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.

Dalbavancin as suppressive antibiotic therapy in patients with prosthetic infections: efficacy and safety.

Suppressive antibiotic therapy (SAT) is a strategy to alleviate symptoms and/or to reduce the progression of an infection when other treatment options cannot be used. Dalbavancin, due to its prolonged half-life, enables (bi) weekly dosing. Here, we report our multicenter real-life clinical experience with dalbavancin used as SAT in patients with prosthetic joint or vascular infections. Medical records of all adult patients with documented vascular or orthopedic chronic prosthetic infections, who received dalbavancin as SAT between 2016 and 2018 from four Spanish hospitals were reviewed for inclusion. Descriptive analysis of demographic characteristics, Charlson Comorbidity index, Barthel index, isolated pathogens and indication, concomitant antibiotic use, adverse events, and clinical outcome of SAT were performed. Eight patients were eligible for inclusion, where six patients had prosthetic vascular infections (aortic valve) and two patients had knee prosthetic joint infections. The most common pathogens were methicillin-susceptible Staphylococcus aureus and Enterococcus faecium. All patients had a history of prior antibiotic treatment for the prosthetic infection [median duration of antibiotic days 125 days (IQR, 28-203 days)]. The median number of dalbavancin doses was 29 (IQR, 9-61) and concomitant antibiotic use (n = 5, 62.5%). Clinical success was reported in 75% (n = 6) of patients. Adverse events were reported in two patients (mild renal and hepatic impairment). The median estimated cost savings due to the avoided hospital days was €60185 (IQR, 19,916-94984) per patient. Despite the limitations of our study, this preliminary data provides valuable insight to support further evaluation of dalbavancin for SAT in patients with prosthetic infections in the outpatient setting when alternative treatments are not feasible.

EN-DALBACEN 2.0 Cohort: real-life study of dalbavancin as sequential/consolidation therapy in patients with infective endocarditis due to Gram-positive cocci.

OBJECTIVES: Infective endocarditis (IE) has high mortality and morbidity and requires long hospital stays to deliver the antibiotic treatment recommended in clinical practice guidelines. We aimed to analyse the health outcomes of the use of dalbavancin (DBV) in the consolidation treatment of IEs caused by Gram-positive cocci and to perform a pharmacoeconomic study. MATERIALS AND METHODS: This observational, retrospective, Spanish multicentre study in patients with IE who received DBV as part of antibiotic treatment in consolidation phase were followed for at least 12 months. The study was approved by the Provincial Committee of the coordinating centre. RESULTS: The study included 124 subjects, 70.2% male, with a mean age of 67.4 years and median Charlson index of 4 (interquartile range: 2.5-6). Criteria for definite IE were met by 91.1%. Coagulase-negative staphylococci (38.8%), Staphylococcus aureus (22.6%), Enterococcus faecalis (19.4%), and Streptococcus Spp. (9.7%) were isolated more frequently, all susceptible to vancomycin. Before DVB administration, 91.2% had undergone surgery; 60.5% had received a second regimen for 24.5 d (16.6-56); and 20.2% had received a third regimen for 14.5 d (12-19.5). DBV was administered to facilitate discharge in 95.2% of cases. At 12 months, the effectiveness was of 95.9%, and there was 0.8% loss to follow-up, 0.8% IE-related death, and 3.2% relapse. Adverse events were recorded in 3.2%. The hospital stay was reduced by 14 d, and there was a mean savings of 5548.57 €/patient vs. conventional treatments. CONCLUSION: DBV is highly effective, safe, and cost-effective as consolidation therapy in patients with IE by Gram-positive cocci, with few adverse events.

Role of IP-10 to Predict Clinical Progression and Response to IL-6 Blockade With Sarilumab in Early COVID-19 Pneumonia. A Subanalysis of the SARICOR Clinical Trial.

Background: The Clinical Trial of Sarilumab in Adults With COVID-19 (SARICOR) showed that patients with coronavirus disease 2019 (COVID-19) pneumonia and increased levels of interleukin (IL)-6 might benefit from blockade of the IL-6 pathway. However, the benefit from this intervention might not be uniform. In this subanalysis, we sought to determine if other immunoactivation markers, besides IL-6, could identify which subgroup of patients benefit most from this intervention. Methods: The SARICOR trial was a phase II, open-label, multicenter, controlled trial (July 2020-March 2021) in which patients were randomized to receive usual care (UC; control group), UC plus a single dose of sarilumab 200 mg (sarilumab-200 group), or UC plus a single dose of sarilumab 400 mg (sarilumab-400 group). Patients who had baseline serum samples for cytokine determination (IL-8, IL-10, monocyte chemoattractant protein-1, interferon-inducible protein [IP]-10) were included in this secondary analysis. Progression to acute respiratory distress syndrome (ARDS) according to cytokine levels and treatment received was evaluated. Results: One hundred one (88%) of 115 patients enrolled in the SARICOR trial had serum samples (control group: n = 33; sarilumab-200: n = 33; sarilumab-400: n = 35). Among all evaluated biomarkers, IP-10 showed the strongest association with treatment outcome. Patients with IP-10 ≥2500 pg/mL treated with sarilumab-400 had a lower probability of progression (13%) compared with the control group (58%; hazard ratio, 0.19; 95% CI, 0.04-0.90; P = .04). Conversely, patients with IP-10 <2500 pg/mL did not show these differences. Conclusions: IP-10 may predict progression to ARDS in patients with COVID-19 pneumonia and IL-6 levels >40 pg/mL. Importantly, IP-10 value <2500 pg/mL might discriminate those individuals who might not benefit from sarilumab therapy among those with high IL-6 levels.

Antimicrobial resistance in Gram-negative bacilli in Spain: an experts’ view / Resistencia a antimicrobianos en bacilos gramnegativos en España: una visión de expertos

Background: Antibiotic resistance in Gram-negative bacilli poses a serious problem for public health. In hospitals, in addition to high mortality rates, the emergence and spread of resistance to practically all antibiotics restricts therapeutic options against serious and frequent infections. Objectives: The aim of this work is to present the views of a group of experts on the following aspects regarding resistance to antimicrobial agents in Gram-negative bacilli: 1) the current epidemiology in Spain, 2) how it is related to local clinical practice and 3) new therapies in this area, based on currently available evidence. Methodology: After reviewing the most noteworthy evidence, the most relevant data on these three aspects were presented at a national meeting to 99 experts in infectious diseases, clinical microbiology, internal medicine, intensive care medicine, anaesthesiology and hospital pharmacy. Results and conclusions: Subsequent local debates among these experts led to conclusions in this matter, including the opinion that the approval of new antibiotics makes it necessary to train the specialists involved in order to optimise how they use them and improve health outcomes; microbiology laboratories in hospitals must be available throughout a continuous timetable; all antibiotics must be available when needed and it is necessary to learn to use them correctly; and the Antimicrobial Stewardship Programs (ASP) play a key role in quickly allocating the new antibiotics within the guidelines and ensure appropriate use of them. (AU)

Contexto: La resistencia a los antibióticos en bacilos gramnegativos representa un grave problema de salud pública. En el hospital, además de unas elevadas tasas de mortalidad, la aparición y propagación de resistencias a la práctica totalidad de los antibióticos limita las opciones terapéuticas frente a infecciones graves y frecuentes. Objetivos: Este trabajo tiene por objetivo dar a conocer la visión de un grupo de expertos en los siguientes aspectos respecto a la resistencia a agentes antimicrobianos en bacilos gramnegativos: 1) la epidemiología actual en España, 2) su relación con la práctica clínica local y 3) las novedades terapéuticas en este ámbito, fundamentada en la evidencia actualmente disponible. Metodología: Tras la revisión de la evidencia más destacada, los datos más relevantes de estos 3 aspectos fueron presentados en una reunión nacional ante 99 expertos en enfermedades infecciosas, microbiología clínica, medicina interna, medicina intensiva, anestesiología y farmacia hospitalaria. Resultados y conclusiones: De debates locales posteriores entre estos expertos se extrajeron conclusiones al respecto entre las que se destacan que la aprobación de nuevos antibióticos hace necesaria la formación de los especialistas implicados para optimizar su uso y mejorar los resultados en salud; los laboratorios de Microbiología de los hospitales deben estar disponibles en horario continuado; todos los antibióticos deben estar disponibles para cuando sean necesarios y se debe aprender a usarlos de forma correcta; y los Programas de Optimización del Uso de Antimicrobianos (PROA) desempeñan una labor clave en ubicar de forma ágil los nuevos antibióticos en las guías y asegurar un uso apropiado de los mismos. (AU)

Pericardial effusion with pembrolizumab.

INTRODUCTION: The treatment of non-small cell lung cancer (NSCLC) has profoundly changed on account of the arrival of new therapies, like immunotherapy. Within this group of drugs, those aimed at the programmed cell death-1 or programmed cell death ligand-1(PD1/PDL-1) are very relevant, for example, Pembrolizumab. Although its adverse reactions are generally mild and well tolerated, it has been associated with certain immune-related adverse events (IrAEs) than can be serious and affect any organ. CASE REPORT: A 62-year-old woman diagnosed with stage IV NSCLC with a single bone metastasis and PD-L1 expression of 60% started treatment with cisplatin-pemetrexed-pembrolizumab, and maintenance with pembrolizumab. MANAGEMENT AND OUTCOME: The patient attended the ER with pericardial effusion that was assumed to be a Pembrolizumab IrAE and was managed with corticosteroids. The patient fully recovered but immunotherapy was not reintroduced due to the severity of the AE. DISCUSSION: The cardiovascular system is among the least affected organs by immunotoxicity, with an incidence between 0.09-0.6%. However, some authors suspect the incidence is underestimated. Median time to onset is highly variable, ranging from 6 weeks since the first dose to 2 years after discontinuation of the treatment. There are not guidelines on the most effective management of the IrAEs, but according to the pharmaceutical reference, corticosteroids should be initiated followed by a progressive reduction. If no response is obtained, another immunosuppressive agent should be added. The determination to restart immunotherapy depends on the severity of the adverse reaction, the availability of other alternative treatments, and the cancer response.

Successful treatment of Verona integron-encoded metallo-ß-lactamase-producing Klebsiella pneumoniae infection using the combination of ceftazidime/avibactam and aztreonam.

The case of a female who had an accident that caused an open fracture is reported. During hospitalisation, Verona integron-encoded metallo-ß-lactamase (VIM)-producing Klebsiella pneumoniae was isolated. Antimicrobial susceptibility testing revealed resistance to ß-lactam antibiotics, quinolones, trimethoprim/sulfamethoxazole, and susceptibility to tigecycline, colistin, fosfomycin and aminoglycosides. Synergistic activity of ceftazidime-avibactam and aztreonam was proved in vitro and a combined therapy with tigecycline was started. Combination with aminoglycosides was ruled out as it was not described in the literature and also in order to avoid side effects. Colistin was rejected because of its nephrotoxicity profile. The antibiotic treatment was assessed by a multidisciplinary team with a pharmacist who closely monitored adverse effects and interactions with other drugs. The total duration of this combination was 25 days, without any adverse events reported. Fourteen weeks after the accident the patient was discharged. After 2 months of follow-up neither relapses nor reinfections have been reported.

Early Use of Sarilumab in Patients Hospitalized with COVID-19 Pneumonia and Features of Systemic Inflammation: the SARICOR Randomized Clinical Trial.

The objective of this study was to investigate the efficacy and safety of early treatment with sarilumab, added to standard of care (SOC), in hospitalized adults with COVID-19. Methods included phase II, open-label, randomized, controlled clinical trial of hospitalized patients with COVID-19 pneumonia and interleukin (IL)-6 levels ≥ 40 pg/mL and/or d-dimer > 1,500 ng/mL. Participants were randomized (1:1:1) to receive SOC (control group), SOC plus a single subcutaneous dose of sarilumab 200 mg (sarilumab-200 group), or SOC plus a single subcutaneous dose of sarilumab 400 mg (sarilumab-400 group). The primary outcome variable was the development of acute respiratory distress syndrome (ARDS) requiring high-flow nasal oxygenation (HFNO), non-invasive mechanical ventilation (NIMV) or invasive mechanical ventilation (IMV) at day 28. One-hundred and 15 participants (control group, n = 39; sarilumab-200, n = 37; sarilumab-400, n = 39) were included. At randomization, 104 (90%) patients had supplemental oxygen and 103 (90%) received corticosteroids. Eleven (28%) patients in the control group, 10 (27%) in sarilumab-200, and five (13%) in sarilumab-400 developed the primary outcome (hazard ratio [95% CI] of sarilumab-400 vs control group: 0.41 [0.14, 1.18]; P = 0.09). Seven (6%) patients died: three in the control group and four in sarilumab-200. There were no deaths in sarilumab-400 (P = 0.079, log-rank test for comparisons with the control group). In patients recently hospitalized with COVID-19 pneumonia and features of systemic inflammation, early IL-6 blockade with a single dose of sarilumab 400 mg was safe and associated with a trend for better outcomes. (This study has been registered at ClinicalTrials.gov under identifier NCT04357860.).

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

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

Admission hyperglycaemia as a predictor of mortality in patients hospitalized with COVID-19 regardless of diabetes status: data from the Spanish SEMI-COVID-19 Registry.

BACKGROUND: Hyperglycaemia has emerged as an important risk factor for death in coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the association between blood glucose (BG) levels and in-hospital mortality in non-critically patients hospitalized with COVID-19. METHODS: This is a retrospective multi-centre study involving patients hospitalized in Spain. Patients were categorized into three groups according to admission BG levels: <140 mg/dL, 140-180 mg/dL and >180 mg/dL. The primary endpoint was all-cause in-hospital mortality. RESULTS: Of the 11,312 patients, only 2128 (18.9%) had diabetes and 2289 (20.4%) died during hospitalization. The in-hospital mortality rates were 15.7% (<140 mg/dL), 33.7% (140-180 mg) and 41.1% (>180 mg/dL), p<.001. The cumulative probability of mortality was significantly higher in patients with hyperglycaemia compared to patients with normoglycaemia (log rank, p<.001), independently of pre-existing diabetes. Hyperglycaemia (after adjusting for age, diabetes, hypertension and other confounding factors) was an independent risk factor of mortality (BG >180 mg/dL: HR 1.50; 95% confidence interval (CI): 1.31-1.73) (BG 140-180 mg/dL; HR 1.48; 95%CI: 1.29-1.70). Hyperglycaemia was also associated with requirement for mechanical ventilation, intensive care unit (ICU) admission and mortality. CONCLUSIONS: Admission hyperglycaemia is a strong predictor of all-cause mortality in non-critically hospitalized COVID-19 patients regardless of prior history of diabetes. KEY MESSAGE Admission hyperglycaemia is a stronger and independent risk factor for mortality in COVID-19. Screening for hyperglycaemia, in patients without diabetes, and early treatment of hyperglycaemia should be mandatory in the management of patients hospitalized with COVID-19. Admission hyperglycaemia should not be overlooked in all patients regardless prior history of diabetes.

Dalbavancina combinada con linezolid en infección protésica de cadera / Dalbavancin combined with linezolid in prosthetic-hip infection

No disponible

Clinical and prognostic differences between methicillin-resistant and methicillin-susceptible Staphylococcus aureus infective endocarditis.

BACKGROUND: S. aureus (SA) infective endocarditis (IE) has a very high mortality, attributed to the age and comorbidities of patients, inadequate or delayed antibiotic treatment, and methicillin resistance, among other causes. The main study objective was to analyze epidemiological and clinical differences between IE by methicillin-resistant versus methicillin-susceptible SA (MRSA vs. MSSA) and to examine prognostic factors for SA endocarditis, including methicillin resistance and vancomycin minimum inhibitory concentration (MIC) values > 1 µg/mL to MRSA. METHODS: Patients with SA endocarditis were consecutively and prospectively recruited from the Andalusia endocarditis cohort between 1984 and January 2017. RESULTS: We studied 437 patients with SA endocarditis, which was MRSA in 13.5% of cases. A greater likelihood of history of COPD (OR 3.19; 95% CI 1.41-7.23), invasive procedures, or recognized infection focus in the 3 months before IE onset (OR 2.9; 95% CI 1.14-7.65) and of diagnostic delay (OR 3.94; 95% CI 1.64-9.5) was observed in patients with MRSA versus MSSA endocarditis. The one-year mortality rate due to SA endocarditis was 44.3% and associated with decade of endocarditis onset (1985-1999) (OR 8.391; 95% CI (2.82-24.9); 2000-2009 (OR 6.4; 95% CI 2.92-14.06); active neoplasm (OR 6.63; 95% CI 1.7-25.5) and sepsis (OR 2.28; 95% CI 1.053-4.9). Methicillin resistance was not associated with higher IE-related mortality (49.7 vs. 43.1%; p = 0.32). CONCLUSION: MRSA IE is associated with COPD, previous invasive procedure or recognized infection focus, and nosocomial or healthcare-related origin. Methicillin resistance does not appear to be a decisive prognostic factor for SA IE.

DALBACEN cohort: dalbavancin as consolidation therapy in patients with endocarditis and/or bloodstream infection produced by gram-positive cocci.

OBJECTIVES: To analyse the effectiveness of dalbavancin (DBV) in clinical practice as consolidation therapy in patients with bloodstream infection (BSI) and/or infective endocarditis (IE) produced by gram-positive cocci (GPC), as well as its safety and pharmacoeconomic impact. METHODS: A multicentre, observational and retrospective study was conducted of hospitalised patients with IE and/or BSI produced by GPC who received at least one dose of DBV. Clinical response was assessed during hospitalization, at 3 months and at 1 year. RESULTS: Eighty-three patients with median age of 73 years were enrolled; 73.5% were male; 59.04% had BSI and 49.04% IE (44.04% prosthetic valve IE, 32.4% native IE, 23.5% pacemaker lead). The most frequently isolated microorganism was Staphylococcus aureus in BSI (49%) and coagulase-negative staphylococci in IE (44.1%). All patients with IE were clinically cured in hospital; at 12 months, there was 2.9% loss to follow-up, 8.8% mortality unrelated to IE, and 2.9% therapeutic failure rate. The percentage effectiveness of DBV to treat IE was 96.7%. The clinical cure rate for BSI was 100% during hospital stay and at 3 months; there were no recurrences or deaths during the follow-up. No patient discontinued treatment for adverse events. The saving in hospital stay was 636 days for BSI (315,424.20€) and 557 days for IE (283,187.45€). CONCLUSIONS: DBV is an effective consolidation antibiotic therapy in clinically stabilized patients with IE and/or BSI. It proved to be a cost-effective treatment, reducing the hospital stay, thanks to the pharmacokinetic/pharmacodynamic profile of this drug.