Impact of a real-time diagnostic and antimicrobial stewardship workflow on time to appropriate therapy for infections caused by multidrug-resistant Gram-negative organisms.

INTRODUCTION: Multidrug-resistant (MDR) Gram-negative organisms cause life-threatening infections, and the incidence is rising globally. Timely therapy for these infections has a direct impact on patient survival. This study aimed to determine the impact of a multidisciplinary diagnostic and antimicrobial stewardship (AMS) workflow on time to appropriate therapy (TAP) for these infections using novel beta-lactam/beta-lactamase inhibitors. METHODS: This was a retrospective quasi-experimental study of adult patients with carbapenem-resistant Enterobacterales (CRE) and multidrug-resistant Pseudomonas (MDR PsA) infections at a 1500 bed university hospital. Included patients who received ≥ 72 hours of ceftazidime-avibactam (CZA) or ceftolozane-tazobactam (C/T) from December 2017 to December 2019. During the pre-intervention period (December 2017 to December 2018), additional susceptibilities (including CZA and C/T) were performed only upon providers' request. In 2019, reflex algorithms were implemented for faster identification and testing of all CRE/MDR PsA isolates. Results were communicated in real-time to the AMS team to tailor therapy. RESULTS: A total of 99 patients were included, with no between-group differences at baseline. The median age was 60 years and 56 (56.7%) were in intensive care at the time of culture collection. Identified organisms included 71 (71.7%) MDR PsA and 26 CRE, of which 18 were carbapenemase producers (Klebsiella-producing carbapenemase = 12, New Delhi metallo-ß-lactamase = 4, Verona integron-encoded metallo-ß-lactamase = 2). The most common infections were pneumonia (49.5%) and bacteraemia (30.3%). A decrease was found in median TAP (103 [IQR 76.0-156.0] vs. 75 [IQR 56-100] hours; P < 0.001). Median time from culture collection to final susceptibility results was shorter in the post-intervention group (123 vs. 93 hours; P < 0.001). CONCLUSION: This study identified improvement in TAP in MDR PsA and CRE infections with implementation of a reflex microbiology workflow and multidisciplinary antimicrobial stewardship initiatives.

Bacteria as Biological Control Agents of Plant Diseases.

Biological control is an effective and sustainable alternative or complement to conventional pesticides for fungal and bacterial plant disease management. Some of the most intensively studied biological control agents are bacteria that can use multiple mechanisms implicated in the limitation of plant disease development, and several bacterial-based products have been already registered and marketed as biopesticides. However, efforts are still required to increase the commercially available microbial biopesticides. The inconsistency in the performance of bacterial biocontrol agents in the biological control has limited their extensive use in commercial agriculture. Pathosystem factors and environmental conditions have been shown to be key factors involved in the final levels of disease control achieved by bacteria. Several biotic and abiotic factors can influence the performance of the biocontrol agents, affecting their mechanisms of action or the multitrophic interaction between the plant, the pathogen, and the bacteria. This review shows some relevant examples of known bacterial biocontrol agents, with especial emphasis on research carried out by Spanish groups. In addition, the importance of the screening process and of the key steps in the development of bacterial biocontrol agents is highlighted. Besides, some improvement approaches and future trends are considered.

Mycobacterium abscessus Infections in Solid Organ Transplant Recipients: Single-Center Experience in the United States, 2013-2018.

Background: Mycobacterium abscessus is increasingly recognized as a human pathogen causing life-threatening infections in immunocompromised patients. There is a paucity of data around this topic in solid organ transplant (SOT) recipients. Methods: This work was a single-center retrospective cohort study of all SOT recipients with a positive culture for M abscessus between 2013 and 2018. Results: A total of 20 patients (55% female) met inclusion criteria, including 1 kidney recipient (5.0%), 2 liver recipients (10.0%), 12 lung recipients (60.0%), 1 heart recipient (5.0%), and 4 combined organ recipients (20.0%). The median time from SOT to infection was 100 days (range, 30-431 days). Thirteen (65.0%) patients (1 kidney, 1 heart, 7 lung, 1 liver, 1 intestine, and 2 multivisceral) were treated with a median duration of 185 antibiotic days (range, 20-523 days). Among them, M abscessus was isolated from respiratory samples in 8 and nonrespiratory samples in 5; 4 of 13 (30.8%) patients had treatment failure and 3 of 13 (23.1%) had unrelated deaths within 1 year after diagnosis. Seven patients (5 lung transplant recipients) with the organism isolated from respiratory samples were not treated as their cultures represented airway colonization or contamination; of those, 2 (28.6%) died (unrelated to infection) and 5 (71.4%) were alive without the infection after 1 year of follow-up. Conclusions: Mycobacterium abscessus infections affect SOT recipients with a high proportion of clinical failures. However, in lung recipients, not all positive cultures correlated with infection, and without treatment some patients had good clinical outcomes. Thus, differentiating colonization from infection is important, and infection prevention measures and novel therapeutic agents are needed for SOT recipients.

Duration of carbapenemase-producing Enterobacteriales carriage among ICU patients in Miami, FL: A retrospective cohort study.

BACKGROUND: Current recommendations by the Centers for Disease Control and Prevention suggest placing patients with carbapenem-producing Enterobacteriales (CPE) in contact precautions, but there is no consensus on the appropriate duration of precautions. AIM: We aimed to evaluate predictors for prolonged CPE carriage and median clearance time. METHODS: Patients with first isolated CPE identified from 2012-2016 were followed for clearance of CPE using at least two rectal or tracheal aspirate surveillance cultures and clinical cultures during intensive-care-unit admission. Predictors associated with prolonged CPE carriage were assessed using Cox proportional-hazards. RESULTS: Out of 75 eligible patients, 25 (33%) cleared their CPE-carrier status; median time to clearance was 80 days (Range, 16-457). Patients who were immunocompromised, had mechanical ventilation exposure, or exposure to carbapenems had 66%, 66%, and 86% (HR, 0.34, 0.34, and 0.14, respectively [P-value <.05]) lower probability of clearing compared to those immunocompetent of without such exposures. Patients with CPE isolated from more than one body site had a 5.3 times higher probability of clearing their CPE-carrier status (P-value <.001). CONCLUSIONS: Patients immunocompromised, with mechanical ventilation exposure, or exposure to carbapenems had higher risk for prolonged CPE carriage. Infection prevention programs should consider these predictors as part of their assessment of discontinuing contact precautions among CPE carriers to prevent horizontal transmission and outbreaks within healthcare facilities.

Predictive and diagnosis models of stroke from hemodynamic signal monitoring.

This work presents a novel and promising approach to the clinical management of acute stroke. Using machine learning techniques, our research has succeeded in developing accurate diagnosis and prediction real-time models from hemodynamic data. These models are able to diagnose stroke subtype with 30 min of monitoring, to predict the exitus during the first 3 h of monitoring, and to predict the stroke recurrence in just 15 min of monitoring. Patients with difficult access to a CT scan and all patients that arrive at the stroke unit of a specialized hospital will benefit from these positive results. The results obtained from the real-time developed models are the following: stroke diagnosis around 98% precision (97.8% sensitivity, 99.5% specificity), exitus prediction with 99.8% precision (99.8% Sens., 99.9% Spec.), and 98% precision predicting stroke recurrence (98% Sens., 99% Spec.). Graphical abstract depicting the complete process since a patient is monitored until the data collected is used to generate models.

Implementing carbapenem-resistance testing algorithms for Enterobacteriales and Pseudomonas aeruginosa: diagnostic and antimicrobial stewardship with timely infection prevention.

Early detection of carbapenem resistance in Gram-negative (CRGN) infections can help tailor therapy sooner and prevent horizontal transmission more efficiently. This involves timely, multidisciplinary communication. To this aim, we describe our experience with implementing reflex testing algorithms for expanded antibiotic susceptibilities and molecular mechanisms of resistance in a large academic hospital.

Biological control of bacterial plant diseases with Lactobacillus plantarum strains selected for their broad-spectrum activity.

The use of lactic acid bacteria (LAB) to control multiple pathogens that affect different crops was studied, namely, Pseudomonas syringae pv. actinidiae in kiwifruit, Xanthomonas arboricola pv. pruni in Prunus and Xanthomonas fragariae in strawberry. A screening procedure based on in vitro and in planta assays of the three bacterial pathogens was successful in selecting potential LAB strains as biological control agents. The antagonistic activity of 55 strains was first tested in vitro and the strains Lactobacillus plantarum CC100, PM411 and TC92, and Leuconostoc mesenteroides CM160 and CM209 were selected because of their broad-spectrum activity. The biocontrol efficacy of the selected strains was assessed using a multiple-pathosystem approach in greenhouse conditions. L. plantarum PM411 and TC92 prevented all three pathogens from infecting their corresponding plant hosts. In addition, the biocontrol performance of PM411 and TC92 was comparable to the reference products (Bacillus amyloliquefaciens D747, Bacillus subtilis QST713, chitosan, acibenzolar-S-methyl, copper and kasugamycin) in semi-field and field experiments. The in vitro inhibitory mechanism of PM411 and TC92 is based, at least in part, on a pH lowering effect and the production of lactic acid. Moreover, both strains showed similar survival rates on leaf surfaces. PM411 and TC92 can easily be distinguished because of their different multilocus sequence typing and random amplified polymorphic DNA profiles.

Tocilizumab-Associated Reversible Cerebral Vasoconstriction: A Case Report.

OBJECTIVES: To report a case of reversible cerebral vasoconstriction syndrome (RCVS) possibly precipitated by tocilizumab. BACKGROUND: Immunosuppressant drugs are a rare cause of reversible cerebral vasoconstriction, a syndrome characterized by segmental vasospasm. However, although it is considered a reversible process that resolves within 3 months, the cerebral vasoconstriction over time may lead to severe complications such as strokes. RESULTS: We describe a 53-year-old woman who presented with a reversible vasoconstriction syndrome possibly associated with tocilizumab, an inhibitor of IL-6 receptor used in inflammatory diseases such as rheumatoid arthritis. The patient developed a cerebellar infarction as the major complication of the vasoconstriction syndrome. CONCLUSION: Tocilizumab could be a trigger of RCVS. It is important to bear in mind the role of tocilizumab as a possible precipitating factor in order to remove it and reduce complications such as strokes. It is, to our knowledge, the first reversible vasoconstriction syndrome possibly precipitated by tocilizumab published to date.

Linezolid- and Vancomycin-resistant Enterococcus faecium in Solid Organ Transplant Recipients: Infection Control and Antimicrobial Stewardship Using Whole Genome Sequencing.

BACKGROUND: Vancomycin-resistant enterococci are an important cause of healthcare-associated infections and are inherently resistant to many commonly used antibiotics. Linezolid is the only drug currently approved by the US Food and Drug Administration to treat vancomycin-resistant enterococci; however, resistance to this antibiotic appears to be increasing. Although outbreaks of linezolid- and vancomycin-resistant Enterococcus faecium (LR-VRE) in solid organ transplant recipients remain uncommon, they represent a major challenge for infection control and hospital epidemiology. METHODS: We describe a cluster of 4 LR-VRE infections among a group of liver and multivisceral transplant recipients in a single intensive care unit. Failure of treatment with linezolid in 2 cases led to a review of standard clinical laboratory methods for susceptibility determination. Testing by alternative methods including whole genome sequencing (WGS) and a comprehensive outbreak investigation including sampling of staff members and surfaces was performed. RESULTS: Review of laboratory testing methods revealed a limitation in the VITEK 2 system with regard to reporting resistance to linezolid. Linezolid resistance in all cases was confirmed by E-test method. The use of WGS identified a resistant subpopulation with the G2376C mutation in the 23S ribosomal RNA. Sampling of staff members' dominant hands as well as sampling of surfaces in the unit identified no contaminated sources for transmission. CONCLUSIONS: This cluster of LR-VRE in transplant recipients highlights the possible shortcomings of standard microbiology laboratory methods and underscores the importance of WGS to identify resistance mechanisms that can inform patient care, as well as infection control and antibiotic stewardship measures.

Predictors of unknown cancer in patients with ischemic stroke.

Stroke is the second most frequent neurologic finding in postmortem studies of cancer patients. It has also been described as the first expression of an occult cancer. We have studied patients diagnosed with cancer after an ischemic stroke (IS) and we analyze differences with non-tumor patients. Single cohort longitudinal retrospective study of patients admitted to our center with IS diagnosis from 1 January 2012 to 12 December 2014. All patients were followed for 18 months. Patients with transient ischemic infarction or cerebral hemorrhage, active cancer or in the last 5 years, inability to follow-up or absence of complete complementary study (holter-EKG, echocardiogram, and dupplex/angiography-CT) were excluded. Demographic, clinical, analytical and prognostic characteristics were compared between both subgroups. From a total of 381 IS patients with no history of cancer, 29 (7.61%) were diagnosed with cancer. The mean time from stroke onset to cancer diagnosis was 6 months. The most frequent location was colon (24%). 35% were diagnosed in a metastatic stage. Older age (p = 0.003), previous cancer (p = 0.042), chronic kidney disease (CKD) (p = 0.006) and lower hemoglobin (p = 0.004) and fibrinogen (p = 0.019) values were predictors of occult neoplasm. No differences were found in other biochemical or epidemiological parameters, prognosis, etiology or clinical manifestations of the IS. In our study, older age, CKD, previous cancer and hemoglobin and fibrinogen values were related to the diagnosis of cancer after IS. More studies are needed to determine which patients could benefit from a larger study on admission that might allow an earlier diagnosis of the underlying neoplasm.

Perfil clínico y satisfacción con el tratamiento anticoagulante en pacientes con fibrilación auricular no valvular atendidos en consultas de medicina interna y neurología de España / Clinical profile and satisfaction with anticoagulated treatment in patients with non-valvular atrial fibrillation attended in Internal Medicine and Neurology departments of Spain

Objetivo. Determinar el perfil clínico, el manejo del tratamiento anticoagulante y la satisfacción relacionada con la anticoagulación en pacientes con fibrilación auricular no valvular atendidos en consultas de neurología o medicina interna de España. Pacientes y métodos. Estudio prospectivo, transversal y multicéntrico en el que se incluyó a 1.337 pacientes, que completaron los cuestionarios Anti-Clot Treatment Scale, Self-Assessment of Treatment Questionnaire y EuroQol-5 dimensions. Resultados. 865 pacientes (64,7%) provenían de consultas de neurología, y 472 (35,3%), de medicina interna. Los atendidos en medicina interna eran mayores, tenían más hipertensión, diabetes, insuficiencia cardíaca, insuficiencia renal y arteriopatía periférica. Los pacientes atendidos en neurología tenían más antecedentes de ictus. Globalmente, la escala CHADS2 fue 3,2 ± 1,3; CHA2DS2Vasc, 4,8 ± 1,5, y HAS-BLED, 2,0 ± 0,9, y las puntuaciones más altas fueron en neurología. El 56,1% tomaba antagonistas de la vitamina K, lo que era más común en medicina interna. El porcentaje de tiempo en rango terapéutico adecuado fue del 47% (Rosendaal), sin diferencias entre los grupos. La satisfacción con el tratamiento anticoagulante oral fue elevada en ambos grupos, aunque mayor en los sujetos atendidos en neurología, y mayor con los anticoagulantes orales de acción directa que con los antagonistas de la vitamina K. Conclusiones. Aunque existieron ciertas diferencias en el perfil clínico de los pacientes con fibrilación auricular atendidos en neurología o medicina interna, todos presentaban múltiples comorbilidades y un riesgo tromboembólico elevado. A pesar de que el control del índice internacional normalizado fue pobre, el anticoagulante oral más empleado fueron los antagonistas de la vitamina K. La satisfacción con el tratamiento anticoagulante oral fue alta (AU)

Aim. To determine the clinical profile, management of anticoagulant treatment and satisfaction related to anticoagulation in outpatients with nonvalvular atrial fibrillation attended in Neurology or Internal Medicine departments of Spain. Patients and methods. Cross-sectional and multicenter study, in which 1,337 outpatients were included. Patients fulfilled ACTS, SAT-Q and EQ-5D questionnaires. Results. 865 patients (64.7%) were recruited from Neurology department and 472 (35.3%) from Internal Medicine department. Those patients attended in Internal Medicine department were older and had more frequently hypertension, diabetes, heart failure, renal insufficiency and peripheral artery disease. Those patients attended in Neurology department had more commonly prior stroke. Overall, CHADS2 score was 3.2 ± 1.3, CHA2DS2-Vasc 4.8 ± 1.5 and HAS-BLED 2.0 ± 0.9. All scores were higher in those patients attended in Neurology department. Globally, 56.1% of patients were taking vitamin K antagonists, more commonly in Internal Medicine department. The adequate percent of time in therapeutic range was 47% (Rosendaal), without significant differences between groups. Satisfaction with oral anticoagulation was high in both groups, but higher in those attended in Neurology department, and higher in those individuals taking direct oral anticoagulants compared with vitamin K antagonists. Conclusions. Although there were some differences in the clinical profile of patients with atrial fibrillation attended in Neurology or Internal Medicine departments, all of them had many comorbidities and a high thromboembolic risk. Despite INR control was poor, the most common oral anticoagulant used were vitamin K antagonists. Satisfaction related to oral anticoagulation was high (AU)

Ideación suicida y conductas autolesivas en adolescentes con Trastornos de la Conducta Alimentaria / Suicidal ideation and self-injurious behavior in adolescents with eating disorders

Introducción. Es conocida la presencia de ideas suicidas y comportamientos autolesivos en pacientes con Trastornos de la Conducta Alimentaria (TCA), sin embargo, esta asociación no está claramente definida empíricamente. El objetivo del estudio es determinar la prevalencia de ideación suicida y conductas autolesivas en adolescentes con TCA. Un segundo objetivo es estudiar la asociación entre conducta autolesiva e ideación suicida, gravedad de la sintomatología alimentaria, depresiva, ansiosa, motivación para el cambio y perfeccionismo. Metodología. Se evaluaron a 109 pacientes (edad media: 14,74 años (DE:1,53); 87,2% mujeres) con el Inventario de TCA (EDI-2), el Inventario de Depresión de Beck (BDI-II), el Inventario de Ansiedad Estado/Rasgo (STAI), la Escala de Perfeccionismo en Niños y Adolescentes (CAPS) y el Cuestionario de Etapas de Cambio en la Anorexia Nerviosa (ANSOCQ). Resultados. Cuarenta y siete pacientes (43,1%) presentaron ideación suicida y 34 (31,2%) conductas autolesivas. La presencia de ideación suicida no discriminó entre pacientes TCA con y sin comportamiento autolesivo. Los pacientes con comportamiento autolesivo presentaron una puntuación significativamente mayor en todas las escalas del EDI-2, a excepción de Miedo a Madurar, en la puntuación total del BDI-II, STAI y en la CAPS. Se encontró una asociación entre la conducta autolesiva y la motivación para el cambio. Conclusiones. Un porcentaje importante de adolescentes con TCA presentan ideación suicida y comportamientos autolesivos, siendo el perfil psicopatológico de estos pacientes más grave. La presencia de ideación suicida en adolescentes con TCA no tiene necesariamente implicaciones con la conducta autolesiva, este comportamiento podría explicarse como consecuencia de la necesidad de regular emociones negativas intensas (AU)

Introduction. The presence of suicidal thoughts and self-injurious behaviors in patients with eating disorders (ED) is well-known; however, this association is currently not defined empirically. The aim of the study is to determine the prevalence of suicidal ideation and self-harm in adolescents with eating disorders. A second objective is to study the association between self-injurious behavior and suicidal ideation, severity of eating disorder symptoms and symptoms of depression and anxiety, motivation to change and perfectionism. Methodology. We evaluated 109 patients (mean age, 14.74 years (SD: 1.53); 87.2% female) using the Eating Disorder Inventory (EDI-2), the Beck Depression Inventory (BDI-II), the State-Trait Anxiety Inventory (STAI), the Child and Adolescent Perfectionism Scale (CAPS) and the Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ). Results. Forty-seven patients (43.1%) had suicidal ideation and 34 (31.2%), self-injurious behavior. The presence of suicidal ideation did not discriminate between patients with or without self-injurious behavior. Patients who self-harm had significantly higher scores on all scales of the EDI-2, except for ‘maturity fears’, in the total scores of BDI-II, STAI and CAPS. An association between self-injurious behavior and motivation to change was found. Conclusions. A significant percentage of adolescents with eating disorders present suicidal ideation and self-injurious behavior, making the psychopathological profile of these patients more severe. The presence of suicidal ideation in adolescents with eating disorders does not necessarily mply that they have self-injurious behavior; rather, such behavior could be a result of the need to regulate intense negative emotions (AU)

Suicidal ideation and self-injurious behavior in adolescents with eating disorders.

INTRODUCTION: The presence of suicidal thoughts and self-injurious behaviors in patients with eating disorders (ED) is well-known; however, this association is currently not defined empirically. The aim of the study is to determine the prevalence of suicidal ideation and self-harm in adolescents with eating disorders. A second objective is to study the association between self-injurious behavior and suicidal ideation, severity of eating disorder symptoms and symptoms of depression and anxiety, motivation to change and perfectionism. METHODOLOGY: We evaluated 109 patients (mean age, 14.74 years (SD: 1.53); 87.2% female) using the Eating Disorder Inventory (EDI-2), the Beck Depression Inventory (BDI-II), the State-Trait Anxiety Inventory (STAI), the Child and Adolescent Perfectionism Scale (CAPS) and the Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ). RESULTS: Forty-seven patients (43.1%) had suicidal ideation and 34 (31.2%), self-injurious behavior. The presence of suicidal ideation did not discriminate between patients with or without self-injurious behavior. Patients who self-harm had significantly higher scores on all scales of the EDI-2, except for “maturity fears”, in the total scores of BDI-II, STAI and CAPS. An association between selfinjurious behavior and motivation to change was found. CONCLUSIONS: A significant percentage of adolescents with eating disorders present suicidal ideation and selfinjurious behavior, making the psychopathological profile of these patients more severe. The presence of suicidal ideation in adolescents with eating disorders does not necessarily imply that they have self-injurious behavior; rather, such behavior could be a result of the need to regulate intense negative emotions.

Somnolence and stuttering as the primary manifestations of a midbrain stroke.

BACKGROUND: Stroke can occasionally manifest with non-lateralizing findings such as somnolence and stuttering. We describe a case and discuss the anatomical and physiological implications of this rare combination of symptoms. CASE REPORT: A 51-year-old woman presented with 3 days of "feeling drunk". She could further specify her symptoms as blurry vision, slurred speech, and gait instability. She had a history of hypertension and hyperlipidemia. Her examination at presentation was remarkable only for marked somnolence. Over the next several hours she developed mild upgaze limitation and vertical nystagmus. Non-enhanced computed tomography of the brain was normal. Brain magnetic resonance imaging (MRI) revealed a 5 mm acute infarct in the caudal midbrain. The first week the patient remained somnolent and manifested marked stuttering. The patient improved gradually with speech therapy. CONCLUSION: Strokes affecting the diencephalic-mesencephalic junction can manifest with stuttering. Defective projections of the reticular formation to the supplementary motor area, damaged extrapyramidal circuits, and/or aberrant propioceptive feedback due to involvement of the mesencephalic nucleus of the trigeminal nerve are the proposed pathophysiological mechanisms. Somnolence can also be part of the presentation and is likely due to disruptions of sleep pathways subserved by the reticular activating system. The accurate diagnosis of these cases depends on careful clinical assessment and high index of suspicion for stroke, especially in lieu of preexisting vascular risk factors and lack of an alternative explanation such as toxic-metabolic encephalopathy.