Cytomegalovirus Reactivations in Allogeneic Hematopoietic Stem Cell Transplantation from HLA-Matched and Haploidentical Donors with Post-Transplantation Cyclophosphamide.

Cytomegalovirus (CMV) reactivations cause significant morbidity in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy) is associated with an increased risk of CMV infections. Data are limited comparing HSCT with PTCy performed from matched sibling donors (MSDs), matched unrelated donors (MUDs), and haploidentical (Haplo) donors. In the present study, we aimed to characterize CMV reactivation and recurrence in patients with hematologic malignancies undergoing HSCT from MSD, MUD, and Haplo donors using PTCy as GVHD prophylaxis in the pre-letermovir era. We also analyzed risk factors of CMV reactivation, including GVHD as a time-dependent variable, on the incidence and mortality associated with CMV infections. We analyzed CMV reactivation in patients undergoing HSCT from 160 MSDs, 124 MUDs, and 82 Haplo donors from a single institution. Uniform GVHD prophylaxis with PTCy, sirolimus, and mycophenolate mofetil was given irrespective of donor type. Overall, 46% of patients had at least 1 CMV reactivation. The 1-year cumulative incidence of CMV infection was 39% for MSD, 44% for MUD, and 62% for Haplo donors (P < .001), with 96% of reactivations occurring before day +100. Multivariate analysis identified factors associated with the first CMV reactivation, including Haplo donor, positive recipient CMV serology, older patient age, and grade II-IV acute GVHD. The 1-year cumulative incidence of second reactivation from HSCT was 13%. Recipient CMV seropositivity, older patient age, and grade II-IV acute GVHD, but not type of donor, were identified as adverse factors for second CMV reactivation in multivariate analysis. The 1-year cumulative incidence of a third reactivation post HSCT was 4.4%. Ten cases of CMV disease were recorded, with no attributable deaths. Nevertheless, the risk for nonrelapse mortality was greater for patients who experienced CMV reactivation in multivariate time-dependent Cox model analysis. CMV reactivation is frequent in HSCT with PTCy in patients not receiving letermovir prophylaxis. Identified risk factors include the use of a Haplo donor, recipient CMV seropositivity, and grade II-IV acute GVHD. The prevalence of recurrent CMV reactivations is a noteworthy issue, especially after acute GVHD, warranting trials of secondary prophylaxis strategies.

Ten Issues for Updating in Community-Acquired Pneumonia: An Expert Review.

Community-acquired pneumonia represents the third-highest cause of mortality in industrialized countries and the first due to infection. Although guidelines for the approach to this infection model are widely implemented in international health schemes, information continually emerges that generates controversy or requires updating its management. This paper reviews the most important issues in the approach to this process, such as an aetiologic update using new molecular platforms or imaging techniques, including the diagnostic stewardship in different clinical settings. It also reviews both the Intensive Care Unit admission criteria and those of clinical stability to discharge. An update in antibiotic, in oxygen, or steroidal therapy is presented. It also analyzes the management out-of-hospital in CAP requiring hospitalization, the main factors for readmission, and an approach to therapeutic failure or rescue. Finally, the main strategies for prevention and vaccination in both immunocompetent and immunocompromised hosts are reviewed.

Ten Issues to Update in Nosocomial or Hospital-Acquired Pneumonia: An Expert Review.

Nosocomial pneumonia, or hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP) are important health problems worldwide, with both being associated with substantial morbidity and mortality. HAP is currently the main cause of death from nosocomial infection in critically ill patients. Although guidelines for the approach to this infection model are widely implemented in international health systems and clinical teams, information continually emerges that generates debate or requires updating in its management. This scientific manuscript, written by a multidisciplinary team of specialists, reviews the most important issues in the approach to this important infectious respiratory syndrome, and it updates various topics, such as a renewed etiological perspective for updating the use of new molecular platforms or imaging techniques, including the microbiological diagnostic stewardship in different clinical settings and using appropriate rapid techniques on invasive respiratory specimens. It also reviews both Intensive Care Unit admission criteria and those of clinical stability to discharge, as well as those of therapeutic failure and rescue treatment options. An update on antibiotic therapy in the context of bacterial multiresistance, in aerosol inhaled treatment options, oxygen therapy, or ventilatory support, is presented. It also analyzes the out-of-hospital management of nosocomial pneumonia requiring complete antibiotic therapy externally on an outpatient basis, as well as the main factors for readmission and an approach to management in the emergency department. Finally, the main strategies for prevention and prophylactic measures, many of them still controversial, on fragile and vulnerable hosts are reviewed.

Reduction in the risk of progression of solid organ transplant recipients infected by SARS-CoV-2 treated with monoclonal antibodies / Reducción del riesgo de progresión en receptores de trasplantes infectados por SARS-CoV-2 tratados con anticuerpos monoclonales

Recipients of solid organ transplants (SOT) are at higher risk of infection by SARS-CoV-2 virus especially due to chronic immunosuppression therapy and frequent multiple comorbid conditions. COVID-19 is a potentially life-threatening disease in SOT recipients, with an increased likelihood of progressing to severe disease, with the need of hospitalization, admission to the intensive care unit (ICU) and mechanical ventilatory support. This article presents an updated review of different aspects related to the outcome of COVID-19 in SOT recipients. In nvaccinated SOT recipients, COVID-19 is associated with a high mortality rate, in-patient care and ICU admission, and impaired graft function or rejection in severe disease. In vaccinated SOT recipients even after full vaccination, there is a reduction of the risk of mortality, but the course of COVID-19 may continue to be severe, influenced by the time from transplant, the net state of immunosuppression and having suffered graft rejection or dysfunction. SOT recipients develop lower immunity from mRNA vaccines with suboptimal response. Treatment with mAbs provides favorable outcomes in non-hospitalized SOT recipients at high risk for severe disease, with lower rates of hospitalization, emergency department visits, ICU care, progression to severe disease, and death. However, broad vaccination and therapeutic options are required, particularly in light of the tendency of the SARS-CoV-2 virus to adapt and evade both natural

Los receptores de trasplantes de órganos sólidos (TOS) presentan un alto riesgo de infección por el virus SARS-CoV-2 debido al tratamiento inmunosupresor y múltiples comorbilidades. La COVID-19 puede ser potencialmente mortal en receptores de TOS, con un aumento de la probabilidad de progresión a enfermedad grave. Este trabajo presenta una revisión actualizada del impacto de la COVID-19 en receptores de TOS. En los receptores de TOS no vacunados, la COVID-19 se asocia con una alta tasa de mortalidad, hospitalización, ingreso en la UCI y deterioro del injerto o rechazo. En los pacientes vacunados, incluso con pauta de vacunación completa, se reduce el riesgo de mortalidad, pero el curso de la COVID-19 puede continuar siendo grave en función del tiempo desde el trasplante, el estado neto de inmunosupresión y haber sufrido rechazo o disfunción del injerto. Los receptores de TOS presentan una baja inmunogenicidad a las vacunas de ARNm y respuesta subóptima. El tratamiento con anticuerpos monoclonales (AMC) en receptores de TOS no hospitalizados con alto riesgo de enfermedad grave, se asocia con menores tasas de hospitalización, visitas a urgencias, ingreso en UCI, progresión a enfermedad grave y muerte. Sin embargo, se requieren nuevas vacunas y opciones terapéuticas, teniendo en cuenta la tendencia del virus SARS-CoV-2 a adaptarse y a evadir tanto la inmunidad natural como la inducida por la vacuna (Au)and vaccine-induced immunity (AU)

Expert Consensus: Main Risk Factors for Poor Prognosis in COVID-19 and the Implications for Targeted Measures against SARS-CoV-2.

The clinical evolution of patients infected with the Severe Acute Respiratory Coronavirus type 2 (SARS-CoV-2) depends on the complex interplay between viral and host factors. The evolution to less aggressive but better-transmitted viral variants, and the presence of immune memory responses in a growing number of vaccinated and/or virus-exposed individuals, has caused the pandemic to slowly wane in virulence. However, there are still patients with risk factors or comorbidities that put them at risk of poor outcomes in the event of having the coronavirus infectious disease 2019 (COVID-19). Among the different treatment options for patients with COVID-19, virus-targeted measures include antiviral drugs or monoclonal antibodies that may be provided in the early days of infection. The present expert consensus is based on a review of all the literature published between 1 July 2021 and 15 February 2022 that was carried out to establish the characteristics of patients, in terms of presence of risk factors or comorbidities, that may make them candidates for receiving any of the virus-targeted measures available in order to prevent a fatal outcome, such as severe disease or death. A total of 119 studies were included from the review of the literature and 159 were from the additional independent review carried out by the panelists a posteriori. Conditions found related to strong recommendation of the use of virus-targeted measures in the first days of COVID-19 were age above 80 years, or above 65 years with another risk factor; antineoplastic chemotherapy or active malignancy; HIV infection with CD4+ cell counts < 200/mm3; and treatment with anti-CD20 immunosuppressive drugs. There is also a strong recommendation against using the studied interventions in HIV-infected patients with a CD4+ nadir <200/mm3 or treatment with other immunosuppressants. Indications of therapies against SARS-CoV-2, regardless of vaccination status or history of infection, may still exist for some populations, even after COVID-19 has been declared to no longer be a global health emergency by the WHO.

Time from symptoms onset to remdesivir is associated with the risk of ICU admission: a multicentric analyses.

BACKGROUND: Shorter duration of symptoms before remdesivir has been associated with better outcomes. Our goal was to evaluate variables associated with the need of ICU admission in a cohort of hospitalized patients for COVID-19 under remdesivir including the period from symptoms onset to remdesivir. METHODS: We conducted a retrospective multicentric study analysing all patients admitted with COVID-19 in 9 Spanish hospitals who received treatment with remdesivir in October 2020. The main outcome was the need of ICU admission after 24 h of the first dose of remdesivir. RESULTS: In our cohort of 497 patients, the median of days from symptom onset to remdesivir was 5 days, and 70 of them (14.1%) were later admitted into ICU. The clinical outcomes associated with ICU admission were days from symptoms onset (5 vs. 6; p = 0.023), clinical signs of severe disease (respiratory rate, neutrophil count, ferritin levels and very-high mortality rate in SEIMC-Score) and the use of corticosteroids and anti-inflammatory drugs before ICU. The only variable significatively associated with risk reduction in the Cox-regression analyses was ≤ 5 days from symptoms onset to RDV (HR: 0.54, CI95%: 0.31-0.92; p = 0.024). CONCLUSION: For patients admitted to the hospital with COVID-19, the prescription of remdesivir within 5 days from symptoms onset diminishes the need of ICU admission.

Climate change, animals, and Candida auris: insights into the ecological niche of a new species from a One Health approach.

BACKGROUND: One of the most puzzling traits of Candida auris is the recent simultaneous and independent emergence of five genetically distinct clades on three continents. Global warming has been proposed as a contributing factor for this emergence owing to high thermotolerance of C. auris compared with phylogenetically close Candida species. This hypothesis postulates that climate change induced an environmental ancestor to become pathogenic through thermal adaptation and was then globally disseminated by an intermediate host. OBJECTIVES: The aim of this review is to compile the current knowledge on the emergence and ecological environmental niches of C. auris and highlight the potential role of animals in transmission. SOURCES: A literature search was conducted using PubMed, MEDLINE, Google Scholar, and Web of Science from May 2022 to January 2023. CONTENT: We discuss the up-to-date data on the ecological niches of this fungus and its mechanisms of emergence, transmission cycle in nature, and worldwide dissemination. We highlight the possibility of an originally intermediate host possibly related to marine or freshwater ecosystems on the basis of recent molecular and microbiological evidence from a One Health perspective. The consequences of harmful human impact on the environment in the rise of new fungal pathogenic species, such as C. auris, are also analysed and compared with other animal precedents. IMPLICATIONS: The present knowledge can prompt the generation of new evidence on the ecological reservoirs of C. auris and its original mechanisms of environmental or interspecies transmission. Further research on the highlighted gaps will help understand the importance of the relationships between human, animal, and ecosystem health as factors involved in the rise and spread of emerging fungal pathogenic species.

Outcomes of octogenarians and nonagenarians with Pseudomonas aeruginosa bacteremia: a multicenter retrospective study.

BACKGROUND: P. aeruginosa bacteremia is a common and severe infection carrying high mortality in older adults. We aimed to evaluate outcomes of P. aeruginosa bacteremia among old adults (≥ 80 years). METHODS: We included the 464/2394 (19%) older adults from a retrospective multinational (9 countries, 25 centers) cohort study of individuals hospitalized with P. aeruginosa bacteremia. Bivariate and multivariable logistic regression models were used to evaluate risk factors for 30-day mortality among older adults. RESULTS: Among 464 adults aged ≥ 80 years, the mean age was 84.61 (SD 3.98) years, and 274 (59%) were men. Compared to younger patients, ≥ 80 years adults had lower Charlson score; were less likely to have nosocomial acquisition; and more likely to have urinary source. Thirty-day mortality was 30%, versus 27% among patients 65-79 years (n = 894) and 25% among patients < 65 years (n = 1036). Multivariate analysis for predictors of mortality among patients ≥ 80 years, demonstrated higher SOFA score (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.23-1.51, p < 0.001), corticosteroid therapy (OR 3.15, 95% CI: 1.24-8.01, p = 0.016) and hospital acquired P. aeruginosa bacteremia (OR 2.30, 95% CI: 1.33-3.98, p = 0.003) as predictors. Appropriate empirical therapy within 24 h, type of definitive anti-pseudomonal drug, and type of regimen (monotherapy or combination) were not associated with 30-day mortality. CONCLUSIONS: In older adults with P. aeruginosa bacteremia, background conditions, place of acquisition, and disease severity are associated with mortality, rather than the antimicrobial regimen. In this regard, preventive efforts and early diagnosis before organ failure develops might be beneficial for improving outcomes.

Dalbavancin in clinical practice in Spain: a 2†year retrospective study.

Objectives: Dalbavancin is approved for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) in adults. Its unique pharmacokinetic properties allow daily dosing to be avoided. The objective was to describe the sociodemographic and clinical characteristics of patients treated with dalbavancin in Spain, and to evaluate its effectiveness and safety in real-world settings. Patients and methods: This non-interventional, retrospective, observational and multicentre study included patients who received at least one dose between 2018 and 2019 in seven Spanish hospitals. Results: In total, 187 patients were included. The most common comorbidities were cardiovascular disease (27.4%) and diabetes mellitus (23.5%). Dalbavancin was used to treat osteoarticular infections (28.3%), ABSSSIs (22.5%), cardiovascular infections (20.9%) and catheter-related infections (18.2%). The most prevalent pathogens were Staphylococcus aureus (34.2%), CoNS (32.6%), and enterococci (12.8%). The main reason for use was early hospital discharge (65.8%). Most patients were treated with 1500 mg in a single dose (35.3%) and the median duration of treatment was 2 weeks. The treatment was clinically successful in 91.4% of cases. Six patients (3.2%) reported adverse events. Physicians agreed on the potential reduction of hospitalization days (85.3%). A subanalysis of patient characteristics and type of pathogen showed similar results in terms of efficacy and safety. Conclusions: Dalbavancin seems to be effective and safe as second-line treatment in severe Gram-positive infections. It improves treatment adherence and allows outpatient management. Furthermore, the effectiveness and safety profile are maintained against diverse microorganisms in Gram-positive infections and regardless of the patients' comorbidities at baseline, or age.

A systematic literature review and expert consensus on risk factors associated to infection progression in adult patients with respiratory tract or rectal colonisation by carbapenem-resistant Gram-negative bacteria / Revisión sistemática de la literatura y consenso de expertos sobre los factores de riesgo asociados a la progresión de la infección en pacientes adultos con colonización del tracto respiratorio o rectal por bacterias gramnegativas resistentes a carbapenémicos

Objective. Risk factors (RFs) associated with infection progression in patients already colonised by carbapenem-resistant Gram-negative bacteria (CRGNB) have been addressed in few and disperse works. The aim of this study is to identify the relevant RFs associated to infection progression in patients with respiratory tract or rectal colonisation.Material and methods. A systematic literature review was developed to identify RFs associated with infectionprogression in patients with CRGNB respiratory tract or rectal colonisation. Identified RFs were then evaluated and discussed by the expert panel to identify those that are relevant according to the evidence and expert’s experience.Results. A total of 8 articles were included for the CRGNB respiratory tract colonisation and 21 for CRGNB rectal colonisation, identifying 19 RFs associated with pneumonia development and 44 RFs associated with infection progression, respectively. After discussion, the experts agreed on 13 RFs to be associated with pneumonia development after respiratory tract CRGNB colonisation and 33 RFs to be associated with infection progression after rectal CRGNB colonisation. Respiratory tract and rectal colonisation, previous stay in the ICU and longer stay in the ICU were classified as relevant RF independently of the pathogen and site of colonisation. Previous exposure to antibiotic therapy or previous carbapenem use were also common relevant RF for patients with CRGNB respiratory tract and rectal colonisation. (AU)

Objetivo. Los factores de riesgo (FR) asociados a la progresión de la infección en pacientes ya colonizados por bacterias gramnegativas resistentes a carbapenémicos (BGNRC) han sido abordados en pocos y dispersos trabajos. El objetivo de este estudio es identificar los factores de riesgo relevantes asociados a la progresión de la infección en pacientes con colonización del tracto respiratorio o rectal.Material y métodos. Se realizó una revisión sistemática de la literatura para identificar los FR asociados a la progresión de la infección en pacientes con colonización del tracto respiratorio o rectal por BGNRC. Los FR identificados fueron luego evaluados y discutidos por el panel de expertos para identificar aquellos que son relevantes según la evidencia disponible y la experiencia de los expertos.Resultados. Un total de 8 artículos fueron incluidos en el análisis de los FR en la colonización del tracto respiratorio y 21 para la colonización rectal, identificándose 19 FR asociados al desarrollo de neumonía y 44 FR asociados a la progresión de la infección respectivamente. Tras la sesión de discusión, los expertos acordaron que 13 FR se asociaban al desarrollo de neumonía tras la colonización del tracto respiratorio por BGNRC y 33 FR a la progresión de la infección tras la colonización rectal por BGNRC. La colonización del tracto respiratorio y rectal, la estancia previa en la UCI y una estancia prolongada en la UCI se clasificaron como FR relevantes independientemente del patógeno y del lugar de colonización. La exposición previa a antibióticos o el uso previo de carbapenémicos se clasificaron como FR relevantes para varios de los patógenos tanto en pacientes con colonización del tracto respiratorio como rectal. (AU)

Current management of CMV infection in cancer patients (solid tumors). Epidemiology and therapeutic strategies

Little evidence is available regarding the incidence of CMV disease in patients with solid cancers. Latest data show that approximately 50 % of these patients with CMV PCR positivity developed clinically relevant CMV-viremia, and would require specific therapy. In the clinical arena, CMV reactivation is an important differential diagnosis in the infectological work up of these patients, but guidelines of management on this subject are not yet available. CMV reactivation should be considered during differential diagnosis for patients with a severe decline in lymphocyte counts when receiving chemoradiotherapy or immunochemotherapy with lymphocyte-depleting or blocking agents. Monitoring of CMV reactivation followed by the implementation of preemptive strategies or the establishment of early antiviral treatment improves the prognosis and reduces the morbidity and mortality of these patients. (AU)

Treatment of Clostridioides difficile infection: from guidelines to clinical practice

The Clostridioides difficile Infection (CDI) treatment guidelines were published in 2021; however, the incorporation of these recommendations into clinical practice was rather irregular and inconsistent. The differences in the implementation of these new guidelines were due, in part, to the variety in the different professionals who provided patient care, as well as to the issues involved in either their accessibility or availability or both. The main requirements for implementation include appropriate reflection on patient stratification, drug positioning, accessibility to drugs, as well as the organization of structured clinical pathways that can facilitate the functionality and evaluation of the management of CDI. (AU)

Lactobacillus supports Clostridiales to restrict gut colonization by multidrug-resistant Enterobacteriaceae.

Infections by multidrug-resistant Enterobacteriaceae (MRE) are life-threatening to patients. The intestinal microbiome protects against MRE colonization, but antibiotics cause collateral damage to commensals and open the way to colonization and subsequent infection. Despite the significance of this problem, the specific commensals and mechanisms that restrict MRE colonization remain largely unknown. Here, by performing a multi-omic prospective study of hospitalized patients combined with mice experiments, we find that Lactobacillus is key, though not sufficient, to restrict MRE gut colonization. Lactobacillus rhamnosus and murinus increase the levels of Clostridiales bacteria, which induces a hostile environment for MRE growth through increased butyrate levels and reduced nutrient sources. This mechanism of colonization resistance, an interaction between Lactobacillus spp. and Clostridiales involving cooperation between microbiota members, is conserved in mice and patients. These results stress the importance of exploiting microbiome interactions for developing effective probiotics that prevent infections in hospitalized patients.

Current Positioning against Severe Infections Due to Klebsiella pneumoniae in Hospitalized Adults.

Infections due to Klebsiella pneumoniae have been increasing in intensive care units (ICUs) in the last decade. Such infections pose a serious problem, especially when antimicrobial resistance is present. We created a task force of experts, including specialists in intensive care medicine, anaesthesia, microbiology and infectious diseases, selected on the basis of their varied experience in the field of nosocomial infections, who conducted a comprehensive review of the recently published literature on the management of carbapenemase-producing Enterobacterales (CPE) infections in the intensive care setting from 2012 to 2022 to summarize the best available treatment. The group established priorities regarding management, based on both the risk of developing infections caused by K. pneumoniae and the risk of poor outcome. Moreover, we reviewed and updated the most important clinical entities and the new antibiotic treatments recently developed. After analysis of the priorities outlined, this group of experts established a series of recommendations and designed a management algorithm.

Duration of Treatment for Pseudomonas aeruginosa Bacteremia: a Retrospective Study.

INTRODUCTION: There is no consensus regarding optimal duration of antibiotic therapy for Pseudomonas aeruginosa bacteremia. We aimed to evaluate the impact of short antibiotic course. METHODS: We present a retrospective multicenter study including patients with P. aeruginosa bacteremia during 2009-2015. We evaluated outcomes of patients treated with short (6-10 days) versus long (11-15 days) antibiotic courses. The primary outcome was a composite of 30-day mortality or bacteremia recurrence and/or persistence. Univariate and inverse probability treatment-weighted (IPTW) adjusted multivariate analysis for the primary outcome was performed. To avoid immortal time bias, the landmark method was used. RESULTS: We included 657 patients; 273 received a short antibiotic course and 384 a long course. There was no significant difference in baseline characteristics of patients. The composite primary outcome occurred in 61/384 patients in the long-treatment group (16%) versus 32/273 in the short-treatment group (12%) (p = 0.131). Mortality accounted for 41/384 (11%) versus 25/273 (9%) of cases, respectively. Length of hospital stay was significantly shorter in the short group [median 13 days, interquartile range (IQR) 9-21 days, versus median 15 days, IQR 11-26 days, p = 0.002]. Ten patients in the long group discontinued antibiotic therapy owing to adverse events, compared with none in the short group. On univariate and multivariate analyses, duration of therapy was not associated with the primary outcome. CONCLUSIONS: In this retrospective study, 6-10 days of antibiotic course for P. aeruginosa bacteremia were as effective as longer courses in terms of survival and recurrence. Shorter therapy was associated with reduced length of stay and less drug discontinuation.

Response to Vaccines in Patients with Immune-Mediated Inflammatory Diseases: A Narrative Review.

Patients with immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis and inflammatory bowel disease, are at increased risk of infection. International guidelines recommend vaccination to limit this risk of infection, although live attenuated vaccines are contraindicated once immunosuppressive therapy has begun. Biologic therapies used to treat IMIDs target the immune system to stop chronic pathogenic process but may also attenuate the protective immune response to vaccines. Here, we review the current knowledge regarding vaccine responses in IMID patients receiving treatment with biologic therapies, with a focus on the interleukin (IL)-12/23 inhibitors. B cell-depleting therapies, such as rituximab, strongly impair vaccines immunogenicity, and tumor necrosis factor (TNF) inhibitors and the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) fusion protein abatacept are also associated with attenuated antibody responses, which are further diminished in patients taking concomitant immunosuppressants. On the other hand, integrin, IL-6, IL-12/23, IL-17, and B-cell activating factor (BAFF) inhibitors do not appear to affect the immune response to several vaccines evaluated. Importantly, treatment with biologic therapies in IMID patients is not associated with an increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or developing severe disease. However, the efficacy of SARS-CoV-2 vaccines on IMID patients may be reduced compared with healthy individuals. The impact of biologic therapies on the response to SARS-CoV-2 vaccines seems to replicate what has been described for other vaccines. SARS-CoV-2 vaccination appears to be safe and well tolerated in IMID patients. Attenuated but, in general, still protective responses to SARS-CoV-2 vaccination in the context of certain therapies warrant current recommendations for a third primary dose in IMID patients treated with immunosuppressive drugs.

Decalogue for the selection of oral antibiotics for lower respiratory tract infections / Decálogo para la selección del antibiótico oral en las infecciones respiratorias de vías bajas

Lower respiratory tract infections, including chronic obstructive pulmonary disease exacerbations (COPD-E) and community acquired pneumonia (CAP), are one of the most frequent reasons for consultation in primary care and hospital emergency departments, and are the cause of a high prescription of antimicrobial agents. The selection of the most appropriate oral antibiotic treatment is based on different aspects and includes to first consider a bacterial aetiology and not a viral infection, to know the bacterial pathogen that most frequently cause these infections and the frequency of their local antimicrobial resistance. Treatment should also be prescribed quickly and antibiotics should be selected among those with a quicker mode of action, achieving the greatest effect in the shortest time and with the fewest adverse effects (toxicity, interactions, resistance and/or ecological impact). Whenever possible, antimicrobials should be rotated and diversified and switched to the oral route as soon as possible. With these premises, the oral treatment guidelines for mild or moderate COPD-E and CAP in Spain include as first options betalactam antibiotics (amoxicillin and amoxicillin-clavulanate and cefditoren), in certain situations associated with a macrolide, and relegating fluoroquinolones as an alternative, except in cases where the presence of Pseudomonas aeruginosa is suspected (AU)

Las infecciones del tracto respiratorio inferior, incluyendo las exacerbaciones de la enfermedad pulmonar obstructiva crónica (EPOC) y la neumonía adquirida en la comunidad (NAC), son uno de los motivos de consulta más frecuentes en atención primaria y los servicios de urgencias hospitalarios, y son la causa de una elevada prescripción de antimicrobianos. La selección del tratamiento oral más adecuado con antibióticos se basa en diferentes aspectos e incluye considerar en primer lugar una etiología bacteriana y no una infección vírica, conocer los patógenos bacterianos que más frecuentemente causa estas infecciones y la frecuencia local de su resistencia antimicrobiana. Además, el tratamiento debe prescribirse rápidamente y los antibióticos deben seleccionarse entre los que tienen un modo de acción más rápido, logrando el mayor efecto en el menor tiempo y con el menor número de efectos adversos (toxicidad, interacciones, resistencia y/o impacto ecológico). Siempre que sea posible, hay que rotar y diversificar los antimicrobianos y pasar a la vía oral lo antes posible. Con estas premisas, las guías de tratamiento oral de la exacerbación leve o moderada de la EPOC y NAC en España incluyen como primera opción los antibióticos betalactámicos (amoxicilina y amoxicilina-clavulánico y cefditoreno), en determinadas situaciones asociados a un macrólido, y relegando las fluoroquinolonas como alternativa, salvo en los casos en que se sospeche la presencia de Pseudomonas aeruginosa (AU)

Observational study to evaluate discontinuation of monotherapy with cobicistat-boosted darunavir in patients with human immunodeficiency virus.

To evaluate the reasons for changing to monotherapy with protease inhibitors, together with the proportion and reasons for the interruption to treatment, in patients who have been treated at some point with cobicistat-boosted darunavir (DRV/c). Outpatients in a tertiary hospital. Observational retrospective study to evaluate monotherapy with DRV/c (800 mg/150 mg) in adult patients with human immunodeficiency virus infection, from December 2014 to July 2022. Demographic variables, viral load, cluster of differentiation 4 lymphocyte lymphocyte count, and antiretroviral therapy were assessed. 42 patients were included. 36% of the patients were undergoing monotherapy at the time of the analysis. The main reason for discontinuation was poor adherence. At time of analysis, 80% of the patients in monotherapy had an undetectable viral load. Antiretroviral therapy recommendations advise against exposing the patient to functional monotherapy with a single drug due to the high risk of virological failure and the onset of resistance to a single drug. Following the analysis of the results, DRV/c in monotherapy is not an effective strategy in the medium and long term due to factors such as lack of adherence or virological failure, although it can be maintained in specific circumstances. Therefore, patients undergoing monotherapy require close monitoring.

Host-pathogen interactions upon Candida auris infection: fungal behaviour and immune response in Galleria mellonella.

Candida auris has globally emerged as a multidrug-resistant fungus linked to healthcare-associated outbreaks. There is still limited evidence on its virulence, pathogenicity determinants, and complex host-pathogen interactions. This study analyzes the in vivo fungal behaviour, immune response, and host-pathogen interactions upon C. auris infection compared to C. albicans and C. parapsilosis in G. mellonella. This was performed by immunolabelling fungal structures and larval plasmatocytes and using a quantitative approach incorporating bioinformatic morphometric techniques into the study of microbial pathogenesis. C. auris presents a remarkably higher immunogenic activity than expected at its moderate degree of tissue invasion. It induces a greater inflammatory response than C. albicans and C. parapsilosis at the expense of plasmatocyte nodule formation, especially in non-aggregative strains. It specifically invades the larval respiratory system, in a pattern not previously observed in other Candida species, and presents inter-phenotypic tissue tropism differences. C. auris filaments in vivo less frequently than C. albicans or C. parapsilosis mostly through pseudohyphal growth. Filamentation might not be a major pathogenic determinant in C. auris, as less virulent aggregative phenotypes form pseudohyphae to a greater extent. C. auris has important both interspecific and intraspecific virulence and phenotype heterogeneity, with aggregative phenotypes of C. auris sharing characteristics with low pathogenic species such as C. parapsilosis. Our work suggests that C. auris owns an important morphogenetic plasticity that distinguishes it from other yeasts of the genus. Routine phenotypic identification of aggregative or non-aggregative phenotypes should be performed in the clinical setting as it may impact patient management.