Pharmacokinetics/pharmacodynamics and therapeutic drug monitoring of ceftazidime/avibactam administered by continuous infusion in patients with MDR Gram-negative bacterial infections.

BACKGROUND: Therapeutic drug monitoring (TDM) of ß-lactams in critically ill patients has been correlated with better clinical outcomes. Evidence on TDM of newer ß-lactams such as ceftazidime/avibactam administered by continuous infusion (CI) is very limited. OBJECTIVES: To describe our experience with TDM of ceftazidime/avibactam and pharmacokinetic/pharmacodynamic (PK/PD) target attainment in patients with MDR bacterial infections. Clinical outcomes of ceftazidime/avibactam administered by CI were also assessed. METHODS: Patients treated with ceftazidime/avibactam administered by CI and undergoing TDM of ceftazidime plasma concentrations were included. Blood samples were obtained as part of the TDM program. The PK/PD therapeutic target of ceftazidime/avibactam was defined as 100%fT > 4 × MIC of the causative pathogen, and 100%fT > 10 × MIC was considered overexposure. Dose changes were made according to the TDM results. RESULTS: Thirty-one patients were included. Ceftazidime/avibactam total daily doses ranged from 1 g/0.25 g to 6 g/1.5 g. Twenty-six patients (83.9%) achieved a 100%fT > 4 × MIC, 15 (48.4%) of which were overexposed (100%fT > 10 × MIC). Dose reduction was suggested in 16/28 (57.1%) patients and dose maintenance in 12/28 (42.9%). Overall clinical cure was observed in 21 (67.7%) patients, and 18 of these (85.7%) achieved a 100%fT > 4 × MIC. CONCLUSIONS: Administering ceftazidime/avibactam by CI enabled the desired PK/PD target to be achieved in a large proportion of patients, even at lower doses than those recommended for a 2 h extended infusion. We suggest that the use of CI with TDM may be a useful tool for reducing initial doses, which could help to reduce antimicrobial-related adverse effects and treatment costs.

Phenological and seismological impacts on airborne pollen types: A case study of Olea pollen in the Region of Murcia, Mediterranean Spanish climate.

The rationale of this paper was to investigate whether earthquakes impact airborne pollen concentrations, considering some meteorological parameters. Atmospheric pollen concentrations in the Region of Murcia Aerobiological Network (Spain) were studied in relation to the occurrence of earthquakes of moment magnitude (up to Mw = 5.1) and intensity (intensity up to grade VII on the European Macroseismic Scale). In this study, a decade (2010-2019) was considered across the cities of the network. Earthquakes were detected in 12 out of 1535 days in the Olea Main Pollen Season in Cartagena, 49 out of 1481 days in the Olea Main Pollen Season in Lorca, and 39 out of 1441 days in the Olea Main Pollen Season in Murcia. The Olea pollen grains in this network were attributed to the species Olea europaea, i.e., the olive tree, a taxon that appears widely in the Mediterranean basin, in both cultivated and wild subspecies. Differences between the Olea concentration on days with and without earthquakes were only found in Lorca (Kruskal-Wallis: p-value = 0.026). The low frequency and intensity of the earthquakes explained these results. The most catastrophic earthquake felt in Lorca on May 11th, 2011 (IVII, Mw = 5.1, 9 casualties) did not result in clear variations in pollen concentrations, while meteorology (e.g., African Dust Outbreak) might have conditioned these pollen concentrations. The research should be broadened to other active seismological areas to reinforce the hypothesis of seismological impact on airborne pollen concentrations.

The effects of continentality, marine nature and the recirculation of air masses on pollen concentration: Olea in a Mediterranean coastal enclave.

Olea pollen concentrations have been studied in relation to the typology of air masses, pollen grain sources and marine nature during advections in a coastal enclave in the south-eastern Iberian Peninsula. Since Spain is the world's leading olive producer, and olive growing extends throughout the Mediterranean basin, this location is ideal for the study of long-distance transport events (LTD) during the main pollen season (MPS). The air masses were classified using the calculation of 48-h back trajectories at 250, 500 and 750 m above ground level using the HYSPLIT model. After that, the frequency of LDT events from Africa and Europe was found to be 8.7% of the MPS days. In contrast, regional air masses were found in 38.6% of the MPS days. This was reflected in pollen concentrations, with significantly higher concentrations (p-value <0.05) on days with regional air masses compared to days with European air masses. Regarding the source areas, the importance of nearby sources with intense olive cultivation was confirmed (i.e., Andalusia). This proximity was relevant beyond the attenuations observed when the advections acquired a marine nature as the air mass back trajectories moved over the sea (p-value <0.001). The review of air mass typologies, source areas and pollen concentrations resulted in establishing peak dates and the detection of LDT associated with these peak dates. Distortions in the typical path of each air mass explained alterations in pollen concentrations on consecutive days. The recirculation and loops of the air mass back trajectories varied the pollen load that every type of air mass could originally contain.

Association Between Seasonal Allergic Rhinitis and Air Pollution, Meteorological Factors, and Grass Pollen Counts in Madrid (1996 and 2009).

OBJECTIVE: The aim of this study was to assess the relationship between meteorological and pollution-related variables and the symptoms of patients with seasonal allergic rhinitis due to sensitization to grass pollen during 2 different time periods in Madrid, Spain. METHODS: Between March 23 and December 31 in 1996 and 2009, we carried out a daily count of grass pollen grains (Burkard spore trap) and recorded the rhinitis symptom scores in 2 groups of patients with a history of seasonal allergic rhinitis (n=25 in 1996 and n=23 in 2009). Descriptive statistics of the same variables during the study periods were recorded. Associations between variables were assessed using the paired-samples Wilcoxon test and categorical principal component analysis (CatPCA, SPSS24 package). RESULTS: The mean symptom score was low in 1996 and moderate in 2009. The 1996 and 2009 CatPCA analysis explained around 66.4% and 70.5% of the variance, respectively. The strongest relationships in 1996 were between symptoms and grass pollen counts (R=0.55) and between temperature and ozone (R=0.63). In 2009, the association between temperature and pollution-related variables was even stronger than in 1996 (ozone [R=0.53] and PM10 [R=0.34], with a positive sign in both cases). CONCLUSIONS: The effect of temperature and pollution (mainly ozone, even at lower atmospheric concentrations than in established guidelines for effects on health) may have contributed to the higher seasonal allergic rhinitis symptom score recorded in 2009.

Infectious postoperative endophthalmitis after cataract surgery performed over 7 years. The role of azithromycin versus ciprofloxacin eye drops.

OBJECTIVE: Although topical antibiotics have been used as antimicrobial prophylaxis after ocular surgery, recent studies have determined that intracameral cefuroxime at the end of surgery significantly reduce the risk to suffer an infection and suggest that the use of topical antibiotics in the prophylaxis of infectious postoperative endophthalmitis (IPOE) is controversial. Moreover, there is no evidence to confirm the higher effectiveness of topical ciprofloxacin, considered the standard of care, or topical azithromycin in preventing IPOE of cataract surgeries. METHODS: IPOE topical prophylaxis was performed with two different strategies: with azithromycin from January 1st, 2010 to December 31st, 2014 (group I) and with ciprofloxacin from January 1st, 2015 to January 31st, 2017 (group II). Patient characteristics and clinical signs and symptoms of IPOE from all consecutive cataract surgeries performed over a 7-year period were collected. RESULTS: A total of 15,146 cataract surgeries were conducted; 10,756 in group I and 4,390 in group II. Two cases of IPOE in each group were diagnosed, showing a 0.019% and 0.046% rate respectively, with no statistically significance. IPOE cases were related with aging, systemic and ocular comorbidities or with a complicated cataract surgery. CONCLUSIONS: The benefit of the application of topical antibiotics after cataract surgery is questionable when intracameral cefuroxime prophylaxis is performed and no better effectiveness with ciprofloxacin or azithromycin was observed.

Analysis of airborne Olea pollen in Cartagena (Spain).

Olive cultivation is of great importance in Southern Europe but olive pollen is the leading cause of allergy in many regions where it is grown. The best preventive measure for allergic patients is to avoid exposure. Thus, aerobiological monitoring networks must supply realistic pollen classes for the different types of allergic pollen. Even though those pollen classes are defined, they do not necessarily fit local data. Altogether, they should use predictive models to assess flowering intensity in advance. In this study, the Olea pollen degree of exposure classes (OPDEC) are defined based on percentiles and a predictive model is suggested for Cartagena, Spain. 24year (1993-2016) Olea pollen counts series was used to characterize the Main Pollen Season (MPS). The aerobiological samples were processed following the methodology proposed by Hirst and developed by the Spanish Aerobiology Network. The aerobiological database was completed with the meteorological data supplied by AEMET (Spanish State Meteorological Agency). MPS evolution over time, and its relation with temperature and rainfall, has been analysed. The study showed an increase in MPS duration and the amount of Olea pollen grains collected both in MPS and the peak day. The OPDEC should fit local data to improve preventive measures. Based on the 24year series, the proposed OPDEC for Cartagena are: Low (≤10grains/m3), Medium (between 10 and 50grains/m3), High (between 51 and 100grains/m3) and Very High (≥100grains/m3). Olea pollen estimations in the MPS and in the peak day were obtained by means of three Regression Methods and climatic factors. The analysis reveals that the Bagging for Regression Trees (BRT) method is a good predictive alternative and stablishes the importance for each meteorological variable.

Ceftolozane-tazobactam for the treatment of ventilator-associated infections by colistin-resistant Pseudomonas aeruginosa.

The use of colistin for the treatment of multiresistant bacteria has led to the emergence of colistin-resistant strains of Gram-negative bacilli. Treatment of infections caused by these pan-drug-resistant bacteria is difficult owing to the paucity of effective antibiotics. We report two cases of ventilator-associated respiratory infection caused by pan-drug-resistant, colistin-resistant Pseudomonas aeruginosa that were successfully treated with ceftolozane-tazobactam.

Modeling olive pollen intensity in the Mediterranean region through analysis of emission sources.

Aerobiological monitoring of Olea europaea L. is of great interest in the Mediterranean basin because olive pollen is one of the most represented pollen types of the airborne spectrum for the Mediterranean region, and olive pollen is considered one of the major cause of pollinosis in this region. The main aim of this study was to develop an airborne-pollen map based on the Pollen Index across a 4-year period (2008-2011), to provide a continuous geographic map for pollen intensity that will have practical applications from the agronomical and allergological points of view. For this purpose, the main predictor variable was an index based on the distribution and abundance of potential sources of pollen emission, including intrinsic information about the general atmospheric patterns of pollen dispersal. In addition, meteorological variables were included in the modeling, together with spatial interpolation, to allow the definition of a spatial model of the Pollen Index from the main olive cultivation areas in the Mediterranean region. The results show marked differences with respect to the dispersal patterns associated to the altitudinal gradient. The findings indicate that areas located at an altitude above 300ma.s.l. receive greater amounts of olive pollen from shorter-distance pollen sources (maximum influence, 27km) with respect to areas lower than 300ma.s.l. (maximum influence, 59km).

Airborne pollen trends in the Iberian Peninsula.

Airborne pollen monitoring is an effective tool for studying the reproductive phenology of anemophilous plants, an important bioindicator of plant behavior. Recent decades have revealed a trend towards rising airborne pollen concentrations in Europe, attributing these trends to an increase in anthropogenic CO2 emissions and temperature. However, the lack of water availability in southern Europe may prompt a trend towards lower flowering intensity, especially in herbaceous plants. Here we show variations in flowering intensity by analyzing the Annual Pollen Index (API) of 12 anemophilous taxa across 12 locations in the Iberian Peninsula, over the last two decades, and detecting the influence of the North Atlantic Oscillation (NAO). Results revealed differences in the distribution and flowering intensity of anemophilous species. A negative correlation was observed between airborne pollen concentrations and winter averages of the NAO index. This study confirms that changes in rainfall in the Mediterranean region, attributed to climate change, have an important impact on the phenology of plants.

A new method for determining the sources of airborne particles.

Air quality is a major issue for humans owing to the fact that the content of particles in the atmosphere has multiple implications for life quality, ecosystem dynamics and environment. Scientists are therefore particularly interested in discovering the origin of airborne particles. A new method has been developed to model the relationship between the emission surface and the total amount of airborne particles at a given distance, employing olive pollen and olive groves as examples. A third-degree polynomial relationship between the air particles at a particular point and the distance from the source was observed, signifying that the nearest area to a point is not that which is most correlated with its air features. This work allows the origin of airborne particles to be discovered and could be implemented in different disciplines related to atmospheric aerosol, thus providing a new approach with which to discover the dynamics of airborne particles.

[Nutritional therapy in traumatic brain injury : Update 2012]. / Ernährungstherapie bei Schädel-Hirn-Trauma : Update 2012.

Severe traumatic brain injury ranks among the most common causes of death in young adults in western countries. Severe traumatic brain injury is typically followed by a pronounced pathophysiological cascade that accounts for many deaths. The aim of intensive care medicine after traumatic brain injury is to minimize and to control the consequences of this potentially fatal cascade. The avoidance of hypoxemia, arterial hypotension, intracranial hypertension, hyperthermia, hyperglycemia, hypoglycemia and thromboembolic complications is essential in preventing this cascade. The effect of nutrition has been rather underestimated as a means of improving the outcome after traumatic brain injury. Nutrition should be started within the first 24 h after trauma. Enteral, wherever applicable, should be the route of administration of nutrition. Enteral administration of the whole calculated calorie requirement on day 1 after trauma, if possible, lowers the infection and overall complication rates. The present review gives an update of a practical approach to nutrition in traumatic brain injury.

Daily effects of air pollutants and pollen types on asthma and COPD hospital emergency visits in the industrial and Mediterranean Spanish city of Cartagena

Background: Associations found in time-series studies on hospital emergency room (ER) visits due to asthma and chronic obstructive pulmonary disease (COPD) with single air pollutants show some lack of consistency. The respiratory effects of aeroallergens in the air pollution mix are not well established. Non-linear relationships of different airborne pollen types with certain respiratory diseases have also been described. We aim to study the short-term effects of major air pollutants and aeroallergen pollen on asthma and COPD hospital ER visits in the industrial and Mediterranean Spanish city of Cartagena during1995-1998. Methods: The association of asthma and COPD to ER visits with mean levels of sulphur and nitrogen dioxides (SO2 and NO2), total suspended particles (TSP), ozone (O3), and the main allergenic airborne pollen types were analysed using Poisson regression with Generalised Additive Models, taking into account delayed effects and adjusting for long-term trends, seasonality, weather conditions, holidays and flu notifications. Results: Multipollutant models showed a similar relative risk (RR) increase (in %), of around 5% in asthma and COPD ER visits per 10 microg/m3 SO2 increments. The risk of an ER visit for the sameNO2 increment was 2.6% for asthma and 3.3% for COPD. Visits to the ER due to asthma showed a positive increase with both Urticaceae and Poaceae levels, but did not substantially modify the previous percentages(AU)

Daily effects of air pollutants and pollen types on asthma and COPD hospital emergency visits in the industrial and Mediterranean Spanish city of Cartagena.

BACKGROUND: Associations found in time-series studies on hospital emergency room (ER) visits due to asthma and chronic obstructive pulmonary disease (COPD) with single air pollutants show some lack of consistency. The respiratory effects of aeroallergens in the air pollution mix are not well established. Non-linear relationships of different airborne pollen types with certain respiratory diseases have also been described. We aim to study the short-term effects of major air pollutants and aeroallergen pollen on asthma and COPD hospital ER visits in the industrial and Mediterranean Spanish city of Cartagena during 1995-1998. METHODS: The association of asthma and COPD to ER visits with mean levels of sulphur and nitrogen dioxides (SO(2) and NO(2)), total suspended particles (TSP), ozone (O(3)), and the main allergenic airborne pollen types were analysed using Poisson regression with Generalised Additive Models, taking into account delayed effects and adjusting for long-term trends, seasonality, weather conditions, holidays and flu notifications. RESULTS: Multipollutant models showed a similar relative risk (RR) increase (in %), of around 5% in asthma and COPD ER visits per 10 µg/m(3) SO(2) increments. The risk of an ER visit for the same NO(2) increment was 2.6% for asthma and 3.3% for COPD. Visits to the ER due to asthma showed a positive increase with both Urticaceae and Poaceae levels, but did not substantially modify the previous percentages. CONCLUSIONS: Air levels of SO(2) and NO(2) were associated with a substantial increased risk in ER visits due to asthma and COPD. The inclusion of Poaceae and Urticaceae pollen did not alter that association.

[Pharmacoeconomic assessment of daptomycin as first-line therapy for bacteraemia and complicated skin and skin structure infections caused by gram-positive pathogens in Spain]. / Evaluación farmacoeconómica de daptomicina como terapia de primera línea en el tratamiento de bacteriemia e infecciones complicadas de piel y tejidos blandos causadas por microorganismos grampositivos en España.

OBJECTIVE: To assess the efficiency of daptomycin as firstline therapy (D) versus daptomycin as salvage therapy after vancomycin (V→D ) or linezolid (L→D) failure in gram-positive bacteraemia and complicated skin and skin-structure infections (cSSTIs). METHODS: Cost-effectiveness analysis of 161 bacteraemia and 84 cSSTIs patients comparing the above mentioned therapeutic alternatives was performed using the data from 27 Spanish hospitals involved in the EUCORE study. Direct medical costs were considered. Patients were observed from the first antibiotic dose for infection until either the end of daptomycin therapy or exitus. A multivariate Monte Carlo probabilistic sensitivity analysis was applied for costs (lognormal distribution) and effectiveness (normal distribution). RESULTS: In terms of effectiveness there were no statistical differences between groups but referring total costs per patient, there were significant differences. Sensitivity analysis confirmed that D dominates over L→D between 44.2%-62.1% of simulations in bacteraemia and between 48.2%-67.5% in cSSTIs. In comparison to V→D, D dominance was detected in 29.2%-33.2% of simulations in bacteraemia and between 48.2%-59.3% in cSSTIs. CONCLUSIONS: Daptomycin as first-line therapy dominates over daptomycin as salvage therapy after linezolid failure both in bacteraemia and cSSTIs. Comparing daptomycin as first-line therapy with its use after vancomycin failure, in cSSTIs the former is dominant. In bacteremia daptomycin as first line therapy is as effective as daptomycin as salvage therapy after vancomycin failure and implies lower costs.

Heavy metals in human bones in different historical epochs.

The concentration of the metals lead, copper, zinc, cadmium and iron was determined in bone remains belonging to 30 individuals buried in the Region of Cartagena dating from different historical periods and in eight persons who had died in recent times. The metals content with respect to lead, cadmium and copper was determined either by anodic stripping voltammetry or by atomic absorption spectroscopy on the basis of the concentrations present in the bone remains. In all cases, zinc and iron were quantified by means of atomic absorption spectroscopy. The lead concentrations found in the bone remains in our city are greater than those reported in the literature for other locations. This led to the consideration of the sources of these metals in our area, both the contribution from atmospheric aerosols as well as that from the soil in the area. Correlation analysis leads us to consider the presence of the studied metals in the analysed bone samples to be the consequence of analogous inputs, namely the inhalation of atmospheric aerosols and diverse contributions in the diet. The lowest values found in the studied bone remains correspond to the Neolithic period, with similar contents to present-day samples with respect to lead, copper, cadmium and iron. As regards the evolution over time of the concentrations of the metals under study, a clear increase in these is observed between the Neolithic period and the grouping made up of the Bronze Age, Roman domination and the Byzantine period. The trend lines used to classify the samples into 7 periods show that the maximum values of lead correspond to the Roman and Byzantine periods. For copper, this peak is found in the Byzantine Period and for iron, in the Islamic Period. Zinc shows an increasing tendency over the periods under study and cadmium is the only metal whose trend lines shows a decreasing slope.

Cost-effectiveness analysis of the treatment of ventilator-associated pneumonia with linezolid or vancomycin in Spain.

UNLABELLED: The aim of this study was to assess the cost-effectiveness of linezolid (LIN) versus vancomycin (VAN) for the treatment of ventilator-associated pneumonia (VAP) using a decision model analysis from the National Health System perspective. Patients and participants comprising four subgroups were analyzed: all, Gram-positive (GP), Staphylococcus aureus (SA), methicillin-resistant SA (MRSA). The treatments were LIN 600 mg i.v., every 12 hours, 10 days and VAN 1,000 mg i.v., every 12 hours 10 days. The primary outcome was the incremental cost-effectiveness of LIN in terms of cost per added quality-adjusted life year (QALY) gained. The secondary outcome was the marginal cost per year of life saved (LYS) generated by using LIN. Clinical cure and survival rates estimates were derived from a retrospective analysis of two trials comparing LIN with VAN. QALY was based on time-trade off study. Resource use and unit costs (Euros 2003) were obtained from Spanish VAP treatment and health cost databases. The additional QALY and LYS per LIN patients were 0.392; 0.688; 0.606; 1.805 and 0.471; 0.829; 0.729; 2.175 respectively, compared with those of VAN in the patients with VAP (all, GP, SA, and MRSA, respectively). The additional costs for LYS with LIN, as compared to VAN were 1,501.31; 827.63; 955.13 and 289.51 Euros, respectively. The additional cost per QALY with LIN was 1,803.87; 997.25; 1,149.00 and 348.85 Euros, respectively. CONCLUSIONS: LIN was more cost-effective than VAN in the treatment of VAP in Spain, with an additional cost per QALY/LYS gained below the acceptable threshold in Spain of Euros 30,000 for new therapies.

Sensitization to Zygophyllum fabago pollen. A clinical and immunologic study.

Zygophyllum fabago is a herbaceous plant found widely in the Mediterranean area. There are no previous reports of its allergenicity. An aerobiologic and clinical survey was conducted in Murcia, southern Spain, to determine the quantity of airborne pollen and establish the possible role of this pollen as a cause of allergic symptoms. With a Hirst volumetric trap, we determined the atmospheric concentrations of this pollen in 1993, 1994, 1995, and 1996. Of 1180 patients tested, 181 (15.34%) had a positive skin test. To determine its allergenicity, we divided 47 patients into three groups: in group 1, all the patients had symptoms of rhinoconjunctivitis plus asthma; in groups 2 and 3, rhinoconjunctivitis. In group 1, we performed a bronchial provocation test (BPT); in groups 2 and 3, we performed nasal provocation (NPT) and conjunctival provocation (CPT) tests, respectively. SDS-PAGE was used to characterize the antigenic fractions and RAST inhibition to determine cross-reactivity with other pollens. The pollen dispersion period is from May to September (445 grains/m3). BPT was positive in 13 of 15 patients, NPT in 14 of 16 patients, and CPT in 13 of 16 patients. RAST inhibition revealed cross-reactivity with Mercurialis, Ricinus, Olea, and Betula. SDS-PAGE identified 25 IgE antibody-binding components, five of which (60, 65, 41, 38, and 15.5/14.7 kDa) were recognized by 40% of the sera. By SDS-PAGE immunoblotting with sunflower antiprofilin rabbit serum and affinity chromatography we established that the Z. fabago extract has profilin. This study shows that this pollen becomes airborne and elicits an IgE response which triggers respiratory symptoms in allergic subjects.

Crustacean peptidergic neurons in culture show immediate outgrowth in simple medium.

The survival and outgrowth of neurons in culture has usually required conditioning factors. We now report that crustacean neurons, taken from the peptidergic neurosecretory system of the eyestalk of crabs (Cardisoma carnifex) and lobsters (Panulirus marginatus), show immediate outgrowth, sustained for a week or more, in defined medium as simple as physiological saline with glucose and glutamine. The neurons show peptide hormone immunoreactivity that is prominent at growth cones, exhibit differences in form correlated with their immunoreactivity, release peptides to the medium, and have voltage-dependent currents, including a well-sustained Ca current. Cd blocks secretion, growth, and the Ca current. Peptidergic secretory neurons may be able to utilize existing membrane from their store of granules and already active synthetic, transport, and secretory mechanisms for immediate outgrowth.