Revisiting the epidemiology of bloodstream infections and healthcare-associated episodes: results from a multicentre prospective cohort in Spain (PRO-BAC Study)

PROBAC REIPI/GEIH-SEIMC/SAEI Group.The epidemiology of bloodstream infections (BSIs) is dynamic as it depends on microbiological, host and healthcare system factors. The aim of this study was to update the information regarding the epidemiology of BSIs in Spain considering the type of acquisition. An observational, prospective cohort study in 26 Spanish hospitals from October 2016 through March 2017 including all episodes of BSI in adults was performed. Bivariate analyses stratified by type of acquisition were performed. Multivariate analyses were performed by logistic regression. Overall, 6345 BSI episodes were included; 2510 (39.8%) were community-acquired (CA), 1661 (26.3%) were healthcare-associated (HCA) and 2056 (32.6%) hospital-acquired (HA). The 30-day mortality rates were 11.6%, 19.5% and 22.0%, respectively. The median age of patients was 71 years (interquartile range 60–81 years) and 3656 (58.3%; 95% confidence interval 57.1–59.6%) occurred in males. The proportions according to patient sex varied according to age strata. Escherichia coli (43.8%), Klebsiella spp. (8.9%), Staphylococcus aureus (8.9%) and coagulase-negative staphylococci (7.4%) were the most frequent pathogens. Multivariate analyses confirmed important differences between CA and HCA episodes, but also between HCA and HA episodes, in demographics, underlying conditions and aetiology. In conclusion, we have updated the epidemiological information regarding patients’ profiles, underlying conditions, frequency of acquisition types and aetiological agents of BSI in Spain. HCA is confirmed as a distinct type of acquisition.This work was financed by grants from Plan Nacional de I+D+i 2013–2016, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades [PI16/01432] and the Spanish Network for Research in Infectious Diseases (REIPI) [RD16/0016/0001; RD16/0016/0008], co‐financed by the European Development Regional Fund ‘A way to achieve Europe’, Operative program Intelligent Growth 2014–2020

Rationale and design of the Concordance study between FFR and iFR for the assessment of lesions in the left main coronary artery. The ILITRO-EPIC-07 Trial

Introduction and objectives: Patients with left main coronary artery (LMCA) stenosis have been excluded from the trials that support the non-inferiority of the instantaneous wave-free ratio (iFR) compared to the fractional flow reserve (FFR) in the decision-making process of coronary revascularization. This study proposes to prospectively assess the concordance between the two indices in LMCA lesions and to validate the iFR cut-off value of 0.89 for clinical use. Methods: National, prospective, and observational multicenter registry of 300 consecutive patients with intermediate lesions in the LMCA (angiographic stenosis, 25% to 60%. A pressure gudiewire study and determination of the RFF and the iFR will be performed: in the event of a negative concordant result (FFR > 0.80/iFR > 0.89), no treatment will be performed; in case of a positive concordant result (FFR 0.80/iFR 0.89), an intravascular echocardiography will be performed and revascularization will be delayed if the minimum lumen area is > 6 mm(2). The primary clinical endpoint will be a composite of cardiovascular death, LMCA lesion-related non-fatal infarction or need for revascularization of the LMCA lesion at 12 months. Conclusions: Confirm that an iFR-guided decision-making process in patients with intermediate LMCA stenosis is clinically safe and would have a significant clinical impact. Also, justify its systematic use when prescribing treatment in these potentially high-risk patients

Cut-offs and response criteria for the Hospital Universitario la Princesa Index (HUPI) and their comparison to widely-used indices of disease activity in rheumatoid arthritis

Objective To estimate cut-off points and to establish response criteria for the Hospital Universitario La Princesa Index (HUPI) in patients with chronic polyarthritis. Methods Two cohorts, one of early arthritis (Princesa Early Arthritis Register Longitudinal PEARL] study) and other of long-term rheumatoid arthritis (Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide EMECAR]) including altogether 1200 patients were used to determine cut-off values for remission, and for low, moderate and high activity through receiver operating curve (ROC) analysis. The areas under ROC (AUC) were compared to those of validated indexes (SDAI, CDAI, DAS28). ROC analysis was also applied to establish minimal and relevant clinical improvement for HUPI. Results The best cut-off points for HUPI are 2, 5 and 9, classifying RA activity as remission if =2, low disease activity if >2 and =5), moderate if >5 and <9 and high if =9. HUPI''s AUC to discriminate between low-moderate activity was 0.909 and between moderate-high activity 0.887. DAS28''s AUCs were 0.887 and 0.846, respectively; both indices had higher accuracy than SDAI (AUCs: 0.832 and 0.756) and CDAI (AUCs: 0.789 and 0.728). HUPI discriminates remission better than DAS28-ESR in early arthritis, but similarly to SDAI. The HUPI cut-off for minimal clinical improvement was established at 2 and for relevant clinical improvement at 4. Response criteria were established based on these cut-off values. Conclusions The cut-offs proposed for HUPI perform adequately in patients with either early or long term arthritis

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020.

Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3–5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes. © 2021, The Author(s), under exclusive licence to Springer Nature Limited

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3

ObjectivesCARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain.MethodsIn total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC &gt; 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.ResultsIn total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were blaOXA–48 (263/377), blaKPC–3 (62/377), blaVIM–1 (28/377), and blaNDM–1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5).ConclusionThis study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3

Factors associated with recruitment success in the phase 2a study of aztreonam-avibactam development programme: a descriptive qualitative analysis among sites in Spain

Objective: Successful clinical trials are subject to recruitment. Recently, the REJUVENATE trial, a prospective phase 2a open-label, single-arm interventional clinical trial conducted within the Innovative Medicines Initiative-supported Combatting Bacterial Resistance in Europe-Carbapenem Resistance project, was published, with 85% of the recruitment performed in Spain. We analysed the recruitment success in this trial by establishing a model of recruitment practice. Methods: A descriptive qualitative study was performed from May 2016 to October 2017 at 10 participating Spanish centres. Data were extracted from: (1) feasibility questionnaires to assess the centre's potential for patient enrolment; (2) delegation of responsibility records; (3) pre-screening records including an anonymised list of potentially eligible and (4) screening and enrolment records. A descriptive analysis of the features was performed by the participating centre. Pearson's and Spearman's correlation coefficients were calculated to determine factors of recruitment success. Results: The highest recruitment rate was observed in Hospitals 3 and 6 (58.8 and 47.0 patients per month, respectively). All the study teams were multidisciplinary with a median of 15 members (range: 7-22). Only Hospitals 3, 5 and 6 had dedicated nursing staff appointed exclusively to this study. Moreover, in those three hospitals and in Hospital 9, the study coordinator performed exclusive functions as a research planner, and did not assume these functions for the other hospitals. The univariate analysis showed a significant association between recruitment success and months of recruitment (p=0.024), number of staff (p<0.001), higher number of pharmacists (p=0.005), infectious disease specialists (p<0.001), the presence of microbiologist in the research team (p=0.018) and specifically dedicated nursing staff (p=0.036). Conclusions: The existence of broad multidisciplinary teams with staff dedicated exclusively to the study as well as the implementation of a well-designed local patient assessment strategy were the essential optimisation factors for recruitment success in Spain. Trial registration number: NCT02655419; EudraCT 2015-002726-39; analysis of pre-screened patients