Efficacy and safety of a structured de-escalation from antipseudomonal ß-lactams in bloodstream infections due to Enterobacterales (SIMPLIFY): an open-label, multicentre, randomised trial.

BACKGROUND: De-escalation from broad-spectrum to narrow-spectrum antibiotics is considered an important measure to reduce the selective pressure of antibiotics, but a scarcity of adequate evidence is a barrier to its implementation. We aimed to determine whether de-escalation from an antipseudomonal ß-lactam to a narrower-spectrum drug was non-inferior to continuing the antipseudomonal drug in patients with Enterobacterales bacteraemia. METHODS: An open-label, pragmatic, randomised trial was performed in 21 Spanish hospitals. Patients with bacteraemia caused by Enterobacterales susceptible to one of the de-escalation options and treated empirically with an antipseudomonal ß-lactam were eligible. Patients were randomly assigned (1:1; stratified by urinary source) to de-escalate to ampicillin, trimethoprim-sulfamethoxazole (urinary tract infections only), cefuroxime, cefotaxime or ceftriaxone, amoxicillin-clavulanic acid, ciprofloxacin, or ertapenem in that order according to susceptibility (de-escalation group), or to continue with the empiric antipseudomonal ß-lactam (control group). Oral switching was allowed in both groups. The primary outcome was clinical cure 3-5 days after end of treatment in the modified intention-to-treat (mITT) population, formed of patients who received at least one dose of study drug. Safety was assessed in all participants. Non-inferiority was declared when the lower bound of the 95% CI of the absolute difference in cure rate was above the -10% non-inferiority margin. This trial is registered with EudraCT (2015-004219-19) and ClinicalTrials.gov (NCT02795949) and is complete. FINDINGS: 2030 patients were screened between Oct 5, 2016, and Jan 23, 2020, of whom 171 were randomly assigned to the de-escalation group and 173 to the control group. 164 (50%) patients in the de-escalation group and 167 (50%) in the control group were included in the mITT population. 148 (90%) patients in the de-escalation group and 148 (89%) in the control group had clinical cure (risk difference 1·6 percentage points, 95% CI -5·0 to 8·2). The number of adverse events reported was 219 in the de-escalation group and 175 in the control group, of these, 53 (24%) in the de-escalation group and 56 (32%) in the control group were considered severe. Seven (5%) of 164 patients in the de-escalation group and nine (6%) of 167 patients in the control group died during the 60-day follow-up. There were no treatment-related deaths. INTERPRETATION: De-escalation from an antipseudomonal ß-lactam in Enterobacterales bacteraemia following a predefined rule was non-inferior to continuing the empiric antipseudomonal drug. These results support de-escalation in this setting. FUNDING: Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases; Spanish Clinical Research and Clinical Trials Platform, co-financed by the EU; European Development Regional Fund "A way to achieve Europe", Operative Program Intelligence Growth 2014-2020.

Non-nosocomial Healthcare-Associated Infective Endocarditis: A Distinct Entity? Data From the GAMES Series (2008-2021).

Background: Patients who acquire infective endocarditis (IE) following contact with the healthcare system, but outside the hospital, are classified as having non-nosocomial healthcare-associated IE (HCIE). Our aim was to characterize HCIE and establish whether its etiology, diagnosis, and therapeutic approach suggest it should be considered a distinct entity. Methods: This study retrospectively analyzes data from a nationwide, multicenter, prospective cohort including consecutive cases of IE at 45 hospitals across Spain from 2008 to 2021. HCIE was defined as IE detected in patients in close contact with the healthcare system (eg, patients receiving intravenous treatment, hemodialysis, or institutionalized). The prevalence and main characteristics of HCIE were examined and compared with those of community-acquired IE (CIE) and nosocomial IE (NIE) and with literature data. Results: IE was diagnosed in 4520 cases, of which 2854 (63%) were classified as CIE, 1209 (27%) as NIE, and 457 (10%) as HCIE. Patients with HCIE showed a high burden of comorbidities, a high presence of intravascular catheters, and a predominant staphylococcal etiology, Staphylococcus aureus being identified as the most frequent causative agent (35%). They also experienced more persistent bacteremia, underwent fewer surgeries, and showed a higher mortality rate than those with CIE (32.4% vs 22.6%). However, mortality in this group was similar to that recorded for NIE (32.4% vs 34.9%, respectively, P = .40). Conclusions: Our data do not support considering HCIE as a distinct entity. HCIE affects a substantial number of patients, is associated with a high mortality, and shares many characteristics with NIE.

Infective endocarditis in patients with cardiac implantable electronic devices: a nationwide study.

AIMS: Patients with infective endocarditis (IE) frequently have cardiac implantable electronic devices (CIEDs). Here, we aim to define the clinical profile and prognostic factors of IE in these patients. METHODS AND RESULTS: Infective endocarditis cases were prospectively identified in the Spanish National Endocarditis Registry. From 3996 IE, 708 (17.7%) had a CIED and 424 CIED-related IE (lead vegetation). Patients with a CIED were older (68 ± 11 vs. 73 ± 8 years); had more comorbidities {pulmonary disease [176 (24.8%) vs. 545 (16.7%)], renal disease [239 (33.8%) vs. 740 (22.7%)], diabetes [248 (35.0%) vs. 867 (26.6%)], and heart failure [348 (49.2%) vs. 978 (29.9%)]}; and fewer complications {intracardiac destruction [106 (15%) vs. 1077 (33.1%)], heart failure [215 (30.3%) vs. 1340 (41.1%)], embolism [107 (15.1%) vs. 714 (21.9%)], and neurological involvement [77 (10.8%) vs. 702 (21.5%)]} (all P-values <0.001) in comparison to subjects without a CIED. In-hospital mortality was similar in patients with and without CIED [171 (24.2%) vs. 881 (27.0%), P = 0.82]. In subjects with a CIED, CIED-related IE was independently associated with in-hospital survival: odds ratio (OR) 0.4 [95% confidence interval (CI) 0.3-0.7, P = 0.001]. Surgery was independently associated with in-hospital survival in CIED-related IE: OR 0.4 (95% CI 0.2-0.7, P = 0.004); but not in subjects with valve IE and no CIED lead involvement: OR 0.9 (95% CI 0.5-1.7, P = 0.77). CONCLUSION: Over a sixth of IE patients have a CIED. This group of patients is older, with more comorbidities and fewer IE-related complications in comparison to subjects without a CIED. In-hospital mortality was similar in patients with and without a CIED.

Cryptococcal meningoencephalitis presenting as cerebral venous thrombosis.

Cerebral venous thrombosis (CVT) is characterized by its variety of neurological manifestations and difficulty in diagnosis. In subacute cases, the main symptoms are secondary to increased intracranial pressure. This condition is associated with an extensive range of medical disorders, but only 2% are caused by a CNS infection in recent series. We report a 45-year-old patient, with no previous medical history, who developed a syndrome of increased intracranial pressure as the presentation of a cryptococcal meningoencephalitis (CM) complicated with a CVT. The patient was first diagnosed of a CVT, and later on, the VIH infection and the CM diagnosis were made. Despite being treated with anticoagulation, liposomal amphotericin B, and a therapeutic lumbar puncture, the patient continued to deteriorate and suffered a respiratory arrest secondary to the increased intracranial pressure, with subsequent brain death. Cryptococcus is an infrequent cause of CNS infection in developed countries, despite being the most frequent cause of meningits in adults in several countries with high rates of HIV infection. CVT is a very rare complication of CM which can contribute to worsen the increased intracranial pressure and in consequence, its prognosis and outcome. A high level of suspicion is needed for diagnosing CM as the underlying cause of CVT and the subsequent increased intracranial pressure should be managed exhaustively.

Executive summary of outpatient parenteral antimicrobial therapy: Guidelines of the Spanish Society of Clinical Microbiology and Infectious Diseases and the Spanish Domiciliary Hospitalisation Society / Resumen ejecutivo del tratamiento antimicrobiano domiciliario endovenoso: guía de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica y la Sociedad Española de Hospitalización a Domicilio

Outpatient parenteral antimicrobial therapy (OPAT) programmes make it possible to start or complete intravenous antimicrobial therapy for practically any type of infection at home, provided that patient selection is appropriate for the type of OPAT programme available. Although the clinical management of infections in the home setting is comparable in many respects to that offered in conventional hospitalization (selection of antibiotics, duration of treatment, etc.), there are many aspects that are specific to this care modality. It is essential to be aware of them so that OPAT continues to be as safe and effective as inpatient care. The objective of this clinical guideline is therefore to provide evidence- and expert-based recommendations with a view to standardizing clinical practice in this care modality and contribute to a progressive increase in the number of patients who can be cared for and receive intravenous therapy in their own homes

Los programas de tratamiento antibiótico domiciliario endovenoso (TADE) permiten iniciar o completar el tratamiento antimicrobiano por vía endovenosa de prácticamente cualquier tipo de infección en el domicilio, siempre y cuando se realice una selección del paciente acorde al tipo de programa de TADE que se dispone. Aunque hay aspectos del manejo clínico de las infecciones en el domicilio que son superponibles en la mayoría de los casos a la realizada en la hospitalización convencional (selección de la antibioterapia, duración del tratamiento, etc.), existen numerosos aspectos que son específicos de esta modalidad asistencial. Resulta imprescindible conocerlos para que el TADE siga siendo igual de eficaz y seguro que la hospitalización convencional. El objetivo de esta guía clínica es por tanto, proporcionar recomendaciones basadas en la evidencia realizadas por expertos para homogeneizar la práctica clínica de esta modalidad asistencial y contribuir a que se incremente progresivamente el número de pacientes que pueden ser atendidos y recibir tratamiento endovenoso en su propio domicilio

Executive summary of outpatient parenteral antimicrobial therapy: Guidelines of the Spanish Society of Clinical Microbiology and Infectious Diseases and the Spanish Domiciliary Hospitalisation Society.

Outpatient parenteral antimicrobial therapy (OPAT) programmes make it possible to start or complete intravenous antimicrobial therapy for practically any type of infection at home, provided that patient selection is appropriate for the type of OPAT programme available. Although the clinical management of infections in the home setting is comparable in many respects to that offered in conventional hospitalization (selection of antibiotics, duration of treatment, etc.), there are many aspects that are specific to this care modality. It is essential to be aware of them so that OPAT continues to be as safe and effective as inpatient care. The objective of this clinical guideline is therefore to provide evidence- and expert-based recommendations with a view to standardizing clinical practice in this care modality and contribute to a progressive increase in the number of patients who can be cared for and receive intravenous therapy in their own homes.

Diagnóstico de endocarditis infecciosa mediante 18F-FDG-PET/TC, presentación de un resultado falso negative / Diagnosis of infective endocarditis by 18F-FDG-PET/CT, presentation of a false negative result

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Etiología de la insuficiencia renal en pacientes con endocarditis infecciosa. Papel de los antibióticos / Aetiology of renal failure in patients with infective endocarditis. The role of antibiotics

Fundamento y objetivos: La toxicidad renal de ciertos antibióticos (AB) es conocida. El objetivo de nuestro trabajo es conocer el posible efecto de los tratamientos AB en el desarrollo de insuficiencia renal (IR) en pacientes con endocarditis infecciosa (EI). Material y método: Recogida en un registro nacional multicéntrico de los datos referentes a la función renal, tanto previa como su deterioro si existiese, durante el tratamiento de las EI y relacionarlo con los posibles factores causantes, entre ellos los AB. Resultados: Entre 2008 y 2012 se han analizado 1.853 episodios de EI remitidos desde 26 centros españoles. De ellos, un 21,6% presentaban una alteración previa de la función renal. Desarrollaron IR de novo o un empeoramiento de la función renal previa un 38,7% de los casos. En aquellos pacientes que presentaban IR previa, el deterioro fue más frecuente (64 frente a 31,7%; p<0,001). Globalmente los pacientes con IR tenían más edad (70,6 frente a 67 años; p<0,01) y comorbilidades (índice de Charlson 5 frente a 4; p<0,01), y la EI era por Staphylococcus aureus (32,1 frente a 16,5%; p<0,01). El uso de AB potencialmente nefrotóxicos solo se asoció a IR en el grupo de pacientes sin IR previa (aminoglucósidos: OR=1,47 [IC 95% 1,096-1,988], p=0,010; aminoglucósidos-vancomicina: OR=1,49 [IC 95% 1,069-2,09], p=0,019]). Conclusiones: En pacientes sin IR previa, los AB nefrotóxicos se asocian a un deterioro de la función renal. En pacientes con IR previa al episodio de EI, el deterioro de renal fue más frecuente, pero parece estar más relacionado con la gravedad de la infección (AU)

Background and objectives: The possible renal toxicity of certain antibiotics (AB) is well known. The objective of our work is to know the possible effect of AB treatments in the development of renal failure (RF) in patients with infective endocarditis (IE). Material and method: Collection from a national multi-centre registry of collection on renal function, both prior and its impairment, if any, during the treatment of IE and in relation to possible causative factors, including the use of AB. Results: Between 2008 and 2012, 1,853 episodes of IE reported from 26 Spanish centres were analysed. Of these, 21.6% had prior RF. They developed new RF or impairment of renal function in 38.7% of the cases. In patients with prior RF, impairment was more frequent (64 vs. 31.7%, P<.001). Overall, patients with RF were older (70.6 vs. 67 years, P<.01), had more comorbidities (Charlson index 5 vs. 4, P<.01), and IE by Staphylococcus aureus (32.1 vs. 16.5%, P<.01). Potentially nephrotoxic AB use was only associated with RF in patients without prior RF (aminoglycosides: OR=1.47 [95% CI 1.096-1.988], P=.010; aminoglycosides with vancomycin: OR=1.49 [95% CI 1.069-2.09], P=.019). Conclusions: In patients without prior RF, the use of nephrotoxic AB is associated with impairment of renal function. In patients with RF prior to the IE episode, impairment of renal function was more frequent but appears to be more related to the severity of infection (AU)

Aetiology of renal failure in patients with infective endocarditis. The role of antibiotics. / Etiología de la insuficiencia renal en pacientes con endocarditis infecciosa. Papel de los antibióticos.

BACKGROUND AND OBJECTIVES: The possible renal toxicity of certain antibiotics (AB) is well known. The objective of our work is to know the possible effect of AB treatments in the development of renal failure (RF) in patients with infective endocarditis (IE). MATERIAL AND METHOD: Collection from a national multi-centre registry of collection on renal function, both prior and its impairment, if any, during the treatment of IE and in relation to possible causative factors, including the use of AB. RESULTS: Between 2008 and 2012, 1,853 episodes of IE reported from 26 Spanish centres were analysed. Of these, 21.6% had prior RF. They developed new RF or impairment of renal function in 38.7% of the cases. In patients with prior RF, impairment was more frequent (64 vs. 31.7%, P<.001). Overall, patients with RF were older (70.6 vs. 67 years, P<.01), had more comorbidities (Charlson index 5 vs. 4, P<.01), and IE by Staphylococcus aureus (32.1 vs. 16.5%, P<.01). Potentially nephrotoxic AB use was only associated with RF in patients without prior RF (aminoglycosides: OR=1.47 [95% CI 1.096-1.988], P=.010; aminoglycosides with vancomycin: OR=1.49 [95% CI 1.069-2.09], P=.019). CONCLUSIONS: In patients without prior RF, the use of nephrotoxic AB is associated with impairment of renal function. In patients with RF prior to the IE episode, impairment of renal function was more frequent but appears to be more related to the severity of infection.

Endocarditis recidivante por Brevibacterium casei: a propósito de un caso y revisión de la literatura / Recurrent endocarditis due to Brevibacterium casei: case presentation and a review of the literature

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[Consensus statement on the clinical management of human immunodeficiency virus-associated neurocognitive disorders]. / Documento de consenso sobre el manejo clínico de los trastornos neurocognitivos asociados a la infección por el virus de la inmunodeficiencia humana (enero 2013).

OBJECTIVE: To develop a consensus document containing clinical recommendations for the management of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND). METHODS: We assembled a panel of experts appointed by GeSIDA and the Secretariat of the National AIDS Plan (PNS), including internal medicine physicians with expertise in the field of HIV, neuropsychologists, neurologists and neuroradiologists. Scientific information was reviewed to October 2012 in publications and conference papers. In support of the recommendations using two levels of evidence: the strength of the recommendation in the opinion of the experts (A, B, C) and the level of empirical evidence (I, II, III), two levels based on the criteria of the Infectious Disease Society of America, already used in previous documents GeSIDA/SPNS. RESULTS: Multiple recommendations for the clinical management of these disorders are provided, including two graphics algorithms, considering both the diagnostic and possible therapeutic strategies. CONCLUSIONS: Neurocognitive disorders associated with HIV infection is currently highly prevalent, are associated with a decreased quality of life and daily activities, and given the possibility of occurrence of an increase in the coming years, there is a need to adequately manage these disorders, from a diagnostic as well as therapeutic point of view, and always from a multidisciplinary perspective.