Cutibacterium species valvular and cardiac device-related infective endocarditis: contemporary data from the GAMES prospective cohort (2008-2023).

BACKGROUND: Information on infective endocarditis (IE) caused by Cutibacterium spp. is limited and new Duke-ISCVID criteria have not yet been properly assessed. We examined clinical characteristics, outcomes and performance of diagnostic tests for Cutibacterium valvular and cardiac implantable electronic device-related IE (CIED-IE). METHODS: Data corresponding to all episodes of Cutibacterium IE recorded from 2008 to 2023 in a prospective national cohort including 46 Spanish hospitals were examined. Possible IE cases were reassessed using the new criteria. The sensitivity of blood cultures, valvular and CIED cultures, and PCR of the 16SrRNA gene and sequencing (16SPCR) was evaluated. RESULTS: There were 67/6,692 (1%) episodes of IE caused by Cutibacterium spp., 85% affecting men. Of these, 50 were valve-related (45 prosthetic, 5 native) and 17 CIED-related. The new criteria identified 8 additional cases and reclassified 15 as definite IE. Intracardiac complications (abscess, pseudoaneurysm, perforation or intracardiac fistula) occurred in 23/50 (46%) valvular IE episodes, leading to 18% mortality, and up to 40% mortality if surgery was indicated but could not be performed. All CIED-IE cases underwent device removal and no deaths were recorded. Positive diagnosis rates for blood cultures, valve/device cultures and 16SPCR were 52%, 70% and 82%, respectively. CONCLUSION: Cutibacterium IE is a rare yet potentially life-threatening condition that warrants a high index of suspicion in men with endovascular prosthetic material. The new Duke-ISCVID criteria and molecular techniques are useful for its diagnosis. Considering a significant complication rate, cardiac surgery and removal of CIEDs play a key role in reducing mortality.

Clinical characteristics and outcomes of aortic prosthetic valve endocarditis: comparison between transcatheter and surgical bioprostheses.

PURPOSE: Most data regarding infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) comes from TAVI registries, rather than IE dedicated cohorts. The objective of our study was to compare the clinical and microbiological profile, imaging features and outcomes of patients with IE after SAVR with a biological prosthetic valve (IE-SAVR) and IE after TAVI (IE-TAVI) from 6 centres with an Endocarditis Team (ET) and broad experience in IE. METHODS: Retrospective analysis of prospectively collected data. From the time of first TAVI implantation in each centre to March 2021, all consecutive patients admitted for IE-SAVR or IE-TAVI were prospectively enrolled. Follow-up was monitored during admission and at 12 months after discharge. RESULTS: 169 patients with IE-SAVR and 41 with IE-TAVI were analysed. Early episodes were more frequent among IE-TAVI. Clinical course during hospitalization was similar in both groups, except for a higher incidence of atrioventricular block in IE-SAVR. The most frequently causative microorganisms were S. epidermidis, Enterococcus spp. and S. aureus in both groups. Periannular complications were more frequent in IE-SAVR. Cardiac surgery was performed in 53.6% of IE-SAVR and 7.3% of IE-TAVI (p=0.001), despite up to 54.8% of IE-TAVI patients had an indication. No differences were observed about death during hospitalization (32.7% vs 35.0%), and at 1-year follow-up (41.8% vs 37.5%), regardless of whether the patient underwent surgery or not. CONCLUSION: Patients with IE-TAVI had a higher incidence of early prosthetic valve IE. Compared to IE-SAVR, IE-TAVI patients underwent cardiac surgery much less frequently, despite having surgical indications. However, in-hospital and 1-year mortality rate was similar between both groups.

Incidence, Clinical Presentation, Relapses and Outcome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Patients Treated With Anti-CD20 Monoclonal Antibodies.

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.

COVID-19-associated pulmonary aspergillosis (CAPA): Risk factors and development of a predictive score for critically ill COVID-19 patients.

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) is a major complication of critically ill COVID-19 patients, with a high mortality rate and potentially preventable. Thus, identifying patients at high risk of CAPA would be of great interest. We intended to develop a clinical prediction score capable of stratifying patients according to the risk for CAPA at ICU admission. METHODS: Single centre retrospective case-control study. A case was defined as a patient diagnosed with CAPA according to 2020 ECMM/ISHAM consensus criteria. 2 controls were selected for each case among critically ill COVID-19 patients. RESULTS: 28 CAPA patients and 56-matched controls were included. Factors associated with CAPA included old age (68 years vs. 62, p = .033), active smoking (17.9% vs. 1.8%, p = .014), chronic respiratory diseases (48.1% vs. 26.3%, p = .043), chronic renal failure (25.0% vs. 3.6%, p = .005), chronic corticosteroid treatment (28.6% vs. 1.8%, p < .001), tocilizumab therapy (92.9% vs. 66.1%, p = .008) and high APACHE II at ICU admission (median 13 vs. 10 points, p = .026). A score was created including these variables, which showed an area under the receiver operator curve of 0.854 (95% CI 0.77-0.92). A punctuation below 6 had a negative predictive value of 99.6%. A punctuation of 10 or higher had a positive predictive value of 27.9%. CONCLUSION: We present a clinical prediction score that allowed to stratify critically ill COVID-19 patients according to the risk for developing CAPA. This CAPA score would allow to target preventive measures. Further evaluation of the score, as well as the utility of these targeted preventive measures, is needed.

Inadequate use of antibiotics in the covid-19 era: effectiveness of antibiotic therapy.

BACKGROUND: Since December 2019, the COVID-19 pandemic has changed the concept of medicine. This work aims to analyze the use of antibiotics in patients admitted to the hospital due to SARS-CoV-2 infection. METHODS: This work analyzes the use and effectiveness of antibiotics in hospitalized patients with COVID-19 based on data from the SEMI-COVID-19 registry, an initiative to generate knowledge about this disease using data from electronic medical records. Our primary endpoint was all-cause in-hospital mortality according to antibiotic use. The secondary endpoint was the effect of macrolides on mortality. RESULTS: Of 13,932 patients, antibiotics were used in 12,238. The overall death rate was 20.7% and higher among those taking antibiotics (87.8%). Higher mortality was observed with use of all antibiotics (OR 1.40, 95% CI 1.21-1.62; p < .001) except macrolides, which had a higher survival rate (OR 0.70, 95% CI 0.64-0.76; p < .001). The decision to start antibiotics was influenced by presence of increased inflammatory markers and any kind of infiltrate on an x-ray. Patients receiving antibiotics required respiratory support and were transferred to intensive care units more often. CONCLUSIONS: Bacterial co-infection was uncommon among COVID-19 patients, yet use of antibiotics was high. There is insufficient evidence to support widespread use of empiric antibiotics in these patients. Most may not require empiric treatment and if they do, there is promising evidence regarding azithromycin as a potential COVID-19 treatment.

A retrospective validation of different scores of guideline adherence and infectious diseases consultation on candidaemia: The higher, the better.

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.

Efficacy and safety of antiviral plus anti-spike monoclonal antibody combination therapy vs. monotherapy for high-risk immunocompromised patients with mild-to-moderate SARS-CoV2 infection during the Omicron era: A prospective cohort study.

INTRODUCTION: Antivirals and monoclonal antibodies lower the risk of progression in immunocompromised patients. However, combination therapy with both types of agents has not been studied. PATIENTS AND METHODS: This was a single-centre, prospective, cohort study. All immunocompromised patients who received treatment for mild-to-moderate COVID-19 from 1 January 2022 to 30 October 2022 were enrolled. The primary endpoint was COVID-19 progression at 90 days, defined as hospital admission or death due to COVID-19 and/or seronegative persistent COVID-19. RESULTS: A total of 304 patients were included: 43 patients (14.1%) received sotrovimab plus a direct-acting antiviral, and 261 (85.9%) received monotherapy. Primary outcome occurred more frequently after monotherapy (4.6% vs. 0%, P=0.154). Among patients with anti-spike immunoglobulin G (anti-S IgG) titre <750 BAU/mL, COVID-19 progression was more common after monotherapy (23.9% vs. 0%, P=0.001), including more frequent COVID-related admission (15.2% vs. 0%, P=0.014) and seronegative persistent COVID-19 (10.9% vs. 0%, P=0.044). Combination therapy was associated with lower risk of progression (odds ratio [OR] 0.08, 95% confidence interval [95% CI] 0.01-0.64). Anti-S IgG titre <750 BAU/mL and previous anti-CD20 were associated with higher risk of progression (OR 13.70, 95% CI 2.77-67.68; and OR 3.05, 95% CI 1.20-10.94, respectively). CONCLUSIONS: In immunocompromised patients, combination therapy with sotrovimab plus an antiviral may be more effective than monotherapy for SARS-CoV2.

Infective endocarditis in HIV-infected patients. Analysis of a national cohort.

BACKGROUND: There is limited recent evidence about infective endocarditis (IE) in HIV-infected patients. Our aim was to compare IE according to HIV infection presence. METHODS: Consecutive inclusion of IE patients at 46 Spanish hospitals between 2008 and 2021. RESULTS: From 5667 patients, 99 were HIV-infected (1·7%; 50 intravenous drugs users). Compared to patients without HIV, HIV-infected patients were more frequently male (84% vs. 67%), had younger median age (46 vs. 69 years), and less comorbidities, except liver disease (52% vs. 9%) and intravenous drug use (51% vs. 1%). They had more common tricuspid location (36% vs. 5%) and community-acquired IE (82% vs. 63%), vascular (29% vs. 17%) and cutaneous (22% vs. 7%) foci of infection, and Staphylococcus aureus aetiology (46% vs. 22%). Vegetations (84% vs. 72%), vascular phenomena (17% vs. 9%), splenomegaly (30% vs. 11%), and embolisation (41% vs 21%) were also more common. Surgical indication and surgery were less frequent in HIV-infected patients (54% vs 67%, 28% vs 47%, respectively). Median CD4 count in HIV-infected patients was 318 cells/mm3. In-hospital mortality (23% vs. 26%) and one-year mortality (25% vs. 32%) were similar in both groups. HIV infection was not independently associated with in-hospital (odds ratio 1·1, 95% CI 0·6-1·9) nor one-year mortality (hazard ratio 0·8, 95% CI 0·4-1·3). CONCLUSIONS: In the combined antiretroviral therapy era, less than 2% of IE patients have HIV infection. HIV-infected patients have a different clinical profile than those without HIV, but the presence of HIV does not seem to impact on IE prognosis.

Trends in epidemiology, surgical management, and prognosis of infective endocarditis during the XXI century in Spain: A population-based nationwide study.

BACKGROUND: Few population-based studies have evaluated the epidemiology of infective endocarditis (IE). Changes in population demographics and guidelines on IE may have affected both the incidence and outcomes of IE. Therefore, the aim of our study is to provide contemporary population-based epidemiological data of IE in Spain. METHODS: Retrospective nationwide observational study using data from the Spanish National Health System Discharge Database. We included all patients hospitalized with IE from January 2000 to December 2019. RESULTS: A total of 64,550 IE episodes were included. The incidence of IE rose from 5.25 cases/100,000 person-year in 2000 to 7.21 in 2019, with a 2% annual percentage change (95% CI 1.3-2.6). IE incidence was higher among those aged 85 or older (43.5 cases/100.000 person-years). Trends across the study period varied with sex and age. Patients with IE were progressively older (63.9 years in 2000-2004 to 70.0 in 2015-2019, p < 0.001) and had more frequent comorbidities and predispositions, including, previous valvular prosthesis (12.1% vs 20.9%, p < 0.001). After adjustment, a progressive reduction in mortality was noted including in 2015-2019 compared to 2010-2014 (adjusted odds ratio 0.93, 95% confident interval 0.88-0.99, p = 0.023)., which was associated with more frequent cardiac surgery in recent years (15.1% in 2010-2014 vs 19.9% in 2015-2019). CONCLUSIONS: In Spain, the incidence of IE has increased during the XXI century, with a more pronounced increase in elderly individuals. Adjusted-mortality decreased over the years, which could be related to a higher percentage of surgery. Our results highlight the changing epidemiology of IE.

Epidemiology and Risk Factors of Mycotic Aneurysm in Patients With Infective Endocarditis and the Impact of its Rupture in Outcomes. Analysis of a National Prospective Cohort.

Background: Several aspects of the occurrence and management of mycotic aneurysm (MA) in patients with infective endocarditis (IE) have not been studied. Objectives: To determine the incidence and factors associated with MA presence and rupture and to assess the evolution of those initially unruptured MA. Methods: Prospective multicenter cohort including all patients with definite IE between January 2008 and December 2020. Results: Of 4548 IE cases, 85 (1.9%) developed MA. Forty-six (54.1%) had intracranial MA and 39 (45.9%) extracranial MA. Rupture of MA occurred in 39 patients (45.9%). Patients with ruptured MA had higher 1-year mortality (hazard ratio, 2.33; 95% confidence interval, 1.49-3.67). Of the 55 patients with initially unruptured MA, 9 (16.4%) presented rupture after a median of 3 days (interquartile range, 1-7) after diagnosis, being more frequent in intracranial MA (32% vs 3.3%, P = .004). Of patients with initially unruptured MA, there was a trend toward better outcomes among those who received early specific intervention, including lower follow-up rupture (7.1% vs 25.0%, P = .170), higher rate of aneurysm resolution in control imaging (66.7% vs 31.3%, P = .087), lower MA-related mortality (7.1% vs 16.7%, P = .232), and lower MA-related sequalae (0% vs 27.8%, P = .045). Conclusions: MA occurred in 2% of the patients with IE. Half of the Mas occurred in an intracranial location. Their rupture is frequent and associated with poor prognosis. A significant proportion of initially unruptured aneurysms result from rupture during the first several days, being more common in intracranial aneurysms. Early specific treatment could potentially lead to better outcomes.

Clinical features of patients inappropriately undiagnosed of pulmonary embolism.

PURPOSES: The objective of this study was to identify clinical factors associated with delayed diagnosis of acute pulmonary embolism (PE) in the emergency department (ED). BASIC PROCEDURES: A retrospective observational study was performed at three University affiliated Hospitals; 436 consecutive patients who presented to the ED with an acute PE confirmed by chest computed tomography from 2008 to 2011 were included. Patients were divided into 3 groups: group 1, PE was diagnosed while the patient was still in the ED; group 2, PE was diagnosed during hospitalization; group 3, patients who were sent home with a wrong alternative diagnosis and returned to the ED and were diagnosed of PE. MAIN FINDINGS: One hundred forty-six patients (33.5%) had a delayed diagnosis of PE--21.5% belong to group 2 and 11.9% to Group 3. Chronic coexisting medical conditions like asthma or chronic obstructive pulmonary disease were independent predictors of a delayed diagnosis in patients who were admitted to hospital whereas non-specific and less severe symptoms like the presence of pleuro-mechanic thoracic pain, fever, hemoptysis, or the presence of a pulmonary infiltrate in chest x-ray were independent predictors of a delayed diagnosis in patients who were sent home. PRINCIPAL CONCLUSIONS: Delay in diagnosis of acute PE is frequent despite current diagnostic strategies. Patients are sent home or admitted to hospital with a wrong diagnosis depending on clinical presentation or coexisting medical conditions.

Determining the usefulness of systematic 18F-FDG PET/CT for the management of invasive fungal infection (PETIFI project): a prospective national multicentre cohort study protocol.

INTRODUCTION: The evaluation of staging and activity of invasive fungal infection (IFI) is used to adjust the type and duration of antifungal therapy (AT). Typically anatomy-based imaging is used. Positron emission tomography/CT with 18F-fluorodeoxyglucose (18F-FDG PET/CT) not only evaluates more than one body area in one session, but adds functional information to the anatomic data provided by usual imaging techniques and can potentially improve staging of IFI and monitoring of the response to therapy. Our objective is to analyse the impact of the systematic use of 18F-FDG PET/CT in IFI diagnostic and therapeutic management. METHODS AND ANALYSIS: Multicentre prospective cohort study of IFI with performance of systematic 18F-FDG PET/CT at diagnosis and follow-up that will be carried out in 14 Spanish tertiary hospitals. It is planned to include 224 patients with IFI over a 2-year study period. Findings and changes in management before and after 18F-FDG PET/CT will be compared. Additionally, the association of initial quantitative 18F-FDG PET/CT parameters with response to therapy will be evaluated.The primary endpoint is to compare the yield of 18F-FDG PET/CT with standard management without 18F-FDG PET/CT in IFI at initial assessment (staging) and in monitoring the response to treatment.The impact of the results of 18F-FDG PET/CT on the diagnostic-therapeutic management of patients with IFI (added value), as well as the prognostic ability of different quantification parameters of 18F-FDG PET/CT will be secondary endpoints. ETHICS AND DISSEMINATION: The Clinical Research Ethics Committee of Puerta de Hierro-Majadahonda University Hospital approved the protocol of the study at the primary site. We plan to publish the results in high-impact journals. TRIAL REGISTRATION NUMBER: NCT05688592.

Increased incidence of giant cell arteritis and associated stroke during the COVID-19 pandemic in Spain: A nation-wide population study.

INTRODUCTION: SARS-CoV-2 infection and COVID-19 vaccines might have increased the incidence of giant-cell arteritis (GCA) and the risk of associated stroke in Spain. METHODS: Retrospective nation-wide observational analysis of all adults hospitalized with GCA in Spain during 5 years (Jan-2016 and Dec-2021). The incidence and proportion of admissions with or because of GCA and GCA-associated stroke were compared between pre-pandemic (2016-2019) and pandemic (2020 and 2021) years. Sensitivity analyses were conducted for the different COVID-19 waves and vaccine timing schedules. RESULTS: A total of 17,268 hospital admissions in patients diagnosed with GCA were identified. During 2020 there were 79.3 and 8.1 per 100,000 admissions of GCA and GCA-associated stroke, respectively. During 2021 these figures were 80.8 and 7.7 per 100,00 admissions, respectively. As comparison, yearly admissions due to GCA and GCA-associated stroke were 72.4 and 5.7 per 100,00, respectively, during the pre-pandemic period (p < 0.05). Coincident with the third wave of COVID-19 (and first vaccine dosing), the rate of GCA-associated stroke admissions increased significantly (from 6.7 to 12%; p < 0.001). Likewise, there was an increase in GCA-associated stroke (6.6% vs 4.1%, p = 0.016) coincident with the third dose vaccination (booster) in patients older than 70 at the end of 2021. In multivariate analysis, only patients admitted during the third COVID-19 wave (and first vaccine dosing) (OR = 1.89, 95% CI 1.22-2.93), and during the third vaccination dosing in patients older than 70 (booster) (OR = 1.66, CI 1.11-2.49), presented a higher GCA-associated stroke risk than the same months of previous years after adjustment by age, sex, classical cardiovascular risk factors and COVID-19 diagnosis. CONCLUSIONS: The COVID-19 pandemic led to an increased incidence of GCA during 2020 and 2021. Moreover, the risk of associated stroke significantly risen accompanying times of COVID-19 vaccine dosing, hypothetically linked to an increased thrombotic risk of mRNA-SARS-CoV-2 vaccines. Hence, forthcoming vaccine policies and indications must weigh the risk of severe COVID-19 with the risk of flare or stroke in patients with GCA.

Risk of Infective Endocarditis Associated with Transcatheter Aortic Valve Implantation versus Surgical Aortic Valve Replacement: A Propensity Score-Based Analysis.

Background: Infective endocarditis (IE) is a feared complication after surgical aortic valve replacement (SAVR)/transcatheter aortic valve implantation (TAVI). It is not certain which procedure carries a higher risk. Our aim was to assess the risk of IE after SAVR/TAVI. Methods: We conducted an observational study of a prospective cohort, including patients with TAVI/SAVR, from March 2015 to December 2020. IE was defined according to the modified Duke's criteria. IE occurring during the first 12 months of the procedure was considered early IE, and an episode occurring after 12 months was considered late IE. The propensity score was designed to include variables previously associated with TAVI/SAVR and IE. An inverse probability of treatment weight was generated. Results: In total, 355 SAVR and 278 TAVI were included. Median follow-up, 38 vs. 41 months, p = 0.550. IE occurred in 5 SAVR (1.41%, 95% CI 0.2−2.6) vs. 13 TAVI (4.65%, 95% CI 2.2−7.2), p = 0.016. TAVI patients had more frequent early IE (3.2% vs. 0.3%, p = 0.006). In the PS analyses, IE risk did not differ: OR 0.65, 95% CI 0.32−1.32. Factors associated with TAVI IE included younger age (74y vs. 83y, p = 0.030), complicated diabetes mellitus (38.5% vs. 6.8%, p = 0.002), COPD (46.2% vs. 16.3%, p = 0.015), advanced heart failure (100% vs. 52.9%, p < 0.001), and peripheral arteriopathy (61.5% vs. 26.7%, p = 0.011). Conclusions: Early IE was higher with TAVI, but in the PS analyses, the risk attributable to each procedure was similar. Studies are needed to identify and optimize the risk factors of IE prior to TAVI.

Use of Monoclonal Antibodies in Immunocompromised Patients Hospitalized with Severe COVID-19: A Retrospective Multicenter Cohort.

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.

Sequential oral antibiotic in uncomplicated Staphylococcus aureus bacteraemia: a propensity-matched cohort analysis.

OBJECTIVES: We aimed to analyse the efficacy and safety of oral sequential therapy (OST) in uncomplicated Staphylococcus aureus bacteraemia (SAB). METHODS: Single-centre observational cohort at a tertiary hospital in Spain, including all patients with the first SAB episode from January 2015 to December 2020. We excluded patients with complicated SAB and those who died during the first week. Patients were classified into the OST group (patients who received oral therapy after initial intravenous antibiotic therapy [IVT]), and IVT group (patients who received exclusively IVT). We performed a propensity-score matching to balance baseline differences. The primary composite endpoint was 90-day mortality or microbiological failure. Secondary endpoints included 90-day SAB relapse. RESULTS: Out of 407 SAB first episodes, 230 (56.5%) were included. Of these, 112 (n = 48.7%) received OST and 118 (51.3%) IVT exclusively. Transition to oral therapy was performed after 7 days (interquartile range, 4-11). The primary endpoint occurred in 10.7% (11/112) in OST vs. 30.5% (36/118) in IVT (p < 0.001). SAB relapses occurred in 3.6% (4/112) vs. 1.7% (2/118) (p 0.436). None of the deaths in OST were related to SAB or its complications. After propensity-score matching, the primary endpoint was not more frequent in the OST group (relative risk, 0.42; 95% CI, 0.22-0.79). Ninety-day relapses occurred similarly in both groups (relative risk, 1.35; 95% CI, 0.75-2.39). DISCUSSION: After an initial intravenous antibiotic, patients with uncomplicated SAB can safely be switched to oral antibiotics without apparent adverse outcomes. This strategy could save costs and complications of prolonged hospital stays. Prospective randomized studies are needed.

Clinical presentation, microbiology, and prognostic factors of prosthetic valve endocarditis. Lessons learned from a large prospective registry.

BACKGROUND: Prosthetic valve endocarditis (PVE) is a serious infection associated with high mortality that often requires surgical treatment. METHODS: Study on clinical characteristics and prognosis of a large contemporary prospective cohort of prosthetic valve endocarditis (PVE) that included patients diagnosed between January 2008 and December 2020. Univariate and multivariate analysis of factors associated with in-hospital mortality was performed. RESULTS: The study included 1354 cases of PVE. The median age was 71 years with an interquartile range of 62-77 years and 66.9% of the cases were male. Patients diagnosed during the first year after valve implantation (early onset) were characterized by a higher proportion of cases due to coagulase-negative staphylococci and Candida and more perivalvular complications than patients detected after the first year (late onset). In-hospital mortality of PVE in this series was 32.6%; specifically, it was 35.4% in the period 2008-2013 and 29.9% in 2014-2020 (p = 0.031). Variables associated with in-hospital mortality were: Age-adjusted Charlson comorbidity index (OR: 1.15, 95% CI: 1.08-1.23), intracardiac abscess (OR:1.78, 95% CI:1.30-2.44), acute heart failure related to PVE (OR: 3. 11, 95% CI: 2.31-4.19), acute renal failure (OR: 3.11, 95% CI:1.14-2.09), septic shock (OR: 5.56, 95% CI:3.55-8.71), persistent bacteremia (OR: 1.85, 95% CI: 1.21-2.83) and surgery indicated but not performed (OR: 2.08, 95% CI: 1.49-2.89). In-hospital mortality in patients with surgical indication according to guidelines was 31.3% in operated patients and 51.3% in non-operated patients (p<0.001). In the latter group, there were more cases of advanced age, comorbidity, hospital acquired PVE, PVE due to Staphylococcus aureus, septic shock, and stroke. CONCLUSIONS: Not performing cardiac surgery in patients with PVE and surgical indication, according to guidelines, has a significant negative effect on in-hospital mortality. Strategies to better discriminate patients who can benefit most from surgery would be desirable.

COVID-19 in hospitalized solid organ transplant recipients in a nationwide registry study.

OBJECTIVES: Underlying immunodeficiency has been associated with worse clinical presentation and increased mortality in patients with COVID-19. We evaluated the mortality of solid organ transplant (SOT) recipients (SOTR) hospitalized in Spain due to COVID-19. METHODS: Nationwide, retrospective, observational analysis of all adults hospitalized because of COVID-19 in Spain during 2020. Stratification was made according to SOT status. The National Registry of Hospital Discharges was used, using the International Classification of Diseases, 10th revision coding list. RESULTS: Of the 117,694 adults hospitalized during this period, 491 were SOTR: kidney 390 (79.4%), liver 59 (12%), lung 27 (5.5%), and heart 19 (3.9%). Overall, the mortality of SOTR was 13.8%. After adjustment for baseline characteristics, SOTR was not associated with higher mortality risk (odds ratio [OR] = 0.79, 95% confidence interval [CI] 0.60-1.03). However, lung transplantation was an independent factor related to mortality (OR = 3.26, 95% CI 1.33-7.43), while kidney, liver, and heart transplantation were not. Being a lung transplant recipient was the strongest prognostic factor in SOT patients (OR = 5.12, 95% CI 1.88-13.98). CONCLUSION: This nationwide study supports that the COVID-19 mortality rate in SOTR in Spain during 2020 did not differ from the general population, except for lung transplant recipients, who presented worse outcomes. Efforts should be focused on the optimal management of lung transplant recipients with COVID-19.

Risk of endocarditis among patients with coagulase-negative Staphylococcus bacteremia.

Coagulase-negative staphylococci (CoNS) are currently considered typical microorganisms causing infective endocarditis (IE) in patients with prosthetic valves. The objective was to determine variables associated with IE in patients with CoNS bacteremia. We performed an analysis of the clinical characteristics of patients with CoNS bacteremia admitted to a university hospital in Madrid (Spain) from 2021 to December 2022 according to the occurrence of IE. This study is an evaluation of a bacteremia registry. During the study period, 106 patients with CoNS bacteremia were detected. In 85 patients an echocardiogram was performed during hospital admission to rule out IE. Among them, 12 episodes were detected that met IE criteria (14.2%). Of the 6 patients with heart valve prostheses, 5 patients (83.3%) had IE (p < 0.001). Patients with IE more frequently had positive blood cultures more than 12 h after the first draw (58.3% versus 13.4%; p < 0.001). There was a tendency to associate community-acquired bacteremia and to that all blood culture bottles obtained were positive with an increased risk of IE (p = 0.091 and p = 0,057, respectively). Attributable mortality to infection was higher in patients with IE relative to all other patients (16.7% vs. 0%; p = 0.033). The multivariable analysis included having valve prosthesis and persistent bacteremia for more than 12 h. Both were independently associated with IE: valve prosthesis OR 38.6 (95% CI 5.8-258; p < 0.001) and persistent bacteremia OR 2.6 (95% CI 1.1-6.8; p = 0.046). In conclusion, a high percentage of cases of CoNS bacteremia may be due to IE. Some of the variables related to a higher risk of IE, such as having a valvular prosthesis or presenting positive blood cultures for more than 12 h, should lead to rule out or confirm the presence of IE by performing echocardiography.

Ceft-to-Ceft Study: Real-Life Experience with Ceftaroline and Ceftobiprole in Treatment of the Principal Infectious Syndromes in a Spanish Multicenter Hospital Cohort.

BACKGROUND: To compare the real-life effectiveness and safety of ceftaroline fosamil (ceftaroline-F) and ceftobiprole medocaril (ceftobiprole-M) for infections in hospitalized patients. METHODS: This comparative, observational, retrospective, and multicenter Spanish study included patients receiving outpatient parenteral antimicrobial therapy (OPAT) and hospitalized patients treated for at least 48 h with ceftaroline-F or ceftobiprole-M between their first incorporation in the clinical protocol of each hospital and 31 July 2022. RESULTS: Ceftaroline-F was administered to 227 patients and ceftobiprole-M to 212. In comparison to the latter, ceftaroline-F-treated participants were younger (63.02 vs. 66.40 years, OR 1.1; 95%CI: 1.001-1.05) and had higher rates of septic shock (OR 0.27; 95%CI: 0.09-0.81) and higher frequencies of targeted (57.7 vs. 29.7%; OR: 0.35; 95%CI: 0.18-0.69) and combined (89.0 vs. 45.8%, OR: 0.13; 95%CI: 0.06-0.28) therapies that were second line or more (82.4% vs. 64.6%%; OR 0.35; 95%CI: 0.18-0.69), and higher rates of infections due to Gram-positive cocci (92.7 vs. 64.7%, p = 0.001), bacteremia (51.9 vs. 21.7%, p = 0.001), infective endocarditis (24.2 vs. 2.4%, p = 0.0001), and mechanical ventilation-associated pneumonia (8.8 vs. 2.4%, p = 0.0001). Ceftobiprole-M was more frequently administered against polymicrobial infections (38.1 vs. 14.0%, p = 0.001), those produced by Gram-negative bacilli (19.7 vs. 6.0%, p = 0.0001), nosocomial pneumonia (33 vs. 10.6%, p = 0.0001), and skin and soft-tissue infections (25.4 vs. 10.1%, p = 0.0001). Patients treated with ceftaroline-F had a longer hospital stay (36 (IQR: 19-60) vs. 19.50 (IQR: 12-30.75, p = 0.0001) days), with no difference in infection-related mortality at 14 (13.2 vs. 8.0%, p = 0.078) or 28 (4.8 vs. 3.3%, p = 0.415) days or in dropout rate for adverse effects (2.2 vs. 0.9%; p = 1). CONCLUSIONS: The fifth-generation cephalosporins, ceftaroline-F and ceftobiprole-M, are safe and effective in real life, with no difference between them in health outcomes.