Patients receiving a high burden of antibiotics in the community in Spain: a cross-sectional study

Some patients in the community receive a high burden of antibiotics. We aimed at describing the characteristics of these patients, antibiotics used, and conditions for which they received antibiotics. We carried out a cross-sectional study. Setting: Thirty Health Primary Care Areas from 12 regions in Spain, covering 5, 960, 191 inhabitants. Patients having at least 30 packages of antibacterials for systemic use dispensed in 2017 were considered. Main outcome measures: Prevalence of antibiotic use, conditions for which antibiotics were prescribed, clinical characteristics of patients, comorbidities, concomitant treatments, and microbiological isolates. Patient''s average age was 70 years; 52% were men; 60% smokers/ex-smokers; 54% obese. Overall, 93% of patients had, at least, one chronic condition, and four comorbidities on average. Most common comorbidities were cardiovascular and/or hypertension (67%), respiratory diseases (62%), neurological/mental conditions (32%), diabetes (23%), and urological diseases (21%); 29% were immunosuppressed, 10% were dead at the time of data collection. Patients received three antibiotic treatments per year, mainly fluoroquinolones (28%), macrolides (21%), penicillins (19%), or cephalosporins (12%). Most frequently treated conditions were lower respiratory tract (infections or prophylaxis) (48%), urinary (27%), and skin/soft tissue infections (11%). Thirty-five percent have been guided by a microbiological diagnosis, being Pseudomonas aeruginosa (30%) and Escherichia coli (16%) the most frequent isolates. In conclusion, high antibiotic consumers in the community were basically elder, with multimorbidity and polymedication. They frequently received broad-spectrum antibiotics for long periods of time. The approach to infections in high consumers should be differentiated from healthy patients receiving antibiotics occasionally

Nanoencapsulated capsaicin changes migration behavior and morphology of madin darby canine kidney cell monolayers

We have developed a drug delivery nanosystem based on chitosan and capsaicin. Both substances have a wide range of biological activities. We investigated the nanosystem’s influence on migration and morphology of Madin Darby canine kidney (MDCK-C7) epithelial cells in comparison to the capsaicin-free nanoformulation, free capsaicin, and control cells. For minimally-invasive quantification of cell migration, we applied label-free digital holographic microscopy (DHM) and single-cell tracking. Moreover, quantitative DHM phase images were used as novel stain-free assay to quantify the temporal course of global cellular morphology changes in confluent cell layers. Cytoskeleton alterations and tight junction protein redistributions were complementary analyzed by fluorescence microscopy. Calcium influx measurements were conducted to characterize the influence of the nanoformulations and capsaicin on ion channel activities. We found that both, capsaicin-loaded and unloaded chitosan nanocapsules, and also free capsaicin, have a significant impact on directed cell migration and cellular motility. Increase of velocity and directionality of cell migration correlates with changes in the cell layer surface roughness, tight junction integrity and cytoskeleton alterations. Calcium influx into cells occurred only after nanoformulation treatment but not upon addition of free capsaicin. Our results pave the way for further studies on the biological significance of these findings and potential biomedical applications, e.g. as drug and gene carriers

Development of controlled release formulations of alachlor in ethylcellulose

The herbicide alachlor (2-chloro-N-(2,6-diethylphenyl)-N-(methoxymethyl)-acetamide) is frequently implicated in groundwater contamination. Microencapsulated alachlor should have reduced potential for leaching in the soil while maintaining effective biological activity. Microspheres of alachlor were prepared using ethylcellulose, according to the solvent evaporation method. The influence of formulation variables affecting the release rate of pesticide, such as the molecular weight of ethylcellulose, the amount of emulsifying agent, the pesticide/polymer ratio and the particle size, were investigated. The results showed that microspheres retarded the release of alachlor in different degrees. Pesticide/polymer ratio and particle size were the more important factors determining the alachler release. Ethylcellulose microspheres may prove useful for the prolonged release of alachlor.Peer Reviewe

Outcomes of the PIRASOA programme, an antimicrobial stewardship programme implemented in hospitals of the Public Health System of Andalusia, Spain: an ecologic study of time-trend analysis.

Inappropriate antimicrobial use favours the spread of resistance, and multidrug-resistant microorganisms (MDR) are currently of major concern. Antimicrobial stewardship programmes (ASPs) are essential for improving antibiotic use in hospitals. However, their impact on entire healthcare systems has not been thoroughly assessed. Our objective was to provide the results of an institutionally supported ASP involving 31 public hospitals in Andalusia, Spain. We designed an ecologic time-series study from 1 January 2014 to 31 December 2017. Quarterly, data on indicators were collected prospectively, and feedback reports were provided. PIRASOA is an ongoing clinically based quality-improvement programme whose key intervention is the educational interview, regular peer-to-peer interventions between advisors and prescribers to reinforce the appropriate use of antibiotics. Seventy-two indicators were monitored to measure prescribing quality (inappropriate treatments), antimicrobial consumption (defined daily doses per 1000 occupied bed-days), incidence density of MDR per 1000 occupied bed-days and crude mortality rate associated with bloodstream infections. We used Joinpoint regression software to analyse the trends. The quality of antimicrobial prescribing improved markedly, and the inappropriate treatment rate was significantly lower, with quarterly percentage change (QPC) = -3.0%, p  To date, the PIRASOA programme has succeeded in optimizing the use of antimicrobial agents and has had a positive ecologic result on bacterial resistance at level of an entire healthcare system

Outcomes of the PIRASOA programme, an antimicrobial stewardship programme implemented in hospitals of the Public Health System of Andalusia, Spain: an ecologic study of time-trend analysis

[Objectives] Inappropriate antimicrobial use favours the spread of resistance, and multidrug-resistant microorganisms (MDR) are currently of major concern. Antimicrobial stewardship programmes (ASPs) are essential for improving antibiotic use in hospitals. However, their impact on entire healthcare systems has not been thoroughly assessed. Our objective was to provide the results of an institutionally supported ASP involving 31 public hospitals in Andalusia, Spain.[Methods] We designed an ecologic time-series study from 1 January 2014 to 31 December 2017. Quarterly, data on indicators were collected prospectively, and feedback reports were provided. PIRASOA is an ongoing clinically based quality-improvement programme whose key intervention is the educational interview, regular peer-to-peer interventions between advisors and prescribers to reinforce the appropriate use of antibiotics. Seventy-two indicators were monitored to measure prescribing quality (inappropriate treatments), antimicrobial consumption (defined daily doses per 1000 occupied bed-days), incidence density of MDR per 1000 occupied bed-days and crude mortality rate associated with bloodstream infections. We used Joinpoint regression software to analyse the trends.[Results] The quality of antimicrobial prescribing improved markedly, and the inappropriate treatment rate was significantly lower, with quarterly percentage change (QPC) = −3.0%, p < 0.001. Total antimicrobial consumption decreased (QPC = −0.9%, p < 0.001), specifically carbapenems, amoxicillin/clavulanic acid, quinolones and antifungal agents, whereas antipseudomonal cephalosporin use increased. While the incidence of MDR showed a sustained decreasing trend (QPC = −1.8%; p 0.002), the mortality of patients with bloodstream infections remained stable (QPC = −0.2%, p 0.605).[Conclusions] To date, the PIRASOA programme has succeeded in optimizing the use of antimicrobial agents and has had a positive ecologic result on bacterial resistance at level of an entire healthcare system.Peer reviewe

Long-term impact of an educational antimicrobial stewardship programme in primary care on infections caused by extended-spectrum β-lactamase-producing Escherichia coli in the community: an interrupted time-series analysis

PIRASOA-FIS team.[Background] There is little evidence on the ecological effect and sustainability of antimicrobial stewardship programmes (ASPs) in primary-care settings. We aimed to determine whether a multimodal, educational ASP would be sustainable in the long-term and reduce the incidence of infections caused by extended-spectrum β-lactamase-producing Escherichia coli in the community by optimising antibiotic use.[Methods] We did this quasi-experimental intervention study in 214 primary health centres of four primary health-care districts in Andalusia, Spain. Local multidisciplinary teams, comprised of general practitioners, paediatricians, primary-care pharmacists, and epidemiologists, were created in each district and implemented a multimodal, education-based ASP. The core activity of the programme consisted of regular one-to-one educational interviews between a reference interviewing physician and prescribing physicians from each centre on the appropriateness of their most recent (same or preceding day) antibiotic prescriptions based on a structured questionnaire. Appropriate prescribing was defined as compliance of all checklist items with the reference guidelines. An average of five educational interviews were scheduled per prescriber per study year. We did an interrupted time-series analysis to assess the effect of the intervention on quarterly antibiotic use (prescription and collection by the patient) and quality of prescriptions (as defined daily doses per 1000 inhabitants per day) and incidence per 1000 inhabitants of E coli producing extended-spectrum β-lactamase (ESBL) isolated from urine samples.[Findings] The study was done between January, 2012, and December, 2017, in a pre-intervention period of 2012–13 and an intervention period of 2014–17. Throughout the study period, there were 1387 physicians (1116 general practicioners and 271 paediatricians) in the included health centres serving a mean population of 1 937 512 people (299 331 children and 1 638 181 adults). 24 150 educational interviews were done over the 4 years. Inappropriate antibiotic prescribing was identified in 1794 (36·5%) of 4917 educational interviews in 2014 compared with 1793 (26·9%) of 6665 in 2017 (p<0·0001). The intervention was associated with a sustained reduction in the use of ciprofloxacin (relative effect −15·9%, 95% CI −23·9 to −8·0) and cephalosporins (−22·6%, −35·9 to −9·2), and a sustained increase in the use of amoxicillin (22·2%, 6·4 to 38·0) and fosfomycin trometamol (6·1%, 2·6 to 9·6). The incidence density of ESBL-producing E coli decreased by −0·028 cases per 1000 inhabitants (95% CI −0·034 to −0·021) after the start of the programme, reversing the pre-intervention increase and leading to a relative reduction of −65·6% (−68·2 to −63·0) 4 years later.[Interpretation] Our data suggest that implementation of a multimodal ASP in primary care that is based on individual educational interviews improves the use of antibiotics and results in a sustained significant reduction of infections by ESBL-producing E coli in the community. This information should encourage the implementation of ASPs in primary care.Instituto de Salud Carlos III, Spanish Government (PI14/01523)

Generation of Nanoparticles of Controlled Size using Ultrasonic Piezoelectric Oscillators in Solution

We demonstrate the operation of a device that can produce chitosan nanoparticles in a tunable size range from 50−300 nm with small size dispersion. A piezoelectric oscillator operated at megahertz frequencies is used to aerosolize a solution containing dissolved chitosan. The solvent is then evaporated from the aerosolized droplets in a heat pipe, leaving monodisperse nanoparticles to be collected. The nanoparticle size is controlled both by the concentration of the dissolved polymer and by the size of the aerosol droplets that are created. Our device can be used with any polymer or polymer/therapeutic combination that can be prepared in a homogeneous solution and vaporized