Consensus statement on the use of alemtuzumab in daily clinical practice in Spain.

INTRODUCTION: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. OBJECTIVE: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. DEVELOPMENT: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. CONCLUSION: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.

Consenso de expertos sobre el uso de alemtuzumab en la práctica clínica diaria en España / Consensus statement on the use of alemtuzumab in daily clinical practice in Spain

Introducción: Alemtuzumab es un fármaco de alta eficacia aprobado por la Agencia Europea de Medicamentos como tratamiento modificador de la enfermedad en pacientes con esclerosis múltiple remitente recurrente.ObjetivoElaborar un documento de consenso sobre el manejo de alemtuzumab en la práctica clínica habitual, que sea de aplicación en el ámbito español.DesarrolloUn grupo de expertos en esclerosis múltiple revisó las publicaciones disponibles hasta diciembre de 2017, de tratamiento con alemtuzumab y esclerosis múltiple. Se incluyeron trabajos sobre eficacia, efectividad y seguridad, despistaje de infecciones y vacunación, administración y monitorización. La propuesta inicial de recomendaciones fue desarrollada por un grupo coordinador con base en la evidencia disponible y en su experiencia clínica. El proceso de consenso se llevó a cabo en 2 etapas; se estableció como porcentaje inicial de acuerdo grupal el 80%. El documento final con todas las recomendaciones acordadas por el grupo de trabajo se sometió a revisión externa y los comentarios recibidos fueron considerados por el grupo coordinador.ConclusionesEl documento aportado pretende ser una herramienta útil para facilitar el manejo del fármaco en condiciones de práctica clínica habitual. (AU)

Introduction: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis.ObjectiveA consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain.DevelopmentA group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group.ConclusionThe present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice. (AU)

Infective endocarditis treated in a secondary hospital: epidemiological, clinical, microbiological characteristics and prognosis, with special reference to patients transferred to a third level hospital.

OBJECTIVE: To analyse the clinical and epidemiological characteristics and mortality-related factors of patients admitted to a secondary hospital with Infective Endocarditis (IE). METHODS: Observational study of a cohort of patients who have been diagnosed with IE in a secondary hospital and evaluated in accordance with a pre-established protocol. RESULTS: A total of 101 cases were evaluated (years 2000-2017), with an average age of 64 years and a male-to-female ratio of 2:1. 76% of the cases had an age-adjusted Charlson comorbidity index of >6, with 21% having had a dental procedure and 36% with a history of heart valve disease. The most common microorganism was methicillin-susceptible S. aureus (36%), with bacterial focus of unknown origin in 54%. The diagnostic delay time was 12 days in patients who were transferred, compared to 8 days in patients who were not transferred (p=0.07); the median surgery indication delay time was 5 days (IQR 13.5). The in-hospital mortality rate was 34.6% and the prognostic factors independently associated with mortality were: cerebrovascular events (OR 98.7%, 95% CI, 70.9-164.4); heart failure (OR 27.3, 95% CI, 10.2-149.1); and unsuitable antibiotic treatment (OR 7.2, 95% CI, 1.5-10.5). The mortality rate of the patients who were transferred and who therefore underwent surgery was 20% (5/25). CONCLUSIONS: The onset of cerebrovascular events, heart failure and unsuitable antibiotic treatment are independently and significantly associated with in-hospital mortality. The mortality rate was higher than the published average (35%); the diagnostic delay was greater in patients for whom surgery was indicated.

Consensus statement on the use of alemtuzumab in daily clinical practice in Spain. / Consenso de expertos sobre el uso de alemtuzumab en la práctica clínica diaria en España.

INTRODUCTION: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. OBJECTIVE: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. DEVELOPMENT: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. CONCLUSION: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.

Linezolid for infective endocarditis: A structured approach based on a national database experience.

ABSTRACT: Current data on the frequency and efficacy of linezolid (LNZ) in infective endocarditis (IE) are based on small retrospective series. We used a national database to evaluate the effectiveness of LNZ in IE.This is a retrospective study of IE patients in the Spanish GAMES database who received LNZ. We defined 3 levels of therapeutic impact: LNZ < 7 days, LNZ high-impact (≥ 7 days, > 50% of the total treatment, and > 50% of the LNZ doses prescribed in the first weeks of treatment), and LNZ ≥ 7 days not fulfilling the high-impact criteria (LNZ-NHI). Effectiveness of LNZ was assessed using propensity score matching and multivariate analysis of high-impact cases in comparison to patients not treated with LNZ from the GAMES database matched for age-adjusted comorbidity Charlson index, heart failure, renal failure, prosthetic and intracardiac IE device, left-sided IE, and Staphylococcus aureus. Primary outcomes were in-hospital mortality and one-year mortality. Secondary outcomes included IE complications and relapses.From 3467 patients included in the GAMES database, 295 (8.5%) received LNZ. After excluding 3 patients, 292 were grouped as follows for the analyses: 99 (33.9%) patients in LNZ < 7 days, 11 (3.7%) in LNZ high-impact, and 178 (61%) in LNZ-NHI. In-hospital mortality was 51.5%, 54.4%, and 19.1% respectively. In the propensity analysis, LNZ high-impact group presented with respect to matched controls not treated with LNZ higher in-hospital mortality (54.5% vs 18.2%, P = .04). The multivariate analysis showed an independent relationship of LNZ use with in-hospital mortality (odds ratio 9.06, 95% confidence interval 1.15--71.08, P = .03).Treatment with LNZ is relatively frequent, but most cases do not fulfill our high-impact criteria. Our data suggest that the use of LNZ as definitive treatment in IE may be associated with higher in-hospital mortality.

Beware of oysters. Rapid advance of non-native species in tropical Pacific islands.

Non-indigenous species can become a problem for the ecosystem health, especially when their distribution grows to the detriment of native species. In this moment, they can become invasive species. In marine ecosystems, the maritime transport is the principal gate and corridor for the movement of alien species. The genetic identification, using barcoding tools, of different oyster species in ports of the remote French Polynesia islands and atolls, showed a significant increase of exotic versus native oyster species between 2011 and 2018. This supports the spread of exotic species with the maritime traffic as the main cause. Moreover, the 11% of inaccurate identification at species level obtained in this study shows the need to complete the genetic databases.

[Pneumonia in patients with SARS-CoV-2 infection: series of 17 cases in the region of Murcia]. / Neumonía neumocócica en pacientes con infección por SARS-CoV-2: serie de 17 casos en la Región de Murcia.

OBJECTIVE: Currently the prevalence of pneumococcal coinfection in patients with COVID-19 is unknown. In this work we present its clinical characteristics, evolution and treatment. METHODS: Retrospective data collection from August to October 2020 in two hospitals in the Murcia region. RESULTS: Eighteen patients had COVID-19 diagnosed by PCR and pneumococcal infection confirmed by antigenuria, which represented a prevalence of 2%. A total of 88% had radiological alterations upon admission (two patients had an X-ray within normality) and 29% had elevated procalcitonin. Mortality in our series was 12%. CONCLUSIONS: It could be reasonable to consider the start of antimicrobial therapy in those cases in which there is a moderate or high suspicion of bacterial coinfection, being essential the early suspension of antibiotic treatment if it is not confirmed.

Building on gAMBI in ports for a challenging biological invasions scenario: Blue-gNIS as a proof of concept.

The status of aquatic ecosystems has historically been monitored by the use of biotic indices. However, few biotic measures consider the presence of non-indigenous species as a sign of anthropogenic pollution and habitat disturbance even when this may seriously affect the metric scores and ecological status classifications of an environment. Today, biological invasions are currently one of the greatest threats to biodiversity and sustainable blue economies around the world. In this work, environmental assessments were conducted in the Port of Gijon, Northern Spain, using eDNA metabarcoding, and the gAMBI (genetics based AZTI Marine Biotic Index) was estimated. Results indicate a high/good ecological status within the port. However, nine non-indigenous species and five invasive species were found, and a modification of the gAMBI that includes species invasiveness was proposed: Blue-gNIS. The index was preliminary tested against existing validated indices such as gAMBI, BENTIX (based on the ecology of macroinvertebrates) and ALEX (based on the invasiveness of the species). Blue-gNIS classified the port in a good ecological status and showed its potential usefulness to achieve more complete water quality assessments of ports.

Risk factors for methicillin-resistant Staphylococcus aureus and extended-spectrum ß-lactamase producing Enterobacterales in patients with diabetic foot infections requiring hospital admission.

OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) may complicate the treatment of diabetic foot infections (DFIs). The aim of this study was to determine the risk factors for these pathogens in DFIs. METHODS: This was a prospective observational study of 167 consecutive adult patients with DFIs. The diagnosis and severity of DFIs were based on the Infectious Disease Society of America (IDSA) classification system. Multivariate analyses were performed in order to identify risk factors for MRSA and ESBL-E infections. RESULTS: S. aureus was the most isolated pathogen (n=82, 37.9 %) followed by Escherichia coli (n= 40, 18.5%). MRSA accounted for 57.3% of all S. aureus and 70% of Klebsiella pneumoniae and 25% of E. coli were ESBL producers, respectively. Deep ulcer [OR 8,563; 95% CI (1,068-4,727)], previous use of fluoroquinolones [OR 2,78; 95% CI (1,156-6,685)] and peripheral vasculopathy [OR 2,47; 95% CI (1.068-4.727)] were the independent predictors for MRSA infections; and osteomyelitis [OR 6,351; 95% CI (1,609-25,068)] and previous use of cephalosporins [OR 5,824; 95% CI (1,517-22,361)] for ESBL-E infections. CONCLUSIONS: MRSA and ESBL-E have adquired a great clinical relevance in DFIs. The availability of their risk factors is very convenient to choose the empirical treatment in severe forms.

DNA barcodes of Antipode marine invertebrates in Bay of Biscay and Gulf of Lion ports suggest new biofouling challenges.

Marine biological invasions threaten global biodiversity nowadays. In this article, we have studied fouling communities from 10 port areas of south Bay of Biscay (Atlantic Ocean) and Gulf of Lion (Mediterranean Sea). A total of 834 individuals were genetically barcoded and corresponded to 95 different species. A total of 76 native species 8 genera and 1 family were identified, 58 from the Bay of Biscay and 23 from the Gulf of Lion. Furthermore, 19 species were identified as non-indigenous or cryptogenic (18 from the Bay of Biscay and 4 from the Gulf of Lion). We found a high proportion of Antipode non-indigenous species (NIS) that represented the 19.3% of all sampled individuals and the 54.21% of NIS specimens of this study. A framework for inference of donor regions based on a phylogenetic screening of genetic sequences was proposed as a proof of concept and tested, as well as models for the relationship between NIS introductions, maritime imports and distance to NIS native range and inferred donor areas. Consistent generalized linear models (GLM) with positive association between NIS genetic diversity and distance, not with maritime growth weight imports, strongly suggest that distant NIS could pose higher invasion risk than closer species. Selection for wider tolerance ranges during the long travel -direct or stepwise, as well as environmental similarity between donor and receiving regions, may explain these results.

Leishmaniasis cutánea agresiva en paciente con esclerosis múltiple tratada con fingolimod / Aggressive cutaneous leishmaniasis in a patient with multiple sclerosis treated with fingolimod

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[Nosocomial infections caused by multiresistant Pseudomonas aeruginosa (carbapenems included): predictive and prognostic factors. A prospective study (2016-2017))]. / Infecciones nosocomiales por Pseudomonas aeruginosa multiresistente incluido carbapenémicos: factores predictivos y pronósticos. Estudio prospectivo 2016-2017.

OBJECTIVE: Pseudomonas aeruginosa is one of the major pathogens causing hospital-acquired infections. In recent years, antimicrobial resistance is increasing and multidrug resistant (MDR) and extremely drug resistant (XDR) isolates have been associated with an increase of mortality. The aim of this study is to assess the clinical significance and analyze predictors and prognostic factors. METHODS: Prospective case-control non-paired study involving 64 patients with P. aeruginosa nosocomial infection, 32 caused by susceptible P. aeruginosa and 32 by MDR/XDR including to carbapenems (XDR-C) strains, admitted at a third level hospital. The follow-up period was till hospital discharge or death and at 30 days after discharge. For all patients, clinical epidemiology and microbiological data were analyzed. RESULTS: The incidence of MDR/XDR-C strains was 2.3 per 1000 admissions. Ten of which were VIM metallo-ß-lactamase-producing. Independent predictor factors associated with MDR/XDR-C infections were: previous ICU or Resuscitation unit admission (OR 14.01; IC 95% 2.105-93.297) appearance >20 days after admission (OR 29.826; IC 95% 4.783-185.997) and leukocytosis (OR 10.0190; IC 95% 1.842-56.369). However, there were not statistically significant differences in clinical severity or mortality between both groups. CONCLUSIONS: The major risk factors associated with MDR/XDR-C infections were previous ICU or Resuscitation unit admission, appearance >20 days after admission and leukocytosis. MDR/XDR-C infections were not associated to increased mortality.

[Antibiotic diffusion to central nervous system]. / Difusión de los antibióticos en el sistema nervioso central.

Central nervous system (CNS) infections caused by pathogens with a reduced sensitivity to drugs are a therapeutic challenge. Transport of fluid and solutes is tightly controlled within CNS, where vasculature exhibits a blood-brain barrier (BBB).The entry of drugs, including antibiotics, into the cerebro-spinal fluid (CSF) is governed by molecular size, lipophilicity, plasma protein binding and their affinity to transport systems at the BBB. The ratio of the AUCCSF (Area under the curve in CSF)/AUCS (Area under the curve in serum) is the most accurate parameter to characterize drug penetration into the CSF. Linezolid, some fluoroquinolones and metronidazole get high CSF concentrations and are useful for treating susceptible pathogens. Some highly active antibiotic compounds with low BBB permeability can be directly administered into the ventricles together with concomitant intravenous therapy. The ideal antibiotic to treat CNS infections should be that with a small moderately lipophilic molecule, low plasma protein binding and low affinity to efflux pumps at BBB. Knowledge of the pharmacokinetics and pharmacodynamics of antibiotics at the BBB will assist to optimize antibiotic treatment in CNS infections. This article reviews the physicochemical properties of the main groups of antibiotics to assess which compounds are most promising for the treatment of CNS infections and how to use them in the daily clinical practice.

[Strategies to optimize the use of antibiotics in hospitals]. / Estrategias para optimizar el uso de antibióticos en los hospitales en urgencias.

The inadequate use of antibiotics is a clinical reality we are faced with day by day. The great peculiarity of this group of drugs is the influence they have not only on the patients and at the time of their use, but also of future infections and the general population, by favoring alterations in the resistance patterns of the bacterial microflora that colonize people. It is our obligation as experts in infectious diseases to work on improving the use of antimicrobials.

Forensic assignment to geographic origin, a useful tool in seafood fraud control.

Seafood fraud is an economically motivated and widely spread problem encompassing drastic consequences in both public health and species conservation. In Northern Spain, only the first Atlantic salmon (Salmo salar) catch of the angling season (named Campanu) can be sold. In the year 2011, an angler denounced it on regional Court claiming that the Campanu (which was sold in 6000€) was fraudulent because it had been caught from another river than the fisherman ("the seller") stated. Here, we report the first judicial case of application of geographical genetic assignment in a fish species in Spain. In order to accomplish this, genetic assignments to their rivers of origin of the Campanu and another three following salmon catches of the angling season of the year 2011 were performed. A panel of eight microsatellite loci together with a comprehensive genetic baseline of the rivers of the region were employed. Results showed that the Campanu was the only case in which genetic assignment and fisherman declaration of the river of origin did not match. The methodology here employed showed to be very useful as a reinforcement of other evidences contributing to fight against seafood fraud in Courts.

[Design and implementation of an outpatient parenteral antimicrobial therapy program in primary care: the experience at a second level hospital]. / Design and implementation of an outpatient parenteral antimicrobial therapy program in primary care: the experience at a second level hospital.

OBJECTIVE: Outpatient parenteral antimicrobial therapy (OPAT) programs are a good assistance option in a wide variety of infectious diseases. Our aim was to design and implement an OPAT program in the area of influence of a second-level hospital, with no Home Hospitalization Service available, being necessary close collaboration between hospitalization and Primary Care teams, describe our cohort, analyse the antimicrobial treatment indicated and evaluate the prognostic and risk factors associated with readmission and mortality. METHODS: Prospective study cohorts of patients admitted to the OPAT programme, from 1 January 2012 to 31 May 2015. RESULTS: During the period of study a total of 98 episodes were recorded. The average age of the cohort was 66 years. The most frequent comorbidity was immunosuppression (33.67 %), with an overall average of Charlson index of 5.21 ± 3.09. The most common source of infection was respiratory (33.67 %). Microbiological isolation was achieved in fifty-eight patients (59.18 %) being Escherichia coli the most frequently isolated (25%). The average number of days of antibiotics administration at home was 10.42 ± 6.02 (SD), being carbapenems (43.48%) the more administered. Eighty-six patients (87.75%) completed the treatment successfully. Thirty-two patients (32.65%) were readmitted within 30 days after being discharged and seven patients (7.14%) died. A statistically significant association was only found in the readmission with variables: elderly patients (p=0.03), being carriers of Porth-a-Cath (p=0.04) and treatment termination related with infection (p<0.05). CONCLUSIONS: This is the first programme of OPAT administration not dependent on Home Hospitalization Service in Spain, which could allow to optimize the hospital and primary care resources available. Nevertheless this pilot study results are poor in terms of optimization of antibiotics choice, transition to oral administration, de-escalation and duration.

Rate of biological invasions is lower in coastal marine protected areas.

Marine biological invasions threaten biodiversity worldwide. Here we explore how Marine Protected areas, by reducing human use of the coast, confer resilience against the introduction of non-indigenous species (NIS), using two very different Pacific islands as case studies for developing and testing mathematical models. We quantified NIS vectors and promoters on Vancouver (Canada) and Moorea (French Polynesia) islands, sampled and barcoded NIS, and tested models at different spatial scales with different types of interaction among vectors and between marine protection and NIS frequency. In our results NIS were negatively correlated with the dimension of the protected areas and the intensity of the protection. Small to medium geographical scale protection seemed to be efficient against NIS introductions. The likely benefit of MPAs was by exclusion of aquaculture, principally in Canada. These results emphasize the importance of marine protected areas for biodiversity conservation, and suggest that small or medium protected zones would confer efficient protection against NIS introduction.