Tratamiento alternativo a los carbapenemas y desarrollo de un sistema pronóstico de puntuación en bacteriemias por enterobacterias productoras de beta-lactamasas de espectro extendido.

Capítulos I y II de resultados embargadosPremio Extraordinario de Doctorado U

Opportunities for antibiotic optimisation and outcome improvement in patients with negative blood cultures: study protocol for a cluster-­randomised crossover trial, the NO-­BACT study.

Introduction Patients with negative blood cultures (BCx) represent 85%–90% of all patients with BCx taken during hospital admission. This population usually includes a heterogeneous group of patients admitted with infectious diseases or febrile syndromes that require a blood culture. There is very little evidence of the clinical characteristics and antibiotic treatment given to these patients. Methods and analysis In a preliminary exploratory prospective cohort study of patients with BCx taken, the clinical/therapeutic characteristics and outcomes/ antimicrobial stewardship opportunities of a population of patients with negative BCx will be analysed. In the second phase, using a cluster randomised crossover design, the implementation of an antimicrobial stewardship intervention targeting patients with negative BCx will be evaluated in terms of quality of antimicrobial use (duration and de-escalation), length of hospital stay and mortality. Ethics and dissemination This study has been and registered with clinicaltrials.gov. The findings of our study may support the implementation in clinical practice of an antimicrobial stewardship intervention to optimise the use of antibiotics in patients with negative BCx. The results of this study will be published in peer-reviewed journals and disseminated at national and international conferences. Trial registration number NCT03535324.Instituto de Salud Carlos III PI17 / 01809Plataforma Española de Investigación Clínica y Ensayos Clínicos, SCReN (Red Española de Investigación Clínica), financiada por la Subdirección General de Evaluación y Promoción de la Investigación ISCIII: PT17 / 0017/0012. Cofinanciado por el Fondo Europeo de Desarrollo Regional (FEDER)

Evaluation of the Kinetics of Antibody Response to COVID-19 Vaccine in Solid Organ Transplant Recipients: The Prospective Multicenter ORCHESTRA Cohort

Previous studies assessing the antibody response (AbR) to mRNA COVID-19 vaccines in solid organ transplant (SOT) recipients are limited by short follow-up, hampering the analysis of AbR kinetics. We present the ORCHESTRA SOT recipients cohort assessed for AbR at first dose (t0), second dose (t1), and within 3 ± 1 month (t2) after the first dose. We analyzed 1062 SOT patients (kidney, 63.7%; liver, 17.4%; heart, 16.7%; and lung, 2.5%) and 5045 health care workers (HCWs). The AbR rates in the SOTs and HCWs were 52.3% and 99.4%. The antibody levels were significantly higher in the HCWs than in the SOTs (p < 0.001). The kinetics showed an increase (p < 0.001) in antibody levels up to 76 days and a non-significant decrease after 118 days in the SOT recipients versus a decrease up to 76 days (p = 0.02) and a less pronounced decrease between 76 and 118 days (p = 0.04) in the HCWs. Upon multivariable analysis, liver transplant, ≥3 years from SOT, mRNA-1273, azathioprine, and longer time from t0 were associated with a positive AbR at t2. Older age, other comorbidities, mycophenolate, steroids, and impaired graft function were associated with lower AbR probability. Our results may be useful to optimize strategies of immune monitoring after COVID-19 vaccination and indications regarding timing for booster dosages calibrated on SOT patients’ characteristics.The ORCHESTRA project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 101016167Peer reviewe

Uncovering the neurological effects of West Nile virus during a record-breaking southern Spain outbreak in 2020–2021

The 2020–21 West Nile Virus (WNV) outbreak in Andalusia, Spain, was the largest reported in the country, with eight cases of West Nile Neuroinvasive Disease (WNND) diagnosed in a tertiary hospital. Diagnosis of WNND is based on detecting WNV RNA, viral isolation, or demonstrating a specific immune response against the virus, with additional tests used to support the diagnosis. Treatment remains supportive, with variable outcomes. The potential efficacy of plasma exchange (PLEX) in select cases raises the possibility of an autoimmune component secondary to infectious pathology of the central nervous system. The influence of climate change on the expansion of WNV into new regions is a significant concern. It is crucial for physicians practicing in high-risk areas to be knowledgeable about the disease for early prevention and effective control measures.Peer reviewe

Antibiotic use and outcome in patients with negative blood cultures, a new target population for antimicrobial stewardship interventions: A prospective multicentre cohort (NO-BACT)

[Objectives] To evaluate the appropriateness of antimicrobial treatment and the risk factors for mortality in patients with negative blood cultures (BC), in order to evaluate whether this population would be a suitable target for antimicrobial stewardship (AMS) interventions.[Methods] A multicentre prospective cohort study of patients with negative BC in three Spanish hospitals between October 2018 and July 2019 was performed. The main endpoints were the appropriateness of antimicrobial treatment (evaluated by two investigators according to local guidelines) and 30-day mortality. Cox-regression was performed to estimate the association between variables and 30-day mortality.[Results] Of 1011 patients in whom BC was obtained, these were negative in 803 (79%) and were included; 30-day mortality was 9% (70 patients); antibiotic treatment was considered inappropriate in 299 (40%) of 747 patients evaluated at day 2, and in 266 (46%) of 573 at day 5–7. The variables independently associated with increased risk of 30-day mortality were higher age (HR 1.05; 95% CI 1.03–1.07), neoplasia (HR 2.73; 95% CI 1.64–4.56), antibiotic treatment in the 48 h prior to BC extraction (HR 2.06; 95% CI 1.23–3.43) and insufficient antibiotic coverage at day 2 after BC obtainment (HR 2.35; 95% CI 1.39–4.00). Urinary, catheter and biliary sources of infection were associated with lower risk (HR 0.40; 95% CI 0.20–0.81).[Conclusions] Antimicrobial treatment is frequently inappropriate among patients with negative BC; insufficient antibiotic coverage at day 2 was associated with mortality. These results suggest that patients with negative BC are a suitable population for AS interventions.[Summary] Antimicrobial treatment in patients with negative blood culture was frequently inappropriate, and inappropriate coverage at day 2 was associated with increased risk of death. These data support the consideration of this population as a potential target for antimicrobial stewardship interventions.This study was funded by Acción Estratégica en Salud, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (PI17/01809), the Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001 and RD16CIII/0004/0002), the Spanish Clinical Research and Clinical Trials Platform (SCReN, PT17/0017/0012), and CIBERINFEC (CB21/13/00012, CB21/13/00087), all from Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades, and co-funded by European Development Regional Fund “A way to achieve Europe,” Operative Program Intelligence Growth 2014–2020 and ERDF/ESF, “Investing in your future.”Peer reviewe

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

Migration and activation marker expressing in monocytes subset in mild and several/critical patients (S/C)

S2 Fig. Migration and activation marker expressing in monocytes subset in mild and several/critical patients (S/C).Peer reviewe

Baseline characteristics of the mild patients who were discharged and worsened during the first week

Quantitative variables are expressing as number (percentage) or median (interquartile range). Pa value for differences between patients who were or not discharged. Pb value for differences between patients who who did and did not get wore. SpO2, peripheral capillary oxygen saturation; CRP, C-reactive protein; LDH, Lactate dehydrogenase; NLR, neutrophil/lymphocyte ratio.Peer reviewe

Receiver operating curve (ROC) analyses to evaluate the ability of clinical and laboratory data to predict worse prognosis during the first week

AUC, area under the curve; SE, sensitivity; S, specificity; PPV, positive predictive value; NPV, negative predictive value. SpO2, peripheral capillary oxygen saturation; CRP, C-reactive protein; LDH, Lactate dehydrogenase; NLR, neutrophil/lymphocyte ratio; TNF-α; tumor necrosis factor α; IL-6, interleukine-6; IL-8, interleukine-8; IL-1β, interleukine-1β; MIP-1β, macrophage inflammatory proteins 1β; sCD25, soluble receptor interleukine-2; IP-10, interferon γ-induced protein 10.Peer reviewe

S1 Fig - Clinical, laboratory data and inflammatory biomarkers at baseline as early discharge predictors in hospitalized SARS-CoV-2 infected patients

A, Predictive models for hospital discharge during the first week in mild patients. B, Predictive models for worsening of clinical status during the first week in patients who were admitted mildly ill. AUC, area under the curve.Peer reviewe