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Objectives: We describe the current epidemiology, causes, and outcomes of breakthrough invasive fungal infections (BtIFI) in patients with haematologic malignancies. Methods: BtIFI in patients with ≥ 7 days of prior antifungals were prospectively diagnosed (36 months across 13 Spanish hospitals) according to revised EORTC/MSG definitions. Results: 121 episodes of BtIFI were documented, of which 41 (33.9%) were proven; 53 (43.8%), probable; and 27 (22.3%), possible. The most frequent prior antifungals included posaconazole (32.2%), echinocandins (28.9%) and fluconazole (24.8%)-mainly for primary prophylaxis (81%). The most common haematologic malignancy was acute leukaemia (64.5%), and 59 (48.8%) patients had undergone a hematopoietic stem-cell transplantation. Invasive aspergillosis, principally caused by non-fumigatus Aspergillus, was the most frequent BtIFI with 55 (45.5%) episodes recorded, followed by candidemia (23, 19%), mucormycosis (7, 5.8%), other moulds (6, 5%) and other yeasts (5, 4.1%). Azole resistance/non-susceptibility was commonly found. Prior antifungal therapy widely determined BtIFI epidemiology. The most common cause of BtIFI in proven and probable cases was the lack of activity of the prior antifungal (63, 67.0%). At diagnosis, antifungal therapy was mostly changed (90.9%), mainly to liposomal amphotericin-B (48.8%). Overall, 100-day mortality was 47.1%; BtIFI was either the cause or an essential contributing factor to death in 61.4% of cases. Conclusions: BtIFI are mainly caused by non-fumigatus Aspergillus, non-albicans Candida, Mucorales and other rare species of mould and yeast. Prior antifungals determine the epidemiology of BtIFI. The exceedingly high mortality due to BtIFI warrants an aggressive diagnostic approach and early initiation of broad-spectrum antifungals different than those previously used. This work was funded by a grant from Gilead Sciences. P.P.-A. (JR20/00012, PI21/00498, and ICI21/00103) and C.G.-V. (FIS PI21/01640 and ICI21/00103) have received research grants funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union. The funders had neither a specific role in study design or collection of data, nor in writing of the paper or decision to submit. Sí

Background Risk factors for nontuberculous mycobacteria (NTM) infections after solid organ transplant (SOT) are not well characterized. Here we aimed to describe these factors. Methods Retrospective, multinational, 1:2 matched case-control study that included SOT recipients ≥12 years old diagnosed with NTM infection from 1 January 2008 to 31 December 2018. Controls were matched on transplanted organ, NTM treatment center, and post-transplant survival greater than or equal to the time to NTM diagnosis. Logistic regression on matched pairs was used to assess associations between risk factors and NTM infections. Results Analyses included 85 cases and 169 controls (59% male, 88% White, median age at time of SOT of 54 years [interquartile range {IQR} 40–62]). NTM infection occurred in kidney (42%), lung (35%), heart and liver (11% each), and pancreas transplant recipients (1%). Median time from transplant to infection was 21.6 months (IQR 5.3–55.2). Most underlying comorbidities were evenly distributed between groups; however, cases were older at the time of NTM diagnosis, more frequently on systemic corticosteroids and had a lower lymphocyte count (all P < .05). In the multivariable model, older age at transplant (adjusted odds ratio [aOR] 1.04; 95 confidence interval [CI], 1.01–1.07), hospital admission within 90 days (aOR, 3.14; 95% CI, 1.41–6.98), receipt of antifungals (aOR, 5.35; 95% CI, 1.7–16.91), and lymphocyte-specific antibodies (aOR, 7.73; 95% CI, 1.07–56.14), were associated with NTM infection. Conclusions Risk of NTM infection in SOT recipients was associated with older age at SOT, prior hospital admission, receipt of antifungals or lymphocyte-specific antibodies. NTM infection should be considered in SOT patients with these risk factors.

The COVID-19 pandemic has brought up a new host for fungal invasive infections [...]

Patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we describe and analyze the outcome of 366 adult patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between February 2020 and January 2022. Median follow-up was 70.5 days (IQR 0-609). Most used targeted drugs were Bruton-kinase inhibitors (BKIs) (N= 201, 55%), anti-CD20 other than rituximab (N=61, 16%), BCL2 inhibitors (N=33, 9%) and lenalidomide (N=28, 8%).Only 16.2% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Mortality was 24% (89/366) on day 30 and 36%(134/366) on the last day of follow-up. Age >75 years (p, EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).

We aimed to evaluate the clinical outcome of Systemic Autoimmune Diseases (SADs) patients hospitalized with COVID-19 in Spain, before the introduction of SARS-CoV-2 vaccines. A nationwide, retrospective and observational analysis of the patients admitted during 2020, based on the ICD10 codes in the National Registry of Hospital Discharges, was performed. Among 117,694 patients, only 892 (0.8%) presented any type of SAD before COVID-19-related admission: Sjogren’s Syndrome constituted 25%, Systemic Vasculitides 21%, Systemic Lupus Erythematosus 19%, Sarcoidosis 17%, Systemic Sclerosis 11%, Mixed and Undifferentiated Connective Tissue Disease 4%, Behçet’s Disease 4% and Inflammatory Myopathies 2%. The in-hospital mortality rate was higher in SAD individuals (20% vs. 16%, p < 0.001). After adjustment by baseline conditions, SADs were not associated with a higher mortality risk (OR = 0.93, 95% CI 0.78–1.11). Mortality in the SADs patients was determined by age (OR = 1.05, 95% CI 1.04–1.07), heart failure (OR = 1.67, 95% CI 1.10–2.49), chronic kidney disease (OR = 1.29, 95% CI 1.05–1.59) and liver disease (OR = 1.97, 95% CI 1.13–3.44). In conclusion, the higher COVID-19 mortality rate seen in SADs patients hospitalized in Spain in 2020 was related to the higher burden of comorbidities, secondary to direct organ damage and sequelae of their condition. Whilst further studies should evaluate the impact of baseline immunosuppression on COVID-19 outcomes in this population, efforts should be focused on the optimal management of SAD to minimize the impact of the organ damage that has been shown to determine COVID-19 prognosis., This research was funded by Sociedad Española de Medicina Interna and Instituto de Salud Carlos III (Expedient Number CM19/00223)

Las infecciones por bacilos gramnegativos multirresistentes son frecuentes y con elevada morbimortalidad, siendo importante reconocer a aquellos pacientes con riesgo alto. Su manejo es complejo y ha presenciado en los últimos años novedades importantes. Entre ellas, encontramos el uso de nuevos antibióticos, como ceftolozano/tazobactam o ceftazidima/avibactam. Presentamos un caso de varón de 50 años, con trasplante hepático reciente, que ingresó por una neumonía por Klebsiella pneumoniae multirresistente, incluyendo resistencia a carbapenémicos.

In 2013–2014, an outbreak involving 14 patients infected by an extensively drug-resistant strain of Pseudomonas aeruginosa was detected in a hospital in Madrid, Spain. Our objective was to evaluate an alternative strategy for investigating the outbreak in depth by means of molecular and genomic approaches. Pulsed-field gel electrophoresis (PFGE) was applied as a first-line approach, followed by a more refined whole genome sequencing analysis. Single nucleotide polymorphisms identified by whole genome sequencing were used to design a specific polymerase chain reaction (PCR) for screening unsuspected cases infected by the outbreak strain. Whole genome sequencing alerted us to the existence of greater genetic diversity than was initially assumed, splitting the PFGE-associated outbreak isolates into 4 groups, 2 of which represented coincidental transmission unrelated to the outbreak. A multiplex allele-specific PCR targeting outbreak-specific single nucleotide polymorphisms was applied to 290 isolates, which allowed us to identify 25 additional cases related to the outbreak during 2011–2017. Whole genome sequencing coupled with an outbreak-strain-specific PCR enabled us to markedly redefine the initial picture of the outbreak by 1) ruling out initially suspected cases, 2) defining likely independent coincidental transmission events, 3) predating the starting point of the outbreak, 4) capturing new unsuspected cases, and 5) revealing that the outbreak was still active.

Pseudomonas aeruginosa; Bacteremia; Neutropenia Pseudomonas aeruginosa; Bacteriemia; Neutropenia Pseudomonas aeruginosa; Bacterièmia; Neutropènia We sought to assess the characteristics and outcomes of neutropenic hematologic patients with Pseudomonas aeruginosa (PA) bloodstream infection (BSI) treated with ceftolozane-tazobactam (C/T). We conducted a multicenter, international, matched-cohort study of PA BSI episodes in neutropenic hematologic patients who received C/T. Controls were patients with PA BSI treated with other antibiotics. Risk factors for overall 7-day and 30-day case fatality rates were analyzed. We compared 44 cases with 88 controls. Overall, 91% of episodes were caused by multidrug-resistant (MDR) strains. An endogenous source was the most frequent BSI origin (35.6%), followed by pneumonia (25.8%). There were no significant differences in patient characteristics between groups. C/T was given empirically in 11 patients and as definitive therapy in 41 patients. Treatment with C/T was associated with less need for mechanical ventilation (13.6% versus 33.3%; P = 0.021) and reduced 7-day (6.8% versus 34.1%; P = 0.001) and 30-day (22.7% versus 48.9%; P = 0.005) mortality. In the multivariate analysis, pneumonia, profound neutropenia, and persistent BSI were independent risk factors for 30-day mortality, whereas lower mortality was found among patients treated with C/T (adjusted OR [aOR] of 0.19; confidence interval [CI] 95% of 0.07 to 0.55; P = 0.002). Therapy with C/T was associated with less need for mechanical ventilation and reduced 7-day and 30-day case fatality rates compared to alternative agents in neutropenic hematologic patients with PA BSI. IMPORTANCE Ceftolozane-tazobactam (C/T) has been shown to be a safe and effective alternative for the treatment of difficult to treat infections due to Pseudomonas aeruginosa (PA) in the general nonimmunocompromised population. However, the experience of this agent in immunosuppressed neutropenic patients is very limited. Our study is unique because it is focused on extremely immunosuppressed hematological patients with neutropenia and bloodstream infection (BSI) due to PA (mainly multidrug resistant [MDR]), a scenario which is often associated with very high mortality rates. In our study, we found that the use of C/T for the treatment of MDR PA BSI in hematological neutropenic patients was significantly associated with improved outcomes, and, in addition, it was found to be an independent risk factor associated with increased survival. To date, this is the largest series involving neutropenic hematologic patients with PA BSI treated with C/T. This study was supported by the Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), (CB21/13/00009), Madrid, Spain. The study was partially funded by the MSD Investigator Initiated Studies Program. The company declares no contributions toward the design and interpretation of the results of the study.

Severely ill COVID-19 patients are at high risk of nosocomial infections. The aim of the study was to describe the characteristics of candidemia during the pre-pandemic period (January 2019–February 2020) compared to the pandemic period (March 2020–September 2021). Antifungal susceptibilities were assessed using the EUCAST E.Def 7.3.2 broth dilution method. Fluconazole-resistant C. parapsilosis isolates (FRCP) were studied for sequencing of the ERG11 gene. The incidence of candidemia and C. parapsilosis bloodstream infection increased significantly in the pandemic period (p = 0.021). ICU admission, mechanical ventilation, parenteral nutrition and corticosteroids administration were more frequent in patients with candidemia who had been admitted due to COVID-19. Fifteen cases of FRCP fungemia were detected. The first case was recorded 10 months before the pandemic in a patient transferred from another hospital. The incidence of FRCP in patients admitted for COVID-19 was 1.34 and 0.16 in all other patients (p < 0.001). ICU admission, previous Candida spp. colonization, arterial catheter use, parenteral nutrition and renal function replacement therapy were more frequent in patients with candidemia due to FRCP. All FRCP isolates showed the Y132F mutation. In conclusion, the incidence of candidemia experienced an increase during the COVID-19 pandemic and FRCP fungemia was more frequent in patients admitted due to COVID-19.

Introduction: Cytomegalovirus (CMV) infection is a well-known factor associated with invasive aspergillosis in immunocompromised hosts. However, its association with COVID-19-associated pulmonary aspergillosis (CAPA) has not been described. We aimed to examine the possible link between CMV replication and CAPA occurrence. Methods: A single-center, retrospective case–control study was conducted. A case was defined as a patient diagnosed with CAPA according to 2020 ECMM/ISHAM consensus criteria. Two controls were selected for each case among critically ill COVID-19 patients. Results: In total, 24 CAPA cases were included, comprising 14 possible CAPA and 10 probable CAPA. Additionally, 48 matched controls were selected. CMV replication was detected more frequently in CAPA than in controls (75.0% vs. 35.4%, p = 0.002). Probable CMV end-organ disease was more prevalent in CAPA (20.8% vs. 4.2%, p = 0.037). After adjusting for possible confounding factors, CMV replication persisted strongly associated with CAPA (OR 8.28 95% CI 1.90–36.13, p = 0.005). Among 11 CAPA cases with CMV PCR available prior to CAPA, in 9 (81.8%) cases, CMV replication was observed prior to CAPA diagnosis. Conclusions: Among critically ill COVID-19 patients, CMV replication was associated with CAPA and could potentially be considered a harbinger of CAPA. Further studies are needed to confirm this association.

Red blood cell distribution width (RDW) could reflect interleukin-6 (IL-6) systemic activity since anisocytosis represents the inhibition of erythropoiesis, leaded by the hyperinflammatory background. Our objective was to analyze RDW performance to predict outcome in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS).Retrospective observational study including 173 patients with COVID-19-associated ARDS. Data was analyzed at hospital admission, inclusion in the TOCICOV Study (day 0), days 1, 3, 7 and 15 post-inclusion.Overall, 57% patients received tocilizumab. Overall mortality was 20.8%. RDW was higher in non-survivors compared to survivors at admission (13.53% vs. 14.35, P=0.0016), day 0 (13.60% vs. 14.42, P=0.026), day 3 (13.43% vs. 14.36, P0.001) and day 7 (13.41% vs. 14.31, P=0.046), presenting better discrimination ability for mortality than other prognostic markers [area under the curve-receiver operating characteristic (AUC-ROC) =0.668 for admission RDW, 0.680 for day 0 RDW, 0.695 for day 3 RDW and 0.666 for day 7 RDW]. RDW values did not vary significantly according to tocilizumab treatment. When adjusted by hemoglobin and tocilizumab treatment, only RDW at admission, day 0, day 3 and C reactive protein (CRP) at day 0 and day 1 were associated with mortality (P0.05). Only in non-tocilizumab treated patients, IL-6 levels at day 0 were correlated with day 3 RDW (r=0.733, P=0.004) and with day 3 CRP (r=0.727, P=0.022). Both parameters showed significant statistical correlation (r=0.255 for day 1 RDW and CRP in the overall cohort and r=0.358 for day 3 RDW and CRP in patients not treated with tocilizumab, P0.015).RDW predicts COVID-19-associated ARDS mortality and reflects the hyperinflammatory background and the effects of cytokines such as IL-6, irrespective of tocilizumab treatment.

It is unclear whether the use of clinical prediction rules is sufficient to rule out infective endocarditis (IE) in patients withWe conducted a unicentric retrospective cohort including all patients with a first SAB episode from January 2015 to December 2020. IE was defined according to modified Duke criteria. We predefined threshold cutoff points to consider that IE was ruled out by means of the mentioned scores. To assess 30-day mortality, we used a multivariable regression model considering performing an echocardiogram as covariate.Out of 404 patients, IE was diagnosed in 50 (12.4%). Prevalence of IE within patients with negative PREDICT, POSITIVE, and VIRSTA scores was: 3.6% (95% CI 0.1-6.9%), 4.9% (95% CI 2.2-7.7%), and 2.2% (95% CI 0.2-4.3%), respectively. Patients with negative VIRSTA and negative TTE had an IE prevalence of 0.9% (95% CI 0-2.8%). Performing an echocardiogram was independently associated with lower 30-day mortality (OR 0.24 95% CI 0.10-0.54,PREDICT and POSITIVE scores were not sufficient to rule out IE without TEE. In patients with negative VIRSTA score, it was doubtful if IE could be discarded with a negative TTE. Not performing an echocardiogram was associated with worse outcomes, which might be related to presence of occult IE. Further studies are needed to assess the usefulness of clinical prediction rules in avoiding echocardiographic evaluation in SAB patients.

(1) To describe the incidence, clinical characteristics, treatment and outcome of Aspergillus Endocarditis (AE) in a nationwide multicentric cohort (GAMES). (2) To compare the AE cases of the GAMES cohort, with the AE cases reported in the literature since 2010. (3) To identify variables related to mortality.We recruited 10 AE cases included in the GAMES cohort (January 2008-December 2018) and 51 cases from the literature published from January 2010 to July 2019.4528 patients with infectious endocarditis (IE) were included in the GAMES cohort, of them 10 (0.2%) were AE. After comparing our 10 cases with the 51 of the literature, no differences were found. Analysing the 61 AE cases together, 55.7% were male, median age 45 years. Their main underlying conditions were as follows: prosthetic valve surgery (34.4%) and solid organ transplant (SOT) (19.7%). Mainly affecting mitral (36.1%) and aortic valve (29.5%). Main isolated species were as follows: Aspergillus fumigatus (47.5%) and Aspergillus flavus (24.6%). Embolisms occurred in 54%. Patients were treated with antifungals (90.2%), heart surgery (85.2%) or both (78.7%). Overall, 52.5% died. A greater mortality was observed in immunosuppressed patients (59.4% vs. 24.1%, OR = 4.09, 95%CI = 1.26-13.19, p = .02), and lower mortality was associated with undergoing cardiac surgery plus azole therapy (28.1% vs. 65.5%, OR = 0.22, 95%CI = 0.07-0.72, p = .01).AE accounts for 0.2% of all IE episodes of a national multicentric cohort, mainly affecting patients with previous valvular surgery or SOT recipients. Mortality remains high especially in immunosuppressed hosts and azole-based treatment combined with surgical resection are related to a better outcome.

Objective: We aim to describe the safety and efficacy of sotrovimab in severe cases of COVID-19 in immunocompromised hosts. Methods: We used a retrospective multicenter cohort including immunocompromised hospitalized patients with severe COVID-19 treated with sotrovimab between October 2021 and December 2021. Results: We included 32 patients. The main immunocompromising conditions were solid organ transplantation (46.9%) and hematological malignancy (37.5%). Seven patients (21.9%) had respiratory progression: 12.5% died and 9.4% required mechanical ventilation. Patients treated within the first 14 days of their symptoms had a lower progression rate: 12.0% vs. 57.1%, p = 0.029. No adverse event was attributed to sotrovimab. Conclusions: Sotrovimab was safe and may be effective in its use for immunocompromised patients with severe COVID-19. More studies are needed to confirm these preliminary data.

Purpose: To analyze the influence of adding gentamicin to a regimen consisting of β-lactam or vancomycin plus rifampicin on survival in patients suffering from Staphylococcal prosthetic valve endocarditis (SPVE). Methods: From January 2008 to September 2016, 334 patients with definite SPVE were attended in the participating hospitals. Ninety-four patients (28.1%) received treatment based on β-lactam or vancomycin plus rifampicin and were included in the study. Variables were analyzed which related to patient survival during admission, including having received treatment with gentamicin. Results: Seventy-seven (81.9%) were treated with cloxacillin (or vancomycin) plus rifampicin plus gentamicin, and 17 patients (18.1%) received the same regimen without gentamicin. The causative microorganism was Staphylococcus aureus in 40 cases (42.6%) and coagulase-negative staphylococci in 54 cases (57.4%). Overall, 40 patients (42.6%) died during hospital admission, 33 patients (42.9%) in the group receiving gentamicin and 7 patients in the group that did not (41.2%, P = 0.899). Worsening renal function was observed in 42 patients (54.5%) who received gentamicin and in 9 patients (52.9%) who did not (p = 0.904). Heart failure as a complication of endocarditis (OR: 4.58; CI 95%: 1.84–11.42) and not performing surgery when indicated (OR: 2.68; CI 95%: 1.03–6.94) increased mortality. Gentamicin administration remained unrelated to mortality (OR: 1.001; CI 95%: 0.29–3.38) in the multivariable analysis. Conclusions: The addition of gentamicin to a regimen containing vancomycin or cloxacillin plus rifampicin in SPVE was not associated to better outcome.

Introduction SARS-CoV-2 pneumonia is often associated with hyper-inflammation. The cytokine-storm-like is one of the targets of current therapies for coronavirus disease 2019 (COVID-19). High Interleukin-6 (IL6) blood levels have been identified in severe COVID-19 disease, but there are still uncertainties regarding the actual role of anti-IL6 antagonists in COVID-19 management. Our hypothesis was that the use of sarilumab plus corticosteroids at an early stage of the hyper-inflammatory syndrome would be beneficial and prevent progression to acute respiratory distress syndrome (ARDS). Methods We randomly assigned (in a 1:1 ratio) COVID-19 pneumonia hospitalized patients under standard oxygen therapy and laboratory evidence of hyper-inflammation to receive sarilumab plus usual care (experimental group) or usual care alone (control group). Corticosteroids were given to all patients at a 1 mg/kg/day of methylprednisolone for at least 3 days. The primary outcome was the proportion of patients progressing to severe respiratory failure (defined as a score in the Brescia-COVID19 scale ≥ 3) up to day 15. Results A total of 201 patients underwent randomization: 99 patients in the sarilumab group and 102 patients in the control group. The rate of patients progressing to severe respiratory failure (Brescia-COVID scale score ≥ 3) up to day 15 was 16.16% in the Sarilumab group versus 15.69% in the control group (RR 1.03; 95% CI 0.48–2.20). No relevant safety issues were identified. Conclusions In hospitalized patients with Covid-19 pneumonia, who were under standard oxygen therapy and who presented analytical inflammatory parameters, an early therapeutic intervention with sarilumab plus standard of care (including corticosteroids) was not shown to be more effective than current standard of care alone. The study was registered at EudraCT with number: 2020-002037-15. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00543-2.

Despite the lack of specific guidelines, surgery has been considered mandatory to treat infective endocarditis (IE) in patients with an ascending aortic prosthetic graft (AAPG), especially when periprosthetic complications are present ([1][1],[2][2]). The indication for surgical treatment contained

To evaluate Red blood cell distribution width (RDW) as a sepsis prognostic biomarker.203 septic patients admitted to the ICU. Analysis of RDW dynamics, hospital mortality discrimination ability and the added value when incorporated to the SOFA, LODS, SAPS-II and APACHE-II scores using the AUC-ROC.Non-survivors presented higher RDW values during the first week after ICU admission (p = 0.048). Only SOFA and RDW were independently associated with mortality when adjusted by Charlson, immunosuppression, nosocomial infection, NEWS2, SAPS-II, septic shock and haemoglobin (p0.05). After adjustment, AUC-ROC was 0.827, 0.822, 0.824, 0.834 and 0.812 for each model including admission, 24, 48 and 72-h and 7-days RDW, respectively. When added to the scores, 24-h RDW and admission RDW improved their discrimination ability (SOFA AUC-ROC = 0.772 vs 0.812 SOFA + admission RDW, p = 0.041; LODS AUC-ROC = 0.687 vs 0.710, p = 0.002; SAPS-II AUC-ROC = 0.734 vs 0.785, p = 0.021; APACHE-II AUC-ROC = 0.672 vs 0.755, p = 0.003). Admission RDW with SOFA presented the better discrimination ability for mortality.RDW is an independent prognostic marker of death in septic patients admitted in the ICU that improves SOFA, LODS, APACHE-II and SAPS-II discrimination ability. This parameter could be incorporated to the prognostic scores as a marker of systemic dysfunction and dysregulated inflammatory response.

Background Our objective is to describe the presentation and complications, including relapses, of coronavirus disease 2019 (COVID-19) in patients under anti-CD20 treatments. In addition, to describe viral clearance and determine the safety of reintroducing anti-CD20 treatment. Methods Retrospective cohort study of 422 patients under anti-CD20 treatment that was administered from 1 January 2019 to 31 December 2020. Results Fifty-seven patients were diagnosed with COVID-19 (13.5%). Twenty-five patients (43.9%) required hospital admission. Five patients died (8.8%), and 10 developed severe COVID-19 and acute respiratory distress syndrome. Mortality rate was higher among patients infected during the first 3 months following the last dose of anti-CD20 (14.7% vs 0%, P = .046). The median time of persistence of positive reverse transcription polymerase chain reaction (RT-PCR) was 22 days (IQR 13–40). Nine out of 52 survivors (17.3%) presented relapses. All of them received the last dose of anti-CD20 less than 6 months before the COVID-19 episode. Clinical presentation was fever (n = 8; 88.9%), dyspnea (n = 7; 77.8%), cough (n = 7; 77.8%), worsening of previous infiltrates (n = 5; 55.6%) and new pulmonary infiltrates (n = 8; 88.9%). An increase in lymphocytes with CD4/CD8 ratio inversion was observed in all cases. Among the 25 patients who resumed anti-CD20 drug, 4 (16.0%) presented relapses vs 5/28 among those who did not (17.9%), (P = .857). Conclusions Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the 6 months after anti-CD20 administration had a worse outcome and a higher mortality rate. The duration of infectivity may be longer. Relapses of COVID-19 occurred in more than 15% and were associated with viral replication. Once the infection is resolved, it is safe to restart treatment with anti-CD20.

BACKGROUND The diagnosis of invasive aspergillosis (IA) can be problematic in solid organ transplantation (SOT). The prognosis greatly varies according to the type of transplant, and the impact of prophylaxis is not well defined. PATIENTS AND METHODS The Diaspersot cohort analyses the impact of IA in SOT in Spain during the last 10 years. Proven and probable/putative IA was included. RESULTS We analysed 126 cases of IA. The incidences of IA were as follows: 6.5%, 2.9%, 1.8% and 0.6% for lung, heart, liver and kidney transplantation, respectively. EORTC/MSG criteria confirmed only 49.7% of episodes. Tree-in-bud sign or ground-glass infiltrates were present in 56.3% of patients, while serum galactomannan (optical density index >0.5) was positive in 50.6%. A total of 41.3% received combined antifungal therapy. Overall mortality at 3 months was significantly lower (p

Background Recently, several scores to quantify compliance with the guidelines in candidaemia management (EQUAL, GEMICOMED, Valerio) have been developed. Evidence supporting the association of these scores to the prognosis is scarce. We aim to evaluate the performance of these candidaemia guideline adherence scores to predict candidaemia outcome. Methods We recorded retrospectively data from candidaemia episodes (January 2017-December 2018). We analysed adherence to guidelines for candidaemia management according to EQUAL, GEMICOMED and Valerio scores, and we correlated those to outcome. Results Fifty-four first episodes of candidaemia were retrieved. Five patients who died in the first 48 hours after blood cultures were not included. Thirty-day mortality in evaluable patients was 18.4%. Median adherence to guidelines according to EQUAL score was 17 (interquartile range [IQR]: 15-19), and according to GEMICOMED was 86% (IQR: 72.5%-100%). According to Valerio score, adequacy of antifungal prescription was 8.5/10 (SD: 1.9). A cut-off of ≥17 for EQUAL or compliance >70% for GEMICOMED was associated with inferior 30-day mortality (7.1% vs 33.3%, P = .028 and 7.9% vs 54.5%, P = .002, respectively). Infectious diseases (ID) evaluated cases obtained a better EQUAL score (>17; 82.1% vs 42.9%, P = .006), had inferior 30-day mortality (9.4% vs 35.3%, P = .049) and a better antifungal prescription adequacy (Valerio score 9.0 vs 7.5, P = .011). Conclusion Adherence to guidelines for candidaemia management evaluated by means of EQUAL and GEMICOMED score was associated with a decreased 30-day mortality. Adequacy of antifungal prescription can be ameliorated. ID consultation improved guideline adherence and was associated with decreased 30-day mortality.

IntroductionSex-dependent differences of infective endocarditis (IE) have been reported. Women suffer from IE less frequently than men and tend to present more severe manifestations. Our objective was to analyse the sex-based differences of IE in the clinical presentation, treatment, and prognosis.Material and methodsWe analysed the sex differences in the clinical presentation, modality of treatment and prognosis of IE in a national-level multicentric cohort between 2008 and 2018. All data were prospectively recorded by the GAMES cohort (Spanish Collaboration on Endocarditis).ResultsA total of 3451 patients were included, of whom 1105 were women (32.0%). Women were older than men (mean age, 68.4 vs 64.5). The most frequently affected valves were the aortic valve in men (50.6%) and mitral valve in women (48.7%). Staphylococcus aureus aetiology was more frequent in women (30.1% vs 23.1%; pSurgery was performed in 38.3% of women and 50% of men. After propensity score (PS) matching for age and estimated surgical risk (European System for Cardiac Operative Risk Evaluation II (EuroSCORE II)), the analysis of the matched cohorts revealed that women were less likely to undergo surgery (OR 0.74; 95% CI 0.59 to 0.91; p=0.05).The observed overall in-hospital mortality was 32.8% in women and 25.7% in men (OR for the mortality of female sex 1.41; 95% CI 1.21 to 1.65; pConclusionsFemale sex was an independent factor related to mortality after adjusting for confounders. In addition, women were less frequently referred for surgical treatment.

We aimed to identify clinical factors associated with recurrent infective endocarditis (IE) episodes. The clinical characteristics of 2816 consecutive patients with definite IE (January 2008–2018) were compared according to the development of a second episode of IE. A total of 2152 out of 2282 (94.3%) patients, who were discharged alive and followed-up for at least the first year, presented a single episode of IE, whereas 130 patients (5.7%) presented a recurrence, 70 cases (53.8%) were due to other microorganisms (reinfection), and 60 cases (46.2%) were due to the same microorganism causing the first episode. Thirty-eight patients (29.2%), whose recurrence was due to the same microorganism, were diagnosed during the first 6 months of follow-up and were considered relapses. Relapses were associated with nosocomial endocarditis (OR: 2.67 (95% CI: 1.37–5.29)), enterococci (OR: 3.01 (95% CI: 1.51–6.01)), persistent bacteremia (OR: 2.37 (95% CI: 1.05–5.36)), and surgical treatment (OR: 0.23 (0.1–0.53)). On the other hand, episodes of reinfection were more common in patients with chronic liver disease (OR: 3.1 (95% CI: 1.65–5.83)) and prosthetic endocarditis (OR: 1.71 (95% CI: 1.04–2.82)). The clinical factors associated with reinfection and relapse in patients with IE appear to be different. A better understanding of these factors would allow the development of more effective therapeutic strategies.

BackgroundCOVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. At the time this clinical trial was planned, there were no available vaccine or therapeutic agents with proven efficacy, but the severity of the condition prompted the use of several pharmacological and non-pharmacological interventions.It has long been hypothesized that the use of convalescent plasma (CP) from infected patients who have developed an effective immune response is likely to be an option for the treatment of patients with a variety of severe acute respiratory infections (SARI) of viral etiology. The aim of this study is to assess the efficacy and safety of convalescent plasma in adult patients with severe COVID-19 pneumonia.Methods/DesignThe ConPlas-19 study is a multicenter, randomized, open-label controlled trial. The protocol has been prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. The study has been planned to include 278 adult patients hospitalized with severe COVID-19 infection not requiring mechanical ventilation (invasive or non-invasive). Subjects are randomly assigned in a 1:1 ratio (139 per treatment arm), stratified by center, to receive intravenously administered CP (single infusion) plus SOC or SOC alone, and are to be followed for 30 days. The primary endpoint of the study is the proportion of patients that progress to categories 5, 6 or 7 (on the 7-point ordinal scale proposed by the WHO) at day 15. Interim analyses for efficacy and/or futility will be conducted once 20%, 40%, and 60% of the planned sample size are enrolled and complete D15 assessment.DiscussionThis clinical trial is designed to evaluate the efficacy and safety of passive immunotherapy with convalescent plasma for the treatment of adult patients hospitalized with COVID-19. The results of this study are expected to contribute to establishing the potential place of CP in the therapeutics for a new viral disease.Trial registrationTrial registration at clinicaltrials.gov; Registration Number: NCT04345523; https://clinicaltrials.gov/ct2/show/NCT04345523; Registered on 30 March, 2020. First posted date: April 14, 2020.

Valganciclovir (VGCV) and ganciclovir (GCV) doses must be adjusted according to indication, renal function and weight. No specific therapeutic exposure values have been established. We aimed to evaluate the adequacy of VGCV/GCV doses, to assess the interpatient variability in GCV serum levels, to identify predictive factors for this variability and to assess the clinical impact. This is a prospective study at a tertiary institution including hospitalized patients receiving VGCV/GCV prophylaxis or treatment. Adequacy of the antiviral dose was defined according to cytomegalovirus guidelines. Serum levels were determined using High-Performance Liquid Chromatography. Blood samples were drawn at least 3 days after antiviral initiation. Outcome was considered favorable if there was no evidence of cytomegalovirus infection during prophylaxis or when a clinical and microbiological resolution was attained within 21 days of treatment and no need for drug discontinuation due to toxicity. Seventy consecutive patients [74.3% male/median age: 59.2 years] were included. VGCV was used in 25 patients (35.7%) and GCV in 45 (64.3%). VGCV/GCV initial dosage was deemed adequate in 47/70 cases (67.1%), lower than recommended in 7/70 (10%) and higher in 16/70 (22.9%). Large inter-individual variability of serum levels was observed, with median trough levels of 2.3 mg/L and median peak levels of 7.8 mg/L. Inadequate dosing of VGCV/GCV and peak levels lower than 8.37 or greater than 11.86 mg/L were related to poor outcome. Further studies must be performed to confirm these results and to conclusively establish if VGCV/GCV therapeutic drug monitoring could be useful to improve outcomes in specific clinical situations.

Background Lymphoid neoplasms treatment has recently been renewed to increase antitumor efficacy and conventional chemotherapies toxicities. Limited data have been published about the infection risk associated with these new drugs, therefore this study analyzes the infectious complications in patients with lymphoproliferative diseases (LPD) treated with monoclonal antibodies (obinutuzumab, ofatumumab, brentuximab, nivolumab, or pembrolizumab), BTK inhibitors (ibrutinib and acalabrutinib), PI3K inhibitors (idelalisib) and BCL2 inhibitors (venetoclax). Methods Multicenter retrospective study of 458 LPD patients treated with targeted therapies in real‐life setting, in 18 Spanish institutions, from the time of their commercial availability to August 2020. Results Severe infections incidence was 23% during 17‐month median follow‐up; cumulative incidence was higher in the first 3–6 months of targeted drug treatment and then decreased. The most frequent etiology was bacterial (54%). Nine (6%) Invasive fungal infections (IFI) were observed, in its majority in chronic lymphocytic leukemia (CLL) patients treated predominantly with ibrutinib. Significant risk factors for severe infection were: severe lymphopenia (p = 0.009, OR 4.7, range 1.3–1.7), combined targeted treatment vs single agent treatment (p = 0.014 OR 2.2 range 1.1–4.2) and previous rituximab (p = 0.03 OR 1.8, range 1.05–3.3). Infection‐related mortality was 6%. In 22% of patients with severe infections, definitive discontinuation of the targeted drug was observed. Conclusion A high proportion of patients presented severe infections during follow‐up, with non‐negligible attributable mortality, but infection incidence is not superior to the one observed during the chemotherapy era. In selected cases with specific risk factors for infection, antimicrobial prophylaxis should be considered., Our data describe the infection risk associated with the use of targeted drugs in the treatment of lymphoproliferative diseases in real‐life setting and suggest some infection risk factors that could identify the need for antimicrobial prophylaxis in a selected group of patients.

The implementation of 1,3 &beta, d-glucan (BDG) has been proposed as a diagnostic tool in antifungal stewardship programs (ASPs). We aimed to analyze the influence of serum BDG in an ASP for oncologic patients and solid organ transplant (SOT) recipients. We conducted a pre&ndash, post study. In the initial period (PRE), the ASP was based on bedside advice, and this was complemented with BDG in the post-period (POST). Performance parameters of the BDG assay were determined. Antifungal (AF) use adequacy was evaluated using a point score. Clinical outcomes and AF costs were also compared before and after the intervention. Overall, 85 patients were included in the PRE-period and 112 in the POST-period. Probable or proven fungal infections were similar in both groups (54.1% vs. 57.1%, p = 0.67). The determination of BDG contributed to improved management in 75 of 112 patients (66.9%). The AF adequacy score improved in the POST-period (mean 7.75 vs. 9.29, p &lt, 0.001). Median days of empiric AF treatment was reduced in the POST-period (9 vs. 5 days, p = 0.04). All-cause mortality (44.7% vs. 34.8%, p = 0.16) was similar in both periods. The cost of AF treatments was reduced in the POST-period with a difference of 779.6 &euro, /patient. Our data suggest that the use of BDG was a cost-effective strategy that contributed to safely improving the results of an ASP for SOT and oncologic patients.

REIPI-SEIMC COVID-19 group and COVID@HULP group., [Background] The clinical presentation of COVID-19 in patients admitted to hospital is heterogeneous. We aimed to determine whether clinical phenotypes of patients with COVID-19 can be derived from clinical data, to assess the reproducibility of these phenotypes and correlation with prognosis, and to derive and validate a simplified probabilistic model for phenotype assignment. Phenotype identification was not primarily intended as a predictive tool for mortality., [Methods] In this study, we used data from two cohorts: the COVID-19@Spain cohort, a retrospective cohort including 4035 consecutive adult patients admitted to 127 hospitals in Spain with COVID-19 between Feb 2 and March 17, 2020, and the COVID-19@HULP cohort, including 2226 consecutive adult patients admitted to a teaching hospital in Madrid between Feb 25 and April 19, 2020. The COVID-19@Spain cohort was divided into a derivation cohort, comprising 2667 randomly selected patients, and an internal validation cohort, comprising the remaining 1368 patients. The COVID-19@HULP cohort was used as an external validation cohort. A probabilistic model for phenotype assignment was derived in the derivation cohort using multinomial logistic regression and validated in the internal validation cohort. The model was also applied to the external validation cohort. 30-day mortality and other prognostic variables were assessed in the derived phenotypes and in the phenotypes assigned by the probabilistic model., [Findings] Three distinct phenotypes were derived in the derivation cohort (n=2667)—phenotype A (516 [19%] patients), phenotype B (1955 [73%]) and phenotype C (196 [7%])—and reproduced in the internal validation cohort (n=1368)—phenotype A (233 [17%] patients), phenotype B (1019 [74%]), and phenotype C (116 [8%]). Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more comorbidities and even higher inflammatory parameters than phenotype B. We developed a simplified probabilistic model (validated in the internal validation cohort) for phenotype assignment, including 16 variables. In the derivation cohort, 30-day mortality rates were 2·5% (95% CI 1·4–4·3) for patients with phenotype A, 30·5% (28·5–32·6) for patients with phenotype B, and 60·7% (53·7–67·2) for patients with phenotype C (log-rank test p, [Interpretation] Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. We developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes. These results might help to better classify patients for clinical management, but the pathophysiological mechanisms of the phenotypes must be investigated., [Funding] Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA., Funding: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA.

BackgroundWe aimed to determine the impact of tocilizumab use in severe COVID-19 pneumonia mortality.MethodsWe performed a multicentre retrospective cohort study in 18 tertiary hospitals in Spain, from March to April 2020. Consecutive patients admitted with severe COVID-19 treated with tocilizumab were compared to patients not treated with tocilizumab, adjusting by Inverse Probability of the Treatment Weights (IPTW). Tocilizumab effect in patients receiving steroids during the 48h following inclusion was analyzed.ResultsDuring the study period, 506 patients with severe COVID-19 fulfilled inclusion criteria. Among them, 268 were treated with tocilizumab and 238 patients were not. Median time to tocilizumab treatment from onset of symptoms was 11 days (IQR 8-14). Global mortality was 23.7%. Mortality was lower in patients treated with tocilizumab than in controls (16.8% versus 31.5%, HR 0.514 [95CI 0.355-0.744], p< 0.001; weighted HR 0.741 [95CI 0.619-0.887], p = 0.001). Tocilizumab treatment reduced mortality by 14.7% relative to no tocilizumab treatment (RRR 46.7%). We calculated a number necessary to treat of 7. Among patients treated with steroids, mortality was lower in patients treated with tocilizumab than in those treated with steroids alone (10.9% versus 40.2%, HR 0.511 [95CI 0.352-0.741], p = 0.036; weighted HR 0.6 [95CI 0.449-0.804], p< 0.001) (Interaction p = 0.094).ConclusionsThese results show that survival of patients with severe COVID-19 is higher in patients treated with tocilizumab than in those not treated, and that tocilizumab effect adds to that of steroids administered to non-intubated cases with COVID-19 during the first 48 hours of presenting with respiratory failure despite of oxygen therapy. Randomised controlled studies are needed to confirm these results.SummaryWe investigated in-hospital mortality of patients with severe SARS-CoV-2 pneumonia in a multicenter series of patients treated with tocilizumab compared to controls, and adjusted using IPTW. Our results show a beneficial impact of tocilizumab treatment in SARS-CoV-2 pneumonia, that adds to that of steroids.

Background. The COVID pandemic has had a major impact on healthcare in hospitals, including the diagnosis and treatment of infections. Hospital-acquired infective endocarditis (HAIE) is a severe complication of medical procedures that has shown a progressive increase in recent years. Objectives. to determine whether the incidence of HAIE during the first two months of the epidemic (March-April 2020) was higher than previously observed and to describe the clinical characteristics of these cases. The probability of studied event (HAIE) during the studied period was calculate by Poisson distribution. Results. Four cases of HAIE were diagnosed in our institution during the study period. The incidence of HAIE during the study period was 2/patient-month and 0.25/patient-month during the previous 5 years (p=0.024). Two cases appeared during admission for COVID-19 with pulmonary involvement treated with metilprednisolone and tocilizumab. The other two cases were admitted to the hospital during the epidemic. All cases underwent central venous and urinary catheterization during admission. The etiology of HAIE was Enterococcus faecalis (2 cases), Staphylococcus aureus and Candida albicans (one case each). A source of infection was identified in three cases (central venous catheter, peripheral venous catheter, sternal wound infection, respectively). One patient was operated on. There were no fatalities during the first 30 days of follow-up. Conclusion. The incidence of HAIE during COVID-19 pandemic in our institution was higher than usual. In order to reduce the risk of this serious infection, optimal catheter care, appropriate use of corticosteroids and interleukin antagonists and early treatment of every local infection should be prioritized during coronavirus outbreaks.

Background: Passive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19 for which evidence from controlled clinical trials is lacking. Methods: We conducted a multi-center, randomized clinical trial in patients hospitalized for COVID-19. All patients received standard of care treatment, including off-label use of marketed medicines, and were randomized 1:1 to receive one dose (250-300 mL) of CP from donors with IgG anti-SARS-CoV-2. The primary endpoint was the proportion of patients in categories 5, 6 or 7 of the COVID-19 ordinal scale at day 15. Results: The trial was stopped after first interim analysis due to the fall in recruitment related to pandemic control. With 81 patients randomized, there were no patients progressing to mechanical ventilation or death among the 38 patients assigned to receive plasma (0%) versus 6 out of 43 patients (14%) progressing in control arm. Mortality rates were 0% vs 9.3% at days 15 and 29 for the active and control groups, respectively. No significant differences were found in secondary endpoints. At inclusion, patients had a median time of 8 days (IQR, 6-9) of symptoms and 49,4% of them were positive for anti-SARS-CoV-2 IgG antibodies. Conclusions: Convalescent plasma could be superior to standard of care in avoiding progression to mechanical ventilation or death in hospitalized patients with COVID-19. The strong dependence of results on a limited number of events in the control group prevents drawing firm conclusions about CP efficacy from this trial. (Funded by Instituto de Salud Carlos III; NCT04345523). This research is funded by the Government of Spain, Ministry of Science and Innovation, Instituto de Salud Carlos III, grant number COV20/00072 (Royal Decree-Law 8/2020, of 17 March, on urgent extraordinary measures to deal with the economic and social impact of COVID-19), co-financed by the European Regional Development Fund (FEDER) ‘‘A way to make Europe’’ and supported by SCReN (Spanish Clinical Research Network), ISCIII, project PT17/0017/0009. Clinical trial insurance coverage was kindly donated by MARCH RS Correduría de Seguros y Reaseguros. Mikel Mancheño-Losa holds a "Río Hortega" research contract (expte. CM19/00226 No

Evidence to support the use of steroids in coronavirus disease 2019 (COVID-19) pneumonia is lacking. We aim to determine the impact of steroid use for COVID-19 pneumonia on hospital mortality. We performed a single-center retrospective cohort study in a university hospital in Madrid, Spain, during March of 2020. To determine the role of steroids in in-hospital mortality, patients admitted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and treated with steroids were compared to patients not treated with steroids, and we adjusted with a propensity score for patients on steroid treatment., Evidence to support the use of steroids in coronavirus disease 2019 (COVID-19) pneumonia is lacking. We aim to determine the impact of steroid use for COVID-19 pneumonia on hospital mortality. We performed a single-center retrospective cohort study in a university hospital in Madrid, Spain, during March of 2020. To determine the role of steroids in in-hospital mortality, patients admitted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and treated with steroids were compared to patients not treated with steroids, and we adjusted with a propensity score for patients on steroid treatment. Survival times were compared using the log rank test. Different steroid regimens were compared and adjusted with a second propensity score. During the study period, 463 out of 848 hospitalized patients with COVID-19 pneumonia fulfilled inclusion criteria. Among them, 396 (46.7%) patients were treated with steroids and 67 patients were not. Global mortality was 15.1%. The median time to steroid treatment from symptom onset was 10 days (interquartile range [IQR], 8 to 13 days). In-hospital mortality was lower in patients treated with steroids than in controls (13.9% [55/396] versus 23.9% [16/67]; hazard ratio [HR], 0.51 [95% confidence interval, 0.27 to 0.96]; P = 0.044). Steroid treatment reduced mortality by 41.8% relative to the mortality with no steroid treatment (relative risk reduction, 0.42 [95% confidence interval, 0.048 to 0.65]). Initial treatment with 1 mg/kg of body weight/day of methylprednisolone versus steroid pulses was not associated with in-hospital mortality (13.5% [42/310] versus 15.1% [13/86]; odds ratio [OR], 0.880 [95% confidence interval, 0.449 to 1.726]; P = 0.710). Our results show that the survival of patients with SARS-CoV-2 pneumonia is higher in patients treated with glucocorticoids than in those not treated. Rates of in-hospital mortality were not different between initial regimens of 1 mg/kg/day of methylprednisolone and glucocorticoid pulses.

Lina Marcela Parra,1 Mireia Cantero,1 Ignacio Morrás,2 Alberto Vallejo,1 Itziar Diego,2 Elena Jiménez-Tejero,1 Elena Múñez,3 Ángel Asensio,1 Ana Fermández-Cruz,3,4 Antonio Ramos-Martinez3,4 On behalf of Puerta de Hierro Hospital Admission Study Group1Servicio de Medicina Preventiva, HU Puerta de Hierro-Majadahonda, Madrid, Spain; 2Servicio de Medicina Interna, HU Puerta de Hierro-Majadahonda, Madrid, Spain; 3Servicio de Medicina Interna, HU Puerta de Hierro-Majadahonda, Unidad de Enfermedades Infecciosas, UAM, Madrid, Spain; 4Instituto Investigación Sanitaria Puerta de Hierro - Segovia de Arana (IDIPHSA), Madrid, SpainCorrespondence: Antonio Ramos-MartinezServicio de Medicina Interna, HU Puerta de Hierro-Majadahonda, Unidad de Enfermedades Infecciosas, Calle Joaquín Rodrigo 2, Majadahonda, Madrid 28222, SpainTel +34 638 211 120Fax +34 91191 6807Email aramos2202@gmail.comObjective: To analyse the rate of occurrence and the clinical variables associated with readmission of patients who had previously been discharged after admission for COVID-19.Setting: University hospital in Madrid (Spain).Participants: Sixty-one patients (74% male) who presented COVID-19 were readmitted during the 3 weeks after discharge from hospital.Interventions: Nested case–control study paired (1:1 ratio) by age, sex and period of admission.Outcome Measures: Rate of readmission rate of patients discharged after suffering COVID-19 and identification of the clinical variables associated with it.Results: Out of 1368 patients who were discharged during the study period, 61 patients (4.4%) were readmitted. Immunocompromised patients (N=10.2%) were at increased risk for readmission (p=0.04). There was also a trend towards a higher probability of readmission in hypertensive patients (p=0.07). Cases had had a shorter hospital stay and a higher prevalence of fever during the 48 hours prior to discharge. There were no significant differences in oxygen levels measured at admission and discharge by pulse oximetry intra-subject or between the groups. Neutrophil-to-lymphocyte ratio at hospital admission tended to be higher in cases than in controls (p=0.06). Neither glucocorticoids nor anticoagulants prescribed at hospital discharge were associated with a lower readmission rate. Patients who were readmitted due to a thrombotic event (8 patients, 13.1%) presented a higher level of D-dimer at discharge of initial admission.Conclusion: The rate of readmission after discharge from hospital for COVID-19 was low. Immunocompromised patients and those presenting with fever during the 48 hours prior to discharge were at greater risk of readmission to hospital.Keywords: coronavirus, pneumonia, viral, patient readmission, pulmonary embolism, heparin

ObjectiveWe aim to determine the impact of steroid use in COVID-19 pneumonia in-hospital mortality.DesignWe performed a single-centre retrospective cohort study.SettingA University hospital in Madrid, Spain, during March 2020.ParticipantsPatients admitted with SARS-CoV-2 pneumonia.ExposuresPatients treated with steroids were compared to patients not treated with steroids. A propensity-score for steroid treatment was developed. Different steroid regimens were also compared, and adjusted with a second propensity score.Main Outcomes and MeasuresTo determine the role of steroids in in-hospital mortality, univariable and multivariable analyses were performed, and adjusted including the propensity score as a covariate. Survival times were compared using a log-rank test.ResultsDuring the study period, 463 out of 848 hospitalized patients with COVID19 pneumonia fulfilled inclusion criteria. Among them, 396 (46.7%) consecutive patients were treated with steroids and 67 patients were assigned to the control cohort. Global mortality was 15.1%. Median time to steroid treatment from symptom onset was 10 days (IQR 8 to13). In-hospital mortality was lower in patients treated with steroids than in controls (13.9% [55/396] versus 23.9% [16/67], OR 0.51 [0.27 to 0.96], p= 0.044). Steroid treatment reduced mortality by 41.8% relative to no steroid treatment (RRR 0,42 [0.048 to 0.65). Initial treatment with 1 mg/kg/day of methylprednisolone (or equivalent) versus steroid pulses was not associated with in-hospital mortality (13.5% [42/310] versus 15.1% [13/86], OR 0.880 [0.449-1.726], p=0.710).ConclusionsOur results show that survival of patients with SARS-CoV2 pneumonia is higher in patients treated with glucocorticoids than in those not treated. In-hospital mortality was not different between initial regimens of 1 mg/kg/day of methylprednisolone or equivalent and glucocorticoid pulses. These results support the use of glucocorticoids in SARS-CoV2 infection.SummaryWe investigated in-hospital mortality of patients with SARS-CoV-2 pneumonia in a large series of patients treated with steroids compared to controls, and adjusted using a propensity score. Our results show a beneficial impact of steroid treatment in SARS-CoV-2 pneumonia.

Introduction Infective endocarditis (IE) still carries high morbidity and mortality and frequently requires surgery. The benefit of mitral valve repair (MVr) in the setting of IE is yet to be proven. The goal of this study was to assess the results of MVr in patients with IE after a minimum follow-up of 1 year. Methods This study is based on a Spanish nationwide prospective registry that included patients operated on for native mitral valve IE. The collaborating Institutions pooled their pre-, peri-, and postoperative data into the database of the GAMES group [Grupo de Apoyo al Manejo de la EndocarditiS (Group for support and management of infective endocarditis)]. Results Data from 27 hospitals were recorded and 3524 cases of active IE identified between 2008 and 2016. There were 1513 cases of mitral IE, of which 898 involved native valves. Of these, 437 patients underwent surgical treatment, and 369 completed the 1-year follow-up. The valve was repaired in 68 cases (18.4%). Preoperative groups were comparable (EuroSCORE MVr 7.7 vs MVR 8.0; p = ns). Mortality in the repair group was inferior to that in the replacement group (16.2% vs 27.2%, p = 0.058). At 1 year, mortality remained higher in the replacement group: 3.7% vs 2.9%. Relapse of the infection was slightly more frequent in the repair group (7.1% vs 3.7%; p = ns), although this did not lead to higher rates of reintervention (MVr/MVR: 2.9% vs 4.9%). Conclusion MVr is an attractive option for specific patients with IE and does not seem to negatively impact on relapses.

For the Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis Infecciosa en España (GAMES) investigators: Hospital Costa del Sol, Marbella: Fernando Fernández Sánchez, Mariam Noureddine, Gabriel Rosas, Javier de la Torre Lima. Hospital Universitario de Cruces, (Bilbao): Roberto Blanco, María Victoria Boado, Marta Campaña Lázaro, Alejandro Crespo, Josune Goikoetxea, José Ramón Iruretagoyena, Josu Irurzun Zuazabal, Leire López-Soria, Miguel Montejo, Javier Nieto, David Rodrigo, Regino Rodríguez, Yolanda Vitoria, Roberto Voces. Hospital Universitario Virgen de la Victoria, Málaga: María (Mª) Victoria García López, Radka Ivanova Georgieva, Guillermo Ojeda, Isabel Rodríguez Bailón, Josefa Ruiz Morales. Hospital Universitario Donostia-Policlínica Gipuzkoa, San Sebastián: Ana María Cuende, Tomás Echeverría, Ana Fuerte, Eduardo Gaminde, Miguel Ángel Goenaga, Pedro Idígoras, José Antonio Iribarren, Alberto Izaguirre Yarza, Xabier Kortajarena Urkola, Carlos Reviejo. Hospital General Universitario de Alicante, Alicante: Rafael Carrasco, Vicente Climent, Patricio Llamas, Esperanza Merino, Joaquín Plazas, Sergio Reus. Complejo Hospitalario Universitario A Coruña, A Coruña: Nemesio Álvarez, José María Bravo-Ferrer, Laura Castelo, José Cuenca, Pedro Llinares, Enrique Miguez Rey, María Rodríguez Mayo, Efrén Sánchez, Dolores Sousa Regueiro. Complejo Hospitalario Universitario de Huelva, Huelva: Francisco Javier Martínez. Hospital Universitario de Canarias, Canarias: Mª del Mar Alonso, Beatriz Castro, Dácil García Rosado, Mª del Carmen Durán, Mª Antonia Miguel Gómez, Juan Lacalzada, Ibrahim Nassar. Hospital Regional Universitario de Málaga, Málaga: Antonio Plata Ciezar, José Mª Reguera Iglesias. Hospital Universitario Central Asturias, Oviedo: Víctor Asensi Álvarez, Carlos Costas, Jesús de la Hera, Jonnathan Fernández Suárez, Lisardo Iglesias Fraile, Víctor León Arguero, José López Menéndez, Pilar Mencia Bajo, Carlos Morales, Alfonso Moreno Torrico, Carmen Palomo, Begoña Paya Martínez, Ángeles Rodríguez Esteban, Raquel Rodríguez García, Mauricio Telenti Asensio. Hospital Clínic-IDIBAPS, Universidad de Barcelona, Barcelona: Manuel Almela, Juan Ambrosioni, Manuel Azqueta, Mercè Brunet, Marta Bodro, Ramón Cartañá, Carlos Falces, Guillermina Fita, David Fuster, Cristina García de la Mària, Laura García-Valls, Marta Hernández-Meneses, Jaume Llopis Pérez, Francesc Marco, José M. Miró, Asunción Moreno, David Nicolás, Salvador Ninot, Eduardo Quintana, Carlos Paré, Daniel Pereda, Juan M. Pericás, José L. Pomar, José Ramírez, Irene Rovira, Elena Sandoval, Marta Sala, Marta Sitges, Dolors Soy, Adrián Téllez, José M. Tolosana, Bárbara Vidal, Jordi Vila. Hospital General Universitario Gregorio Marañón, Madrid: Iván Adán, Javier Bermejo, Emilio Bouza, Daniel Celemín, Gregorio Cuerpo Caballero, Antonia Delgado Montero, Ana Fernández Cruz, Ana García Mansilla, Mª Eugenia García Leoni, Víctor González Ramallo, Martha Kestler Hernández, Amaia Mari Hualde, Mercedes Marín, Manuel Martínez-Sellés, Mª Cruz Menárguez, Patricia Muñoz, Cristina Rincón, Hugo Rodríguez-Abella, Marta Rodríguez-Créixems, Blanca Pinilla, Ángel Pinto, Maricela Valerio, Pilar Vázquez, Eduardo Verde Moreno. Hospital Universitario La Paz, Madrid: Isabel Antorrena, Belén Loeches, Alejandro Martín Quirós, Mar Moreno, Ulises Ramírez, Verónica Rial Bastón, María Romero, Araceli Saldaña. Hospital Universitario Marqués de Valdecilla, Santander: Jesús Agüero Balbín, Carlos Armiñanzas Castillo, Ana Arnaiz, Francisco Arnaiz de las Revillas, Manuel Cobo Belaustegui, María Carmen Fariñas, Concepción Fariñas-Álvarez, Rubén Gómez Izquierdo, Iván García, Claudia González Rico, Manuel Gutiérrez-Cuadra, José Gutiérrez Díez, Marcos Pajarón, José Antonio Parra, Ramón Teira, Jesús Zarauza. Hospital Universitario Puerta de Hierro, Madrid: Fernando Domínguez, Pablo García Pavía, Jesús González, Beatriz Orden, Antonio Ramos. Hospital Universitario Ramón y Cajal, (Madrid): Tomasa Centella, José Manuel Hermida, José Luis Moya, Pilar Martín-Dávila, Enrique Navas, Enrique Oliva, Alejandro del Río, Jorge Rodríguez-Roda Stuart, Soledad Ruiz Rodríguez. Hospital Universitario Virgen de las Nieves, Granada: Carmen Hidalgo Tenorio. Hospital Universitario Virgen Macarena, Sevilla: Manuel Almendro Delia, Omar Araji, José Miguel Barquero, Román Calvo Jambrina, Marina de Cueto, Juan Gálvez Acebal, Irene Méndez, Isabel Morales, Luis Eduardo López-Cortés. Hospital Universitario Virgen del Rocío, Sevilla: Arístides de Alarcón, Emilio García, Juan Luis Haro, José Antonio Lepe, Francisco López, Rafael Luque. Hospital San Pedro, Logroño: Luis Javier Alonso, Pedro Azcárate, José Manuel Azcona Gutiérrez, José Ramón Blanco, Lara García-Álvarez, José Antonio Oteo, Mercedes Sanz. Hospital de la Santa Creu i Sant Pau, Barcelona: Natividad de Benito, Mercé Gurguí, Cristina Pacho, Roser Pericas, Guillem Pons. Complejo Hospitalario Universitario de Santiago de Compostela, A Coruña: M. Álvarez, A. L. Fernández, Amparo Martínez, A. Prieto, Benito Regueiro, E. Tijeira, Marino Vega. Hospital Santiago Apóstol, Vitoria: Andrés Canut Blasco, José Cordo Mollar, Juan Carlos Gainzarain Arana, Oscar García Uriarte, Alejandro Martín López, Zuriñe Ortiz de Zárate, José Antonio Urturi Matos. Hospital SAS Línea de la Concepción, Cádiz: Gloria García Domínguez, Antonio Sánchez-Porto. Hospital Clínico Universitario Virgen de la Arrixaca, Murcia: José Mª Arribas Leal, Elisa García Vázquez, Alicia Hernández Torres, Ana Blázquez, Gonzalo de la Morena Valenzuela. Hospital de Txagorritxu, Vitoria: Ángel Alonso, Javier Aramburu, Felicitas Elena Calvo, Anai Moreno Rodríguez, Paola Tarabini-Castellani. Hospital Virgen de la Salud, Toledo: Eva Heredero Gálvez, Carolina Maicas Bellido, José Largo Pau, Mª Antonia Sepúlveda, Pilar Toledano Sierra, Sadaf Zafar Iqbal-Mirza. Hospital Rafael Méndez, Lorca-Murcia: Eva Cascales Alcolea, Pilar Egea Serrano, José Joaquín Hernández Roca, Ivan Keituqwa Yañez, Ana Peláez Ballesta, Víctor Soriano. Hospital Universitario San Cecilio, Granada: Eduardo Moreno Escobar, Alejandro Peña Monje, Valme Sánchez Cabrera, David Vinuesa García. Hospital Son Llátzer, Palma de Mallorca: María Arrizabalaga Asenjo, Carmen Cifuentes Luna, Juana Núñez Morcillo, Mª Cruz Pérez Seco, Aroa Villoslada Gelabert. Hospital Universitario Miguel Servet, Zaragoza: Carmen Aured Guallar, Nuria Fernández Abad, Pilar García Mangas, Marta Matamala Adell, Mª Pilar Palacián Ruiz, Juan Carlos Porres. Hospital General Universitario Santa Lucía, Cartagena: Begoña Alcaraz Vidal, Nazaret Cobos Trigueros, María Jesús Del Amor Espín, José Antonio Giner Caro, Roberto Jiménez Sánchez, Amaya Jimeno Almazán, Alejandro Ortín Freire, Monserrat Viqueira González. Hospital Universitario Son Espases, Palma de Mallorca: Pere Pericás Ramis, Mª Ángels Ribas Blanco, Enrique Ruiz de Gopegui Bordes, Laura Vidal Bonet. Complejo Hospitalario Universitario de Albacete, Albacete: Mª Carmen Bellón Munera, Elena Escribano Garaizabal, Antonia Tercero Martínez, Juan Carlos Segura Luque., [Background] Outpatient parenteral antibiotic treatment (OPAT) has proven efficacious for treating infective endocarditis (IE). However, the 2001 Infectious Diseases Society of America (IDSA) criteria for OPAT in IE are very restrictive. We aimed to compare the outcomes of OPAT with those of hospital-based antibiotic treatment (HBAT). [Methods] Retrospective analysis of data from a multicenter, prospective cohort study of 2000 consecutive IE patients in 25 Spanish hospitals (2008–2012) was performed. [Results] A total of 429 patients (21.5%) received OPAT, and only 21.7% fulfilled IDSA criteria. Males accounted for 70.5%, median age was 68 years (interquartile range [IQR], 56–76), and 57% had native-valve IE. The most frequent causal microorganisms were viridans group streptococci (18.6%), Staphylococcus aureus (15.6%), and coagulase-negative staphylococci (14.5%). Median length of antibiotic treatment was 42 days (IQR, 32–54), and 44% of patients underwent cardiac surgery. One-year mortality was 8% (42% for HBAT; P < .001), 1.4% of patients relapsed, and 10.9% were readmitted during the first 3 months after discharge (no significant differences compared with HBAT). Charlson score (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.04–1.42; P = .01) and cardiac surgery (OR, 0.24; 95% CI, .09–.63; P = .04) were associated with 1-year mortality, whereas aortic valve involvement (OR, 0.47; 95% CI, .22–.98; P = .007) was the only predictor of 1-year readmission. Failing to fulfill IDSA criteria was not a risk factor for mortality or readmission. [Conclusions] OPAT provided excellent results despite the use of broader criteria than those recommended by IDSA. OPAT criteria should therefore be expanded., This work was supported by the Ministerio de Economia and Competitividad (Madrid, Spain) (FIS NCT00871104, Instituto de Salud Carlos III). J. M. P. received a “Rio Hortega” research grant from Instituto de Salud Carlos III and the Ministerio de Economia and Competitividad (Madrid, Spain) and the European Society for Clinical Microbiology and Infectious Diseases and Federation of European Microbiological Societies Research Fellowship 2016. Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (Madrid, Spain) provided J. M. M. with a personal intensification research grant (INT15/00168) during 2016 and a personal 80:20 research grant from the Institut d’Investigacions Biomèdiques Pi i Sunyer for the period 2017–2019.

Correspondence