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

Conventional Hospitalization versus Sequential Outpatient Parenteral Antibiotic Therapy for Staphylococcus aureus Bacteremia: Post-Hoc Analysis of a Multicenter Observational Cohort

Staphylococcus aureus; Bacteremia; Outpatient parenteral antimicrobial therapyStaphylococcus aureus; Bacterièmia; Teràpia antimicrobiana parenteral ambulatòriaStaphylococcus aureus; Bacteriemia; Terapia antimicrobiana parenteral ambulatoriaIt is not known whether sequential outpatient parenteral antimicrobial (OPAT) is as safe and effective as conventional hospitalization in patients with S. aureus bacteremia (SAB). A post-hoc analysis of the comparative effectiveness of conventional hospitalization versus sequential OPAT was performed in two prospective Spanish cohorts of patients with S. aureus bacteremia. The PROBAC cohort is a national, multicenter, prospective observational cohort of patients diagnosed in 22 Spanish hospitals between October 2016 and March 2017. The DOMUS OPAT cohort is a prospective observational cohort including patients from two university hospitals in Seville, Spain from 2012 to 2021. Multivariate regression was performed, including a propensity score (PS) for receiving OPAT, stratified analysis according to PS quartiles, and matched pair analyses based on PS. Four hundred and thirteen patients were included in the analysis: 150 in sequential OPAT and 263 in the full hospitalization therapy group. In multivariate analysis, including PS and center effect as covariates, 60-day treatment failure was lower in the OPAT group than in the full hospitalization group (p < 0.001; OR 0.275, 95%CI 0.129−0.584). In the PS-based matched analyses, sequential treatment under OPAT was not associated with higher 60-day treatment failure (p = 0.253; adjusted OR 0.660; % CI 0.324−1.345). OPAT is a safe and effective alternative to conventional in-patient therapy for completion of treatment in well-selected patients with SAB, mainly those associated with a low-risk source and without end-stage kidney disease

Uso de pulsos de metilprednisolona de repetición en adultos hospitalizados por neumonía y síndrome de distrés respiratorio agudo por COVID-19: un estudio preliminar de tipo antes-después (estudio CortiCOVID)

[EN] 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.[ES] 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

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.NIH (contract to AS, DW), Grant/AwardNumber: 75N9301900065; “Contratación de Personal Investigador Doctor”supported by the European Social Fund and Junta de Andalucía (PAIDIDOCTOR- Convocatoria 2019-2020 toFJO, SB); Instituto de Salud Carlos III,Fondos FEDER. ERM was supported bythe Spanish Research Council (CSIC);Consejería de Transformación Económica, Industria, Conocimiento y Universidades Junta de Andalucía (research project to ERM), Grant/AwardNumber: CV20-85418; Red Temática de Investigación Cooperativa en SIDA, whichis included in the Acción Estratégica en Salud, Plan Nacional de InvestigaciónCientífica, Desarrollo e Innovación Tecnológica, 2008 to 2011 and 2013 to 2016,Grant/Award Numbers: RD16/0025/0020,RD16/0025/0026; Consejeria de Salud Junta de Andalucia (Research contract toJV), Grant/Award Number:RH-0037-2020; Instituto de Salud CarlosIII (PI19/01127 to ERM, CP19/00159 toAGV, FI17/00186 to MRJL, FI19/00083 toCGC, CM20/00243 to APG andCOV20/00698 to support COHVID-GS)Peer reviewe

Description of SARS-CoV-2 T-cell polyfunctionality features

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-gamma; with absence of perforin production predominated in severe disease. Seven months after infection, both non-hospitalized and previously hospitalized patients presented robust anti-S IgG levels and SARS-CoV-2 specific T-cell response. In addition, only previously hospitalized 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 samples from healthy donors. These results 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.Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades Junta de Andalucia (research Project CV20-85418) (ERM) NIH contract 75N9301900065 (AS, DW) Consejeria de Salud Junta de Andalucia (Research Contract RH-0037-2020 to JV) Instituto de Salud Carlos III (CP19/00159 to AGV, FI17/00186 to MRJL, FI19/00083 to CGC, CM20/00243 to APG and COV20/00698 to support COHVID-GS) Red Temática de Investigación Cooperativa en SIDA (RD16/0025/0020; RD16/0025/0026), which is included in the Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, 2008 to 2011 and 2013 to 2016 Instituto de Salud Carlos III, Fondos FEDER. ERM was supported by the Spanish Research Council (CSIC). “Contratación de Personal Investigador Doctor” supported by the European Social Fund and Junta de Andalucía (PAIDI DOCTOR- Convocatoria 2019-2020). (FJO, SB).N

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19

A case of fatal monkeypox infection: necropsy and molecular findings, with some considerations related to clinical management

[Objective] Human monkeypox (mpox) is usually self-limited infection; however, rising data show a worse outcome in patients with impaired immune status, particularly those co-infected with HIV [Mitjà O, Alemany A, Marks M, Lezama Mora JI, Rodríguez-Aldama JC, Torres Silva MS et al. Mpox in people with advanced HIV infection: A global case series. Lancet. 2023; 401:939–49. DOI:https://doi.org/10.1016/S0140-6736(23)00273-8] [Govind A, Lazarte SM, Kitchell E, Chow JY, Estelle CD, Fixsen E et al. Severe mpox infections in people with uncontrolled human immunodeficiency virus (HIV). Clin Infect Dis. 2023; 76:1843–6. DOI:https://doi.org/10.1093/cid/ciad052].[Methods] We report the clinical, pathological, and molecular study of a patient with mpox infection and a late HIV diagnosis, with fatal outcome.[Results] Necropsy revealed visceral spread of mpox. Mpox virus was sequenced twice during the admission, uncovering an emerging mutation near a genomic region where mutations associated with tecovirimat resistance have been documented.[Discussion] Monkeypox can manifest as an opportunistic infection in individuals with advanced HIV-associated immunosuppression.Peer reviewe

Tratamiento antifúngico endovenoso domiciliario: una alternativa segura y eficaz

[EN ]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.[ES] 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

Predicting outcome in COVID-19 patients

As COVID-19 pandemic continues to escalate, hospitals around the world confront with the need to attend an increasing number of patients. Therefore, we read with much interest the recent study published in the Journal of Infection by Galloway JB et al., reinforcing the importance of stratifying patients to ease their management and their incorporation to potential clinical trials [1]. For this purpose, these authors developed a valuable and complex risk score based on twelve parameters, including, among others, age, gender, diabetes mellitus, hypertension, and chronic lung disease. Since knowing the risk of clinical deterioration can assist medical decisions about appropriate level of care, predictive models for COVID-19 are becoming notably frequent. However, many of them are notably biased, non-validated, or present a construction lacking in clarity [2,3]. Moreover, they often conclude that male older patients with comorbidities are more likely to experience unfavourable outcomes [4,5], even when such determinants are already well-known predictors of worse result in community-acquired pneumonia [6]. Although the medical assessment of patients must always address demographics and underlying comorbidities, it is known that the evaluation of disease severity and prognosis should not only depend on the above-mentioned risk markers.N

Conventional hospitalization versus sequential outpatient parenteral antibiotic therapy for Staphylococcus aureus bacteremia: post-hoc analysis of a multicenter observational cohort

It is not known whether sequential outpatient parenteral antimicrobial (OPAT) is as safe and effective as conventional hospitalization in patients with S. aureus bacteremia (SAB). A post-hoc analysis of the comparative effectiveness of conventional hospitalization versus sequential OPAT was performed in two prospective Spanish cohorts of patients with S. aureus bacteremia. The PROBAC cohort is a national, multicenter, prospective observational cohort of patients diagnosed in 22 Spanish hospitals between October 2016 and March 2017. The DOMUS OPAT cohort is a prospective observational cohort including patients from two university hospitals in Seville, Spain from 2012 to 2021. Multivariate regression was performed, including a propensity score (PS) for receiving OPAT, stratified analysis according to PS quartiles, and matched pair analyses based on PS. Four hundred and thirteen patients were included in the analysis: 150 in sequential OPAT and 263 in the full hospitalization therapy group. In multivariate analysis, including PS and center effect as covariates, 60-day treatment failure was lower in the OPAT group than in the full hospitalization group (p < 0.001; OR 0.275, 95%CI 0.129–0.584). In the PS-based matched analyses, sequential treatment under OPAT was not associated with higher 60-day treatment failure (p = 0.253; adjusted OR 0.660; % CI 0.324–1.345). OPAT is a safe and effective alternative to conventional in-patient therapy for completion of treatment in well-selected patients with SAB, mainly those associated with a low-risk source and without end-stage kidney disease