Deciphering the quality of SARS-CoV-2 specific T-cell response associated with disease severity, immune memory and heterologous response.

SARS-CoV-2 specific T-cell response has been associated with disease severity, immune memory and heterologous response to endemic coronaviruses. However, an integrative approach combining a comprehensive analysis of the quality of SARS-CoV-2 specific T-cell response with antibody levels in these three scenarios is needed. In the present study, we found that, in acute infection, while mild disease was associated with high T-cell polyfunctionality biased to IL-2 production and inversely correlated with anti-S IgG levels, combinations only including IFN-γ with the absence of perforin production predominated in severe disease. Seven months after infection, both non-hospitalised and previously hospitalised patients presented robust anti-S IgG levels and SARS-CoV-2 specific T-cell response. In addition, only previously hospitalised patients showed a T-cell exhaustion profile. Finally, combinations including IL-2 in response to S protein of endemic coronaviruses were the ones associated with SARS-CoV-2 S-specific T-cell response in pre-COVID-19 healthy donors' samples. These results could have implications for protective immunity against SARS-CoV-2 and recurrent COVID-19 and may help for the design of new prototypes and boosting vaccine strategies.

Clinical Outcomes of an Innovative Cefazolin Delivery Program for MSSA Infections in OPAT.

Cefazolin is a recommended treatment for methicillin-susceptible Staphylococcus aureus (MSSA) infections that has been successfully used in outpatient parenteral antibiotic therapy (OPAT) programs. The aim of this study was to assess the clinical outcomes of cefazolin delivered each day (Group 24) vs. every two days (Group 48) for MSSA infections in OPAT programs. It was a prospective observational study with retrospective analysis of a cohort of MSSA infections attended in OPAT. The primary outcome was treatment success, defined as completing the antimicrobial regimen without death, treatment discontinuation, or readmission during treatment and follow-up. A univariate and multivariate logistic regression model was built. A two-sided p < 0.05 was considered statistically significant. Of the 149 MSSA infections treated with cefazolin 2 g/8 h in OPATs, 94 and 55 patients were included in the delivery Group 24 and Group 48, respectively. Treatment failure and unplanned readmission rates were similar in both groups (11.7% vs. 7.3% p = 0.752 and 8.5% vs. 5.5% p = 0.491). There was a significant increase in vascular access complications in Group 24 (33.0%) with respect to Group 48 (7.3%) (p < 0.001). Treating uncomplicated MSSA infection with cefazolin home-delivered every two days through an OPAT program is not associated with an increased risk of treatment failure and entails a significant reduction in resource consumption compared to daily delivery.

Seven-versus 14-day course of antibiotics for the treatment of bloodstream infections by Enterobacterales: a randomized, controlled trial.

OBJECTIVE: To prove that 7-day courses of antibiotics for bloodstream infections caused by members of the Enterobacterales (eBSIs) allow a reduction in patients' exposure to antibiotics while achieving clinical outcomes similar to those of 14-day schemes. METHODS: A randomized trial was performed. Adult patients developing eBSI with appropriate source control were assigned to 7 or 14 days of treatment, and followed 28 days after treatment cessation; treatments could be resumed whenever necessary. The primary endpoint was days of treatment at the end of follow-up. Clinical outcomes included clinical cure, relapse of eBSI and relapse of fever. A superiority margin of 3 days was set for the primary endpoint, and a non-inferiority margin of 10% was set for clinical outcomes. Efficacy and safety were assessed together with a DOOR/RADAR (desirability of outcome ranking and response adjusted for duration of antibiotic risk) analysis. RESULTS: 248 patients were assigned to 7 (n = 119) or 14 (n = 129) days of treatment. In the intention-to-treat analysis, median days of treatment at the end of follow-up were 7 and 14 days (difference 7, 95%CI 7-7). The non-inferiority margin was also met for clinical outcomes, except for relapse of fever (-0.2%, 95%CI -10.4 to 10.1). The DOOR/RADAR showed that 7-day schemes had a 77.7% probability of achieving better results than 14-day treatments. CONCLUSIONS: 7-day schemes allowed a reduction in antibiotic exposure of patients with eBSI while achieving outcomes similar to those of 14-day schemes. The possibility of relapsing fever in a limited number of patients, without relevance to final outcomes, may not be excluded, but was overcome by the benefits of shortening treatments.

Prosthetic Shoulder Joint Infection by Cutibacterium acnes: Does Rifampin Improve Prognosis? A Retrospective, Multicenter, Observational Study.

This retrospective, multicenter observational study aimed to describe the outcomes of surgical and medical treatment of C. acnes-related prosthetic joint infection (PJI) and the potential benefit of rifampin-based therapies. Patients with C. acnes-related PJI who were diagnosed and treated between January 2003 and December 2016 were included. We analyzed 44 patients with C. acnes-related PJI (median age, 67.5 years (IQR, 57.3-75.8)); 75% were men. The majority (61.4%) had late chronic infection according to the Tsukayama classification. All patients received surgical treatment, and most antibiotic regimens (43.2%) included ß-lactam. Thirty-four patients (87.17%) were cured; five showed relapse. The final outcome (cure vs. relapse) showed a nonsignificant trend toward higher failure frequency among patients with previous prosthesis (OR: 6.89; 95% CI: 0.80-58.90) or prior surgery and infection (OR: 10.67; 95% IC: 1.08-105.28) in the same joint. Patients treated with clindamycin alone had a higher recurrence rate (40.0% vs. 8.8%). Rifampin treatment did not decrease recurrence in patients treated with ß-lactams. Prior prosthesis, surgery, or infection in the same joint might be related to recurrence, and rifampin-based combinations do not seem to improve prognosis. Debridement and implant retention appear a safe option for surgical treatment of early PJI.

Implant Removal in the Management of Prosthetic Joint Infection by Staphylococcus aureus: Outcome and Predictors of Failure in a Large Retrospective Multicenter Study.

OBJECTIVES: To compare the characteristics and outcomes of cases with acute prosthetic joint infection (PJI; early post-surgical or hematogenous) by Staphylococcus aureus managed with implant removal (IRm) or debridement and retention (DAIR). To analyze the outcomes of all cases managed with IRm (initially or after DAIR failure). METHODS: Retrospective, multicenter, cohort study of PJI by S. aureus (2003-2010). Overall failure included mortality within 60 days since surgery and local failure due to staphylococcal persistence/relapse. RESULTS: 499 cases, 338 initially managed with DAIR, 161 with IRm. Mortality was higher in acute PJI managed initially with IRm compared to DAIR, but not associated with the surgical procedure, after propensity score matching. Underlying conditions, hemiarthroplasty, and methicillin-resistant S. aureus were risk factors for mortality. Finally, 249 cases underwent IRm (88 after DAIR failure); overall failure was 15.6%. Local failure (9.3%) was slightly higher in cases with several comorbidities, but independent of previous DAIR, type of IRm, and rifampin treatment. CONCLUSIONS: In a large multicenter study of S. aureus PJI managed with IRm, failure was low, but mortality significant, especially in cases with acute PJI and underlying conditions, but not associated with the IRm itself. Rifampin efficacy was limited in this setting.

Repeated Pulses of Methyl-Prednisolone in Adults Hospitalized With COVID-19 Pneumonia and Acute Respiratory Distress Syndrome: A Preliminary Before-After Study (CortiCOVID Study).

Introduction: The use of systemic corticosteroids in severely ill patients with coronavirus disease 2019 (COVID-19) is controversial. We aimed to evaluate the efficacy and safety of corticosteroid pulses in patients with COVID-19 pneumonia. Methods: A quasi-experimental study, before and after, was performed in a tertiary referral hospital, including admitted patients showing COVID-19-associated pneumonia. The standard treatment protocol included targeted COVID-19 antiviral therapy from 23rd March 2020, and additionally pulses of methylprednisolone from 30th March 2020. The primary outcome was a composite endpoint combining oro-tracheal intubation (OTI) and death within 7 days. Results: A total of 24 patients were included. Standard of care (SOC) (before intervention) was prescribed in 14 patients, while 10 received SOC plus pulses of methylprednisolone (after intervention). The median age of patients was 64.5 years and 83.3% of the patients were men. The primary composite endpoint occurred in 13 patients (92.9%) who received SOC vs. 2 patients (20%) that received pulses of methylprednisolone (odds ratio, 0.02; 95% confidence interval, 0.001 to 0.25; p = 0.019). Length of hospitalization in survivors was shorter in the corticosteroids group (median, 14.5 [8.5-21.8] days vs. 29 [23-31] days, p = 0.003). There were no differences in the development of infections between both groups. There were 3 deaths, none of them in the corticosteroids group. Conclusions: In patients with severe pneumonia due to COVID-19, the administration of methylprednisolone pulses was associated with a lower rate of OTI and/or death and a shorter hospitalization episode.

Introducción: El uso de corticosteroides sistémicos en pacientes gravemente enfermos por enfermedad coronavírica de 2019 (covid-19) es controvertido. Nuestro objetivo fue evaluar la eficacia y la seguridad de los pulsos de corticoesteroides en los pacientes con neumonía por covid-19. Métodos: Se realizó un ensayo cuasiexperimental, tipo antes y después, en un hospital terciario de referencia que incluyó a pacientes ingresados por neumonía asociada a covid-19. El protocolo de tratamiento estándar incluía un tratamiento antiviral dirigido contra el virus de la covid-19 desde el 23 de marzo de 2020 y añadió pulsos de metilprednisolona desde el 30 de marzo de 2020. El resultado primario fue un criterio combinado compuesto por la intubación orotraqueal y el fallecimiento durante los siguientes siete días. Resultados: Se incluyó un total de 24 pacientes. El protocolo de tratamiento (antes de la intervención) se prescribió en 14 pacientes, mientras que 10 recibieron el protocolo de tratamiento además de los pulsos de metilprednisolona (después de la intervención). La edad media de los pacientes fue de 64,5 años y el 83,3% de los pacientes eran hombres. El resultado combinado primario tuvo lugar en 13 pacientes (92,9%) que recibieron el protocolo de tratamiento frente a 2 pacientes (20%) que recibieron los pulsos de metilprednisolona (odds ratio = 0,02; intervalo de confianza del 95% = 0,001-0,25; p = 0,019). La duración de la hospitalización en los supervivientes fue más corta en el grupo que recibió corticoesteroides (media = 14,5 [8,5-21,8] días frente a 29 [23-31] días, p = 0,003). No hubo diferencias en el desarrollo de infecciones entre ambos grupos. Hubo tres fallecimientos, ninguno de ellos en el grupo que recibió corticoesteroides. Conclusiones: En los pacientes con neumonía grave por covid-19, la administración de pulsos de metilprednisolona se asoció a unas tasas menores de intubación orotraqueal y/o muerte y a episodios de hospitalización más cortos.

Antifungal treatment administered in OPAT programs is a safe and effective option in selected patients / Tratamiento antifúngico endovenoso domiciliario: una alternativa segura y eficaz

INTRODUCTION: Outpatient parenteral antimicrobial therapy (OPAT) has been recognised as a useful, cost-effective and safe alternative to inpatient treatment. Nevertheless, the most common antimicrobials used are antibiotics, and there is less information about the use of antifungal therapy (AT). The aim of this study is to analyse a cohort of patients treated with AT administered via OPAT and to compare them with patients from the rest of the cohort (RC) treated with antibiotics. METHODS: Prospective observational study with post hoc (or retrospective) analysis of a cohort of patients treated in the OPAT program. We selected the patients treated with antifungals between July 2012 and December 2018. We recorded demographic and clinical data to analyse the validity of the treatment and to compare the differences between the AT and the RC. RESULTS: Of the 1101 patients included in the OPAT program, 24 (2.18%) were treated with AT, 12 Liposomal Amphotericin B, 6 echinocandins and 6 fluconazole. This result is similar to other cohorts. There were differences between the AT vs RC in the number of patients with neoplasia (58.3% vs 28%; p = 0.001), IC Charlson > 2 (58.3% vs 38.8; p = 0.053), duration of treatment (15 days vs 10.39 days; p = 0.001) and patients with central catheters (54.2% vs 21.7%; p = 0.0001). These differences are justified because there were more hematologic patients included in the AT group. Nevertheless, there were no differences in adverse reactions (25% vs 32.3%; p = 0.45) or re-admissions (12.5% vs 10%; p = 0.686) and OPAT with AT was successful in 21/24 patients (87.5%). CONCLUSIONS: AT can be successfully administered in OPAT programs in selected patients, that are clinically stable and monitored by an infectious disease physician

INTRODUCCIÓN: El tratamiento antimicrobiano domiciliario endovenoso (TADE) ha sido reconocido como una alternativa al tratamiento hospitalario útil, eficiente y seguro. Sin embargo, los antimicrobianos más utilizados son los antibióticos, y existe menos información sobre el uso de la terapia antimicótica (TA). El objetivo de este estudio es analizar una cohorte de pacientes tratados con TA administrada mediante TADE y compararlos con pacientes del resto de la cohorte (RC) tratados con otros antibióticos. MÉTODOS: Estudio prospectivo observacional con análisis post hoc (o retrospectivo) de una cohorte de pacientes atendidos en el programa TADE. Seleccionamos a los pacientes tratados con antifúngicos entre julio de 2012 y diciembre de 2018. Registramos los datos demográficos y clínicos para analizar la validez del tratamiento y comparar las diferencias entre la TA y el RC. RESULTADOS: De los 1.101 pacientes incluidos en el programa TADE, 24 (2,18%) fueron tratados con TA: 12 anfotericina B liposómica, 6 equinocandinas y 6 fluconazol. Este resultado es similar a otras cohortes. Hubo diferencias entre la TA vs. RC en el número de pacientes con neoplasia (58,3 vs. 28%; p = 0,001), índice de Charlson > 2 (58,3 vs. 38,8; p = 0,053), duración del tratamiento (15 vs. 10,39 días; p = 0,001) y pacientes con catéteres centrales (54,2 vs. 21,7%; p = 0,0001). Estas diferencias están justificadas porque en el grupo TA se incluyeron más pacientes hematológicos. Sin embargo, no hubo diferencias en las reacciones adversas (25 vs. 32,3%; p = 0,45) o reingresos (12,5 vs. 10%; p = 0,686) y el TADE con TA tuvo éxito en 21/24 pacientes (87,5%). CONCLUSIONES: En pacientes seleccionados, clínicamente estables y en seguimiento por un médico de enfermedades infecciosas, la TA podría administrarse en programas TADE

Quasiexperimental intervention study protocol to optimise the use of new antibiotics in Spain: the NEW_SAFE project.

INTRODUCTION: Ceftaroline, tedizolid, dalbavancin, ceftazidime-avibactam and ceftolozane-tazobactam are novel antibiotics used to treat infections caused by multidrug-resistant pathogens (MDR). Their use should be supervised and monitored as part of an antimicrobial stewardship programme (ASP). Appropriate use of the new antibiotics will be improved by including consensual indications for their use in local antibiotic guidelines, together with educational interventions providing advice to prescribers to ensure that the recommendations are clearly understood. METHODS AND ANALYSIS: This study will be implemented in two phases. First, a preliminary historical cohort (2017-2019) of patients from 13 Andalusian hospitals treated with novel antibiotics will be analysed. Second, a quasiexperimental intervention study will be developed with an interrupted time-series analysis (2020-2021). The intervention will consist of an educational interview between prescribers and ASP leaders at each hospital to reinforce the proper use of novel antibiotics. The educational intervention will be based on a consensus guideline designed and disseminated by leaders after the retrospective cohort data have been analysed. The outcomes will be acceptance of the intervention and appropriateness of prescription. Incidence of infection and colonisation with MDR organisms as well as incidence of Clostridioides difficile infection will also be analysed. Changes in prescription quality between periods and the safety profile of the antibiotics in terms of mortality rate and readmissions will also be measured. ETHICS AND DISSEMINATION: Ethical approval will be obtained from the Andalusian Coordinating Institutional Review Board. The study is being conducted in compliance with the protocol and regulatory requirements consistent with International Council of Harmonisation E6 Good Clinical Practice and the ethical principles of the latest version of the Declaration of Helsinki. The results will be published in peer-reviewed journals and disseminated at national and international conferences. TRIAL REGISTRATION NUMBER: NCT03941951; Pre-results.

Antifungal treatment administered in OPAT programs is a safe and effective option in selected patients.

INTRODUCTION: Outpatient parenteral antimicrobial therapy (OPAT) has been recognised as a useful, cost-effective and safe alternative to inpatient treatment. Nevertheless, the most common antimicrobials used are antibiotics, and there is less information about the use of antifungal therapy (AT). The aim of this study is to analyse a cohort of patients treated with AT administered via OPAT and to compare them with patients from the rest of the cohort (RC) treated with antibiotics. METHODS: Prospective observational study with post hoc (or retrospective) analysis of a cohort of patients treated in the OPAT program. We selected the patients treated with antifungals between July 2012 and December 2018. We recorded demographic and clinical data to analyse the validity of the treatment and to compare the differences between the AT and the RC. RESULTS: Of the 1101 patients included in the OPAT program, 24 (2.18%) were treated with AT, 12 Liposomal Amphotericin B, 6 echinocandins and 6 fluconazole. This result is similar to other cohorts. There were differences between the AT vs RC in the number of patients with neoplasia (58.3% vs 28%; p=0.001), IC Charlson>2 (58.3% vs 38.8; p=0.053), duration of treatment (15 days vs 10.39 days; p=0.001) and patients with central catheters (54.2% vs 21.7%; p=0.0001). These differences are justified because there were more hematologic patients included in the AT group. Nevertheless, there were no differences in adverse reactions (25% vs 32.3%; p=0.45) or re-admissions (12.5% vs 10%; p=0.686) and OPAT with AT was successful in 21/24 patients (87.5%). CONCLUSIONS: AT can be successfully administered in OPAT programs in selected patients, that are clinically stable and monitored by an infectious disease physician.

Hepatitis aguda grave y anemia hemolítica por crioaglutininas secundarias a primoinfección por virus Epstein-Barr / Severe acute hepatitis and cold agglutinin-related hemolytic anemia secondary to prime infection with Epstein-Barr virus

El virus Ebstein-Barr, miembro de la familia Herpesviridae, es responsable del síndrome clínico conocido como mononucleosis infecciosa, que consiste principalmente en la triada faringitis, fiebre y linfadenopatía, tras un periodo de incubación de entre 30 y 50 días. La afectación hepática suele darse en el 80-90% de los pacientes de forma autolimitada y transitoria, mientras que es bastante menos frecuente que se produzca ictericia (5%). Desde el punto de vista hematológico puede cursar con anemia hemolítica, anemia aplásica, neutropenia y trombocitopenia. Presentamos un caso clínico de mononucleosis infecciosa que cursó con hepatitis aguda grave y asoció anemia hemolítica severa secundaria a crioaglutininas. Tras descartar otras etiologías y ante la sospecha clínica y posterior confirmación analítica de la asociación antes mencionada, se instauró tratamiento empírico con antivirales (aciclovir + valganciclovir) y corticoides, objetivando mejoría progresiva hasta la resolución completa del cuadro clínico. Creemos, por tanto, que este caso sirve para reforzar el cuerpo de evidencia clínica que apoya esta terapia conjunta en los casos más graves de mononucleosis infecciosa como paso previo al trasplante hepático (AU)

Epstein-Barr virus, a member of the Herpesviridae family, is responsible for the infectious mononucleosis clinical syndrome, which mainly includes the pharyngitis, fever, and lymphadenopathy triad after incubation for 30-50 days. The liver is involved in 80-90% of patients in a self-limiting transient manner, with jaundice being much more uncommon (5%). From a hematological standpoint it may manifest aplastic anemia, neutropenia, and thrombocytopenia. We report a case of infectious mononucleosis that included severe acute hepatitis and was associated with severe hemolytic anemia secondary to cold agglutinins. After exclusion of other etiologies, and given the clinical suspicion of the above association, which was later confirmed by lab tests, empiric therapy was initiated with antiviral agents (aciclovir + valganciclovir) and corticoids, which resulted in a progressive clinical improvement until complete remission. Therefore, we believe that this case report will reinforce the clinical evidence in support of the above combined therapy for serious infectious mononucleosis as a step prior to liver transplantation (AU)

Severe acute hepatitis and cold agglutinin-related hemolytic anemia secondary to prime infection with Epstein-Barr virus.

Epstein-Barr virus, a member of the Herpesviridae family, is responsible for the infectious mononucleosis clinical syndrome, which mainly includes the pharyngitis, fever, and lymphadenopathy triad after incubation for 30-50 days. The liver is involved in 80-90% of patients in a self-limiting transient manner, with jaundice being much more uncommon (5%). From a hematological standpoint it may manifest aplastic anemia, neutropenia, and thrombocytopenia. We report a case of infectious mononucleosis that included severe acute hepatitis and was associated with severe hemolytic anemia secondary to cold agglutinins. After exclusion of other etiologies, and given the clinical suspicion of the above association, which was later confirmed by lab tests, empiric therapy was initiated with antiviral agents (aciclovir + valganciclovir) and corticoids, which resulted in a progressive clinical improvement until complete remission. Therefore, we believe that this case report will reinforce the clinical evidence in support of the above combined therapy for serious infectious mononucleosis as a step prior to liver transplantation.

Aproximación clínica a la eosinofilia importada / Clinical approach to imported eosinophilia

La eosinofilia es frecuente en viajeros e inmigrantes, siendo las helmintosis su principal etiología. El valor predictivo positivo de la eosinofilia para una infección parasitaria es bajo en viajeros. La eosinofilia puede ser un hallazgo incidental o sintomático, y constituye un reto clínico debido a la baja sensibilidad y especificidad de las técnicas parasitológicas directas e indirectas, respectivamente. Requiere una aproximación estructurada basada en áreas geográficas, riesgos de exposición ambientales y conductuales, y síntomas asociados. La evaluación inicial debe incluir anamnesis y exploración física dirigidas, analítica básica, examen coproparasitológico completo y serología de Strongyloides stercoralis, complementada con otras pruebas según procedencia y sospecha clínica. El tratamiento empírico con albendazol y/o ivermectina (más praziquantel si hay riesgo de esquistosomiasis) es una opción en eosinofilias persistentes no filiadas tras estudio, y en personas en las que la evaluación inicial o el seguimiento no se puedan asegurar. En pacientes con riesgo de estrongiloidosis candidatos a inmunodepresión farmacológica está indicado el cribado y tratamiento previo para prevenir el síndrome de hiperinfestación

Eosinophilia is a common finding in international travelers and immigrants, being an helmintic infection its main etiology. The positive predictive value of eosinophilia for an helmintosis is low in travellers. Eosinophilia may be an incidental finding, or symptomatic, and it represents a clinical challenge due to the low sensitivity and specificity of direct and indirect parasitological diagnostic tests, respectively. It requires a structured approach based on geographical areas, environmental exposures and behavioral risks, and associated symptoms. The initial assessment should include a comprehensive and tailored anamnesis and physical examination, basic laboratory tests, a complete parasitological examination of stool samples and a Strongyloides stercoralis serology, supplemented with other explorations guided by epidemiological and clinical suspicion. Empiric treatment with albendazole and/or ivermectin (plus praziquantel if risk of schistosomiasis) is an option for unidentified persistent eosinophilia after study, and in persons in whom a proper assessment or follow-up cannot be assured. In patients at risk for estrongiloidosis who are candidates for immunosuppressive therapies, it is indicated a prior screening and treatment to prevent a future hyperinfestation syndrome

[Clinical approach to imported eosinophilia]. / Aproximación clínica a la eosinofilia importada.

Eosinophilia is a common finding in international travelers and immigrants, being an helmintic infection its main etiology. The positive predictive value of eosinophilia for an helmintosis is low in travellers. Eosinophilia may be an incidental finding, or symptomatic, and it represents a clinical challenge due to the low sensitivity and specificity of direct and indirect parasitological diagnostic tests, respectively. It requires a structured approach based on geographical areas, environmental exposures and behavioral risks, and associated symptoms. The initial assessment should include a comprehensive and tailored anamnesis and physical examination, basic laboratory tests, a complete parasitological examination of stool samples and a Strongyloides stercoralis serology, supplemented with other explorations guided by epidemiological and clinical suspicion. Empiric treatment with albendazole and/or ivermectin (plus praziquantel if risk of schistosomiasis) is an option for unidentified persistent eosinophilia after study, and in persons in whom a proper assessment or follow-up can not be assured. In patients at risk for estrongiloidosis who are candidates for immunosuppressive therapies, it is indicated a prior screening and treatment to prevent a future hyperinfestation syndrome.