Correlation Between Tacrolimus Levels in Blood Samples Obtained from Central Catheter and Peripheral Venipuncture in Lung Transplant Patients (Ven-Cat Study).

BACKGROUND: Following lung transplantation (LT), receiving immunosuppressive therapy is crucial. Tacrolimus is considered a drug with a narrow therapeutic range and its use requires constant monitoring. This study aimed to evaluate the correlation between tacrolimus levels obtained from central venous catheter and direct venipuncture in adult patients undergoing LT. METHODS: This prospective study included LT patients hospitalized in conventional ward carrying a central catheter through which no intravenous tacrolimus was administered. Trough samples were obtained through direct puncture and from the central catheter. Pearson correlation coefficient was calculated to quantify the mean difference between the 2 measures. RESULTS: A total of 54 sample pairs from 16 LT patients were obtained, mostly male (81.3%) and bilateral transplant recipients (93.8%); the transplant procedure was the primary reason for admission (81.3%). The difference in tacrolimus levels between both samples was 0.3 (0.1-0.6) mcg/L, with the measurement for the samples obtained through venipuncture being mostly higher than that for those obtained from the catheter. A strong correlation was observed between the tacrolimus levels in the samples obtained from the catheter and through venipuncture (Pearson correlation coefficient, 0.991; P < 0.001; R2 = 0.982). CONCLUSIONS: There is an excellent correlation between tacrolimus levels obtained from venipuncture and those obtained from central venous catheter in LT patients undergoing oral tacrolimus therapy.

Influence of quality of life related to perceived foot health between in a rural an urban population: A case-control research.

Foot problems are very common in the community. Studies indicate that between 18% and 63% of people have foot pain or stiffness and that foot problems have a large impact on people's functional decline and a significant detrimental impact on measures of quality of life related to health. The general objective of this research was to compare foot health in people from the rural population compared to people from the urban population and its relationship with quality of life. A case-control descriptive study was developed with a sample of 304 patients, 152 patients from the rural population and 152 patients from the urban population. Quality of life was measured through the SF-36 Health Questionnaire in its Spanish version. The rural population group had a mean age of 46.67 ± 13.69 and the urban population group 49.02 ± 18.29. Regarding the score of the lowest levels of quality of life related to foot problems, the rural population group compared to the urban population group showed: for body pain (52.21 ± 30.71 vs. 67.80 ± 25.28, p < 0.001); and for mental health (69.58 ± 18.98 vs. 64.60 ± 14.88, p < 0.006). Differences between groups were analysed using Student's t-test for independent samples, which showed statistical significance (p < 0.05). This research offers evidence that the rural population presents better levels of mental health and lower levels of bodily pain in the domains of the SF-36 Health Questionnaire comparing with the urban population.

Prognostic Factors Associated with Acute Heart Failure in Patients Admitted for COVID-19: Analysis of the SEMI-COVID-19 Registry.

INTRODUCTION: Since the beginning of the COVID-19 pandemic in March 2020, an intimate relationship between this disease and cardiovascular diseases has been seen. However, few studies assess the development of heart failure during this infection. This study aims to determine the predisposing factors for the development of heart failure (HF) during hospital admission of COVID-19 patients. METHODOLOGY: A retrospective and multicenter study of patients with HF admitted for COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry). A bivariate analysis was performed to relate the different variables evaluated in patients developing heart failure during hospital admission. A multivariate analysis including the most relevant clinical variables obtained in bivariate analyses to predict the outcome of heart failure was performed. RESULTS: A total of 16.474 patients hospitalized for COVID-19 were included (57.5% men, mean age 67 years), 958 of them (5.8%) developed HF during hospitalization. The risk factors for HF development were: age (odds ratio [OR]): 1.042; confidence interval 95% (CI 95%): 1.035-1.050; p < 0.001), atrial fibrillation (OR: 2.022; CI 95%: 1.697-2.410; p < 0.001), BMI > 30 kg/m2 (OR: 1.460 CI 95%: 1.230-1.733; p < 0001), and peripheral vascular disease (OR: 1.564; CI 95%: 1.217-2.201; p < 0.001). Patients who developed HF had a higher rate of mortality (54.1% vs. 19.1%, p < 0.001), intubation rate (OR: 2,36; p < 0.001), and ICU admissions (OR: 2.38; p < 0001). CONCLUSIONS: Patients who presented a higher risk of developing HF were older with cardiovascular risk factors. The risk factors for HF development were age, atrial fibrillation, obesity, and peripheral vascular disease. In addition, patients who developed HF more frequently required to be intubated or admitted to the ICU.

Effect of foot health-related quality of life in rural population: A case-control study.

BACKGROUND: Foot health problems can affect quality of life and general health producing a source of discomfort and pain. Low levels of foot health-related quality of life (HRQoL) are present in patients with foot disabilities, such as hallux valgus, plantar fasciitis, or minor toe deformities. OBJECTIVE: The objective was to analyze the foot health status in patients with and without foot problems in a rural population and its relationship with quality of life. MATERIAL AND METHODS: A prospective case-control study was developed with a sample of 152 patients, 76 subjects with podiatric pathologies and 76 without, in a rural population. HRQoL was measured through the SF-36 Health Questionnaire in the Spanish version. RESULTS: The case group had a mean age of 49.18 ± 14.96 and the control group 44.16 ± 11.79. Regarding the score of the lowest levels of quality of life related to foot problems, the case group compared to the controls showed: for physical function (79.86 ± 26.38 vs. 92.63 ± 11 0.17, p < 0.001); for the physical role (73.68 ± 41.00 vs. 88.48 ± 27.51, p < 0.0022); for body pain (45.81 ± 27.18 vs. 73.68 ± 41.00, p < 0.035); and for general health (60.36 ± 30.58 vs. 68.71 ± 18.52, p < 0.047). The differences between groups were analyzed using the Mann-Whitney U test, which showed statistical significance (P < 0.05). CONCLUSIONS: In the rural population, people with foot pathologies present a worse quality of life compared to those who do not present foot pathology, especially for the health domains: physical function, physical role, body pain and health general.

Spanish Outbreak Isolates Bridge Phylogenies of European and American Bacillus anthracis.

The geographical origin of a major present-day phylogenetic group (A branch WNA; A.Br.WNA) of American Bacillus anthracis is controversial. One hypothesis postulated that the anthrax pathogen reached North America via a then-existing land bridge from northeastern Asia thousands of years ago. A competing hypothesis suggested that B. anthracis was introduced to America a couple of hundred years ago, related to European colonization. The latter view is strongly supported by genomic analysis of a group of French B. anthracis isolates that are phylogenetically closely related to the North American strains of the A branch A.Br.WNA clade. In addition, three West African strains also belong to this relationship group. Recently, we have added a Spanish strain to these close relatives of the WNA lineage of American B. anthracis. Nevertheless, the diversity of Spanish B. anthracis remains largely unexplored, and phylogenetic links to European or American relatives are not well resolved. Here, we genome sequenced and characterized 29 new B. anthracis isolates (yielding 18 unique genotypes) from outbreaks in west central and central Spain in 2021. Applying comparative chromosomal analysis, we placed the chromosomes of these isolates within the established phylogeny of the A.Br.008/009 (A.Br.TEA) canonical SNP group. From this analysis, a new sub-clade, named A.Br.11/ESPc, emerged that constitutes a sister group of American A.Br.WNA.

Development of a specific real-time PCR assay for simultaneous detection and differentiation of Coxiella burnetii strains from environmental soil samples.

Coxiella burnetii, the causative agent of Q fever, is a small, coccoid, Gram-negative strict intracellular pathogen. One of the most common ways of acquiring Q fever is through inhalation of aerosols containing the bacteria. Because C. burnetii is highly infectious, spreads easily through the air, and is very resistant to environmental conditions, it is considered a biological threat. This paper presents the development and validation of a specific real-time polymerase chain reaction (real-time PCR or qPCR) assay for the detection of C. burnetii, based on the amplification of a fragment of the isocitrate dehydrogenase (icd) encoding gene. This real-time PCR is highly specific, reproducible, and sensitive, allowing the detection of as few as 5 genome equivalents (GEs) of C. burnetii per reaction. The method enables a rapid preliminary differentiation among strains, based on a point mutation at nucleotide 745 of the icd gene. The assay was successfully evaluated in environmental soil samples; a limit of detection of 3 × 104 colony forming units per 0.5 g of soil (∼3 GEs per reaction) was achieved. The newly developed real-time PCR offers a valuable tool for differential detection of C. burnetii strains in environmental soil samples.

"Translated and adaptation into Persian of the podiatric health questionnaire (PHQ)".

The Podiatric Health Questionnaire (PHQ) is a foot health psicometric tool consisting of six items for measuring foot health status. Currently, PHQ has been adapted into Spanish. Thus, this research focused on develop the Persian translation and adaptation of the PHQ. The translation into Persian and test-retest reliability methods were applied from english version questionnarie. As regards to the total mark for each sub-scale, internal consistency and reliability were determined by the Cronbach α and intraclass correlation coefficient (ICC) with a confidence interval (CI) of 95%. High internal consistency was shown for the six sub-scales: a) walk with a Cronbach α of 0.775; b) hygiene and c) nail care with 0.789 and 0.796 respectively; d) foot on pain with 0.779; e) concern domain with 0.788; and f) quality of life with 0.798; and g) visual analogic scale with 0.803. Excellent test-retest reliability (ICC = 0.912 [95% CI = 0.845-0.950]) was shown for the total score. Conclusions: The persian version of the PHQ was shown to be a valid and reliable tool for an acceptable use in the Iran population.

Experiencia en la generación de estrategias de monitorización y evaluación en la implantación de Guías de Práctica Clínica en España / Experience Generating Evaluation and Monitoring Strategies in the Implementation of Clinical Practice Guidelines in Spain / Experiência na geração de estratégias de monitoramento e avaliação na implementação de manuais de prática clínica na Espanha

Introducción. La monitorización de la utilización del conocimiento y la evaluación de resultados permiten conocer la aplicación de la evidencia, cambios en los conocimientos y actitudes, el impacto en resultados de salud y la integración y el mantenimiento de las prácticas adoptadas. Existen debilidades relacionadas con la falta de sistematización, limitaciones de los registros y calidad del proceso. El objetivo de este artículo es describir la experiencia en la generación de estrategias de monitorización y evaluación de resultados de implantación de Guías de Buenas Prácticas en España. División de temas tratados. En primer lugar, se revisan los procesos de medición de resultados en la implantación de Guías, en el marco del Programa Best Practice Spotlight Organizations®, cuya herramienta para liderar el cambio incluye la monitorización y evaluación como una de las seis fases del ciclo de acción. En segundo lugar, se analizan las estrategias de monitorización y evaluación propuestas en la literatura, destacando la Asociación Profesional de Enfermeras de Ontario. Finalmente, se analizan las estrategias de monitorización y evaluación generadas por dos instituciones españolas participantes en el programa, centradas en adecuación de registros, explotación y análisis de indicadores, desarrollo de herramientas, procedimientos de evaluación y mecanismos de difusión y retroalimentación. Conclusiones. La definición de estrategias de monitorización y evaluación planificada de forma temprana contribuye a la viabilidad de la evaluación de la implantación y su sostenibilidad. Es necesario adaptarlas al contexto, con estrategias transversales que alcancen a toda la institución, facilitadas por la institución. Palabras clave: Ciencia de la Implementación; Práctica Clínica Basada en la Evidencia; Evaluación de Resultado en la Atención de Salud; Mecanismos de Evaluación de la Atención de Salud; Indicadores de Calidad de la Atención de Salud

Introduction. Monitoring the usage of knowledge and evaluating results permits one to know the application of the evidence, knowledge, and attitude changes, the impact on health results, integration, and maintenance of the adopted practices. There exist weaknesses related to lack of systematization, limitation of the records, and quality of the process. This article's objective is to describe the experience generating monitoring strategies and evaluation of the results regarding the implementation of good practice guides in Spain. Topics for Reflection. In the first place, the measurement process of the results regarding the implementation of guides are reviewed, in the Best Practice Spotlight Organizations® program frame, whose tool to lead the change includes monitoring and evaluation as one of the sixth phases of the action cycle. In the second place, monitoring and evaluation strategies proposed in the literature are analyzed, highlighting the Professional Nurses Association of Ontario. Finally, the monitoring and evaluation strategies are analyzed by two Spanish institutions participating in the program, focused on the adequation of records, exploitation and indicator analysis, tools development, evaluation procedures, dissemination, and feedback mechanisms. Conclusions: The definition of monitoring and evaluation strategies planned in advance contributes to the viability of the evaluation regarding the implementation and its sustainability. Is necessary to adapt them to the context, with transversal strategies that reach the whole institution, facilitated by the institution. Keywords: Implementation Science; Evidence-Based Practice; Outcome Assessment, Health Care; Health Care Evaluation Mechanisms; Quality Indicators, Health Care

Introdução. Monitorizar a utilização do conhecimento e avaliar os resultados permite-nos conhecer a aplicação das evidências, as mudanças nos conhecimentos e atitudes, o impacto nos resultados de saúde e a integração e manutenção das práticas adotadas. Existem fragilidades relacionadas à falta de sistematização, limitações de registros e qualidade do processo. O objetivo deste artigo é descrever a experiência na geração de estratégias de monitoramento e avaliação dos resultados da implementação de Manuais de Boas Práticas na Espanha. Divisão dos temas abordados. Em primeiro lugar, são revistos os processos de medição de resultados na implementação dos Manuais, no âmbito do Programa Best Practice Spotlight Organizations®, cuja ferramenta para liderar a mudança inclui a monitorização e avaliação como uma das seis fases do ciclo de ação. Em segundo lugar, são analisadas as estratégias de monitoramento e avaliação propostas na literatura, com destaque para a Associação Profissional de Enfermeiros de Ontário. Por fim, são analisadas as estratégias de monitoramento e avaliação geradas por duas instituições espanholas participantes do programa, focadas na adaptação de registros, exploração e análise de indicadores, desenvolvimento de ferramentas, procedimentos de avaliação e mecanismos de divulgação e feedback. Conclusões. A definição de estratégias de monitoramento e avaliação planeadas antecipadamente contribui para a viabilidade da avaliação da implementação e para a sua sustentabilidade. É necessário adaptá-los ao contexto, com estratégias transversais que alcancem toda a instituição, facilitadas pela instituição. Palavras-chave: Ciência da Implementação; Prática Clínica Baseada em Evidências; Avaliação de Resultados em Cuidados de Saúde; Mecanismos de Avaliação da Assistência à Saúde; Indicadores de Qualidade em Assistência à Saúde

Visceral extra-abdominal panniculitis after COVID19.

"Retractile mesenteritis" was the first name given to a rare, benign, inflammatory disease that affects the adipose tissue of the intestinal mesentery and less frequently other locations. Now labeled as mesenteric panniculitis, the pathogenic mechanism remains unclear. Several stimuli could be involved, and it is sometimes associated with other conditions such as malignancy or autoimmune diseases. We present a case of mesenteric panniculitis with extensive abdominal and extra-abdominal involvement that developed a few months after SARS-COV2 infection, raising the hypothesis of this virus as a potential trigger for autoinflammatory and autoimmune diseases.

WHO Ordinal Scale and Inflammation Risk Categories in COVID-19. Comparative Study of the Severity Scales.

BACKGROUND: The WHO ordinal severity scale has been used to predict mortality and guide trials in COVID-19. However, it has its limitations. OBJECTIVE: The present study aims to compare three classificatory and predictive models: the WHO ordinal severity scale, the model based on inflammation grades, and the hybrid model. DESIGN: Retrospective cohort study with patient data collected and followed up from March 1, 2020, to May 1, 2021, from the nationwide SEMI-COVID-19 Registry. The primary study outcome was in-hospital mortality. As this was a hospital-based study, the patients included corresponded to categories 3 to 7 of the WHO ordinal scale. Categories 6 and 7 were grouped in the same category. KEY RESULTS: A total of 17,225 patients were included in the study. Patients classified as high risk in each of the WHO categories according to the degree of inflammation were as follows: 63.8% vs. 79.9% vs. 90.2% vs. 95.1% (p<0.001). In-hospital mortality for WHO ordinal scale categories 3 to 6/7 was as follows: 0.8% vs. 24.3% vs. 45.3% vs. 34% (p<0.001). In-hospital mortality for the combined categories of ordinal scale 3a to 5b was as follows: 0.4% vs. 1.1% vs. 11.2% vs. 27.5% vs. 35.5% vs. 41.1% (p<0.001). The predictive regression model for in-hospital mortality with our proposed combined ordinal scale reached an AUC=0.871, superior to the two models separately. CONCLUSIONS: The present study proposes a new severity grading scale for COVID-19 hospitalized patients. In our opinion, it is the most informative, representative, and predictive scale in COVID-19 patients to date.

Equine infection with Leishmania spp. in Costa Rica: Study of five cases.

BACKGROUND: Cutaneous forms of leishmaniosis due to Leishmania braziliensis have been reported in horses in the New World. Domestic animals play a role in the transmission of the disease. In Costa Rica, human cases of L. braziliensis, L. panamensis and L. infantum have been reported. OBJECTIVES: The present report describes five cases of equine cutaneous leishmaniosis in Costa Rica. The aetiological diagnosis was based on the presence of the parasite within the lesions. METHODS: Skin biopsies were used to perform histopathological analyses of the lesions. Immunohistochemistry was used to detect the presence of the Leishmania spp. antigens in tissue sections. Laser-capture micro-dissection and quantitative real-time PCR techniques were carried out to detect the pathogen nucleic acid within the microscopic lesions. RESULTS: Histopathological analyses showed a granulomatous inflammation within the dermis, with multi-nucleated giant cells, macrophages, lymphocytes and few neutrophils and eosinophils. We detected the parasite by immunohistochemistry, using a rabbit polyclonal antibody raised against Leishmania spp. However, we could not identify Leishmania spp. by quantitative real-time PCR in formalin-fixed paraffin-embedded tissues, using specific primers for the conserved region in the minicircle of the Leishmania DNA kinetoplast. CONCLUSIONS: Our results emphasise the importance of Leishmania spp. not only as a causative agent of equine cutaneous disease in the New World, but also as a possible emerging pathogen. Leishmaniosis is one of the most prevalent parasitic public health problems worldwide, and equines may have a role in the epidemiology of the disease.

Effectiveness of a best practice guideline to manage pain in surgical patients.

BACKGROUND: The prevention and control of acute postoperative pain is essential, not only to avoid unnecessary suffering, but to reduce postoperative morbidity, recovery time, hospital stay and associated costs. AIM: To evaluate the effectiveness of implementing the Clinical Best Practice Guideline (BPG) "Assessment and Management of Pain" recommendations for pain control in surgical patients. METHODS: Prospective, observational, longitudinal study. SUBJECTS: Surgical patients over 14 admitted to the University Hospital Complex of Albacete, and discharged during the last working days of every month. VARIABLES: 1) demographic data, hospital stay. 2) The process indicators of BPG implementation. 3) Patient outcomes: prevalence and intensity of pain in the first 24 postsurgical hours, maximum intensity of pain during hospitalization. TOOLS: Scales of assessment of pain intensity (0-10). DATA COLLECTION: Database of BPSO/CCEC® Program. ETHICAL ASPECTS: Anonymous data. DATA ANALYSIS (SPSS® V12): Descriptive during four periods: baseline (T0: December 2012); initial (T1: June-December 2013); intermediate (T2: 2014-2015); consolidation (T3: 2016-2017). Measurements of central tendency and dispersion, absolute and relative frequencies, according to variables. Comparison of proportions (Chi-Square) and averages (Student t-test, ANOVA). STATISTICAL SIGNIFICANCE: p < 0.05. RESULTS: Included 3934 patients, 52.3% (2058) men. Daily intervention of pain detection was performed in 73.5% (2890) of patients (28% T0; 67.4% T1; 66.7% T2; 89.9% T3; p < 0.0001), assessment of pain with a scale in 65.2% (2567) (0% T0; 48.8% T1; 59.4% T2; 85.6% T3; p < 0.0001); 35.3% (1389) had a care plan for assessment and management of pain (0% T0; 34.6% T1; 32.3% T2; 42.3% T3; p < 0.0001). The percentage of patients who had serious pain (>5) during the first 24 h was reduced from 12.4% (T1) to 5.3% (T3) (p < 0.0001). CONCLUSION: Implementation of recommendations has led to a statistically significant improvement over the periods in the study. Pain intensity and the percentage of patients with severe pain have decreased in a significant way.

[Peritoneal recurrence prediction for colon cancer based on immunoexpression]. / Predicción de recurrencia peritoneal mediante inmunoexpresión en cáncer de colon.

INTRODUCTION AND OBJECTIVES: Peritoneal relapse as an isolated form of recurrence in colon cancer occurs in 25% of cases during the first two years subsequent to a curative colectomy. Currently, the diagnostic limitations of imaging studies and the absence of predictive scales for peritoneal recurrence warrant "second look" surgery in high-risk patients. The aim of this study is to assess features of some epithelial-mesenchymal transition biomarkers (c-Met, IGF-1R and plexin ß1) in order to predict post-surgical peritoneal colonization and develop a mathematical model to predict carcinomatous relapse. METHODS: A retrospective study of the histopathological samples of 87 patients diagnosed with colon cancer who underwent radical resection was carried out, using immunohistochemical techniques for c-Met, IGF-1R and plexin ß1. The patients were divided into two groups; those who had presented peritoneal recurrence and those who only had risk factors for this kind of relapse. Every stained sample was assessed by the rate of stained cells and immunostaining intensity. A possible association between immunohistochemical findings and peritoneal relapse was evaluated. Statistical analysis of the biomarkers with higher prognostic value allowed a risk mathematical formula to be developed based on coefficients, providing a specific value to each biomarker and patient. RESULTS: c-Met expression in the primary tumour showed a high statistical trend (p: .074) while IGF-1 (p: .022) and plexin ß1 (p: .021) revealed a significative association with peritoneal relapse. However, the multivariate analysis selected c-Met y plexin ß1 as useful factors for a predictive mathematical model on peritoneal recurrence with a 75.8% sensitivity and 80.5% specificity in patients with a staining more than 50% for both biomarkers. CONCLUSION: c-Met and plexin B1 overexpression is related to an increased risk of peritoneal relapse in cases of colon cancer where a radical resection is feasible. The encouraging outcomes of the proposed mathematical model may prove useful clinically in the identification of candidates for carcinoprophylaxis.

Phosphorylation in Novel Mitochondrial Creatine Kinase Tyrosine Residues Render Cardioprotection against Hypoxia/Reoxygenation Injury.

OBJECTIVE: Ischemic cardiomyopathy (ICM) is the leading cause of heart failure. Proteomic and genomic studies have demonstrated ischemic preconditioning (IPC) can assert cardioprotection against ICM through mitochondrial function regulation. Considering IPC is conducted in a relatively brief period, regulation of protein expression also occurs very rapidly, highlighting the importance of protein function modulation by post-translational modifications. This study aimed to identify and analyze novel phosphorylated mitochondrial proteins that can be harnessed for therapeutic strategies for preventing ischemia/reperfusion (I/R) injury. METHODS: Sprague-Dawley rat hearts were used in an ex vivo Langendorff system to simulate normal perfusion, I/R, and IPC condition, after which the samples were prepared for phosphoproteomic analysis. Employing human cardiomyocyte AC16 cells, we investigated the cardioprotective role of CKMT2 through overexpression and how site-directed mutagenesis of putative CKMT2 phosphorylation sites (Y159A, Y255A, and Y368A) can affect cardioprotection by measuring CKMT2 protein activity, mitochondrial function and protein expression changes. RESULTS: The phosphoproteomic analysis revealed dephosphorylation of mitochondrial creatine kinase (CKMT2) during ischemia and I/R, while preserving its phosphorylated state during IPC. CKMT2 overexpression conferred cardioprotection against hypoxia/reoxygenation (H/R) by increasing cell viability and mitochondrial adenosine triphosphate level, preserving mitochondrial membrane potential, and reduced reactive oxygen species (ROS) generation, while phosphomutations, especially in Y368, nullified cardioprotection by significantly reducing cell viability and increasing ROS production during H/R. CKMT2 overexpression increased mitochondrial function by mediating the proliferator-activated receptor γ coactivator-1α/estrogen-related receptor-α pathway, and these effects were mostly inhibited by Y368A mutation. CONCLUSION: These results suggest that regulation of quantitative expression and phosphorylation site Y368 of CKMT2 offers a unique mechanism in future ICM therapeutics.

Blood culture-negative infective endocarditis: a worse outcome? Results from a large multicentre retrospective Spanish cohort study.

BACKGROUND: To assess the impact of blood cultures negative infective endocarditis (BCNIE) on in-hospital mortality. METHODS: Prospective multicentre study with retrospective analysis of a Spanish cohort including adult patients with definite IE. Cardiac implantable devices infection were excluded. Comparisons between blood cultures positive and BCNIE groups were performed to analyse in-hospital mortality. RESULTS: 1001 cases were included of which 83 (8.3%) had BCNIE. Alternative microbiological diagnosis was achieved for 39 (47%) out 83 cases. The most frequent identifications were: Coxiella burnetii (11; 28.2%), Tropheryma whipplei (4; 10.3%), Streptococcus gallolyticus (4;10.3%) and Staphylococcus epidermidis (3; 7.7%). Surgery was performed more frequently in BCNIE group (57.8 vs. 36.9%, p < .001). All-cause in-hospital mortality rate was 26.7% without statistical difference between compared groups. BCNIE was not associated to worse mortality rate in Cox regression model (aHR = 1.37, 95% CI 0.90-2.07, p = .14). Absence of microbiological diagnosis was also not associated to worse in-hospital prognosis (aHR = 1.62, 95% CI 0.99-2.64, p = .06). CONCLUSIONS: In our cohort, BCNIE was not associated to greater in-hospital mortality based in multivariate Cox regression models. The variables most frequently associated with mortality were indicated but not performed surgery (aHR = 2.48, 95% CI 1.73-3.56, p < .001), septic shock (aHR = 2.24, 95% CI 1.68-2.99, p < .001), age over 65 years (aHR = 1.88, 95% CI 1.40-2.52, p < .001) and complicated endocarditis (aHR = 1.79, 95% CI 1.36-2.37, p < .001).

Do specific antimicrobial stewardship interventions have an impact on carbapenem resistance in Gram-negative bacilli? A multicentre quasi-experimental ecological study: time-trend analysis and characterization of carbapenemases.

BACKGROUND: Carbapenem-resistant Gram-negative bacilli (CR-GNB) are among the most threatening microorganisms worldwide and carbapenem use facilitates their spread. Antimicrobial stewardship programmes (ASPs) can help to optimize the use of antibiotics. This study evaluates the impact of a multifaceted educational ASP on carbapenem use and on the epidemiology of CR-GNB. METHODS: We conducted a quasi-experimental, time-series study in seven hospitals, from January 2014 to September 2018. The key intervention was composed of educational interviews promoting the appropriate use of carbapenems. The primary endpoints were carbapenem consumption and incidence density (ID) of CR-GNB. All non-duplicated CR-GNB clinical isolates were tested using phenotypic assays and PCR for the presence of carbapenemases. Joinpoint regression and interrupted time-series analyses were used to determine trends. RESULTS: A decrease in carbapenem consumption throughout the study period [average quarterly percentage change (AQPC) -1.5%, P < 0.001] and a -8.170 (-16.064 to -0.277) level change following the intervention were observed. The ID of CR-Acinetobacter baumannii decreased (AQPC -3.5%, P = 0.02) and the overall ID of CR-GNB remained stable (AQPC -0.4%, P = 0.52). CR-GNB, CR-Pseudomonas aeruginosa and CR-A. baumannii IDs per hospital correlated with the local consumption of carbapenems. The most prevalent carbapenem resistance mechanisms were OXA-23 for CR-A. baumannii (76.1%), OXA-48 for CR-Klebsiella pneumoniae (66%) and no carbapenemases for CR-P. aeruginosa (91.7%). The epidemiology of carbapenemases was heterogeneous throughout the study, especially for carbapenemase-producing Enterobacteriaceae. CONCLUSIONS: In conclusion, a multifaceted, educational interview-based ASP targeting carbapenem prescribing reduced carbapenem use and the ID of CR-A. baumannii.