anomalous Internal Pair Creation in 8^8Be: A Possible Signature of a Light, Neutral Boson

Electron-positron angular correlations were measured for the isovector magnetic dipole 17.6 MeV state ($J^\pi=1^+$, $T=1$) $\rightarrow$ ground state ($J^\pi=0^+$, $T=0$) and the isoscalar magnetic dipole 18.15 MeV ($J^\pi=1^+$, $T=0$) state $\rightarrow$ ground state transitions in $^{8}$Be. Significant deviation from the internal pair creation was observed at large angles in the angular correlation for the isoscalar transition with a confidence level of $> 5\sigma$. This observation might indicate that, in an intermediate step, a neutral isoscalar particle with a mass of 16.70$\pm0.35$ (stat)$\pm 0.5$ (sys) MeV$/c^2$ and $J^\pi = 1^+$ was created.Comment: 5 pages, 5 figure

SU(2) Flux Distributions on Finite Lattices

We studied SU(2) flux distributions on four dimensional euclidean lattices with one dimension very large. By choosing the time direction appropriately we can study physics in two cases: one is finite volume in the zero temperature limit, another is finite temperature in the the intermediate to large volume limit. We found that for cases of beta > beta crit there is no intrinsic string formation. Our lattices with beta > beta crit belong to intermediate volume region, and the string tension in this region is due to finite volume effects. In large volumes we found evidence for intrinsic string formation.Comment: 21 pages text, 12 pages of postscript figure

Expression of the MexXY-OprM efflux system in Pseudomonas aeruginosa with discordant cefepime/ceftazidime susceptibility profiles

While MIC distributions and percent susceptibility for cefepime and ceftazidime are generally similar among Pseudomonas aeruginosa, we noted an increasing discordance in susceptibility favoring ceftazidime at our hospital. Quantitative reverse transcriptase-polymerase chain reaction was utilized to explore overexpression of the MexXY-OprM efflux as the mechanism for this phenotype profile. Thirteen of 15 (87%) randomly selected isolates had mexY gene expression levels of 5.8–40.8-fold relative to the wild-type reference strain. While mexY overexpression was noted in the majority of isolates, other resistance mechanisms appear to contribute to the observed phenotypic profile of the Pseudomonas aeruginosa studied. Clinicians must understand not only the magnitude of difference in the MIC profiles between agents, but also the mechanism(s) responsible for these observations if strategies (ie, pharmacodynamic dosing) are to be designed to optimize patient care outcomes in the face of increasing resistance

Population Pharmacokinetics and Safety of Ceftolozane-Tazobactam in Adult Cystic Fibrosis Patients Admitted with Acute Pulmonary Exacerbation

ABSTRACT Ceftolozane-tazobactam has potent activity against Pseudomonas aeruginosa , a pathogen associated with cystic fibrosis (CF) acute pulmonary exacerbations (APE). Due to the rapid elimination of many antibiotics, CF patients frequently have altered pharmacokinetics. In this multicenter, open-label study, we described the population pharmacokinetics and safety of ceftolozane-tazobactam at 3 g every 8 h (q8h) in 20 adult CF patients admitted with APE. Population pharmacokinetics were determined using the nonparametric adaptive grid program in Pmetrics for R. A 5,000-patient Monte Carlo simulation was performed to determine the probability of target attainment (PTA) for the ceftolozane component at 1.5 g and 3 g of ceftolozane-tazobactam q8h across a range of MICs using a primary threshold exposure of 60% free time above the MIC ( fT >MIC). In these 20 adult CF patients, ceftolozane and tazobactam concentration data were best described by 2-compartment models, and ceftolozane clearance (CL) was significantly correlated with creatinine clearance ( r = 0.71, P MIC, ceftolozane-tazobactam regimens of 1.5 g and 3 g q8h should achieve PTAs of ≥90% at MICs up to 4 and 8 μg/ml, respectively. Ceftolozane-tazobactam at 3 g q8h was well tolerated. These observations support additional studies of ceftolozane-tazobactam for Pseudomonas aeruginosa APE in CF patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02421120.

Chiral properties of SU(3) sextet fermions

SU(3) gauge theory with overlap fermions in the 2-index symmetric (sextet) and fundamental representations is considered. A priori it is not known what the pattern of chiral symmetry breaking is in a higher dimensional representation although the general expectation is that if two representations are both complex, the breaking pattern will be the same. This expectation is verified for the sextet at N_f = 0 in several exact zero mode sectors. It is shown that if the volume is large enough the same random matrix ensemble describes both the sextet and fundamental Dirac eigenvalues. The number of zero modes for the sextet increases approximately 5-fold relative to the fundamental in accordance with the index theorem for small lattice spacing but zero modes which do not correspond to integer topological charge do exist at larger lattice spacings. The zero mode number dependence of the random matrix model predictions correctly match the simulations in each sector and each representation.Comment: 38 pages (12 pages text and gazillion tables/figures), minor modification, references adde

Dual variables for the SU(2) lattice gauge theory at finite temperature

We study the three-dimensional SU(2) lattice gauge theory at finite temperature using an observable which is dual to the Wilson line. This observable displays a behaviour which is the reverse of that seen for the Wilson line. It is non-zero in the confined phase and becomes zero in the deconfined phase. At large distances, it's correlation function falls off exponentially in the deconfined phase and remains non-zero in the confined phase. The dual variable is non-local and has a string attached to it which creates a Z(2) interface in the system. It's correlation function measures the string tension between oppositely oriented Z(2) domains. The construction of this variable can also be made in the four-dimensional theory where it measures the surface tension between oppositely oriented Z(2) domains.Comment: 13 pages, LaTeX, 4 figures are included in the latex fil