Quasiexperimental intervention study protocol to optimise the use of new antibiotics in Spain: the NEW_SAFE project

[Introduction] Ceftaroline, tedizolid, dalbavancin, ceftazidime-avibactam and ceftolozane-tazobactam are novel antibiotics used to treat infections caused by multidrug-resistant pathogens (MDR). Their use should be supervised and monitored as part of an antimicrobial stewardship programme (ASP). Appropriate use of the new antibiotics will be improved by including consensual indications for their use in local antibiotic guidelines, together with educational interventions providing advice to prescribers to ensure that the recommendations are clearly understood.[Methods and analysis] This study will be implemented in two phases. First, a preliminary historical cohort (2017–2019) of patients from 13 Andalusian hospitals treated with novel antibiotics will be analysed. Second, a quasiexperimental intervention study will be developed with an interrupted time-series analysis (2020–2021). The intervention will consist of an educational interview between prescribers and ASP leaders at each hospital to reinforce the proper use of novel antibiotics. The educational intervention will be based on a consensus guideline designed and disseminated by leaders after the retrospective cohort data have been analysed. The outcomes will be acceptance of the intervention and appropriateness of prescription. Incidence of infection and colonisation with MDR organisms as well as incidence of Clostridioides difficile infection will also be analysed. Changes in prescription quality between periods and the safety profile of the antibiotics in terms of mortality rate and readmissions will also be measured.[Ethics and dissemination] Ethical approval will be obtained from the Andalusian Coordinating Institutional Review Board. The study is being conducted in compliance with the protocol and regulatory requirements consistent with International Council of Harmonisation E6 Good Clinical Practice and the ethical principles of the latest version of the Declaration of Helsinki. The results will be published in peer-reviewed journals and disseminated at national and international conferences.[Trial registration number] NCT03941951; Pre-results.The study is funded by the Consejería de Salud, Junta de Andalucía, grant PI-0077-2018. The investigators also receive funds for research from the Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001) through the Plan Nacional de I+D+ i 2013‐2016, cofinanced by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014‐2020

Ten Issues for Updating in Community-Acquired Pneumonia: An Expert Review

Community-acquired pneumonia represents the third-highest cause of mortality in industrialized countries and the first due to infection. Although guidelines for the approach to this infection model are widely implemented in international health schemes, information continually emerges that generates controversy or requires updating its management. This paper reviews the most important issues in the approach to this process, such as an aetiologic update using new molecular platforms or imaging techniques, including the diagnostic stewardship in different clinical settings. It also reviews both the Intensive Care Unit admission criteria and those of clinical stability to discharge. An update in antibiotic, in oxygen, or steroidal therapy is presented. It also analyzes the management out-of-hospital in CAP requiring hospitalization, the main factors for readmission, and an approach to therapeutic failure or rescue. Finally, the main strategies for prevention and vaccination in both immunocompetent and immunocompromised hosts are reviewed

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Pharmacokinetics and safety of aztreonam/avibactam for the treatment of complicated intra-abdominal infections in hospitalized adults: results from the REJUVENATE study

Objectives: To investigate pharmacokinetics (PK) and safety (primary objectives) and efficacy (secondary objective) of the investigational monobactam/b-lactamase inhibitor combination aztreonam/avibactam in patients with complicated intra-abdominal infection (cIAI). Methods: This Phase 2a open-label, multicentre study (NCT02655419; EudraCT 2015-002726-39) enrolled adults with cIAI into sequential cohorts for 5–14 days treatment. Cohort 1 patients received an aztreonam/avibactam loading dose of 500/137 mg (30 min infusion), followed by maintenance doses of 1500/410 mg (3 h infusions) q6h; Cohort 2 received 500/167 mg (30 min infusion), followed by 1500/500 mg (3 h infusions) q6h. Cohort 3 was an extension of exposure at the higher dose regimen. Doses were adjusted for creatinine clearance of 31–50 mL/min (Cohorts 2!3). All patients received IV metronidazole 500 mg q8h. PK, safety and efficacy were assessed. Results: Thirty-four patients (Cohort 1, n = 16; Cohorts 2!3, n = 18) comprised the modified ITT (MITT) population. Mean exposures of aztreonam and avibactam in Cohorts 2!3 were consistent with those predicted to achieve joint PK/pharmacodynamic target attainment in >90% patients. Adverse events (AEs) were similar between cohorts. The most common AEs were hepatic enzyme increases [n = 9 (26.5%)] and diarrhoea [n = 5 (14.7%)]. Clinical cure rates at the test-of-cure visit overall were 20/34 (58.8%) (MITT) and 14/23 (60.9%) (microbiological-MITT population). Conclusions: Observed AEs were consistent with the known safety profile of aztreonam monotherapy, with no new safety concerns identified. These data support selection of the aztreonam/avibactam 500/167 mg (30 min infusion) loading dose and 1500/500 mg (3 h infusions) maintenance dose q6h regimen, in patients with creatinine clearance >50 mL/min, for the Phase 3 development programm

Epidemiologic changes in bloodstream infections in Andalucía (Spain) during the last decade.

During the last decade, some changes in the epidemiology of invasive infections have been reported; however, specific studies with patient-level data are scarce. The aim of this study was to describe and evaluate the epidemiologic changes in bloodstream infections (BSI) during the last decade in Andalucía, Spain. Data from two prospective cohorts of BSI in adults with the same methodology performed 10 years apart in 11 hospitals (eight tertiary and three community) in Andalucía, Spain, were compared; the 2006-7 cohort study was performed between October 2006 and March 2007, and the 2016-17 cohort study was performed between October 2016 and March 2017. Population-based incidence rates were calculated and extrapolated for 1 year. Relative risk ratios were calculated between the 2 periods. Multivariate analyses were performed by logistic regression. Overall, 1262 episodes of BSI were included, 563 (44.6%) in 2006-7 and 699 (55.3%) in 2016-17. Multivariate models selected the following changes in patients' features in 2016-17, after controlling for type of acquisition: higher age (odds ratio (OR) = 1.02; 95% confidence interval [CI] 1.01-1.03), lower urinary catheter (OR = 0.37; 95% CI, 0.26-0.48) and lower Pitt score (OR = 0.76; 95% CI, 0.71-0.82). Adjusted estimations considering patients' features and exposure to procedures showed a reduction in coagulase-negative staphylococci (OR = 0.47; 95% CI, 0.32-0.69), and an increase in Proteus spp. (OR = 3.12; 95% CI, 1.18-8.23) and Candida spp. (OR = 3.01; 95% CI, 1.03-8.86). We found relevant epidemiologic changes in BSI in our area, including rates, frequency of acquisition types, changes in patient's profiles and aetiologic agents

Guía de Terapéutica Antimicrobiana del Área Aljarafe, 3ª edición

Coordinadora: Rocío Fernández Urrusuno. Co-coordinadora: Carmen Serrano Martino.YesEstas guías son un recurso indispensable en los Programas de Optimización de Antibióticos (PROA). No sólo constituyen una herramienta de ayuda para la toma de decisiones en los principales síndromes infecciosos, proporcionando recomendaciones para el abordaje empírico de dichos procesos, sino que son el patrón/estándar de referencia que permitirá determinar la calidad o adecuación de los tratamientos realizados. Las guías pueden ser utilizadas, además, como herramienta de base para la formación y actualización en antibioterapia, ya que permiten mantener actualizados los conocimientos sobre las nuevas evidencias en el abordaje de las infecciones. Por último, deberían incorporar herramientas que faciliten el proceso de toma de decisiones compartidas con el paciente. El objetivo de esta guía es proporcionar recomendaciones para el abordaje de las enfermedades infecciosas más prevalentes en la comunidad, basadas en las últimas evidencias disponibles y los datos de resistencias de los principales patógenos que contribuyan a mejorar la calidad de la prescripción de antimicrobianos