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BACKGROUND: Plitidepsin has shown potent preclinical activity against SARS-CoV-2 and was generally well tolerated in a Phase I trial of hospitalized patients with COVID-19. NEPTUNO, a Phase III, multicenter, randomized, controlled trial, was designed to evaluate the efficacy and safety of plitidepsin in the management of moderate COVID-19 in hospitalized adult patients. METHODS: Included patients had documented SARS-CoV-2 infection, required oxygen therapy, and had adequate organ function. The planned sample size was 609 patients. Patients were randomized 1:1:1 to at least 3 days of dexamethasone plus either plitidepsin (1.5 mg/day or 2.5 mg/day, for 3 days) or standard of care (control). The primary endpoint was the time to sustained withdrawal of supplemental oxygen. Secondary endpoints included time to sustained hospital discharge, clinical status, duration of oxygen support, percentage of patients requiring admission to the intensive care unit, and safety. FINDINGS: After randomizing 205 patients, NEPTUNO was discontinued due to a notable drop in COVID-19-related hospitalizations. Available data suggest a 2-day improvement in the median time to sustained oxygen therapy discontinuation (5 vs 7 days) favoring both plitidepsin arms (hazard ratio [HR] 1.37, 95% confidence interval [CI] 0.96-1.96, p=0.08 for plitidepsin 1.5 mg vs control; HR 1.06, 95% CI 0.73-1.53, p=0.78 for plitidepsin 2.5 mg vs control). Plitidepsin was generally well tolerated. INTERPRETATION: Despite the trial limitations, these results suggest that plitidepsin may have a positive benefit-risk ratio in the management of patients requiring oxygen therapy. Further studies with plitidepsin, including those in immunosuppressed patients, are warranted. FUNDING: This trial has been funded by Pharmamar, S.A. (Madrid, Spain).
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OBJECTIVES: Bloodstream infections (BSI) are an important cause of mortality, although they show heterogeneity depending on patients and aetiological factors. Comprehensive and specific mortality scores for BSI are scarce. The objective of this study was to develop a mortality predictive score in BSI based on a multicentre prospective cohort. METHODS: A prospective cohort including consecutive adults with bacteraemia recruited between October 2016 and March 2017 in 26 Spanish hospitals was randomly divided into a derivation cohort (DC) and a validation cohort (VC). The outcome was all-cause 30-day mortality. Predictors were assessed the day of blood culture growth. A logistic regression model and score were developed in the DC for mortality predictors; the model was applied to the VC. RESULTS: Overall, 4102 patients formed the DC and 2009 the VC. Mortality was 11.8% in the DC and 12.34% in the CV; the patients and aetiological features were similar for both cohorts. The mortality predictors selected in the final multivariate model in the DC were age, cancer, liver cirrhosis, fatal McCabe underlying condition, polymicrobial bacteraemia, high-risk aetiologies, high-risk source of infection, recent use of broad-spectrum antibiotics, stupor or coma, mean blood pressure <70â mmHg and PaO2/FiO2â≤â300 or equivalent. Mortality in the DC was <2% for ≤2 points, 6%-14% for 3-7 points, 26%-45% for 8-12 points and ≥60% for ≥13 points. The predictive score had areas under the receiving operating curves of 0.81 (95% CI 0.79-0.83) in the DC and 0.80 (0.78-0.83) in the VC. CONCLUSIONS: A 30â day mortality predictive score in BSI with good discrimination ability was developed and internally validated.
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Bacteriemia , Humanos , Estudios Prospectivos , Masculino , Femenino , Bacteriemia/mortalidad , Bacteriemia/microbiología , Anciano , Persona de Mediana Edad , España/epidemiología , Anciano de 80 o más Años , Adulto , Factores de Riesgo , Pronóstico , Modelos LogísticosRESUMEN
PURPOSES: Enterococcal BSI is associated with significant morbidity and mortality, with fatality rates of approximately 20-30%. There are microbiological and clinical differences between E. faecalis and E. faecium infections. The aim of this study was to investigate differences in predisposing factors for E. faecalis and E. faecium BSI and to explore prognostic factors. METHODS: This study was a post-hoc analysis of PROBAC, a Spanish prospective, multicenter, cohort in 2016-2017. Patients with E. faecalis or E. faecium BSI were eligible. Independent predictors for BSI development in polymicrobial and monomicrobial BSI and in-hospital mortality in the monomicrobial group were identified by logistic regression. RESULTS: A total of 431 patients were included. Independent factors associated with E. faecium BSI were previous use of penicillins (aOR 1.99 (95% CI 1.20-3.32)) or carbapenems (2.35 (1.12-4.93)), hospital-acquired BSI (2.58 (1.61-4.12)), and biliary tract source (3.36 (1.84-6.13)), while congestive heart failure (0.51 (0.27-0.97)), cerebrovascular disease (0.45 (0.21-0.98)), and urinary tract source (0.49 (0.26-0.92)) were associated with E. faecalis BSI. Independent prognostic factors for in-hospital mortality in E. faecalis BSI were Charlson Comorbidity Index (1.27 (1.08-1.51)), SOFA score (1.47 (1.24-1.73)), age (1.06 (1.02-1.10)), and urinary/biliary source (0.29 (0.09-0.90)). For E. faecium BSI, only SOFA score (1.34 (1.14-1.58) was associated with in-hospital mortality. CONCLUSIONS: The factors associated with E. faecium and E. faecalis BSI are different. These variables may be helpful in the suspicion of one or other species for empiric therapeutic decisions and provide valuable information on prognosis.
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BACKGROUND: Klebsiella aerogenes has been reclassified from Enterobacter to Klebsiella genus due to its phenotypic and genotypic similarities with Klebsiella pneumoniae. It is unclear if clinical outcomes are also more similar. This study aims to assess clinical outcomes of bloodstreams infections (BSI) caused by K. aerogenes, K. pneumoniae and Enterobacter cloacae, through secondary data analysis, nested in PRO-BAC cohort study. METHODS: Hospitalized patients between October 2016 and March 2017 with monomicrobial BSI due to K. aerogenes, K. pneumoniae or E. cloacae were included. Primary outcome was a composite clinical outcome including all-cause mortality or recurrence until 30 days follow-up. Secondary outcomes were fever ≥ 72 h, persistent bacteraemia, and secondary device infection. Multilevel mixed-effect Poisson regression was used to estimate the association between microorganisms and outcome. RESULTS: Overall, 29 K. aerogenes, 77 E. cloacae and 337 K. pneumoniae BSI episodes were included. Mortality or recurrence was less frequent in K. aerogenes (6.9%) than in E. cloacae (20.8%) or K. pneumoniae (19.0%), but statistical difference was not observed (rate ratio (RR) 0.35, 95% CI 0.08 to 1.55; RR 0.42, 95% CI 0.10 to 1.71, respectively). Fever ≥ 72 h and device infection were more common in K. aerogenes group. In the multivariate analysis, adjusted for confounders (age, sex, BSI source, hospital ward, Charlson score and active antibiotic therapy), the estimates and direction of effect were similar to crude results. CONCLUSIONS: Results suggest that BSI caused by K. aerogenes may have a better prognosis than E. cloacae or K. pneumoniae BSI.
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Bacteriemia , Enterobacter aerogenes , Enterobacter cloacae , Infecciones por Enterobacteriaceae , Infecciones por Klebsiella , Klebsiella pneumoniae , Humanos , Enterobacter cloacae/aislamiento & purificación , Klebsiella pneumoniae/aislamiento & purificación , Klebsiella pneumoniae/efectos de los fármacos , Masculino , Femenino , Bacteriemia/microbiología , Bacteriemia/mortalidad , Anciano , Persona de Mediana Edad , Infecciones por Klebsiella/mortalidad , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/tratamiento farmacológico , Enterobacter aerogenes/aislamiento & purificación , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/mortalidad , Estudios de Cohortes , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Recurrencia , Resultado del TratamientoRESUMEN
PURPOSE: The management of post-surgical subdural empyema and subdural abscess is not standardised. The objective was to analyse the efficacy and safety of oral sequential therapy (OST). METHODS: Retrospective observational study in a tertiary hospital in Vigo (Spain). We included adult patients with subdural abscess or epidural empyema with microbiological isolation. Clinical and demographic variables, isolated microorganisms and treatment regimens were included, as well as mortality and adverse effects during the follow-up period. RESULTS: Thirty patients were reviewed, two died due to causes other than infection. Six-month recurrence rate was 2/28 and all other patients (26/28) had clinical cure at the end of the treatment. The commonest isolated microorganisms were Gram-positive, especially Staphylococcus aureus. The most widely used oral antibiotic was trimethoprim-sulfamethoxazole (80%). No side effects related to oral treatment were observed. CONCLUSION: After adequate source control, OST can be a safe practice in the management of post-surgical epidural abscess and subdural empyema.
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Empiema Subdural , Absceso Epidural , Infecciones Estafilocócicas , Adulto , Antibacterianos/uso terapéutico , Empiema Subdural/tratamiento farmacológico , Empiema Subdural/cirugía , Absceso Epidural/complicaciones , Absceso Epidural/tratamiento farmacológico , Absceso Epidural/cirugía , Humanos , Infecciones Estafilocócicas/complicaciones , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/cirugía , Combinación Trimetoprim y SulfametoxazolRESUMEN
BACKGROUND AND OBJECTIVES: Available information about infection after spine instrumentation (IASI) and its management are scarce. We aimed to analyse DAIR (debridement, antibiotics and implant retention) prognosis and evaluate effectiveness of short antibiotic courses on early forms. METHODS: Multicentre retrospective study of patients with IASI managed surgically (January 2010-December 2016). Risk factors for failure were analysed by multivariate Cox regression and differences between short and long antibiotic treatment were evaluated with a propensity score-matched analysis. RESULTS: Of the 411 IASI cases, 300 (73%) presented in the first month after surgery, 48 in the second month, 22 in the third and 41 thereafter. Infections within the first 2 months (early cases) occurred mainly to older patients, with local inflammatory signs and predominance of Enterobacteriaceae, unlike those in the later periods. When managed with DAIR, prognosis of early cases was better than later ones (failure rate 10.4% versus 26.1%, respectively; P = 0.02). Risk factors for DAIR failure in early cases were female sex, Charlson Score, large fusions (>6 levels) and polymicrobial infections (adjusted HRs of 2.4, 1.3, 2.6 and 2.26, respectively). Propensity score matching proved shorter courses of antibiotics (4-6 weeks) as effective as longer courses (failure rates 11.4% and 10.5%, respectively; P = 0.870). CONCLUSIONS: IASIs within the first 2 months could be managed effectively with DAIR and shorter antibiotic courses. Clinicians should be cautious when faced with patients with comorbidities, large fusions and/or polymicrobial infections.
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Infecciones Relacionadas con Prótesis , Antibacterianos/uso terapéutico , Desbridamiento , Femenino , Humanos , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Some evidence-based bundles have tried to standardize the management of Staphylococcus aureus bacteraemia (SAB) to improve the outcome. The aim of our study was to analyse the additional impact on mortality of a structured intervention in patients with SAB. METHODS: Compliance with the bundle was evaluated in an ambispective cohort of patients with SAB, which included a retrospective cohort [including patients treated before and after the implementation of a bacteraemia programme (no-BP and BP, respectively)] and a prospective cohort (i-BP), in which an additional specific intervention for bundle application was implemented. Multivariate logistic regression was used to measure the influence of the independent variables including compliance with the bundle on 14 and 30 day crude mortality. RESULTS: A total of 271 adult patients with SAB were included. Mortality was significantly different among the three groups (no-BP, BP and i-BP): mortality at 14 days was 18% versus 7% versus 2%, respectively, P = 0.002; and mortality at 30 days was 20% versus 12% versus 5%, respectively, P = 0.011. The factors associated with 14 and 30 day mortality in multivariable analysis were heart failure (OR = 7.63 and OR = 2.27, respectively), MRSA infection (OR = 4.02 and OR = 4.37, respectively) and persistent bacteraemia (OR = 11.01 and OR = 7.83, respectively); protective factors were catheter-related bacteraemia (OR = 0.16 and OR = 0.19, respectively) and >75% bundle compliance (OR = 0.15 and OR = 0.199, respectively). Time required to perform the intervention and the follow-up was 50 min (IQR 40-55 min) per patient. CONCLUSIONS: High-level compliance with a standardized bundle of intervention for management of SAB that requires little time was associated with lower mortality at 14 and 30 days.
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Bacteriemia , Derivación y Consulta , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/mortalidad , Staphylococcus aureus , Adulto , Anciano , Anciano de 80 o más Años , Manejo de la Enfermedad , Práctica Clínica Basada en la Evidencia , Femenino , Evaluación del Impacto en la Salud , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina , Persona de Mediana Edad , Oportunidad Relativa , Indicadores de Calidad de la Atención de Salud , Factores de Riesgo , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/epidemiologíaRESUMEN
Bacteremia due to gram-negative bacilli (GNB) is one of the most frequent causes of admission and prolongation of hospital stay. Nevertheless, optimal duration of antibiotic treatment is not clearly established. We designed an observational, prospective study of a cohort of adult patients with uncomplicated GNB bacteremia. They were classified according to the duration of treatment in short (7-10 days) or long (> 10 days) course. Mortality and bacteremia recurrence rate were evaluated, and propensity score for receiving short-course treatment was calculated. A total of 395 patients met eligibility criteria including 232 and 163 who received long- and short-course therapy, respectively. Median age was 71 years, 215 (54.4% male) and 51% had a urinary source. Thirty-day mortality was 12%. In multivariate analysis by logistic regression stratified according to propensity score quartile for receiving short-course therapy showed no association of duration of treatment with 30-day mortality or 90-day recurrence rate. Based on the results observed in our cohort, short-course therapy could be as safe and effective as longer courses.
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Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Bacteriemia/diagnóstico , Bacteriemia/microbiología , Estudios de Cohortes , Femenino , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Background: Experience in real clinical practice with ceftazidime/avibactam is limited, and there are even fewer data on infections due to OXA-48-producing Enterobacteriaceae. Methods: We designed an observational study of a prospectively collected cohort of adult patients receiving ceftazidime/avibactam in our centre. Only the first treatment course of each patient was analysed. Efficacy and safety were evaluated as 14 and 30 day mortality, recurrence rate at 90 days, resistance development and occurrence of adverse effects. Results: Fifty-seven patients were treated with ceftazidime/avibactam. The median age was 64 years (range 26-86), 77% were male and the median Charlson index was 3. The most frequent sources of infection were intra-abdominal (28%), followed by respiratory (26%) and urinary (25%). Thirty-one (54%) patients had a severe infection (defined as presence of sepsis or septic shock). Most patients received ceftazidime/avibactam as monotherapy (81%) and the median duration of treatment was 13 days. Mortality at 14 days was 14%. In multivariate analysis, the only mortality risk factor was INCREMENT-CPE score >7 (HR 11.7, 95% CI 4.2-20.6). There was no association between mortality and monotherapy with ceftazidime/avibactam. The recurrence rate at 90 days was 10%. Ceftazidime/avibactam resistance was not detected in any case and only two patients developed adverse events related to treatment. Conclusions: Ceftazidime/avibactam shows promising results, even in monotherapy, for the treatment of patients with severe infections due to OXA-48-producing Enterobacteriaceae and limited therapeutic options. The emergence of resistance to ceftazidime/avibactam was not observed.
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Antibacterianos/uso terapéutico , Compuestos de Azabiciclo/uso terapéutico , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Ceftazidima/uso terapéutico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Terapia Recuperativa , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/efectos adversos , Compuestos de Azabiciclo/efectos adversos , Enterobacteriaceae Resistentes a los Carbapenémicos/enzimología , Ceftazidima/efectos adversos , Combinación de Medicamentos , Farmacorresistencia Bacteriana Múltiple , Infecciones por Enterobacteriaceae/mortalidad , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios Prospectivos , Inhibidores de beta-Lactamasas/efectos adversos , Inhibidores de beta-Lactamasas/uso terapéutico , beta-LactamasasRESUMEN
Mycotic aneurysms account for 1% of abdominal aortic aneurysms. There are very few cases published that describe the formation of mycotic aneurysms after septic embolism due to graft infection. We present the first case to our knowledge to be described in the literature of a mycotic aneurysm caused by septic embolism derived from a thoracic aorta graft infection, treated with conventional surgery leading to a successful outcome and evolution.
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Aneurisma Infectado/microbiología , Aneurisma de la Aorta Abdominal/microbiología , Aneurisma de la Aorta Torácica/cirugía , Implantación de Prótesis Vascular/efectos adversos , Prótesis Vascular/efectos adversos , Embolia/microbiología , Infecciones Relacionadas con Prótesis/microbiología , Infecciones Estreptocócicas/microbiología , Streptococcus constellatus/aislamiento & purificación , Adulto , Aneurisma Infectado/diagnóstico por imagen , Aneurisma Infectado/cirugía , Antibacterianos/uso terapéutico , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/cirugía , Aortografía/métodos , Implantación de Prótesis Vascular/instrumentación , Angiografía por Tomografía Computarizada , Embolia/diagnóstico por imagen , Embolia/cirugía , Femenino , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Infecciones Relacionadas con Prótesis/diagnóstico por imagen , Infecciones Relacionadas con Prótesis/cirugía , Reoperación , Choque Séptico/microbiología , Infecciones Estreptocócicas/diagnóstico por imagen , Infecciones Estreptocócicas/cirugía , Resultado del TratamientoRESUMEN
OBJECTIVES: Due to its long half-life, dalbavancin offers benefits for long-duration treatments, especially osteoarticular and infective endocarditis (IE). We evaluated the efficacy and costs of IE treatment, comparing dalbavancin with standard of care (SOC). METHODS: Retrospective multicenter cohort study of adult patients with Gram-positive cocci definite IE. Dalbavancin was used as a sequential therapy before discharge. Efficacy was a combined variable of clinical cure and absence of recurrence in 12-month follow-up. Length of hospital stay and the associated costs were analyzed in both groups of treatment. RESULTS: Twenty-two patients received dalbavancin and 47 SOC. The efficacy was similar between the groups (dalbavancin 18 [72%] vs SOC 44 [94%], P = 0.198). Hospital stay was shorter in the dalbavancin group (dalbavancin 22 days [16-34] vs SOC 37 days [23-49], P = 0.001), especially in those with E. faecalis IE (dalbavancin 30 days [20-36] vs SOC 65 days [46-74], P <0.001). A reduction of cost was observed between both groups (dalbavancin, 12,206 [8998-17,283] vs SOC 16,249 [11,496-22,367], P = 0.032). CONCLUSION: Dalbavancin could be a safe and effective option in the sequential treatment of patients with IE. Also, a cost reduction was detected, due to a significant shortness of hospital stay.
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Endocarditis Bacteriana , Endocarditis , Adulto , Humanos , Antibacterianos/efectos adversos , Estudios de Cohortes , Nivel de Atención , Estudios Retrospectivos , Teicoplanina/efectos adversos , Endocarditis Bacteriana/tratamiento farmacológico , Endocarditis/tratamiento farmacológico , Costos y Análisis de CostoRESUMEN
Cardiac Magnetic Resonance (CMR) Imaging is currently considered the gold standard imaging modality in cardiology. However, it is accompanied by a tradeoff between spatial resolution and acquisition time. Providing accurate measures of thin walls relative to the image resolution may prove challenging. One such anatomical structure is the cardiac right ventricle. Methods for measuring thickness of wall-like anatomical structures often rely on the Laplace equation to provide point-to-point correspondences between both boundaries. This work presents limex, a novel method to solve the Laplace equation using ghost nodes and providing extrapolated values, which is tested on three different datasets: a mathematical phantom, a set of biventricular segmentations from CMR images of ten pigs and the database used at the RV Segmentation Challenge held at MICCAI'12. Thickness measurements using the proposed methodology are more accurate than state-of-the-art methods, especially with the coarsest image resolutions, yielding mean L1 norms of the error between 43.28% and 86.52% lower than the second-best methods on the different test datasets. It is also computationally affordable. Limex has outperformed other state-of-the-art methods in classifying RV myocardial segments by their thickness.
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Ventrículos Cardíacos , Imagen por Resonancia Cinemagnética , Animales , Porcinos , Imagen por Resonancia Cinemagnética/métodos , Corazón , Imagen por Resonancia Magnética , MiocardioRESUMEN
OBJECTIVES: The early initiation of the empirical antibiotic treatment and its impact on mortality in patients with bacteraemia has been extensively studied. However, information on the impact of precocity of the targeted antibiotic treatment is scarce. We aimed to study the impact of further delay in active antibiotic therapy on 30-day mortality among patients with bloodstream infection who had not received appropriate empirical therapy. DESIGN: We worked with PROBAC cohort (prospective and compound by patients from 26 different Spanish hospitals). We selected a total of 1703 patients, who survived to day 2 without having received any active antibiotic therapy against the causative pathogen. RESULTS: The 30-day mortality was 14% (238 patients). The adjusted odds of mortality increased for every day of delay, from 1.53 (95% confidence interval (CI) 1.13-2.08) for day 3 or after to 11.38 (95% CI 7.95-16.38) for day 6 or after. CONCLUSION: We concluded that among patients who had not received active treatment within the first 2 days of blood culture collection, additional delays in active targeted therapy were associated with increased mortality. These results emphasize the importance of active interventions in the management of patients with bloodstream infections.
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Antibacterianos , Bacteriemia , Humanos , Bacteriemia/tratamiento farmacológico , Bacteriemia/mortalidad , Bacteriemia/microbiología , Antibacterianos/uso terapéutico , Masculino , Femenino , Estudios Prospectivos , Anciano , Persona de Mediana Edad , España/epidemiología , Tiempo de Tratamiento , Anciano de 80 o más Años , Factores de TiempoRESUMEN
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.
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Bacteriemia , beta-Lactamas , Humanos , beta-Lactamas/efectos adversos , Antibacterianos/efectos adversos , Ceftriaxona , Ertapenem , Bacteriemia/tratamiento farmacológico , Resultado del TratamientoRESUMEN
According to clinical guidelines, the management of catheter-related bloodstream infections (CRBSI) due to coagulase-negative staphylococci (CoNS) includes catheter removal and antibiotic treatment for 5 to 7 days. However, in low-risk episodes, it remains uncertain whether antibiotic therapy is necessary. This randomized clinical trial aims to determine whether the non-administration of antibiotic therapy is as safe and effective as the recommended strategy in low-risk episodes of CRBSI caused by CoNS. With this purpose, a randomized, open-label, multicenter, non-inferiority clinical trial was conducted in 14 Spanish hospitals from 1 July 2019 to 31 January 2022. Patients with low-risk CRBSI caused by CoNS were randomized 1:1 after catheter withdrawal to receive/not receive parenteral antibiotics with activity against the isolated strain. The primary endpoint was the presence of any complication related to bacteremia or to antibiotic therapy within 90 days of follow-up. The secondary endpoints were persistent bacteremia, septic embolism, time until microbiological cure, and time until the disappearance of a fever. EudraCT: 2017-003612-39 INF-BACT-2017. A total of 741 patients were assessed for eligibility. Of these, 27 were included in the study; 15 (55.6%) were randomized to the intervention arm (non-antibiotic administration) and 12 (44.4%) to the control arm (antibiotic therapy as per standard practice). The primary endpoint occurred in one of the 15 patients in the intervention group (septic thrombophlebitis) and in no patients in the control group. The median time until microbiological cure was 3 days (IQR 1-3) in the intervention arm and 1.25 days (IQR 0.5-2.62) in the control arm, while the median time until fever resolution was zero days in both arms. The study was stopped due to the insufficient number of recruited patients. These results seem to indicate that low-risk CRBSI caused by CoNS can be managed without antibiotic therapy after catheter removal; efficacy and safety are not affected.
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In 2012, The Spanish Societies of Infectious Diseases and Clinical Microbiology (SEIMC), Hospital Pharmacy (SEFH), and Preventive Medicine, Public Health and Healthcare Management (SEMPSGS) lead a consensus document including recommendations for the implementation of antimicrobial stewardship (AMS) programs (AMSP; PROA in Spanish) in acute care hospitals in Spain. While these recommendations were critical for the development of these programs in many centres, there is a need for guidance in the development of AMS activities for specific patient populations, syndromes or other specific aspects which were not included in the previous document or have developed significantly since then. The objective of this expert recommendation guidance document is to review the available information about these activities in these patient populations or circumstances, and to provide guidance recommendations about them. With this objective the SEIMC, SEFH, SEMPSPGS, the Spanish Society of Intensive Care Medicine (SEMICYUC) and the Spanish Pediatric Infectious Disease Society (SEIP) selected a panel of experts who chose the different aspects to include in the document. Because of the lack of high-level evidence in the implementation of the activities, the panel opted to perform a narrative review of the literature for the different topics for which recommendations were agreed by consensus. The document was open to public consultation for the members of these societies for their comments and suggestions, which were reviewed and considered by the panel.
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Programas de Optimización del Uso de los Antimicrobianos , Enfermedades Transmisibles , Niño , Humanos , Hospitales , España , Cuidados CríticosRESUMEN
INTRODUCTION: Ceftazidime-avibactam has proven activity against multidrug-resistant (MDR) bacteria in clinical trials and real-world studies. This study was conducted to describe the patterns of use of ceftazidime-avibactam (including indications and associated antibiotics), and the effectiveness and safety of ceftazidime-avibactam in real-world clinical practice. METHODS: This non-interventional medical chart review study was conducted in 11 countries across the European and Latin American (LATAM) regions. Consecutive patients treated in clinical practice with at least one dose of ceftazidime-avibactam for an approved indication per country label since 01 January 2018 (or launch date in the country if posterior) were enrolled. Effectiveness analyses were conducted in patients treated with ceftazidime-avibactam for at least 72 h. RESULTS: Of the 569 eligible patients enrolled, 516 (90.7%) were treated for at least 72 h (354 patients from Europe and 162 patients from LATAM); 390 patients (75.7%) had switched from another antibiotic line for Gram-negative coverage. Infection sources were intra-abdominal, urinary, respiratory, bloodstream infections, and other infections (approximately 20% each). K. pneumoniae was the most common microorganism identified in the latest microbiological evaluation before starting ceftazidime-avibactam (59.3%). Two-thirds of microorganisms tested for susceptibility were MDR, of which 89.3% were carbapenem-resistant. The common MDR mechanisms for K. pneumoniae were carbapenemase (33.9%), oxacillinase 48 (25.2%), extended-spectrum beta-lactamase (21.5%), or metallo-beta-lactamase (14.2%) production. Without prior patient exposure, 17 isolates (mostly K. pneumoniae) were resistant to ceftazidime-avibactam. Treatment success was achieved in 77.3% of patients overall (88.3% among patients with urinary infection), regardless of first or second treatment line. In-hospital mortality rate was 23.1%. Adverse events were reported for six of the 569 patients enrolled. CONCLUSION: This study provides important real-world evidence on treatment patterns, effectiveness, and safety of ceftazidime-avibactam in clinical practice through its recruitment in the European and LATAM regions. Ceftazidime-avibactam is one of the antibiotics to consider for treatment of MDR bacteria. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03923426.
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It is not known whether sequential outpatient parenteral antimicrobial (OPAT) is as safe and effective as conventional hospitalization in patients with S. aureus bacteremia (SAB). A post-hoc analysis of the comparative effectiveness of conventional hospitalization versus sequential OPAT was performed in two prospective Spanish cohorts of patients with S. aureus bacteremia. The PROBAC cohort is a national, multicenter, prospective observational cohort of patients diagnosed in 22 Spanish hospitals between October 2016 and March 2017. The DOMUS OPAT cohort is a prospective observational cohort including patients from two university hospitals in Seville, Spain from 2012 to 2021. Multivariate regression was performed, including a propensity score (PS) for receiving OPAT, stratified analysis according to PS quartiles, and matched pair analyses based on PS. Four hundred and thirteen patients were included in the analysis: 150 in sequential OPAT and 263 in the full hospitalization therapy group. In multivariate analysis, including PS and center effect as covariates, 60-day treatment failure was lower in the OPAT group than in the full hospitalization group (p < 0.001; OR 0.275, 95%CI 0.129−0.584). In the PS-based matched analyses, sequential treatment under OPAT was not associated with higher 60-day treatment failure (p = 0.253; adjusted OR 0.660; % CI 0.324−1.345). OPAT is a safe and effective alternative to conventional in-patient therapy for completion of treatment in well-selected patients with SAB, mainly those associated with a low-risk source and without end-stage kidney disease.
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BACKGROUND: Infections of cardiovascular implantable electronic devices (CIED) are mainly due to Gram-positive bacteria (GPB). Data about Gram-negative bacteria CIED (GNB-CIED) infections are limited. This study aimed to investigate risk factors, clinical and diagnostic characteristics, and outcome of patients with GNB-CIED. METHODS: A multicentre, international, retrospective, case-control-control study was performed on patients undergoing CIED implantation from 2015 to 2019 in 17 centres across Europe. For each patient diagnosed with GNB-CIED, one matching control with GPB-CIED infection and two matching controls without infection were selected. RESULTS: A total of 236 patients were enrolled: 59 with GNB-CIED infection, 59 with GPB-CIED infection and 118 without infection. No between-group differences were found regarding clinical presentation, diagnostic and therapeutic management. A trend toward a higher rate of fluorodeoxyglucose positron emission computed tomography (FDG PET/CT) positivity was observed among patients with GNB than in those with GPB-CIED infection (85.7% vs. 66.7%; P = 0.208). Risk factors for GNB-CIED infection were Charlson Comorbidity Index Score (relative risk reduction, RRR = 1.211; P = 0.011), obesity (RRR = 5.122; P = 0.008), ventricular-pacing ventricular-sensing inhibited-response pacemaker implantation (RRR = 3.027; P = 0.006) and right subclavian vein site of implantation (RRR = 5.014; P = 0.004). At 180-day survival analysis, GNB-CIED infection was associated with increased mortality risk (HR = 1.842; P = 0.067). CONCLUSIONS: Obesity, high number of comorbidities and right subclavian vein implantation site were associated with increased risk of GNB-CIED infection. A prompt therapeutic intervention that may be guided using FDG PET/CT is suggested in patients with GNB-CIED infection, considering the poorer outcome observed in this group.